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Sample records for bone regenerative potential

  1. Bone Marrow Stem Cell Derived Paracrine Factors for Regenerative Medicine: Current Perspectives and Therapeutic Potential

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    Tom J. Burdon

    2011-01-01

    Full Text Available During the past several years, there has been intense research in the field of bone marrow-derived stem cell (BMSC therapy to facilitate its translation into clinical setting. Although a lot has been accomplished, plenty of challenges lie ahead. Furthermore, there is a growing body of evidence showing that administration of BMSC-derived conditioned media (BMSC-CM can recapitulate the beneficial effects observed after stem cell therapy. BMSCs produce a wide range of cytokines and chemokines that have, until now, shown extensive therapeutic potential. These paracrine mechanisms could be as diverse as stimulating receptor-mediated survival pathways, inducing stem cell homing and differentiation or regulating the anti-inflammatory effects in wounded areas. The current review reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many logistical and technical issues regarding cell therapy and evaluates its future potential as an effective regenerative therapy.

  2. Hydroxyapatite from fish scale for potential use as bone scaffold or regenerative material

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    Pon-On, Weeraphat, E-mail: fsciwpp@ku.ac.th [Department of Physics, Faculty of Science, Kasetsart University, Bangkok (Thailand); Suntornsaratoon, Panan [Center of Calcium and Bone Research, Faculty of Science, Mahidol University, Bangkok (Thailand); Charoenphandhu, Narattaphol [Center of Calcium and Bone Research, Faculty of Science, Mahidol University, Bangkok (Thailand); Department of Physiology, Faculty of Science, Mahidol University, Bangkok (Thailand); Thongbunchoo, Jirawan [Center of Calcium and Bone Research, Faculty of Science, Mahidol University, Bangkok (Thailand); Krishnamra, Nateetip [Center of Calcium and Bone Research, Faculty of Science, Mahidol University, Bangkok (Thailand); Department of Physiology, Faculty of Science, Mahidol University, Bangkok (Thailand); Tang, I. Ming [Department of Materials Science, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand)

    2016-05-01

    The present paper studies the physico-chemical, bioactivity and biological properties of hydroxyapatite (HA) which is derived from fish scale (FS) (FSHA) and compares them with those of synthesized HA (sHA) obtained by co-precipitation from chemical solution as a standard. The analysis shows that the FSHA is composed of flat-plate nanocrystal with a narrow width size of about 15–20 nm and having a range of 100 nm in length and that the calcium phosphate ratio (Ca/P) is 2.01 (Ca-rich CaP). Whereas, synthesized HA consists of sub-micron HA particle having a Ca/P ratio of 1.65. Bioactivity test shows that the FSHA forms more new apatite than does the sHA after being incubated in simulated body fluid (SBF) for 7 days. Moreover, the biocompatibility study shows a higher osteoblast like cell adhesion on the FSHA surface than on the sHA substrate after 3 days of culturing. Our results also show the shape of the osteoblast cells on the FSHA changes from being a rounded shape to being a flattened shape reflecting its spreading behavior on this surface. MTT assay and ALP analysis show significant increases in the proliferation and activity of osteoblasts over the FSHA scaffold after 5 days of culturing as compared to those covering the sHA substrates. These results confirm that the bio-materials derived from fish scale (FSHA) are biologically better than the chemically synthesized HA and have the potential for use as a bone scaffold or as regenerative materials. - Highlights: • Preparation of hydroxyapatite (HA) which is derived from fish scale (FS) (FSHA) and their bioactivities • The FSHA is composed of flat-plate nanocrystal with a narrow size of 15–20 nm. • Bioactivity test shows that the FSHA forms more new apatite than does the sHA after being incubated SBF. • In vitro cell availability tests show a higher cell adhesion on the FSHA surface.

  3. Glycol chitosan/nanohydroxyapatite biocomposites for potential bone tissue engineering and regenerative medicine.

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    Dumont, Vitor C; Mansur, Herman S; Mansur, Alexandra A P; Carvalho, Sandhra M; Capanema, Nádia S V; Barrioni, Breno R

    2016-12-01

    In the last few decades, research on biocomposite nanomaterials has grown exponentially due to the global demand for novel solutions in bone tissue engineering and repair. In the present study, it is reported the design and synthesis of biocomposites based on glycol chitosan (GLY-CHI) matrices incorporated with nano-hydroxyapatite particles (nHA) produced via an eco-friendly chemical colloidal process in water media followed by solvent casting and evaporation methods at room temperature. The structure, morphology, and crystallinity of the components and biocomposites were extensively characterized by light microscopy (LM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), wavelength dispersive X-ray fluorescence spectroscopy (WD-XRF), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray micro-computed tomography analysis (μCT). Furthermore, cytotoxicity and cell viability tests were performed on three cell lines using a 3-(4,5-dimethylthiazol-2yl) 2,5-diphenyl tetrazolium bromide (MTT) assay, an alkaline phosphatase (ALP) activity test, and LIVE/DEAD(®) assays. The results demonstrated that the GLY-CHI ligand played a major role in the nucleation, growth and colloidal stabilization of calcium phosphate particles at nanoscale dimensions with a narrow distribution and average size of 74±15nm. The FTIR spectroscopy associated with the XRD results indicated that nanosized hydroxyapatite (nHA) was the predominant calcium phosphate phase produced in the colloidal processing route. In addition, the X-ray micro-CT analysis of the nanocomposite membranes showed that nHA particles were homogenously dispersed in the glycol-chitosan polymeric matrix. Moreover, according to the in vitro bioassays, the biocomposites showed an adequate cell viability response and non-cytotoxic behavior toward osteoblastic-like (SAOS) and embryonic cell lines (HEK293T). Finally, the results of

  4. Regenerative potential of immature permanent teeth with necrotic pulps after different regenerative protocols.

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    Nagy, Mohamed M; Tawfik, Hosam E; Hashem, Ahmed Abdel Rahman; Abu-Seida, Ashraf M

    2014-02-01

    Regenerative endodontics is a promising alternative treatment for immature teeth with necrotic pulps. The present study was performed to assess the regenerative potential of young permanent immature teeth with necrotic pulp after the following treatment protocols: (1) a mineral trioxide aggregate (MTA) apical plug, (2) the regenerative endodontic protocol (blood clot scaffold), and (3) the regenerative endodontic protocol with a blood clot and an injectable scaffold impregnated with basic fibroblast growth factor. Immature necrotic permanent maxillary central incisors (n = 36) of patients 9-13 years old were divided into 3 groups according to the treatment protocol: the MTA group (MTA apical plug), the REG group (regenerative endodontic protocol [blood clot]), and the FGF group (regenerative endodontic protocol [blood clot + injectable scaffold]). Follow-up was done up to 18 months. Standardized radiographs were digitally evaluated for an increase in root length and thickness, a decrease in the apical diameter, and a change in periapical bone density. After a follow-up period of 18 months, most of the cases showed radiographic evidence of periapical healing. Groups 2 and 3 showed a progressive increase in root length and width and a decrease in apical diameter. The regenerative endodontic procedure allowed the continued development of roots in teeth with necrotic pulps. The use of artificial hydrogel scaffold and basic fibroblast growth factor was not essential for repair. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  5. Adipose-Derived Stem Cells: A Review of Signaling Networks Governing Cell Fate and Regenerative Potential in the Context of Craniofacial and Long Bone Skeletal Repair

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    Kshemendra Senarath-Yapa

    2014-05-01

    Full Text Available Improvements in medical care, nutrition and social care are resulting in a commendable change in world population demographics with an ever increasing skew towards an aging population. As the proportion of the world’s population that is considered elderly increases, so does the incidence of osteodegenerative disease and the resultant burden on healthcare. The increasing demand coupled with the limitations of contemporary approaches, have provided the impetus to develop novel tissue regeneration therapies. The use of stem cells, with their potential for self-renewal and differentiation, is one potential solution. Adipose-derived stem cells (ASCs, which are relatively easy to harvest and readily available have emerged as an ideal candidate. In this review, we explore the potential for ASCs to provide tangible therapies for craniofacial and long bone skeletal defects, outline key signaling pathways that direct these cells and describe how the developmental signaling program may provide clues on how to guide these cells in vivo. This review also provides an overview of the importance of establishing an osteogenic microniche using appropriately customized scaffolds and delineates some of the key challenges that still need to be overcome for adult stem cell skeletal regenerative therapy to become a clinical reality.

  6. Bioreactor-Based Online Recovery of Human Progenitor Cells with Uncompromised Regenerative Potential: A Bone Tissue Engineering Perspective.

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    Maarten Sonnaert

    Full Text Available The use of a 3D perfusion culture environment for stem cell expansion has been shown to be beneficial for maintenance of the original cell functionality but due to several system inherent characteristics such as the presence of extracellular matrix, the continued development and implementation of 3D perfusion bioreactor technologies is hampered. Therefore, this study developed a methodology for harvesting a progenitor cell population from a 3D open porous culture surface after expansion in a perfusion bioreactor and performed a functional characterization of the expanded cells. An initial screening showed collagenase to be the most interesting reagent to release the cells from the 3D culture surface as it resulted in high yields without compromising cell viability. Subsequently a Design of Experiment approach was used to obtain optimized 3D harvest conditions by assessing the interplay of flow rate, collagenase concentration and incubation time on the harvest efficiency, viability and single cell fraction. Cells that were recovered with the optimized harvest protocol, by perfusing a 880 U/ml collagenase solution for 7 hours at a flow rate of 4 ml/min, were thereafter functionally analyzed for their characteristics as expanded progenitor cell population. As both the in vitro tri-lineage differentiation capacity and the in vivo bone forming potential were maintained after 3D perfusion bioreactor expansion we concluded that the developed seeding, culture and harvest processes did not significantly compromise the viability and potency of the cells and can contribute to the future development of integrated bioprocesses for stem cell expansion.

  7. Adaptive scapula bone remodeling computational simulation: Relevance to regenerative medicine

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    Sharma, Gulshan B., E-mail: gbsharma@ucalgary.ca [Emory University, Department of Radiology and Imaging Sciences, Spine and Orthopaedic Center, Atlanta, Georgia 30329 (United States); University of Pittsburgh, Swanson School of Engineering, Department of Bioengineering, Pittsburgh, Pennsylvania 15213 (United States); University of Calgary, Schulich School of Engineering, Department of Mechanical and Manufacturing Engineering, Calgary, Alberta T2N 1N4 (Canada); Robertson, Douglas D., E-mail: douglas.d.robertson@emory.edu [Emory University, Department of Radiology and Imaging Sciences, Spine and Orthopaedic Center, Atlanta, Georgia 30329 (United States); University of Pittsburgh, Swanson School of Engineering, Department of Bioengineering, Pittsburgh, Pennsylvania 15213 (United States)

    2013-07-01

    actual specimen. Low predicted bone density was lower than actual specimen. Differences were probably due to applied muscle and joint reaction loads, boundary conditions, and values of constants used. Work is underway to study this. Nonetheless, the results demonstrate three dimensional bone remodeling simulation validity and potential. Such adaptive predictions take physiological bone remodeling simulations one step closer to reality. Computational analyses are needed that integrate biological remodeling rules and predict how bone will respond over time. We expect the combination of computational static stress analyses together with adaptive bone remodeling simulations to become effective tools for regenerative medicine research.

  8. Stem cells: A potential regenerative future in dentistry

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    Sumit Narang

    2012-01-01

    Full Text Available In recent years, the field of dentistry has embossed its presence by taking major leaps in research and further bringing it into practice. The most valuable ongoing research in regenerative dentistry is the study on stem cells. It was instituted that stem cells grow rapidly and have the potential to form specialized dentin, bone, and neuronal cells. These neuronal cells can be used for dental therapies and can provide better treatment options for patients. The stem cells based therapies could help in new advances in treating damaged teeth, inducing bone regeneration and treating neural injury as well.

  9. The rational use of animal models in the evaluation of novel bone regenerative therapies

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    Perić, Mihaela; DUMIĆ-ČULE, Ivo; Grčević, Danka; Matijašić, Mario; Verbanac, Donatella; Paul, Ruth; Grgurević, Lovorka; Trkulja, Vladimir; Bagi, Čedo M.; Vukičević, Slobodan

    2015-01-01

    Bone has a high potential for endogenous self-repair. However, due to population aging, human diseases with impaired bone regeneration are on the rise. Current strategies to facilitate bone healing include various biomolecules, cellular therapies, biomaterials and different combinations of these. Animal models for testing novel regenerative therapies remain the gold standard in pre-clinical phases of drug discovery and development. Despite improvements in animal experimentation, excessive poo...

  10. Alteration of hedgehog signaling by chronic exposure to different pesticide formulations and unveiling the regenerative potential of recombinant sonic hedgehog in mouse model of bone marrow aplasia.

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    Chaklader, Malay; Law, Sujata

    2015-03-01

    Chronic pesticide exposure-induced downregulation of hedgehog signaling and its subsequent degenerative effects on the mammalian hematopoietic system have not been investigated yet. However a number of concurrent studies have pointed out the positive correlation between chronic pesticide exposure induced bone marrow failure and immune suppression. Here, we have given an emphasis on the recapitulation of human marrow aplasia like condition in mice by chronic mixed pesticide exposures and simultaneously unravel the role of individual pesticides in the said event. Unlike the effect of mixed pesticide, individual pesticides differentially alter the hedgehog signaling in the bone marrow primitive hematopoietic compartment (Sca1 + compartment) and stromal compartment. Individually, hexaconazole disrupted hematopoietic as well as stromal hedgehog signaling activation through inhibiting SMO and facilitating PKC δ expression. On contrary, both chlorpyriphos and cypermethrin increased the sequestration and degradation of GLI1 by upregulating SU(FU) and βTrCP, respectively. However, cypermethrin-mediated inhibition of hedgehog signaling has partly shown to be circumvented by non-canonical activation of GLI1. Finally, we have tested the regenerative response of sonic hedgehog and shown that in vitro supplemented recombinant SHH protein augmented clonogenic stromal progenitors (CFU-F) as well as primitive multipotent hematopoietic clones including CFU-GEMM and CFU-GM of mixed pesticide-induced aplastic marrow. It is an indication of the marrow regeneration. Finally, our findings provide a gripping evidence that downregulated hedgehog signaling contribute to pesticide-mediated bone marrow aplasia but it could be recovered by proper supplementation of recombinant SHH along with hematopoietic base cocktail. Furthermore, SU(FU) and GLI1 can be exploited as future theradiagnostic markers for early marrow aplasia diagnosis.

  11. Biomimetically Enhanced Demineralized Bone Matrix for Bone Regenerative Applications

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    Sriram eRavindran

    2015-10-01

    Full Text Available Demineralized bone matrix (DBM is one of the most widely used bone graft materials in dentistry. However, the ability of DBM to reliably and predictably induce bone regeneration has always been a cause for concern. The quality of DBM varies greatly depending on several donor dependent factors and also manufacturing techniques. In order to standardize the quality and to enable reliable and predictable bone regeneration, we have generated a biomimetically-enhanced version of DBM (BE-DBM using clinical grade commercial DBM as a control. We have generated the BE-DBM by incorporating a cell-derived pro-osteogenic extracellular matrix (ECM within clinical grade DBM. In the present study, we have characterized the BE-DBM and evaluated its ability to induce osteogenic differentiation of human marrow derived stromal cells (HMSCs with respect to clinical grade commercial DBM. Our results indicate that the BE-DBM contains significantly more pro-osteogenic factors than DBM and enhances HMSC differentiation and mineralized matrix formation in vitro and in vivo. Based on our results, we envision that the BE-DBM has the potential to replace DBM as the bone graft material of choice.

  12. Extracellular Vesicles: potential roles in Regenerative Medicine

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    Olivier G de Jong

    2014-12-01

    Full Text Available Extracellular vesicles (EV consist of exosomes, which are released upon fusion of the multivesicular body with the cell membrane, and microvesicles, which are released directly from the cell membrane. EV can mediate cell-cell communication and are involved in many processes, including immune signaling, angiogenesis, stress response, senescence, proliferation, and cell differentiation. The vast amount of processes that EV are involved in and the versatility of manner in which they can influence the behavior of recipient cells make EV an interesting source for both therapeutic and diagnostic applications. Successes in the fields of tumor biology and immunology sparked the exploration of the potential of EV in the field of regenerative medicine. Indeed, EV are involved in restoring tissue and organ damage, and may partially explain the paracrine effects observed in stem cell based therapeutic approaches. The function and content of EV may also harbor information that can be used in tissue engineering, in which paracrine signaling is employed to modulate cell recruitment, differentiation, and proliferation. In this review, we discuss the function and role of EV in regenerative medicine and elaborate on potential applications in tissue engineering.

  13. From regenerative dentistry to regenerative medicine: progress, challenges, and potential applications of oral stem cells.

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    Xiao, Li; Nasu, Masanori

    2014-01-01

    Adult mesenchymal stem cells (MSCs) and epithelial stem cells play essential roles in tissue repair and self-healing. Oral MSCs and epithelial stem cells can be isolated from adult human oral tissues, for example, teeth, periodontal ligament, and gingiva. Cocultivated adult oral epithelial stem cells and MSCs could represent some developmental events, such as epithelial invagination and tubular structure formation, signifying their potentials for tissue regeneration. Oral epithelial stem cells have been used in regenerative medicine over 1 decade. They are able to form a stratified cell sheet under three-dimensional culture conditions. Both experimental and clinical data indicate that the cell sheets can not only safely and effectively reconstruct the damaged cornea in humans, but also repair esophageal ulcer in animal models. Oral MSCs include dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP), periodontal ligament stem cells (PDLSCs), and mesenchymal stem cells from gingiva (GMSCs). They are widely applied in both regenerative dentistry and medicine. DPSCs, SHED, and SCAP are able to form dentin-pulp complex when being transplanted into immunodeficient animals. They have been experimentally used for the regeneration of dental pulp, neuron, bone muscle and blood vessels in animal models and have shown promising results. PDLSCs and GMSCs are demonstrated to be ideal cell sources for repairing the damaged tissues of periodontal, muscle, and tendon. Despite the abovementioned applications of oral stem cells, only a few human clinical trials are now underway to use them for the treatment of certain diseases. Since clinical use is the end goal, their true regenerative power and safety need to be further examined.

  14. From regenerative dentistry to regenerative medicine: progress, challenges, and potential applications of oral stem cells

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    Xiao L

    2014-12-01

    Full Text Available Li Xiao,1 Masanori Nasu2 1Department of Pharmacology, 2Research Center, The Nippon Dental University, Tokyo, Japan Abstract: Adult mesenchymal stem cells (MSCs and epithelial stem cells play essential roles in tissue repair and self-healing. Oral MSCs and epithelial stem cells can be isolated from adult human oral tissues, for example, teeth, periodontal ligament, and gingiva. Cocultivated adult oral epithelial stem cells and MSCs could represent some developmental events, such as epithelial invagination and tubular structure formation, signifying their potentials for tissue regeneration. Oral epithelial stem cells have been used in regenerative medicine over 1 decade. They are able to form a stratified cell sheet under three-dimensional culture conditions. Both experimental and clinical data indicate that the cell sheets can not only safely and effectively reconstruct the damaged cornea in humans, but also repair esophageal ulcer in animal models. Oral MSCs include dental pulp stem cells (DPSCs, stem cells from exfoliated deciduous teeth (SHED, stem cells from apical papilla (SCAP, periodontal ligament stem cells (PDLSCs, and mesenchymal stem cells from gingiva (GMSCs. They are widely applied in both regenerative dentistry and medicine. DPSCs, SHED, and SCAP are able to form dentin–pulp complex when being transplanted into immunodeficient animals. They have been experimentally used for the regeneration of dental pulp, neuron, bone muscle and blood vessels in animal models and have shown promising results. PDLSCs and GMSCs are demonstrated to be ideal cell sources for repairing the damaged tissues of periodontal, muscle, and tendon. Despite the abovementioned applications of oral stem cells, only a few human clinical trials are now underway to use them for the treatment of certain diseases. Since clinical use is the end goal, their true regenerative power and safety need to be further examined.Keywords: oral mesenchymal stem cells, oral

  15. Therapeutic Potential of Mesenchymal Stem Cells in Regenerative Medicine

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    Devang M. Patel

    2013-01-01

    Full Text Available Mesenchymal stem cells (MSCs are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation into both mesenchymal and nonmesenchymal lineages. The intrinsic properties of these cells make them an attractive candidate for clinical applications. MSCs are of keen interest because they can be isolated from a small aspirate of bone marrow or adipose tissues and can be easily expanded in vitro. Moreover, their ability to modulate immune responses makes them an even more attractive candidate for regenerative medicine as allogeneic transplant of these cells is feasible without a substantial risk of immune rejection. MSCs secrete various immunomodulatory molecules which provide a regenerative microenvironment for a variety of injured tissues or organ to limit the damage and to increase self-regulated tissue regeneration. Autologous/allogeneic MSCs delivered via the bloodstream augment the titers of MSCs that are drawn to sites of tissue injury and can accelerate the tissue repair process. MSCs are currently being tested for their potential use in cell and gene therapy for a number of human debilitating diseases and genetic disorders. This paper summarizes the current clinical and nonclinical data for the use of MSCs in tissue repair and potential therapeutic role in various diseases.

  16. Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

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    Tsuno, Hiroaki [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Yoshida, Toshiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nogami, Makiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Orthopedic Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Koike, Chika; Okabe, Motonori [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Noto, Zenko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Arai, Naoya; Noguchi, Makoto [Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nikaido, Toshio, E-mail: tnikaido@med.u-toyama.ac.jp [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan)

    2012-12-01

    Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAM{alpha} cells and induced to osteogenic status-their in vivo osteogenesis was subsequently investigated in rats. It was found that HAM{alpha} cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAM{alpha} cells. The expression of osteocalcin mRNA was increased in HAM{alpha} cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAM{alpha} cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: Black-Right-Pointing-Pointer Human amniotic mesenchymal cells include cells (HAM{alpha} cells) that have the properties of MSCs. Black-Right-Pointing-Pointer HAM{alpha} cells have excellent osteogenic differentiation potential. Black-Right-Pointing-Pointer Osteogenic differentiation ability of HAM{alpha} was amplified by calcium phosphate scaffolds. Black-Right-Pointing-Pointer HAM{alpha} cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

  17. Trophic Effects and Regenerative Potential of Mobilized Mesenchymal Stem Cells From Bone Marrow and Adipose Tissue as Alternative Cell Sources for Pulp/Dentin Regeneration.

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    Murakami, Masashi; Hayashi, Yuki; Iohara, Koichiro; Osako, Yohei; Hirose, Yujiro; Nakashima, Misako

    2015-01-01

    Dental pulp stem cell (DPSC) subsets mobilized by granulocyte-colony-stimulating factor (G-CSF) are safe and efficacious for complete pulp regeneration. The supply of autologous pulp tissue, however, is very limited in the aged. Therefore, alternative sources of mesenchymal stem/progenitor cells (MSCs) are needed for the cell therapy. In this study, DPSCs, bone marrow (BM), and adipose tissue (AD)-derived stem cells of the same individual dog were isolated using G-CSF-induced mobilization (MDPSCs, MBMSCs, and MADSCs). The positive rates of CXCR4 and G-CSFR in MDPSCs were similar to MADSCs and were significantly higher than those in MBMSCs. Trophic effects of MDPSCs on angiogenesis, neurite extension, migration, and antiapoptosis were higher than those of MBMSCs and MADSCs. Pulp-like loose connective tissues were regenerated in all three MSC transplantations. Significantly higher volume of regenerated pulp and higher density of vascularization and innervation were observed in response to MDPSCs compared to MBMSC and MADSC transplantation. Collagenous matrix containing dentin sialophosphoprotein (DSPP)-positive odontoblast-like cells was the highest in MBMSCs and significantly higher in MADSCs compared to MDPSCs. MBMSCs and MADSCs, therefore, have potential for pulp regeneration, although the volume of regenerated pulp tissue, angiogenesis, and reinnervation, were less. Thus, in conclusion, an alternative cell source for dental pulp/dentin regeneration are stem cells from BM and AD tissue.

  18. Therapeutic potential of nanoceria in regenerative medicine

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    Das, Soumen [Univ. of Central Florida, Orlando, FL (United States); Chigurupati, Srinivasulu [U.S. Food and Drug Administration, Silver Spring, MD (United States); Dowding, Janet [Univ. of Central Florida, Orlando, FL (United States); Munusamy, Prabhakaran [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Baer, Donald R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); McGinnis, James F. [Univ. of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Mattson, Mark P. [National Inst. on Aging Intramural Research Program, Bethesda, MD (United States); Self, William [Univ. of Central Florida, Orlando, FL (United States); Seal, Sudipta [Univ. of Central Florida, Orlando, FL (United States)

    2014-11-01

    Tissue engineering and regenerative medicine aim to achieve functional restoration of tissue or cells damaged through disease, aging or trauma. Advancement of tissue engineering requires innovation in the field of 3D scaffolding, and functionalization with bioactive molecules. Nanotechnology offers advanced materials with patterned nano-morphologies for cell growth and different molecular substrates which can support cell survival and functions. Cerium oxide nanoparticles (nanoceria) can control intracellular as well as extracellular reactive oxygen and nitrogen species. Recent findings suggest that nanoceria can enhance long-term cell survival, enable cell migration and proliferation, and promote stem cell differentiation. Moreover, the self-regenerative property of nanoceria permits a small dose to remain catalytically active for extended time. This review summarizes the possibilities and applications of nanoceria in the field of tissue engineering and regenerative medicine.

  19. New regenerative treatment for tooth and periodontal bone defect associated with posttraumatic alveolar bone crush fracture.

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    Kiyokawa, Kensuke; Kiyokawa, Munekatsu; Takagi, Mikako; Rikimaru, Hideaki; Fukaya, Takuji

    2009-05-01

    We developed a new regenerative treatment of tooth and periodontal defect and tooth dislocation associated with posttraumatic alveolar bone crush fracture in the region of the maxillary anterior teeth. Using this method, dislocated teeth are first extracted and crushed alveolar bone is debrided. The dislocated teeth are then reimplanted, and cancellous iliac bone (bone marrow) is grafted to the area surrounding the teeth to regenerate periodontal bone. Tooth reimplantation was completely successful in 2 cases, and periodontal bone regenerated to a sufficient height with the iliac bone graft. Compared with the general method of treatment with a prosthesis (bridge), when using this method to treat cases such as these, there is no sacrifice of healthy teeth adjacent to the defect, and sufficient esthetic and functional recovery is possible. It is thought that this method could be applied as a new treatment of alveolar bone fracture in the future.

  20. Are bone marrow regenerative cells ideal seed cells for the treatment of cerebral ischemia?★

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    Li, Yi; Hua, Xuming; Hua, Fang; Mao, Wenwei; Wan, Liang; Li, Shiting

    2013-01-01

    Bone marrow cells for the treatment of ischemic brain injury may depend on the secretion of a large number of neurotrophic factors. Bone marrow regenerative cells are capable of increasing the secretion of neurotrophic factors. In this study, after tail vein injection of 5-fluorouracil for 7 days, bone marrow cells and bone marrow regenerative cells were isolated from the tibias and femurs of rats, and then administered intravenously via the tail vein after focal cerebral ischemia. Immunohist...

  1. Regenerative Potential of Mesenchymal Stromal Cells: Age-Related Changes

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    Bruna, Flavia; Contador, David; Conget, Paulette; Erranz, Benjamín; Sossa, Claudia L.; Arango-Rodríguez, Martha L.

    2016-01-01

    Preclinical and clinical studies have shown that a therapeutic effect results from mesenchymal stromal cells (MSCs) transplant. No systematic information is currently available regarding whether donor age modifies MSC regenerative potential on cutaneous wound healing. Here, we evaluate whether donor age influences this potential. Two different doses of bone marrow MSCs (BM-MSCs) from young, adult, or old mouse donors or two doses of their acellular derivatives mesenchymal stromal cells (acd-MSCs) were intradermally injected around wounds in the midline of C57BL/6 mice. Every two days, wound healing was macroscopically assessed (wound closure) and microscopically assessed (reepithelialization, dermal-epidermal junction, skin appendage regeneration, granulation tissue, leukocyte infiltration, and density dermal collagen fibers) after 12 days from MSC transplant. Significant differences in the wound closure kinetic, quality, and healing of skin regenerated were observed in lesions which received BM-MSCs from different ages or their acd-MSCs compared to lesions which received vehicle. Nevertheless, our data shows that adult's BM-MSCs or their acd-MSCs were the most efficient for recovery of most parameters analyzed. Our data suggest that MSC efficacy was negatively affected by donor age, where the treatment with adult's BM-MSCs or their acd-MSCs in cutaneous wound promotes a better tissue repair/regeneration. This is due to their paracrine factors secretion. PMID:27247575

  2. Are bone marrow regenerative cells ideal seed cells for the treatment of cerebral ischemia?

    Institute of Scientific and Technical Information of China (English)

    Yi Li; Xuming Hua; Fang Hua; Wenwei Mao; Liang Wan; Shiting Li

    2013-01-01

    Bone marrow cells for the treatment of ischemic brain injury may depend on the secretion of a large number of neurotrophic factors. Bone marrow regenerative cells are capable of increasing the secretion of neurotrophic factors. In this study, after tail vein injection of 5-fluorouracil for 7 days, bone marrow cells and bone marrow regenerative cells were isolated from the tibias and femurs of rats, and then administered intravenously via the tail vein after focal cerebral ischemia. Immunohistological staining and reverse transcription-PCR detection showed that transplanted bone marrow cells and bone marrow regenerative cells could migrate and survive in the ischemic regions, such as the cortical and striatal infarction zone. These cells promote vascular endothelial cell growth factor mRNA expression in the ischemic marginal zone surrounding the ischemic penumbra of the cortical and striatal infarction zone, and have great advantages in promoting the recovery of neurological function, reducing infarct size and promoting angiogenesis. Bone marrow regenerative cells exhibited stronger neuroprotective effects than bone marrow cells. Our experimental findings indicate that bone marrow regenerative cells are preferable over bone marrow cells for cell therapy for neural regeneration after cerebral ischemia. Their neuroprotective effect is largely due to their ability to induce the secretion of factors that promote vascular regeneration, such as vascular endothelial growth factor.

  3. Changes of Bone Turnover Markers in Long Bone Nonunions Treated with a Regenerative Approach

    Directory of Open Access Journals (Sweden)

    Donatella Granchi

    2017-01-01

    Full Text Available In this clinical trial, we investigated if biochemical bone turnover markers (BTM changed according to the progression of bone healing induced by autologous expanded MSC combined with a biphasic calcium phosphate in patients with delayed union or nonunion of long bone fractures. Bone formation markers, bone resorption markers, and osteoclast regulatory proteins were measured by enzymatic immunoassay before surgery and after 6, 12, and 24 weeks. A satisfactory bone healing was obtained in 23 out of 24 patients. Nine subjects reached a good consolidation already at 12 weeks, and they were considered as the “early consolidation” group. We found that bone-specific alkaline phosphatase (BAP, C-terminal propeptide of type I procollagen (PICP, and beta crosslaps collagen (CTX changed after the regenerative treatment, BAP and CTX correlated to the imaging results collected at 12 and 24 weeks, and BAP variation along the healing course differed in patients who had an “early consolidation.” A remarkable decrease in BAP and PICP was observed at all time points in a single patient who experienced a treatment failure, but the predictive value of BTM changes cannot be determined. Our findings suggest that BTM are promising tools for monitoring cell therapy efficacy in bone nonunions, but studies with larger patient numbers are required to confirm these preliminary results.

  4. The rational use of animal models in the evaluation of novel bone regenerative therapies.

    Science.gov (United States)

    Peric, Mihaela; Dumic-Cule, Ivo; Grcevic, Danka; Matijasic, Mario; Verbanac, Donatella; Paul, Ruth; Grgurevic, Lovorka; Trkulja, Vladimir; Bagi, Cedo M; Vukicevic, Slobodan

    2015-01-01

    Bone has a high potential for endogenous self-repair. However, due to population aging, human diseases with impaired bone regeneration are on the rise. Current strategies to facilitate bone healing include various biomolecules, cellular therapies, biomaterials and different combinations of these. Animal models for testing novel regenerative therapies remain the gold standard in pre-clinical phases of drug discovery and development. Despite improvements in animal experimentation, excessive poorly designed animal studies with inappropriate endpoints and inaccurate conclusions are being conducted. In this review, we discuss animal models, procedures, methods and technologies used in bone repair studies with the aim to assist investigators in planning and performing scientifically sound experiments that respect the wellbeing of animals. In the process of designing an animal study for bone repair investigators should consider: skeletal characteristics of the selected animal species; a suitable animal model that mimics the intended clinical indication; an appropriate assessment plan with validated methods, markers, timing, endpoints and scoring systems; relevant dosing and statistically pre-justified sample sizes and evaluation methods; synchronization of the study with regulatory requirements and additional evaluations specific to cell-based approaches. This article is part of a Special Issue entitled "Stem Cells and Bone". Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Stem cells have the potential to rejuvenate regenerative medicine research.

    Science.gov (United States)

    Eve, David J; Fillmore, Randolph; Borlongan, Cesar V; Sanberg, Paul R

    2010-10-01

    The increasing number of publications featuring the use of stem cells in regenerative processes supports the idea that they are revolutionizing regenerative medicine research. In an analysis of the articles published in the journal Cell Transplantation - The Regenerative Medicine Journal between 2008 and 2009, which reveals the topics and categories that are on the cutting edge of regenerative medicine research, stem cells are becoming increasingly relevant as the "runner-up" category to "neuroscience" related articles. The high volume of stem cell research casts a bright light on the hope for stem cells and their role in regenerative medicine as a number of reports deal with research using stem cells entering, or seeking approval for, clinical trials. The "methods and new technologies" and "tissue engineering" sections were almost equally as popular, and in part, reflect attempts to maximize the potential of stem cells and other treatments for the repair of damaged tissue. Transplantation studies were again more popular than non-transplantation, and the contribution of stem cell-related transplants was greater than other types of transplants. The non-transplantation articles were predominantly related to new methods for the preparation, isolation and manipulation of materials for transplant by specific culture media, gene therapy, medicines, dietary supplements, and co-culturing with other cells and further elucidation of disease mechanisms. A sizeable proportion of the transplantation articles reported on how previously new methods may have aided the ability of the cells or tissue to exert beneficial effects following transplantation.

  6. Enzymatically synthesized inorganic polymers as morphogenetically active bone scaffolds: application in regenerative medicine.

    Science.gov (United States)

    Wang, Xiaohong; Schröder, Heinz C; Müller, Werner E G

    2014-01-01

    In recent years a paradigm shift in understanding of human bone formation has occurred that starts to change current concepts in tissue engineering of bone and cartilage. New discoveries revealed that fundamental steps in biomineralization are enzyme driven, not only during hydroxyapatite deposition, but also during initial bioseed formation, involving the transient deposition and subsequent transformation of calcium carbonate to calcium phosphate mineral. The principal enzymes mediating these reactions, carbonic anhydrase and alkaline phosphatase, open novel targets for pharmacological intervention of bone diseases like osteoporosis, by applying compounds acting as potential activators of these enzymes. It is expected that these new findings will give an innovation boost for the development of scaffolds for bone repair and reconstruction, which began with the use of bioinert materials, followed by bioactive materials and now leading to functional regenerative tissue units. These new developments have become possible with the discovery of the morphogenic activity of bioinorganic polymers, biocalcit, bio-polyphosphate and biosilica that are formed by a biogenic, enzymatic mechanism, a driving force along with the development of novel rapid-prototyping three-dimensional (3D) printing methods and bioprinting (3D cell printing) techniques that may allow a fabrication of customized implants for patients suffering in bone diseases in the future.

  7. Bone regenerative properties of rat, goat and human platelet-rich plasma.

    NARCIS (Netherlands)

    Plachokova, A.S.; Dolder, J. van den; Beucken, J.J.J.P. van den; Jansen, J.A.

    2009-01-01

    To explore the reported contradictory osteogenic capacity of platelet-rich plasma (PRP), the aim of the study was to examine and compare the bone regenerative effect of: PRPs of different species (rat, goat, human); human bone graft (HB) vs. HB combined with human PRP (HB+hPRP); and HB+hPRP vs. synt

  8. Concise review: cell-based strategies in bone tissue engineering and regenerative medicine

    NARCIS (Netherlands)

    Ma, J.; Both, S.K.; Yang, F.; Cui, F.Z.; Pan, J.; Meijer, G.J.; Jansen, J.A.; Beucken, J.J.J.P van den

    2014-01-01

    Cellular strategies play an important role in bone tissue engineering and regenerative medicine (BTE/RM). Variability in cell culture procedures (e.g., cell types, cell isolation and expansion, cell seeding methods, and preculture conditions before in vivo implantation) may influence experimental ou

  9. Analysing regenerative potential in zebrafish models of congenital muscular dystrophy.

    Science.gov (United States)

    Wood, A J; Currie, P D

    2014-11-01

    The congenital muscular dystrophies (CMDs) are a clinically and genetically heterogeneous group of muscle disorders. Clinically hypotonia is present from birth, with progressive muscle weakness and wasting through development. For the most part, CMDs can mechanistically be attributed to failure of basement membrane protein laminin-α2 sufficiently binding with correctly glycosylated α-dystroglycan. The majority of CMDs therefore arise as the result of either a deficiency of laminin-α2 (MDC1A) or hypoglycosylation of α-dystroglycan (dystroglycanopathy). Here we consider whether by filling a regenerative medicine niche, the zebrafish model can address the present challenge of delivering novel therapeutic solutions for CMD. In the first instance the readiness and appropriateness of the zebrafish as a model organism for pioneering regenerative medicine therapies in CMD is analysed, in particular for MDC1A and the dystroglycanopathies. Despite the recent rapid progress made in gene editing technology, these approaches have yet to yield any novel zebrafish models of CMD. Currently the most genetically relevant zebrafish models to the field of CMD, have all been created by N-ethyl-N-nitrosourea (ENU) mutagenesis. Once genetically relevant models have been established the zebrafish has several important facets for investigating the mechanistic cause of CMD, including rapid ex vivo development, optical transparency up to the larval stages of development and relative ease in creating transgenic reporter lines. Together, these tools are well suited for use in live-imaging studies such as in vivo modelling of muscle fibre detachment. Secondly, the zebrafish's contribution to progress in effective treatment of CMD was analysed. Two approaches were identified in which zebrafish could potentially contribute to effective therapies. The first hinges on the augmentation of functional redundancy within the system, such as upregulating alternative laminin chains in the candyfloss

  10. Development of electrospun bone-mimetic matrices for bone regenerative applications

    Science.gov (United States)

    Phipps, Matthew Christopher

    Although bone has a dramatic capacity for regeneration, certain injuries and procedures present defects that are unable to heal properly, requiring surgical intervention to induce and support osteoregeneration. Our research group has hypothesized that the development of a biodegradable material that mimics the natural composition and architecture of bone extracellular matrix has the potential to provide therapeutic benefit to these patients. Utilizing a process known as electrospinning, our lab has developed a bone-mimetic matrix (BMM) consisting of composite nanofibers of the mechanically sta-ble polymer polycaprolactone (PCL), and the natural bone matrix molecules type-I colla-gen and hydroxyapatite nanocrystals (HA). We herein show that BMMs supported great-er adhesion, proliferation, and integrin activation of mesenchymal stem cells (MSCs), the multipotent bone-progenitor cells within bone marrow and the periosteum, in comparison to electrospun PCL alone. These cellular responses, which are essential early steps in the process of bone regeneration, highlight the benefits of presenting cells with natural bone molecules. Subsequently, evaluation of new bone formation in a rat cortical tibia defect showed that BMMs are highly osteoconductive. However, these studies also revealed the inability of endogenous cells to migrate within electrospun matrices due to the inherently small pore sizes. To address this limitation, which will negatively impact the rate of scaf-fold-to-bone turnover and inhibit vascularization, sacrificial fibers were added to the ma-trix. The removal of these fibers after fabrication resulted in BMMs with larger pores, leading to increased infiltration of MSCs and endogenous bone cells. Lastly, we evaluat-ed the potential of our matrices to stimulate the recruitment of MSCs, a vital step in bone healing, through the sustained delivery of platelet derived growth factor-BB (PDGF-BB). BMMs were found to adsorb and subsequently release greater

  11. Platelet-rich fibrin (PRF) in implant dentistry in combination with new bone regenerative technique in elderly patients.

    Science.gov (United States)

    Cortese, Antonio; Pantaleo, Giuseppe; Borri, Antonio; Caggiano, Mario; Amato, Massimo

    2016-01-01

    Some studies have demonstrated that platelet rich fibrin (PRF) is a healing biomaterial with a great potential for bone and soft tissue regeneration, without any inflammatory reactions and may be used alone or in combination with bone grafts, promoting hemostasis, bone growth, and maturation. PRF appears as a natural and satisfactory aid in bone regenerative surgery in elderly patients with favorable results and low risks. This study wants to demonstrate how PRF in association with a new split crest augmentation technique can be a great aid in implant rehabilitation, especially in the elderly patients, when bone regeneration is required. Ten patients were treated in this study, five following the flapless split crest new procedure and other five patients following traditional procedure without split crest as control. Five patients with an average age between 50 and 60 years were selected to be operated with a split crest flapless modified technique in order to optimize the regenerative conditions with a bone augmentation and implant insertion in one single stage procedure. For all the patients autologous PRF has been used to fill the split crest gap or simply as regenerative material. Orthopantomography, intraoral radiography and CT DentaScan/CT Cone beam were performed for every patient before the treatment and at follow-up time exeption made for CT. All cases were successful, there were no problems at surgery time, at post-operative and at osteointegration periods. All implants achieved osteointegration. These results were obtained by accurately managing immediate and late post operative period in all of the operated cases. Mean difference for height bone loss between the two groups of patients was 2.4mm at T1 and 2.2mm at T3. The rationale of this split crest flapless modified technique is to obtain a proper buccal cortex expansion preserving its vascular supply avoiding periosteal elevation for better cortical bone nourishing. Moreover, advantages are reported

  12. Pericytes and their potential in regenerative medicine across species.

    Science.gov (United States)

    Esteves, C L; Donadeu, F X

    2017-09-20

    The discovery that pericytes are in vivo counterparts of Mesenchymal Stem/Stromal Cells (MSCs) has placed these perivascular cells in the research spotlight, bringing up hope for a well-characterized cell source for clinical applications, alternative to poorly defined, heterogeneous MSCs preparations currently in use. Native pericytes express typical MSC markers and, after isolation by fluorescence-activated cell sorting, display an MSC phenotype in culture. These features have been demonstrated in different species, including humans and horses, the main targets of regenerative treatments. Significant clinical potential of pericytes has been shown by transplantation of human cells into rodent models of tissue injury, and it is hoped that future studies will demonstrate clinical potential in veterinary species. Here, we provide an overview of the current knowledge on pericytes across different species including humans, companion and large animal models, in relation to their identification in different body tissues, methodology for prospective isolation, characterization, and potential for tissue regeneration. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

  13. Stem cells from amniotic fluid--Potential for regenerative medicine.

    Science.gov (United States)

    Loukogeorgakis, Stavros P; De Coppi, Paolo

    2016-02-01

    Regenerative medicine has recently been established as an emerging field focussing on repair, replacement or regeneration of cells, tissues and whole organs. The significant recent advances in the field have intensified the search for novel sources of stem cells with potential for therapy. Recently, researchers have identified the amniotic fluid as an untapped source of stem cells that are multipotent, possess immunomodulatory properties and do not have the ethical and legal limitations of embryonic stem cells. Stem cells from the amniotic fluid have been shown to differentiate into cell lineages representing all three embryonic germ layers without generating tumours, which make them an ideal candidate for tissue engineering applications. In addition, their ability to engraft in injured organs and modulate immune and repair responses of host tissues suggest that transplantation of such cells may be useful for the treatment of various degenerative and inflammatory diseases affecting major tissues/organs. This review summarises the evidence on amniotic fluid cells over the past 15 years and explores the potential therapeutic applications of amniotic fluid stem cells and amniotic fluid mesenchymal stem cells.

  14. Clinical evaluation of regenerative potential of type I collagen membrane along with xenogenic bone graft in the treatment of periodontal intrabony defects assessed with surgical re-entry and radiographic linear and densitometric analysis

    Directory of Open Access Journals (Sweden)

    Sowmya N

    2010-01-01

    Full Text Available Background and Objectives: The primary goal of periodontal therapy is to restore the tooth supporting tissues lost due to periodontal disease. The aim of the present study was to compare the efficacy of combination of type I collagen (GTR membrane and xenogenic bone graft with open flap debridement (OFD in treatment of periodontal intrabony defects. Materials and Methods: Twenty paired intrabony defects were surgically treated using split mouth design. The defects were randomly assigned to treatment with OFD + collagen membrane + bone graft (Test or OFD alone (Control. The clinical efficacy of two treatment modalities was evaluated at 9 month postoperatively by clinical, radiographical, and intrasurgical (re-entry parameters. The measurements included probing pocket depth (PD, clinical attachment level (CAL, gingival recession (GR, bone fill (BF, bone density (BD and intra bony component (INTRA. Results: The mean reduction in PD at 0-9 month was 3.3±0.82 mm and CAL gain of 3.40±1.51 mm occurred in the collagen membrane + bone graft (Test group; corresponding values for OFD (Control were 2.20±0.63 mm and 1.90±0.57 mm. Similar pattern of improvement was observed when radiographical and intra-surgical (re-entry post operative evaluation was made. All improvement in different parameters was statistically significant (P< 0.01. Interpretation and Conclusion: Treatment with a combination of collagen membrane and bone graft led to a significantly more favorable clinical outcome in intrabony defects as compared to OFD alone.

  15. [Effect of combined therapeutic methods on healing of periodontal vertical bone defects in regenerative surgery].

    Science.gov (United States)

    Dori, Ferenc

    2009-03-15

    Several methods are available to enhance the healing and regeneration of periodontal tissues after surgical therapy of intrabony defects. The main indications for the use of combined regenerative procedures are the extent and morphology of the osseous lesions. The six studies of the present dissertation focused on the clinical effect of different barrier techniques, bone substitutes, enamel matrix derivatives and a growth factors containing adjuvant used in various combinations on the healing of severe periodontal intrabony impairments. Synthetic, xenogenetic and autologous materials were used in these randomized clinical studies. Mechanical barriers (polytetrafluoroethylene and collagen membranes) for GTR, biological barriers/enamel matrix proteins (EMD), synthetic (beta-TCP) and xenogeneic (NBM) bone grafts and autologous platelet-rich plasma (PRP) were combined in the test and control groups of the trials. The main clinical variable was the clinical attachment level (CAL) and the subsidiary one was the probing pocket depth (PPD), estimated at baseline and after one year. The summation of the results after the statistical analysis takes cognizance of the followings: a) Each of the eleven regenerative methods evaluated (ten combined procedures) leads to significant CAL gain and PPD decrease. b) Using beta-TCP or NBM with EMD or with PRP+GTR and GTR's, the difference between the parameters of the test and control groups were not statistically significant. c) It was confirmed in four studies that the addition of PRP to graft materials has not increased significantly the positive outcomes independent of the type of barrier or graft. d) Adding platelet-rich plasma to natural bone mineral, no benefit was observed from the point of view of the clinical variables. e) The polypeptide proteins of the platelet-rich plasma do not enhance the clinical regenerative effect of enamel matrix proteins. In conclusion, the option of the periodontal surgeons between these methods

  16. Mesenchymal Stem and Progenitor Cells in Regeneration: Tissue Specificity and Regenerative Potential

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    Rokhsareh Rohban

    2017-01-01

    Full Text Available It has always been an ambitious goal in medicine to repair or replace morbid tissues for regaining the organ functionality. This challenge has recently gained momentum through considerable progress in understanding the biological concept of the regenerative potential of stem cells. Routine therapeutic procedures are about to shift towards the use of biological and molecular armamentarium. The potential use of embryonic stem cells and invention of induced pluripotent stem cells raised hope for clinical regenerative purposes; however, the use of these interventions for regenerative therapy showed its dark side, as many health concerns and ethical issues arose in terms of using these cells in clinical applications. In this regard, adult stem cells climbed up to the top list of regenerative tools and mesenchymal stem cells (MSC showed promise for regenerative cell therapy with a rather limited level of risk. MSC have been successfully isolated from various human tissues and they have been shown to offer the possibility to establish novel therapeutic interventions for a variety of hard-to-noncurable diseases. There have been many elegant studies investigating the impact of MSC in regenerative medicine. This review provides compact information on the role of stem cells, in particular, MSC in regeneration.

  17. Transient Regenerative Potential of the Neonatal Mouse Heart

    Science.gov (United States)

    Porrello, Enzo R.; Mahmoud, Ahmed I.; Simpson, Emma; Hill, Joseph A.; Richardson, James A.; Olson, Eric N.; Sadek, Hesham A.

    2011-01-01

    Certain fish and amphibians retain a robust capacity for cardiac regeneration throughout life, but the same is not true of the adult mammalian heart. Whether the capacity for cardiac regeneration is absent in mammals or whether it exists and is switched off early after birth has been unclear. We found that the hearts of 1-day-old neonatal mice can regenerate after partial surgical resection, but this capacity is lost by 7 days of age. This regenerative response in 1-day-old mice was characterized by cardiomyocyte proliferation with minimal hypertrophy or fibrosis, thereby distinguishing it from repair processes. Genetic fate mapping indicated that the majority of cardiomyocytes within the regenerated tissue originated from preexisting cardiomyocytes. Echocardiography performed 2 months after surgery revealed that the regenerated ventricular apex had normal systolic function. Thus, for a brief period after birth, the mammalian heart appears to have the capacity to regenerate. PMID:21350179

  18. Adipose-derived stem cells retain their regenerative potential after methotrexate treatment

    Energy Technology Data Exchange (ETDEWEB)

    Beane, Olivia S. [Center for Biomedical Engineering, Brown University, Providence, RI (United States); Fonseca, Vera C. [Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI (United States); Darling, Eric M., E-mail: Eric_Darling@brown.edu [Center for Biomedical Engineering, Brown University, Providence, RI (United States); Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI (United States); Department of Orthopaedics, Brown University, Providence, RI (United States); School of Engineering, Brown University, Providence, RI (United States)

    2014-10-01

    In musculoskeletal tissues like bone, chemotherapy can impair progenitor cell differentiation and proliferation, resulting in decreased bone growth and mineralization throughout a patient's lifetime. In the current study, we investigated the effects of chemotherapeutics on adipose-derived stem cell (ASC) function to determine whether this cell source could be a candidate for repairing, or even preventing, chemotherapy-induced tissue damage. Dose-dependent proliferation rates of ASCs and normal human fibroblasts (NHFs) were quantified after treatment with cytarabine (CY), etoposide (ETO), methotrexate (MTX), and vincristine (VIN) using a fluorescence-based assay. The influence of MTX on the multipotency of ASCs and freshly isolated stromal vascular fraction (SVF) cells was also evaluated using lineage-specific stains and spectrophotometry. ASC and NHF proliferation were equally inhibited by exposure to CY and ETO; however, when treated with MTX and VIN, ASCs exhibited greater resistance. This was especially apparent for MTX-treated samples, with ASC proliferation showing no inhibition for clinically relevant MTX doses ranging from 0.1 to 50 μM. Additional experiments revealed that the differentiation potential of ASCs was not affected by MTX treatment and that upregulation of dihydrofolate reductase possibly contributed to this response. Moreover, SVF cells, which include ASCs, exhibited similar resistance to MTX impairment, with respect to cellular proliferation, clonogenicity, and differentiation capability. Therefore, we have shown that the regenerative properties of ASCs resist the cytotoxicity of MTX, identifying these cells as a potential key for repairing musculoskeletal damage in patients undergoing chemotherapy. - Highlights: • Long-term effects of chemotherapeutics can include musculoskeletal dysfunction. • A screen of common drugs showed disparate effects on ASCs and fibroblasts. • One drug, methotrexate, did not impair ASC growth

  19. Cardiac regenerative potential of cardiosphere-derived cells from adult dog hearts.

    Science.gov (United States)

    Hensley, Michael Taylor; de Andrade, James; Keene, Bruce; Meurs, Kathryn; Tang, Junnan; Wang, Zegen; Caranasos, Thomas G; Piedrahita, Jorge; Li, Tao-Sheng; Cheng, Ke

    2015-08-01

    The regenerative potential of cardiosphere-derived cells (CDCs) for ischaemic heart disease has been demonstrated in mice, rats, pigs and a recently completed clinical trial. The regenerative potential of CDCs from dog hearts has yet to be tested. Here, we show that canine CDCs can be produced from adult dog hearts. These cells display similar phenotypes in comparison to previously studied CDCs derived from rodents and human beings. Canine CDCs can differentiate into cardiomyocytes, smooth muscle cells and endothelial cells in vitro. In addition, conditioned media from canine CDCs promote angiogenesis but inhibit cardiomyocyte death. In a doxorubicin-induced mouse model of dilated cardiomyopathy (DCM), intravenous infusion of canine CDCs improves cardiac function and decreases cardiac fibrosis. Histology revealed that injected canine CDCs engraft in the mouse heart and increase capillary density. Out study demonstrates the regenerative potential of canine CDCs in a mouse model of DCM.

  20. Potential sources of stem cells as a regenerative therapy for Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Abir Oueida El-Sadik

    2010-12-01

    Full Text Available Abir Oueida El-SadikDepartment of Anatomy and Embryology, Scientific Research Unit, Female Health Science College, King Saud University, Riyadh, Kingdom of Saudi ArabiaAbstract: Stem cells are believed to hold enormous promise as potential replacement therapy in the treatment of neurodegenerative diseases such as Parkinson's disease (PD. Stem cells were investigated to be the alternative therapeutic source capable of differentiating into dopamine (DA neurons. Multiple important signaling factors were recorded for the induction of DA neuronal traits from mouse embryonic stem cells (ESCs such as fibroblast growth factor 8, sonic hedgehog, and Wnt 1. Recent protocols were described for the differentiation of human ESCs into DA neurons, achieving high efficiency of DA neuronal derivation. Despite that, the use of human ESCs is still ethically controversial. The transcription factors necessary for DA neuron development from adult neural stem cells (NSCs, such as Pitx3, Nurr1, En-1, En-2, Lmx1a, Lmx1b, Msx1, and Ngn2, were investigated. In addition to replacement of lost DA neurons, adult NSCs were recorded to provide neuroprotective and neurogenic factors for the mesencephalon. In addition, induced pluripotent stem cells and bone marrow-derived mesenchymal stem cells represent reliable stem cell sources of DA neurons. Future studies are recommended to provide further insight into the regenerative capacity of stem cells needed for the treatment of PD.Keywords: dopamine, embryonic stem cells, neural stem cells, Parkinson's disease, induced pluripotent stem cells, mesenchymal stem cells

  1. Harnessing the potential of lung stem cells for regenerative medicine.

    Science.gov (United States)

    McQualter, Jonathan L; Anthony, Desiree; Bozinovski, Steven; Prêle, Cecilia M; Laurent, Geoffrey J

    2014-11-01

    In response to recurrent exposure to environmental insults such as allergens, pollution, irritants, smoke and viral/bacterial infection, the epithelium of the lung is continually damaged. Homeostasis of the lung requires a balance between immune regulation and promotion of tissue regeneration, which requires the co-ordinated proliferation and differentiation of stem and progenitor cells. In this review we reflect on the current understanding of lung epithelial stem and progenitor cells and advocate a model hierarchy in which self-renewing multipotent lung epithelial stem cells give rise to lineage restricted progenitor cells that repopulate airway and alveolar epithelial cell lineages during homeostasis and repair. We also discuss the role of mesenchymal progenitor cells in maintaining the structural integrity of the lung and propose a model in which mesenchymal cells act as the quintessential architects of lung regeneration by providing molecular signals, such as FGF-10, to regulate the fate and specificity of epithelial stem and progenitor cells. Moreover, we discuss the current status and future prospects for translating lung stem cell therapies to the clinic to replace, repair, or regenerate diseased lung tissue. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation.

  2. Natural-based nanocomposites for bone tissue engineering and regenerative medicine: a review.

    Science.gov (United States)

    Pina, Sandra; Oliveira, Joaquim M; Reis, Rui L

    2015-02-18

    Tissue engineering and regenerative medicine has been providing exciting technologies for the development of functional substitutes aimed to repair and regenerate damaged tissues and organs. Inspired by the hierarchical nature of bone, nanostructured biomaterials are gaining a singular attention for tissue engineering, owing their ability to promote cell adhesion and proliferation, and hence new bone growth, compared with conventional microsized materials. Of particular interest are nanocomposites involving biopolymeric matrices and bioactive nanosized fillers. Biodegradability, high mechanical strength, and osteointegration and formation of ligamentous tissue are properties required for such materials. Biopolymers are advantageous due to their similarities with extracellular matrices, specific degradation rates, and good biological performance. By its turn, calcium phosphates possess favorable osteoconductivity, resorbability, and biocompatibility. Herein, an overview on the available natural polymer/calcium phosphate nanocomposite materials, their design, and properties is presented. Scaffolds, hydrogels, and fibers as biomimetic strategies for tissue engineering, and processing methodologies are described. The specific biological properties of the nanocomposites, as well as their interaction with cells, including the use of bioactive molecules, are highlighted. Nanocomposites in vivo studies using animal models are also reviewed and discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Capturing the Regenerative Potential of Periodontal Ligament Fibroblasts

    Directory of Open Access Journals (Sweden)

    Christina Springstead Scanlon

    2011-01-01

    Full Text Available The cell population within the periodontal ligament (PDL tissue is remarkably heterogeneous1. Fibroblasts, a mixed population of cells, are the main cellular component of the PDL and the cell type most often studied for periodontal regeneration. Osteoblasts and osteoclasts are found on the bone side, while fibroblasts, macrophages, undifferentiated adult/mesenchymal stem cells, neural elements, and endothelial cells are found throughout the PDL. Epithelial rests of Malassez cells and cementoblasts are focused near the root surface. PDL tissue also includes loose connective tissue between dense fiber bundles that contain branches of the periodontal blood vessels and nerves2. The complexity of the PDL tissue, with its various cell types and cell progenitor components, explains the challenges involved in therapies to restore tissue following periodontal disease. Cementoblasts, osteoblasts, and endothelial cells must migrate, differentiate, and coordinately interact with a variety of soluble mediators to regenerate the periodontium3. Stem cells located in the PDL tissue are key contributors to this process4. Stem cells in the PDL are important not only for formation and maintenance of the tissue but also for repair, remodeling, and regeneration of adjacent alveolar bone and cementum5. Our laboratory has shown that progenitor cells isolated from PDL tissue by selection with cell surface markers STRO-1+ and CD146+ are capable of differentiating into chondrogenic, osteogenic, and adipogenic phenotypes under appropriate culture conditions6.

  4. Platelet-rich fibrin (PRF in implant dentistry in combination with new bone regenerative technique in elderly patients

    Directory of Open Access Journals (Sweden)

    Antonio Cortese, MD, DDS

    2016-01-01

    Conclusions: The main advantages in using the platelet-rich fibrin are healing and bone regenerative properties in combination with its complete resorption after surgery, thus avoiding a second surgery time, important factor in the elderly patients. Currently, it is a minimally invasive technique with low risks and satisfactory clinical results such preventing complications or implant failure particularly in elderly patients for age related conditions.

  5. Qualifying stem cell sources: how to overcome potential pitfalls in regenerative medicine?

    Science.gov (United States)

    Reinke, Simon; Dienelt, Anke; Blankenstein, Antje; Duda, Georg N; Geissler, Sven

    2016-01-01

    Regenerative medicine aims to replace lost cells and to restore damaged tissues and organs by either tissue-engineering approaches or stimulation of endogenous processes. Due to their biological properties, stem cells promise to be an effective source for such strategies. Especially adult multipotent stem cells (ASCs) are believed to be applicable in a broad range of therapies for the treatment of multifactorial diseases or age-related degeneration, although the molecular and cellular mechanisms underlying their regenerative function are often hardly described. Moreover, in some demanding clinical situations their efficiency remains limited. Thus, a basic understanding of ASCs regenerative function, their complex interplay with their microenvironment and how compromising conditions interfere with their efficiency is mandatory for any regenerative strategy. Concerning this matter, the impact of patient-specific constraints are often underestimated in research projects and their influence on the study results disregarded. Thus, researchers are urgently depending on well-characterized tissue samples or cells that are connected with corresponding donor information, such as secondary diseases, medication. Here, we outline principle pitfalls during experimental studies using human samples, and describe a potential strategy to overcome these challenges by establishing a core unit for cell and tissue harvesting. This facility aims to bridge the gap between clinic and research laboratories by the provision of a direct link to the clinical operating theatres. Such a strategy clearly supports basic and clinical research in the conduct of their studies and supplies highly characterized human samples together with the corresponding donor information.

  6. The potential role of regenerative medicine in the management of traumatic patients

    Directory of Open Access Journals (Sweden)

    Mahmoudreza Moradi

    2015-01-01

    Full Text Available Abstract: Traumatic injury represents the most common cause of death in ages 1 to 44 years and a significant proportion of patients treated in hospital emergency wards each year. Unfortunately, for patients who survive their injuries, survival is not equal to complete recovery. Many traumatic injuries are difficult to treat with conventional therapy and result in permanent disability. In such situations, regenerative medicine has the potential to play an important role in recovery of function. Regenerative medicine is a field that seeks to maintain or restore function with the development of biological substitutes for diseased or damaged tissues. Several regenerative approaches are currently under investigation, with a few achieving clinical application. For example, engineered skin has gained FDA approval, and more than 20 tissue engineered skin substitutes are now commercially available. Other organ systems with promising animal models and small human series include the central and peripheral nervous systems, the musculoskeletal system, the respiratory and genitourinary tracts, and others. This paper will be a clinically oriented review of the regenerative approaches currently under investigation of special interest to those caring for traumatic patients.

  7. AMNIOTIC FLUID STEM CELLS: THE KNOWN, THE UNKNOWN AND POTENTIAL REGENERATIVE MEDICINE APPLICATIONS.

    Science.gov (United States)

    Loukogeorgakis, Stavros P; De Coppi, Paolo

    2016-12-23

    The amniotic fluid has been identified as an untapped source of cells with broad potential, which possess immunomodulatory properties and don't have the ethical and legal limitations of embryonic stem cells. CD117(c-Kit)+ cells selected from amniotic fluid have been shown to differentiate into cell lineages representing all three embryonic germ layers without generating tumours, making them ideal candidates for regenerative medicine applications. Moreover, their ability to engraft in injured organs and modulate immune and repair responses of host tissues, suggest that transplantation of such cells may be useful for the treatment of various degenerative and inflammatory diseases. Although significant questions remain regarding the origin, heterogeneous phenotype and expansion potential of amniotic fluid stem cells, evidence to date supports their potential role as a valuable stem cell source for the field of regenerative medicine. This article is protected by copyright. All rights reserved.

  8. Bone marrow pathology in dogs and cats with non-regenerative immune-mediated haemolytic anaemia and pure red cell aplasia.

    Science.gov (United States)

    Weiss, D J

    2008-01-01

    Many dogs and cats with immune-mediated haemolytic anaemia (IMHA) lack a bone marrow erythroid regenerative response. To better understand the failure of the bone marrow to respond to the anaemia, bone marrow pathology associated with non-regenerative IMHA and pure red cell aplasia (PRCA) was reviewed. Eighty-two affected dogs and 57 affected cats were identified from a population presenting to a referral hospital over a 10-year period. Fifty-five dogs had non-regenerative IMHA (38 had bone marrow erythroid hyperplasia and 17 had erythroid maturation arrest) and 27 had pure red cell aplasia (PRCA). Twenty-eight cats had non-regenerative IMHA (24 had erythroid hyperplasia and 4 had erythroid maturation arrest) and 29 had PRCA. A variety of pathological changes were observed in bone marrow aspirates and core biopsy specimens taken from these animals. These changes included dysmyelopoiesis, myelonecrosis, myelofibrosis, interstitial oedema, haemorrhage, acute inflammation, haemophagocytic syndrome, lymphocyte aggregation, and lymphocyte or plasma cell hyperplasia. In both dogs and cats, dysmyelopoiesis, myelonecrosis, myelofibrosis, interstitial oedema, haemorrhage, acute inflammation and haemophagocytic syndrome were primarily noted in bone marrow specimens where there was evidence of erythroid hyperplasia. These animals were also more often neutropenic and thrombocytopenic, and had decreased 60 day survival when compared with dogs or cats with non-regenerative anaemia associated with erythroid maturation arrest or PRCA. Therefore, the pathogenesis of the non-regenerative anaemia in non-regenerative IMHA may involve both antibody-mediated destruction of bone marrow precursor cells and pathological events within the bone marrow that result in ineffective erythropoiesis.

  9. "Young at heart": Regenerative potential linked to immature cardiac phenotypes.

    Science.gov (United States)

    Gomes, Renata S M; Skroblin, Philipp; Munster, Alex B; Tomlins, Hannah; Langley, Sarah R; Zampetaki, Anna; Yin, Xiaoke; Wardle, Fiona C; Mayr, Manuel

    2016-03-01

    The adult human myocardium is incapable of regeneration; yet, the zebrafish (Danio rerio) can regenerate damaged myocardium. Similar to the zebrafish heart, hearts of neonatal, but not adult mice are capable of myocardial regeneration. We performed a proteomics analysis of adult zebrafish hearts and compared their protein expression profile to hearts from neonatal and adult mice. Using difference in-gel electrophoresis (DIGE), there was little overlap between the proteome from adult mouse (>8weeks old) and adult zebrafish (18months old) hearts. Similarly, there was a significant degree of mismatch between the protein expression in neonatal and adult mouse hearts. Enrichment analysis of the selected proteins revealed over-expression of DNA synthesis-related proteins in the cardiac proteome of the adult zebrafish heart similar to neonatal and 4days old mice, whereas in hearts of adult mice there was a mitochondria-related predominance in protein expression. Importantly, we noted pronounced differences in the myofilament composition: the adult zebrafish heart lacks many of the myofilament proteins of differentiated adult cardiomyocytes such as the ventricular isoforms of myosin light chains and nebulette. Instead, troponin I and myozenin 1 were expressed as skeletal isoforms rather than cardiac isoforms. The relative immaturity of the adult zebrafish heart was further supported by cardiac microRNA data. Our assessment of zebrafish and mammalian hearts challenges the assertions on the translational potential of cardiac regeneration in the zebrafish model. The immature myofilament composition of the fish heart may explain why adult mouse and human cardiomyocytes lack this endogenous repair mechanism.

  10. Ultrasound-Assisted Liposuction Does Not Compromise the Regenerative Potential of Adipose-Derived Stem Cells.

    Science.gov (United States)

    Duscher, Dominik; Atashroo, David; Maan, Zeshaan N; Luan, Anna; Brett, Elizabeth A; Barrera, Janos; Khong, Sacha M; Zielins, Elizabeth R; Whittam, Alexander J; Hu, Michael S; Walmsley, Graham G; Pollhammer, Michael S; Schmidt, Manfred; Schilling, Arndt F; Machens, Hans-Günther; Huemer, Georg M; Wan, Derrick C; Longaker, Michael T; Gurtner, Geoffrey C

    2016-02-01

    Human mesenchymal stem cells (MSCs) have recently become a focus of regenerative medicine, both for their multilineage differentiation capacity and their excretion of proregenerative cytokines. Adipose-derived mesenchymal stem cells (ASCs) are of particular interest because of their abundance in fat tissue and the ease of harvest via liposuction. However, little is known about the impact of different liposuction methods on the functionality of ASCs. Here we evaluate the regenerative abilities of ASCs harvested via a third-generation ultrasound-assisted liposuction (UAL) device versus ASCs obtained via standard suction-assisted lipoaspiration (SAL). Lipoaspirates were sorted using fluorescent assisted cell sorting based on an established surface-marker profile (CD34+/CD31-/CD45-), to obtain viable ASCs. Yield and viability were compared and the differentiation capacities of the ASCs were assessed. Finally, the regenerative potential of ASCs was examined using an in vivo model of tissue regeneration. UAL- and SAL-derived samples demonstrated equivalent ASC yield and viability, and UAL ASCs were not impaired in their osteogenic, adipogenic, or chondrogenic differentiation capacity. Equally, quantitative real-time polymerase chain reaction showed comparable expression of most osteogenic, adipogenic, and key regenerative genes between both ASC groups. Cutaneous regeneration and neovascularization were significantly enhanced in mice treated with ASCs obtained by either UAL or SAL compared with controls, but there were no significant differences in healing between cell-therapy groups. We conclude that UAL is a successful method of obtaining fully functional ASCs for regenerative medicine purposes. Cells harvested with this alternative approach to liposuction are suitable for cell therapy and tissue engineering applications. Significance: Adipose-derived mesenchymal stem cells (ASCs) are an appealing source of therapeutic progenitor cells because of their multipotency

  11. Amniotic membrane and amniotic fluid-derived cells: potential tools for regenerative medicine?

    Science.gov (United States)

    Parolini, Ornella; Soncini, Maddalena; Evangelista, Marco; Schmidt, Dörthe

    2009-03-01

    Human amniotic membranes and amniotic fluid have attracted increasing attention in recent years as a possible reserve of stem cells that may be useful for clinical application in regenerative medicine. Many studies have been conducted to date in terms of the differentiation potential of these cells, with several reports demonstrating that cells from both the amniotic fluid and membrane display high plasticity. In addition, cells from the amniotic membrane have also been shown to display immunomodulatory characteristics both in vivo and in vitro, which could make them useful in an allotransplantation setting. Here, we provide an overview comparing the latest findings regarding the stem characteristics of cells from both the amniotic membrane and amniotic fluid, as well as on the potential utility of these cells for future clinical application in regenerative medicine.

  12. Chitosan and Its Potential Use as a Scaffold for Tissue Engineering in Regenerative Medicine

    Science.gov (United States)

    Rodríguez-Vázquez, Martin; Vega-Ruiz, Brenda; Ramos-Zúñiga, Rodrigo; Saldaña-Koppel, Daniel Alexander; Quiñones-Olvera, Luis Fernando

    2015-01-01

    Tissue engineering is an important therapeutic strategy to be used in regenerative medicine in the present and in the future. Functional biomaterials research is focused on the development and improvement of scaffolding, which can be used to repair or regenerate an organ or tissue. Scaffolds are one of the crucial factors for tissue engineering. Scaffolds consisting of natural polymers have recently been developed more quickly and have gained more popularity. These include chitosan, a copolymer derived from the alkaline deacetylation of chitin. Expectations for use of these scaffolds are increasing as the knowledge regarding their chemical and biological properties expands, and new biomedical applications are investigated. Due to their different biological properties such as being biocompatible, biodegradable, and bioactive, they have given the pattern for use in tissue engineering for repair and/or regeneration of different tissues including skin, bone, cartilage, nerves, liver, and muscle. In this review, we focus on the intrinsic properties offered by chitosan and its use in tissue engineering, considering it as a promising alternative for regenerative medicine as a bioactive polymer. PMID:26504833

  13. Chitosan and Its Potential Use as a Scaffold for Tissue Engineering in Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Martin Rodríguez-Vázquez

    2015-01-01

    Full Text Available Tissue engineering is an important therapeutic strategy to be used in regenerative medicine in the present and in the future. Functional biomaterials research is focused on the development and improvement of scaffolding, which can be used to repair or regenerate an organ or tissue. Scaffolds are one of the crucial factors for tissue engineering. Scaffolds consisting of natural polymers have recently been developed more quickly and have gained more popularity. These include chitosan, a copolymer derived from the alkaline deacetylation of chitin. Expectations for use of these scaffolds are increasing as the knowledge regarding their chemical and biological properties expands, and new biomedical applications are investigated. Due to their different biological properties such as being biocompatible, biodegradable, and bioactive, they have given the pattern for use in tissue engineering for repair and/or regeneration of different tissues including skin, bone, cartilage, nerves, liver, and muscle. In this review, we focus on the intrinsic properties offered by chitosan and its use in tissue engineering, considering it as a promising alternative for regenerative medicine as a bioactive polymer.

  14. Assessment of bone-fill following regenerative periodontal therapy by image subtraction using commercially available software

    National Research Council Canada - National Science Library

    Pavan Yellarthi; Viswa Rampalli; Naveen Anumala; Rama Devaraju

    2014-01-01

    .... Settings and Design: For the bone-fill assessment, radiographs of 78 angular bone defects from 30 subjects who underwent periodontal flap surgery with hydroxyapatite bone graft placement were utilized...

  15. Stem cells, a two-edged sword: Risks and potentials of regenerative medicine

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The recent advancements in stem cell (SC) biology have led to the concept of regenerative medicine, which is based on the potential of SC for therapies aimed to facilitate the repair of degenerating or injured tissues. Nonetheless, prior to large scale clinical appli- cations, critical aspects need to be further addressed, including the long-term safety, tolerability, and efficacy of SC-based treatments. Most problematic among the risks of SC-based therapies, in addition to the pos- sible rejection or loss of function of the infused cells, is their potential neoplastic transformation. Indeed, SCs may be used to cure devastating diseases, but their specific properties of self-renewal and clonogenicity may render them prone to generate cancers. In this respect, 'Stemness' might be seen as a two-edged sword, its bright side being represented by normal SCs, its dark side by cancer SCs. A better understand- ing of SC biology will help fulfill the promise of regen- erative medicine aimed at curing human pathologies and fighting cancer from its roots.

  16. Bone marrow derived stem cells in regenerative medicine as advanced therapy medicinal products.

    Science.gov (United States)

    Astori, Giuseppe; Soncin, Sabrina; Lo Cicero, Viviana; Siclari, Francesco; Sürder, Daniel; Turchetto, Lucia; Soldati, Gianni; Moccetti, Tiziano

    2010-05-15

    Bone marrow derived stem cells administered after minimal manipulation represent an important cell source for cell-based therapies. Clinical trial results, have revealed both safety and efficacy of the cell reinfusion procedure in many cardiovascular diseases. Many of these early clinical trials were performed in a period before the entry into force of the US and European regulation on cell-based therapies. As a result, conflicting data have been generated on the effectiveness of those therapies in certain conditions as acute myocardial infarction. As more academic medical centers and private companies move toward exploiting the full potential of cell-based medicinal products, needs arise for the development of the infrastructure necessary to support these investigations. This review describes the regulatory environment surrounding the production of cell based medicinal products and give practical aspects for cell isolation, characterization, production following Good Manufacturing Practice, focusing on the activities associated with the investigational new drug development.

  17. Mesenchymal stem cells from rats with chronic kidney disease exhibit premature senescence and loss of regenerative potential.

    Directory of Open Access Journals (Sweden)

    Barbara Mara Klinkhammer

    Full Text Available Mesenchymal stem cell (MSC transplantation has the potential for organ repair. Nevertheless, some factors might lessen the regenerative potential of MSCs, e.g. donor age or systemic disease. It is thus important to carefully assess the patient's suitability for autologous MSC transplantation. Here we investigated the effects of chronic kidney disease (CKD on MSC function. We isolated bone marrow MSCs from remnant kidney rats (RK with CKD (CKD-RK-MSC and found signs of premature senescence: spontaneous adipogenesis, reduced proliferation capacity, active senescence-associated-β-galactosidase, accumulation of actin and a modulated secretion profile. The functionality of CKD-RK-MSCs in vivo was tested in rats with acute anti-Thy1.1-nephritis, where healthy MSCs have been shown to be beneficial. Rats received healthy MSCs, CKD-RK-MSC or medium by injection into the left renal artery. Kidneys receiving healthy MSCs exhibited accelerated healing of glomerular lesions, whereas CKD-RK-MSC or medium exerted no benefit. The negative influence of advanced CKD/uremia on MSCs was confirmed in a second model of CKD, adenine nephropathy (AD. MSCs from rats with adenine nephropathy (CKD-AD-MSC also exhibited cellular modifications and functional deficits in vivo. We conclude that CKD leads to a sustained loss of in vitro and in vivo functionality in MSCs, possibly due to premature cellular senescence. Considering autologous MSC therapy in human renal disease, studies identifying uremia-associated mechanisms that account for altered MSC function are urgently needed.

  18. Potential of Adipose-derived stem cells in muscular regenerative therapies

    Directory of Open Access Journals (Sweden)

    Sonia eForcales

    2015-07-01

    Full Text Available Regenerative capacity of skeletal muscles resides in satellite cells, a self-renewing population of muscle cells. Several studies are investigating epigenetic mechanisms that control myogenic proliferation and differentiation to find new approaches that could boost regeneration of endogenous myogenic progenitor populations. In recent years, a lot of effort has been applied to purify, expand and manipulate adult stem cells from muscle tissue. However, this population of endogenous myogenic progenitors in adults is limited and their access is difficult and invasive. Therefore, other sources of stem cells with potential to regenerate muscles need to be examined. An excellent candidate could be a population of adult stromal cells within fat characterized by mesenchymal properties, which have been termed adipose-derived stem cells (ASCs. These progenitor adult stem cells have been successfully differentiated in vitro to osteogenic, chondrogenic, neurogenic and myogenic lineages. Autologous adipose-derived stem cells are multipotent and can be harvested with low morbidity; thus, they hold promise for a range of therapeutic applications. This review will discuss the use of ASCs in muscle regenerative approaches.

  19. Regenerative potential of human airway stem cells in lung epithelial engineering.

    Science.gov (United States)

    Gilpin, Sarah E; Charest, Jonathan M; Ren, Xi; Tapias, Luis F; Wu, Tong; Evangelista-Leite, Daniele; Mathisen, Douglas J; Ott, Harald C

    2016-11-01

    Bio-engineered organs for transplantation may ultimately provide a personalized solution for end-stage organ failure, without the risk of rejection. Building upon the process of whole organ perfusion decellularization, we aimed to develop novel, translational methods for the recellularization and regeneration of transplantable lung constructs. We first isolated a proliferative KRT5(+)TP63(+) basal epithelial stem cell population from human lung tissue and demonstrated expansion capacity in conventional 2D culture. We then repopulated acellular rat scaffolds in ex vivo whole organ culture and observed continued cell proliferation, in combination with primary pulmonary endothelial cells. To show clinical scalability, and to test the regenerative capacity of the basal cell population in a human context, we then recellularized and cultured isolated human lung scaffolds under biomimetic conditions. Analysis of the regenerated tissue constructs confirmed cell viability and sustained metabolic activity over 7 days of culture. Tissue analysis revealed extensive recellularization with organized tissue architecture and morphology, and preserved basal epithelial cell phenotype. The recellularized lung constructs displayed dynamic compliance and rudimentary gas exchange capacity. Our results underline the regenerative potential of patient-derived human airway stem cells in lung tissue engineering. We anticipate these advances to have clinically relevant implications for whole lung bioengineering and ex vivo organ repair.

  20. Nicotine alters MicroRNA expression and hinders human adult stem cell regenerative potential.

    Science.gov (United States)

    Ng, Tsz Kin; Carballosa, Carlos M; Pelaez, Daniel; Wong, Hoi Kin; Choy, Kwong Wai; Pang, Chi Pui; Cheung, Herman S

    2013-03-01

    Adult stem cells are critical for the healing process in regenerative medicine. However, cigarette smoking inhibits stem cell recruitment to tissues and delays the wound-healing process. This study investigated the effect of nicotine, a major constituent in the cigarette smoke, on the regenerative potentials of human mesenchymal stem cells (MSC) and periodontal ligament-derived stem cells (PDLSC). The cell proliferation of 1.0 μM nicotine-treated MSC and PDLSC was significantly reduced when compared to the untreated control. Moreover, nicotine also retarded the locomotion of these adult stem cells. Furthermore, their osteogenic differentiation capabilities were reduced in the presence of nicotine as evidenced by gene expression (RUNX2, ALPL, BGLAP, COL1A1, and COL1A2), calcium deposition, and alkaline phosphatase activity analyses. In addition, the microRNA (miRNA) profile of nicotine-treated PDLSC was altered; suggesting miRNAs might play an important role in the nicotine effects on stem cells. This study provided the possible mechanistic explanations on stem cell-associated healing delay in cigarette smoking.

  1. A case of cellular alchemy: lineage reprogramming and its potential in regenerative medicine

    Institute of Scientific and Technical Information of China (English)

    Grace E.Asuelime; Yanhong Shi

    2012-01-01

    The field of regenerative medicine is rapidly gaining momentum as an increasing number of reports emerge concerning the induced conversions observed in cellular fate reprogramming.While in recent years,much attention has been focused on the conversion of fate-committed somatic cells to an embryonic-like or pluripotent state,there are still many limitations associated with the applications of induced pluripotent stem cell reprogramming,including relatively low reprogramming efficiency,the times required for the reprogramming event to take place,the epigenetic instability,and the tumorigenicity associated with the pluripotent state.On the other hand,lineage reprogramming involves the conversion from one mature cell type to another without undergoing conversion to an unstable intermediate.It provides an alternative approach in regenerative medicine that has a relatively lower risk of tumorigenesis and increased efficiency within specific cellular contexts.While lineage reprogramming provides exciting potential,there is still much to be assessed before this technology is ready to be applied in a clinical setting.

  2. The bone-regenerative properties of Emdogain adsorbed onto poly(D,L-lactic-coglycolic acid)/calcium phosphate composites in an ectopic and an orthotopic rat model.

    NARCIS (Netherlands)

    Plachokova, A.S.; Dolder, J. van den; Jansen, J.A.

    2008-01-01

    BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the bone-regenerative properties of Emdogain in osseous and nonosseous sites. MATERIAL AND METHODS: For the orthotopic study, unloaded poly(D,L-lactic-coglycolic acid)/calcium phosphate implants, and poly(D,L-lactic-coglycolic acid)/cal

  3. Signaling pathways involved in osteogenesis and their application for bone regenerative medicine

    NARCIS (Netherlands)

    Hayrapetyan, A.; Jansen, J.A.; Beucken, J.J.J.P van den

    2015-01-01

    Bone regeneration is a well organized but complex physiological process, in which different cell types and their activated signaling pathways are involved. In bone regeneration and remodeling processes, mesenchymal stem cells (MSCs) have a crucial role, and their differentiation during these

  4. Origin and Regenerative Potential of Vertebrate Mechanoreceptor-Associated Stem Cells

    Directory of Open Access Journals (Sweden)

    Darius Widera

    2012-01-01

    Full Text Available Meissner corpuscles and Merkel cell neurite complexes are highly specialized mechanoreceptors present in the hairy and glabrous skin, as well as in different types of mucosa. Several reports suggest that after injury, such as after nerve crush, freeze injury, or dissection of the nerve, they are able to regenerate, particularly including reinnervation and repopulation of the mechanoreceptors by Schwann cells. However, little is known about mammalian cells responsible for these regenerative processes. Here we review cellular origin of this plasticity in the light of newly described adult neural crest-derived stem cell populations. We also discuss further potential multipotent stem cell populations with the ability to regenerate disrupted innervation and to functionally recover the mechanoreceptors. These capabilities are discussed as in context to cellularly reprogrammed Schwann cells and tissue resident adult mesenchymal stem cells.

  5. Does Fetal antigen 1 (FA1) identify cells with regenerative, endocrine and neuroendocrine potentials?

    DEFF Research Database (Denmark)

    Jensen, Charlotte Floridon; Jensen, Charlotte Harken; Thorsen, Poul

    2000-01-01

    in the subcellular localisation indicating differential post-translational/post-transcriptional modifications during fetal development. FA1 may be a new marker of cellular subtypes with a regenerative potential and of specific cells with endocrine or neuroendocrine functions. Udgivelsesdato: 2000-Aug......, the localisation of FA1/dlk was analysed in embryonic and fetal tissues between week 5 to 25 of gestation and related to germinal origin and development. FA1 was observed in endodermally derived hepatocytes, glandular cells of the pancreas anlage, and in respiratory epithelial cells. FA1 was also present...... in mesodermally derived cells of the renal proximal tubules, adrenal cortex, Leydig and Hilus cells of the testes and ovaries, fetal chondroblasts, and skeletal myotubes. Ectodermally derived neuro- and adenohypophysial cells, cells in the floor of the 3rd ventricle and plexus choroideus were also FA1 positive...

  6. Stem cell technology for bone regeneration: current status and potential applications

    Directory of Open Access Journals (Sweden)

    Asatrian G

    2015-02-01

    Full Text Available Greg Asatrian,1 Dalton Pham,1,2 Winters R Hardy,3 Aaron W James,1–3 Bruno Peault3,4 1Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, 2Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, 3UCLA/Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Los Angeles, CA, USA; 4Medical Research Council Centre for Regenerative Medicine, Edinburgh, Scotland, UK Abstract: Continued improvements in the understanding and application of mesenchymal stem cells (MSC have revolutionized tissue engineering. This is particularly true within the field of skeletal regenerative medicine. However, much remains unknown regarding the native origins of MSC, the relative advantages of different MSC populations for bone regeneration, and even the biologic safety of such unpurified, grossly characterized cells. This review will first summarize the initial discovery of MSC, as well as the current and future applications of MSC in bone tissue engineering. Next, the relative advantages and disadvantages of MSC isolated from distinct tissue origins are debated, including the MSC from adipose, bone marrow, and dental pulp, among others. The perivascular origin of MSC is next discussed. Finally, we briefly comment on pluripotent stem cell populations and their possible application in bone tissue engineering. While continually expanding, the field of MSC-based bone tissue engineering and regeneration shows potential to become a clinical reality in the not-so-distant future.Keywords: mesenchymal stem cell, pericyte, bone tissue engineering, MSC, ASC, DMSC

  7. Mesenchymal stem cells: Identification, phenotypic characterization, biological properties and potential for regenerative medicine through biomaterial micro-engineering of their niche.

    Science.gov (United States)

    Kobolak, Julianna; Dinnyes, Andras; Memic, Adnan; Khademhosseini, Ali; Mobasheri, Ali

    2016-04-15

    Mesenchymal stem cells (MSCs) are multipotent stem cells. Although they were originally identified in bone marrow and described as 'marrow stromal cells', they have since been identified in many other anatomical locations in the body. MSCs can be isolated from bone marrow, adipose tissue, umbilical cord and other tissues but the richest tissue source of MSCs is fat. Since they are adherent to plastic, they may be expanded in vitro. MSCs have a distinct morphology and express a specific set of CD (cluster of differentiation) molecules. The phenotypic pattern for the identification of MSCs cells requires expression of CD73, CD90, and CD105 and lack of CD34, CD45, and HLA-DR antigens. Under appropriate micro-environmental conditions MSCs can proliferate and give rise to other cell types. Therefore, they are ideally suited for the treatment of systemic inflammatory and autoimmune conditions. They have also been implicated as key players in regenerating injured tissue following injury and trauma. MSC populations isolated from adipose tissue may also contain regulatory T (Treg) cells, which have the capacity for modulating the immune system. The immunoregulatory and regenerative properties of MSCs make them ideal for use as therapeutic agents in vivo. In this paper we review the literature on the identification, phenotypic characterization and biological properties of MSCs and discuss their potential for applications in cell therapy and regenerative medicine. We also discuss strategies for biomaterial micro-engineering of the stem cell niche.

  8. 3D silicon doped hydroxyapatite scaffolds decorated with Elastin-like Recombinamers for bone regenerative medicine.

    Science.gov (United States)

    Vila, Mercedes; García, Ana; Girotti, Alessandra; Alonso, Matilde; Rodríguez-Cabello, Jose Carlos; González-Vázquez, Arlyng; Planell, Josep A; Engel, Elisabeth; Buján, Julia; García-Honduvilla, Natalio; Vallet-Regí, María

    2016-11-01

    The current study reports on the manufacturing by rapid prototyping technique of three-dimensional (3D) scaffolds based on silicon substituted hydroxyapatite with Elastin-like Recombinamers (ELRs) functionalized surfaces. Silicon doped hydroxyapatite (Si-HA), with Ca10(PO4)5.7(SiO4)0.3(OH)1.7h0.3 nominal formula, was surface functionalized with two different types of polymers designed by genetic engineering: ELR-RGD that contain cell attachment specific sequences and ELR-SNA15/RGD with both hydroxyapatite and cells domains that interact with the inorganic phase and with the cells, respectively. These hybrid materials were subjected to in vitro assays in order to clarify if the ELRs coating improved the well-known biocompatible and bone regeneration properties of calcium phosphates materials. The in vitro tests showed that there was a total and homogeneous colonization of the 3D scaffolds by Bone marrow Mesenchymal Stromal Cells (BMSCs). In addition, the BMSCs were viable and able to proliferate and differentiate into osteoblasts. Bone tissue engineering is an area of increasing interest because its main applications are directly related to the rising life expectancy of the population, which promotes higher rates of several bone pathologies, so innovative strategies are needed for bone tissue regeneration therapies. Here we use the rapid prototyping technology to allow moulding ceramic 3D scaffolds and we use different bio-polymers for the functionalization of their surfaces in order to enhance the biological response. Combining the ceramic material (silicon doped hydroxyapatite, Si-HA) and the Elastin like Recombinamers (ELRs) polymers with the presence of the integrin-mediate adhesion domain alone or in combination with SNA15 peptide that possess high affinity for hydroxyapatite, provided an improved Bone marrow Mesenchymal Stromal Cells (BMSCs) differentiation into osteoblastic linkage. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights

  9. Osteogenic differentiation of amniotic fluid mesenchymal stromal cells and their bone regeneration potential.

    Science.gov (United States)

    Pipino, Caterina; Pandolfi, Assunta

    2015-05-26

    In orthopedics, tissue engineering approach using stem cells is a valid line of treatment for patients with bone defects. In this context, mesenchymal stromal cells of various origins have been extensively studied and continue to be a matter of debate. Although mesenchymal stromal cells from bone marrow are already clinically applied, recent evidence suggests that one may use mesenchymal stromal cells from extra-embryonic tissues, such as amniotic fluid, as an innovative and advantageous resource for bone regeneration. The use of cells from amniotic fluid does not raise ethical problems and provides a sufficient number of cells without invasive procedures. Furthermore, they do not develop into teratomas when transplanted, a consequence observed with pluripotent stem cells. In addition, their multipotent differentiation ability, low immunogenicity, and anti-inflammatory properties make them ideal candidates for bone regenerative medicine. We here present an overview of the features of amniotic fluid mesenchymal stromal cells and their potential in the osteogenic differentiation process. We have examined the papers actually available on this regard, with particular interest in the strategies applied to improve in vitro osteogenesis. Importantly, a detailed understanding of the behavior of amniotic fluid mesenchymal stromal cells and their osteogenic ability is desirable considering a feasible application in bone regenerative medicine.

  10. Post chemotherapy blood and bone marrow regenerative changes in childhood acute lymphoblastic leukemia a prospective study

    Directory of Open Access Journals (Sweden)

    Rashmi Kushwaha

    2014-01-01

    Full Text Available Context: This study was done to assess the Serial peripheral blood and bone marrow changes in patients of Acute Lymphoblastic Leukemia on chemotherapy. Aims: To assess the therapy related serial bone marrow changes in patients of Acute Lymphoblastic Leukemia. Settings and Design: Prospective study, carried out in Lymphoma- Leukemia Lab, Department of Pathology, K.G.M.U from March 2011 to March 2012. A total of 60 cases were studied Materials and Methods: History, complete hemogram, bone marrow examination at pretherapy (Day-0, intratherapy (Day-14, and end of induction chemotherapy (Day-28 were done. Peripheral blood smears were evaluated at regular interval to assess clearance of blast cells. Statistical analysis used: The statistical analysis was done using SPSS (Statistical Package for Social Sciences Version 15.0 statistical Analysis Software. The values were represented in Number (% and Mean ± SD. The following Statistical formulas were used: Mean, standard deviation, Chi square test, Paired "t" test, Student ′t′ test, Level of significance P Results: Incidence of ALL-L1 (46.7% and ALL-L2 (53.3% was equal. ALL-L2 patients had poor survival.Day 0 (D-0 bone marrow was hypercellular with flooding of marrow by leukemic cells. High levels of tumor load at D′0′ were associated with poor survival. 14 th day of Induction phase showed significant decrease in hemoglobin and TLC as compared to D ′0′ parameters. D28 showed marrow regeneration. Cellularity, Blast%, and Leukemic Index showed significant drop from day ′0′ to day 14 due to myelosupression, whereas regeneration reflected by increased cellularity as per day 28 marrow. Lymphocytosis (>20% at end of induction chemotherapy had better survival and longer remission.Risk of mortality was directly proportional to blast clearance and was a major independent prognostic factor for achievement of complete remission. Conclusions: A bone marrow examination at the end of induction

  11. A regenerative microchannel device for recording multiple single-unit action potentials in awake, ambulatory animals.

    Science.gov (United States)

    Srinivasan, Akhil; Tipton, John; Tahilramani, Mayank; Kharbouch, Adel; Gaupp, Eric; Song, Chao; Venkataraman, Poornima; Falcone, Jessica; Lacour, Stéphanie P; Stanley, Garrett B; English, Arthur W; Bellamkonda, Ravi V

    2016-02-01

    Despite significant advances in robotics, commercially advanced prosthetics provide only a small fraction of the functionality of the amputated limb that they are meant to replace. Peripheral nerve interfacing could provide a rich controlling link between the body and these advanced prosthetics in order to increase their overall utility. Here, we report on the development of a fully integrated regenerative microchannel interface with 30 microelectrodes and signal extraction capabilities enabling evaluation in an awake and ambulatory rat animal model. In vitro functional testing validated the capability of the microelectrodes to record neural signals similar in size and nature to those that occur in vivo. In vitro dorsal root ganglia cultures revealed striking cytocompatibility of the microchannel interface. Finally, in vivo, the microchannel interface was successfully used to record a multitude of single-unit action potentials through 63% of the integrated microelectrodes at the early time point of 3 weeks. This marks a significant advance in microchannel interfacing, demonstrating the capability of microchannels to be used for peripheral nerve interfacing.

  12. Microtissues in Cardiovascular Medicine: Regenerative Potential Based on a 3D Microenvironment

    Directory of Open Access Journals (Sweden)

    Julia Günter

    2016-01-01

    Full Text Available More people die annually from cardiovascular diseases than from any other cause. In particular, patients who suffer from myocardial infarction may be affected by ongoing adverse remodeling processes of the heart that may ultimately lead to heart failure. The introduction of stem and progenitor cell-based applications has raised substantial hope for reversing these processes and inducing cardiac regeneration. However, current stem cell therapies using single-cell suspensions have failed to demonstrate long-lasting efficacy due to the overall low retention rate after cell delivery to the myocardium. To overcome this obstacle, the concept of 3D cell culture techniques has been proposed to enhance therapeutic efficacy and cell engraftment based on the simulation of an in vivo-like microenvironment. Of great interest is the use of so-called microtissues or spheroids, which have evolved from their traditional role as in vitro models to their novel role as therapeutic agents. This review will provide an overview of the therapeutic potential of microtissues by addressing primarily cardiovascular regeneration. It will accentuate their advantages compared to other regenerative approaches and summarize the methods for generating clinically applicable microtissues. In addition, this review will illustrate the unique properties of the microenvironment within microtissues that makes them a promising next-generation therapeutic approach.

  13. Placenta Derived Mesenchymal Stem Cells Hosted on RKKP Glass-Ceramic: A Tissue Engineering Strategy for Bone Regenerative Medicine Applications

    Directory of Open Access Journals (Sweden)

    Mario Ledda

    2016-01-01

    Full Text Available In tissue engineering protocols, the survival of transplanted stem cells is a limiting factor that could be overcome using a cell delivery matrix able to support cell proliferation and differentiation. With this aim, we studied the cell-friendly and biocompatible behavior of RKKP glass-ceramic coated Titanium (Ti surface seeded with human amniotic mesenchymal stromal cells (hAMSCs from placenta. The sol-gel synthesis procedure was used to prepare the RKKP glass-ceramic material, which was then deposited onto the Ti surface by Pulsed Laser Deposition method. The cell metabolic activity and proliferation rate, the cytoskeletal actin organization, and the cell cycle phase distribution in hAMSCs seeded on the RKKP coated Ti surface revealed no significant differences when compared to the cells grown on the treated plastic Petri dish. The health of of hAMSCs was also analysed studying the mRNA expressions of MSC key genes and the osteogenic commitment capability using qRT-PCR analysis which resulted in being unchanged in both substrates. In this study, the combination of the hAMSCs’ properties together with the bioactive characteristics of RKKP glass-ceramics was investigated and the results obtained indicate its possible use as a new and interesting cell delivery system for bone tissue engineering and regenerative medicine applications.

  14. Placenta Derived Mesenchymal Stem Cells Hosted on RKKP Glass-Ceramic: A Tissue Engineering Strategy for Bone Regenerative Medicine Applications

    Science.gov (United States)

    Fosca, Marco; De Bonis, Angela; Curcio, Mariangela; Lolli, Maria Grazia; De Stefanis, Adriana; Marchese, Rodolfo; Rau, Julietta V.

    2016-01-01

    In tissue engineering protocols, the survival of transplanted stem cells is a limiting factor that could be overcome using a cell delivery matrix able to support cell proliferation and differentiation. With this aim, we studied the cell-friendly and biocompatible behavior of RKKP glass-ceramic coated Titanium (Ti) surface seeded with human amniotic mesenchymal stromal cells (hAMSCs) from placenta. The sol-gel synthesis procedure was used to prepare the RKKP glass-ceramic material, which was then deposited onto the Ti surface by Pulsed Laser Deposition method. The cell metabolic activity and proliferation rate, the cytoskeletal actin organization, and the cell cycle phase distribution in hAMSCs seeded on the RKKP coated Ti surface revealed no significant differences when compared to the cells grown on the treated plastic Petri dish. The health of of hAMSCs was also analysed studying the mRNA expressions of MSC key genes and the osteogenic commitment capability using qRT-PCR analysis which resulted in being unchanged in both substrates. In this study, the combination of the hAMSCs' properties together with the bioactive characteristics of RKKP glass-ceramics was investigated and the results obtained indicate its possible use as a new and interesting cell delivery system for bone tissue engineering and regenerative medicine applications. PMID:28078286

  15. Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine

    Energy Technology Data Exchange (ETDEWEB)

    Tomar, Geetanjali B.; Srivastava, Rupesh K.; Gupta, Navita; Barhanpurkar, Amruta P.; Pote, Satish T. [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India); Jhaveri, Hiral M. [Department of Periodontics and Oral Implantology, Dr. D.Y. Patil Dental College and Hospital, Pune (India); Mishra, Gyan C. [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India); Wani, Mohan R., E-mail: mohanwani@nccs.res.in [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India)

    2010-03-12

    Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into multiple cell lineages. Presently, bone marrow is considered as a prime source of MSCs; however, there are some drawbacks and limitations in use of these MSCs for cell therapy. In this study, we demonstrate that human gingival tissue-derived MSCs have several advantages over bone marrow-derived MSCs. Gingival MSCs are easy to isolate, homogenous and proliferate faster than bone marrow MSCs without any growth factor. Importantly, gingival MSCs display stable morphology and do not loose MSC characteristic at higher passages. In addition, gingival MSCs maintain normal karyotype and telomerase activity in long-term cultures, and are not tumorigenic. Thus, we reveal that human gingiva is a better source of MSCs than bone marrow, and large number of functionally competent clinical grade MSCs can be generated in short duration for cell therapy in regenerative medicine and tissue engineering.

  16. Generation of thyroid follicular cells from pluripotent stem cells: potential for regenerative medicine.

    Science.gov (United States)

    Sewell, Will; Lin, Reigh-Yi

    2014-01-01

    Nearly 12% of the population in the United States will be afflicted with a thyroid related disorder during their lifetime. Common treatment approaches are tailored to the specific disorder and include surgery, radioactive iodine ablation, antithyroid drugs, thyroid hormone replacement, external beam radiation, and chemotherapy. Regenerative medicine endeavors to combat disease by replacing or regenerating damaged, diseased, or dysfunctional body parts. A series of achievements in pluripotent stem cell research have transformed regenerative medicine in many ways by demonstrating "repair" of a number of body parts in mice, of which, the thyroid has now been inducted into this special group. Seminal work in pluripotent cells, namely embryonic stem cells and induced pluripotent stem cells, have made possible their path to becoming key tools and biological building blocks for cell-based regenerative medicine to combat the gamut of human diseases, including those affecting the thyroid.

  17. Generation of thyroid follicular cells from pluripotent stem cells: Potential for regenerative medicine

    Directory of Open Access Journals (Sweden)

    Will eSewell

    2014-06-01

    Full Text Available Nearly 12 percent of the population in the United States will be afflicted with a thyroid related disorder during their lifetime. Common treatment approaches are tailored to the specific disorder and include surgery, radioactive iodine ablation, antithyroid drugs, thyroid hormone replacement, external beam radiation, and chemotherapy. Regenerative medicine endeavors to combat disease by replacing or regenerating damaged, diseased or dysfunctional body parts. A series of achievements in pluripotent stem cell research have transformed regenerative medicine in many ways by demonstrating repair of a number of body parts in mice, of which, the thyroid has now been inducted into this special group. Seminal work in pluripotent cells, namely embryonic stem cells and induced pluripotent stem cells, have made possible their path to becoming key tools and biological building blocks for cell-based regenerative medicine to combat the gamut of human diseases, including those affecting the thyroid.

  18. Biomolecule delivery to engineer the cellular microenvironment for regenerative medicine.

    Science.gov (United States)

    Bishop, Corey J; Kim, Jayoung; Green, Jordan J

    2014-07-01

    To realize the potential of regenerative medicine, controlling the delivery of biomolecules in the cellular microenvironment is important as these factors control cell fate. Controlled delivery for tissue engineering and regenerative medicine often requires bioengineered materials and cells capable of spatiotemporal modulation of biomolecule release and presentation. This review discusses biomolecule delivery from the outside of the cell inwards through the delivery of soluble and insoluble biomolecules as well as from the inside of the cell outwards through gene transfer. Ex vivo and in vivo therapeutic strategies are discussed, as well as combination delivery of biomolecules, scaffolds, and cells. Various applications in regenerative medicine are highlighted including bone tissue engineering and wound healing.

  19. Multilayer bioactive glass/zirconium titanate thin films in bone tissue engineering and regenerative dentistry

    Directory of Open Access Journals (Sweden)

    Mozafari M

    2013-04-01

    Full Text Available Masoud Mozafari,1,2 Erfan Salahinejad,1,3 Vahid Shabafrooz,1 Mostafa Yazdimamaghani,1 Daryoosh Vashaee,4 Lobat Tayebi1,5 1Helmerich Advanced Technology Research Center, School of Materials Science and Engineering, Oklahoma State University, Tulsa, OK, USA; 2Biomaterials Group, Faculty of Biomedical Engineering (Center of Excellence, Amirkabir University of Technology, Tehran, Iran; 3Department of Materials Science and Engineering, School of Engineering, Shiraz University, Shiraz, Iran; 4Helmerich Advanced Technology Research Center, School of Electrical and Computer Engineering, Oklahoma State University, Tulsa, OK, USA; 5School of Chemical Engineering, Oklahoma State University, Tulsa, OK, USA Abstract: Surface modification, particularly coatings deposition, is beneficial to tissue-engineering applications. In this work, bioactive glass/zirconium titanate composite thin films were prepared by a sol-gel spin-coating method. The surface features of the coatings were studied by scanning electron microscopy, atomic force microscopy, and spectroscopic reflection analyses. The results show that uniform and sound multilayer thin films were successfully prepared through the optimization of the process variables and the application of carboxymethyl cellulose as a dispersing agent. Also, it was found that the thickness and roughness of the multilayer coatings increase nonlinearly with increasing the number of the layers. This new class of nanocomposite coatings, comprising the bioactive and inert components, is expected not only to enhance bioactivity and biocompatibility, but also to protect the surface of metallic implants against wear and corrosion. Keywords: bioactive glass, zirconium titanate, spin-coating, microstructural properties, bone/dental applications, tissue engineering

  20. Platelet-rich fibrin: a boon in regenerative endodontics.

    Science.gov (United States)

    Rebentish, Priyanka D; Umashetty, Girish; Kaur, Harpreet; Doizode, Trupthi; Kaslekar, Mithun; Chowdhury, Shouvik

    2016-12-01

    Research into regenerative dentistry has contributed momentum to the field of molecular biology. Periapical surgery aims at removing periapical pathology to achieve complete wound healing and regeneration of bone and periodontal tissue. Regenerative endodontic procedures are widely being added to the current armamentarium of pulp therapy procedures. The regenerative potential of platelets has been deliberated. Platelet-rich fibrin (PRF) is a wonderful tissue-engineering product and has recently gained much popularity due its promising results in wound healing bone induction. The features of this product are an attribute of platelets which, after cellular interactions, release growth factors and have shown application in diverse disciplines of dentistry. This paper is intended to shed light onto the various prospects of PRF and to provide clinical insight into regenerative endodontic therapy.

  1. Dynamic analyses of regenerative fuel cell power for potential use in renewable residential applications

    OpenAIRE

    Maclay, JD; J. Brouwer; Samuelsen, GS

    2006-01-01

    A model of a solar-hydrogen powered residence, in both stand-alone and grid parallel configurations, was developed using Matlab / Simulink®. The model assesses the viability of employing a regenerative fuel cell (RFC) as an energy storage device to be used with photovoltaic (PV) electrical generation. Other modes of energy storage such as batteries and hybrid storage were also evaluated. Analyses of various operating conditions, system configurations, and control strategies were performed. De...

  2. Induced pluripotent stem cells (iPSCs) derived from different cell sources and their potential for regenerative and personalized medicine.

    Science.gov (United States)

    Shtrichman, R; Germanguz, I; Itskovitz-Eldor, J

    2013-06-01

    Human induced pluripotent stem cells (hiPSCs) have great potential as a robust source of progenitors for regenerative medicine. The novel technology also enables the derivation of patient-specific cells for applications to personalized medicine, such as for personal drug screening and toxicology. However, the biological characteristics of iPSCs are not yet fully understood and their similarity to human embryonic stem cells (hESCs) is still unresolved. Variations among iPSCs, resulting from their original tissue or cell source, and from the experimental protocols used for their derivation, significantly affect epigenetic properties and differentiation potential. Here we review the potential of iPSCs for regenerative and personalized medicine, and assess their expression pattern, epigenetic memory and differentiation capabilities in relation to their parental tissue source. We also summarize the patient-specific iPSCs that have been derived for applications in biological research and drug discovery; and review risks that must be overcome in order to use iPSC technology for clinical applications.

  3. Cardiac Regenerative Medicine: The Potential of a New Generation of Stem Cells.

    Science.gov (United States)

    Cambria, Elena; Steiger, Julia; Günter, Julia; Bopp, Annina; Wolint, Petra; Hoerstrup, Simon P; Emmert, Maximilian Y

    2016-07-01

    Cardiac stem cell therapy holds great potential to prompt myocardial regeneration in patients with ischemic heart disease. The selection of the most suitable cell type is pivotal for its successful application. Various cell types, including crude bone marrow mononuclear cells, skeletal myoblast, and hematopoietic and endothelial progenitors, have already advanced into the clinical arena based on promising results from different experimental and preclinical studies. However, most of these so-called first-generation cell types have failed to fully emulate the promising preclinical data in clinical trials, resulting in heterogeneous outcomes and a critical lack of translation. Therefore, different next-generation cell types are currently under investigation for the treatment of the diseased myocardium. This review article provides an overview of current stem cell therapy concepts, including the application of cardiac stem (CSCs) and progenitor cells (CPCs) and lineage commitment via guided cardiopoiesis from multipotent cells such as mesenchymal stem cells (MSCs) or pluripotent cells such as embryonic and induced pluripotent stem cells. Furthermore, it introduces new strategies combining complementary cell types, such as MSCs and CSCs/CPCs, which can yield synergistic effects to boost cardiac regeneration.

  4. Lgr5⁺ amacrine cells possess regenerative potential in the retina of adult mice.

    Science.gov (United States)

    Chen, Mengfei; Tian, Shenghe; Glasgow, Nathan G; Gibson, Gregory; Yang, Xiaoling; Shiber, Christen E; Funderburgh, James; Watkins, Simon; Johnson, Jon W; Schuman, Joel S; Liu, Hongjun

    2015-08-01

    Current knowledge indicates that the adult mammalian retina lacks regenerative capacity. Here, we show that the adult stem cell marker, leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), is expressed in the retina of adult mice. Lgr5(+) cells are generated at late stages of retinal development and exhibit properties of differentiated amacrine interneurons (amacrine cells). Nevertheless, Lgr5(+) amacrine cells contribute to regeneration of new retinal cells in the adult stage. The generation of new retinal cells, including retinal neurons and Müller glia from Lgr5(+) amacrine cells, begins in early adulthood and continues as the animal ages. Together, these findings suggest that the mammalian retina is not devoid of regeneration as previously thought. It is rather dynamic, and Lgr5(+) amacrine cells function as an endogenous regenerative source. The identification of such cells in the mammalian retina may provide new insights into neuronal regeneration and point to therapeutic opportunities for age-related retinal degenerative diseases.

  5. Evaluation of bone regenerative capacity in rats claverial bone defect using platelet rich fibrin with and without beta tri calcium phosphate bone graft material

    Directory of Open Access Journals (Sweden)

    Walid Ahmed Abdullah

    2016-07-01

    Conclusion: The addition of β-TCP to PRF significantly improved bone regeneration in the first 2 weeks after surgery. Although the differences between results with and without the addition of β-TCP to PRF were statistically insignificant from weeks 3 to 6, it was nevertheless apparent that the group receiving the combination showed better results. We suggest a synergistic mechanism for this effect.

  6. The potential of mesenchymal stem cells derived from amniotic membrane and amniotic fluid for neuronal regenerative therapy.

    Science.gov (United States)

    Kim, Eun Young; Lee, Kyung-Bon; Kim, Min Kyu

    2014-03-01

    The mesenchymal stem cells (MSCs), which are derived from the mesoderm, are considered as a readily available source for tissue engineering. They have multipotent differentiation capacity and can be differentiated into various cell types. Many studies have demonstrated that the MSCs identified from amniotic membrane (AM-MSCs) and amniotic fluid (AF-MSCs) are shows advantages for many reasons, including the possibility of noninvasive isolation, multipotency, self-renewal, low immunogenicity, anti-inflammatory and nontumorigenicity properties, and minimal ethical problem. The AF-MSCs and AM-MSCs may be appropriate sources of mesenchymal stem cells for regenerative medicine, as an alternative to embryonic stem cells (ESCs). Recently, regenerative treatments such as tissue engineering and cell transplantation have shown potential in clinical applications for degenerative diseases. Therefore, amnion and MSCs derived from amnion can be applied to cell therapy in neuro-degeneration diseases. In this review, we will describe the potential of AM-MSCs and AF-MSCs, with particular focus on cures for neuronal degenerative diseases.

  7. Probing Regenerative Potential of Moringa oleifera Aqueous Extracts Using In vitro Cellular Assays

    Science.gov (United States)

    Fernandes, Evangeline E.; Pulwale, Anubha V.; Patil, Gauri A.; Moghe, Alpana S.

    2016-01-01

    showed relatively less potential to stimulate cells but had prominent cytotoxic effect on cancer cell lines. Abbreviations Used: ALT: Alanine transaminase, AST: Asparatate amino transferase, ATCC: American type culture collection, BMMSC: Bone marrow mesenchymal stem cells (used in this paper), CAM: Chick chorioallantoic membrane, CCl4: Carbon tetra chloride, DMEM: Dulbecco's modified Eagle medium, DMSO: Dimethyl sulfoxide, EDTA: Ethylene diamine tetraacetic acid, HBL 100: Human breast epithelial cell line, Mcf-7: Human breast adenocarcinoma cell line, aMEM: Minimum Essential Medium Eagle alpha modification, MOF: Moringa oleifera aqueous flower extract (used in this paper), MOL: Moringa oleifera aqueos leaf extract (Used in this paper), OD: Optical density, PBS: Phosphate buffered saline PMID:27695260

  8. Probing Regenerative Potential of Moringa oleifera Aqueous Extracts Using In vitro Cellular Assays.

    Science.gov (United States)

    Fernandes, Evangeline E; Pulwale, Anubha V; Patil, Gauri A; Moghe, Alpana S

    2016-01-01

    Molecules stimulating regeneration and proliferation of cells are of significance in combating ailments caused due to tissue injury, inflammation, and degenerative disorders. Moringa oleifera is one of the most valued food plants having the profile of important nutrients and impressive range of medicinal uses. To evaluate the potential of M. oleifera aqueous leaf and flower extracts to promote the proliferation of cells and explore their effect on cancer cell lines for assessment of safety. Aqueous leaf and flower extracts of M. oleifera were investigated for effect on rat-derived primary fibroblast, mesenchymal stem cells (MSCs), and cancer cell lines using cell proliferation assay. They were also tested and compared for wound healing, angiogenesis, and hepatoprotective effect using in vitro assays. Statistically significant increase in the proliferation of primary rat fibroblast, MSCs, and angiogenesis was observed after treatment with aqueous flower extract. The aqueous leaf extract determined a comparatively moderate increment in the proliferation of MSCs and angiogenesis. It however showed prominent cytotoxicity to cancer cell lines and a significant hepatoprotective effect. A very clear difference in response of the two extracts to different types of cells was detected in this study. The aqueous flower extract exhibited a higher potential to stimulate cell proliferation while not exerting the same effect on cancer cell lines. The leaf extract on the other hand, had a prominent antitumor and hepatoptotective effects. Moringa oleifera flower extract showed significant ability to promote proliferation of rat fibroblast and mesenchymal stem cells. The extract also had prominent angiogenic and hepatoprotective effects.The extract did not influence proliferation of cancer cell lines indicating its safety for human consumption and use in pharmaceuticals.The Moringa oleifera leaf extract showed relatively less potential to stimulate cells but had prominent cytotoxic

  9. Metastatic potential of an aneurysmal bone cyst.

    NARCIS (Netherlands)

    Luijtgaarden, A.C.M. van de; Veth, R.P.H.; Slootweg, P.J.; Wijers-Koster, P.M.; Schultze Kool, L.J.; Bovee, J.V.; Graaf, W.T.A. van der

    2009-01-01

    Aneurysmal bone cysts (ABCs) are benign bone tumors consisting of blood-filled cavities lined by connective tissue septa. Recently, the hypothesis that ABCs are lesions reactive to local hemodynamics has been challenged after the discovery of specific recurrent chromosomal abnormalities. Multiple

  10. Alveolar bone loss: mechanisms, potential therapeutic targets, and interventions.

    Science.gov (United States)

    Intini, G; Katsuragi, Y; Kirkwood, K L; Yang, S

    2014-05-01

    This article reviews recent research into mechanisms underlying bone resorption and highlights avenues of investigation that may generate new therapies to combat alveolar bone loss in periodontitis. Several proteins, signaling pathways, stem cells, and dietary supplements are discussed as they relate to periodontal bone loss and regeneration. RGS12 is a crucial protein that mediates osteoclastogenesis and bone destruction, and a potential therapeutic target. RGS12 likely regulates osteoclast differentiation through regulating calcium influx to control the calcium oscillation-NFATc1 pathway. A working model for RGS10 and RGS12 in the regulation of Ca(2+) oscillations during osteoclast differentiation is proposed. Initiation of inflammation depends on host cell-microbe interactions, including the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Oral p38 inhibitors reduced lipopolysaccharide (LPS)-induced bone destruction in a rat periodontitis model but showed unsatisfactory safety profiles. The p38 substrate MK2 is a more specific therapeutic target with potentially superior tolerability. Furthermore, MKP-1 shows anti-inflammatory activity, reducing inflammatory cytokine biosynthesis and bone resorption. Multipotent skeletal stem cell (SSC) populations exist within the bone marrow and periosteum of long bones. These bone-marrow-derived SSCs and periosteum-derived SSCs have shown therapeutic potential in several applications, including bone and periodontal regeneration. The existence of craniofacial bone-specific SSCs is suggested based on existing studies. The effects of calcium, vitamin D, and soy isoflavone supplementation on alveolar and skeletal bone loss in post-menopausal women were investigated. Supplementation resulted in stabilization of forearm bone mass density and a reduced rate of alveolar bone loss over 1 yr, compared with placebo. Periodontal attachment levels were also well-maintained and alveolar bone loss suppressed during 24 wk of

  11. Assessment of the Regenerative Potential of Organic Waste Streams in Lagos Mega-City

    Science.gov (United States)

    Opejin, Adenike Kafayat

    There is never a better time for this study than now when Nigeria as a country is going through the worst time in power supply. In Lagos city about 12,000 tons of waste is generated daily, and is expected to increase as the city adds more population. The management of these waste has generated great concern among professionals, academia and government agencies. This study examined the regenerative management of organic waste, which accounts for about 45% of the total waste generated in Lagos. To do this, two management scenarios were developed: landfill methane to electricity and compost; and analyzed using data collected during field work and from government reports. While it is understood that landfilling waste is the least sustainable option, this study argued that it could be a viable method for developing countries. Using U.S EPA LandGEM and the IPCC model, estimates of capturable landfill methane gas was derived for three landfills studied. Furthermore, a 35-year projection of waste and landfill methane was done for three newly proposed landfills. Assumptions were made that these new landfills will be sanitary. It was established that an average of 919,480,928m3 methane gas could be captured to generate an average of 9,687,176 MW of electricity annually. This makes it a significant source of power supply to a city that suffers from incessant power outages. Analysis of composting organics in Lagos was also done using descriptive method. Although, it could be argued that composting is the most regenerative way of managing organics, but it has some problems associated with it. Earthcare Compost Company processes an average of 600 tons of organics on a daily basis. The fraction of waste processed is infinitesimal compared to the rate of waste generated. One major issue identified in this study as an obstacle to extensive use of this method is the marketability of compost. The study therefore suggests that government should focus on getting the best out of the

  12. Microgravity Reduces the Differentiation and Regenerative Potential of Embryonic Stem Cells

    Science.gov (United States)

    Blaber, Elizabeth A.; Finkelstein, Hayley; Dvorochkin, Natalya; Sato, Kevin Y.; Yousuf, Rukhsana; Burns, Brendan P.; Globus, Ruth K.

    2015-01-01

    Mechanical unloading in microgravity is thought to induce tissue degeneration by various mechanisms, including inhibition of regenerative stem cell differentiation. To address this hypothesis, we investigated the effects of microgravity on early lineage commitment of mouse embryonic stem cells (mESCs) using the embryoid body (EB) model of tissue differentiation. We found that exposure to microgravity for 15 days inhibits mESC differentiation and expression of terminal germ layer lineage markers in EBs. Additionally, microgravity-unloaded EBs retained stem cell self-renewal markers, suggesting that mechanical loading at Earth's gravity is required for normal differentiation of mESCs. Finally, cells recovered from microgravity-unloaded EBs and then cultured at Earth's gravity showed greater stemness, differentiating more readily into contractile cardiomyocyte colonies. These results indicate that mechanical unloading of stem cells in microgravity inhibits their differentiation and preserves stemness, possibly providing a cellular mechanistic basis for the inhibition of tissue regeneration in space and in disuse conditions on earth. PMID:26414276

  13. The Effect of PEI and PVP-Stabilized Gold Nanoparticles on Equine Platelets Activation: Potential Application in Equine Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Mateusz Hecold

    2017-01-01

    Full Text Available The aim of this work was to assess the effect of different stabilizing agents, for example, polyethylenimine (PEI and polyvinylpyrrolidone (PVP, on gold nanoparticles (AuNPs and their influence on equine platelet activation and release of particular growth factors. The gold nanoparticles were produced by chemical reduction of chloroauric acid. UV-Vis spectroscopy confirmed the presence of gold nanoparticles in investigated solutions. The AuNPs were incubated with whole blood at various concentrations. The morphology of platelets in PRP prepared from the blood incubated with AuNPs was characterized by scanning transmission electron microscopy, whereas the concentrations of growth factors and cytokines were evaluated by ELISA assays. The most promising results were obtained with equine platelets incubated with 5% AuNPs stabilized by PEI, which lead to secretion of bone morphogenetic protein 2 (BMP-2, vascular endothelial growth factor (VEGF, and fibroblast growth factor 1 (FGF-1 and simultaneously cause decrease in concentration of interleukin-1 alpha (IL-1α. The qRT-PCR confirmed ELISA test results. The incubation with 5% AuNPs stabilized by PEI leads to upregulation of BMP-2 and VEGF transcripts of mRNA level and to downregulating expression of interleukin-6 (IL-6. Obtained data shed a promising light on gold nanoparticle application for future regenerative medicine application.

  14. Regenerative potential of the cartilaginous tissue in mesenchymal stem cells: update, limitations, and challenges.

    Science.gov (United States)

    Cruz, Ivana Beatrice Mânica da; Severo, Antônio Lourenço; Azzolin, Verônica Farina; Garcia, Luiz Filipe Machado; Kuhn, André; Lech, Osvandré

    2017-01-01

    Advances in the studies with adult mesenchymal stem cells (MSCs) have turned tissue regenerative therapy into a promising tool in many areas of medicine. In orthopedics, one of the main challenges has been the regeneration of cartilage tissue, mainly in diarthroses. In the induction of the MSCs, in addition to cytodifferentiation, the microenvironmental context of the tissue to be regenerated and an appropriate spatial arrangement are extremely important factors. Furthermore, it is known that MSC differentiation is fundamentally determined by mechanisms such as cell proliferation (mitosis), biochemical-molecular interactions, movement, cell adhesion, and apoptosis. Although the use of MSCs for cartilage regeneration remains at a research level, there are important questions to be resolved in order to make this therapy efficient and safe. It is known, for instance, that the expansion of chondrocytes in cultivation, needed to increase the number of cells, could end up producing fibrocartilage instead of hyaline cartilage. However, the latest results are promising. In 2014, the first stage I/II clinical trial to evaluate the efficacy and safety of the intra-articular injection of MSCs in femorotibial cartilage regeneration was published, indicating a decrease in injured areas. One issue to be explored is how many modifications in the articulate inflammatory environment could induce differentiation of MSCs already allocated in that region. Such issue arose from studies that suggested that the suppression of the inflammation may increase the efficiency of tissue regeneration. Considering the complexity of the events related to the chondrogenesis and cartilage repair, it can be concluded that the road ahead is still long, and that further studies are needed.

  15. Regenerative potential of the cartilaginous tissue in mesenchymal stem cells: update, limitations, and challenges

    Directory of Open Access Journals (Sweden)

    Ivana Beatrice Mânica da Cruz

    Full Text Available ABSTRACT Advances in the studies with adult mesenchymal stem cells (MSCs have turned tissue regenerative therapy into a promising tool in many areas of medicine. In orthopedics, one of the main challenges has been the regeneration of cartilage tissue, mainly in diarthroses. In the induction of the MSCs, in addition to cytodifferentiation, the microenvironmental context of the tissue to be regenerated and an appropriate spatial arrangement are extremely important factors. Furthermore, it is known that MSC differentiation is fundamentally determined by mechanisms such as cell proliferation (mitosis, biochemical-molecular interactions, movement, cell adhesion, and apoptosis. Although the use of MSCs for cartilage regeneration remains at a research level, there are important questions to be resolved in order to make this therapy efficient and safe. It is known, for instance, that the expansion of chondrocytes in cultivation, needed to increase the number of cells, could end up producing fibrocartilage instead of hyaline cartilage. However, the latest results are promising. In 2014, the first stage I/II clinical trial to evaluate the efficacy and safety of the intra-articular injection of MSCs in femorotibial cartilage regeneration was published, indicating a decrease in injured areas. One issue to be explored is how many modifications in the articulate inflammatory environment could induce differentiation of MSCs already allocated in that region. Such issue arose from studies that suggested that the suppression of the inflammation may increase the efficiency of tissue regeneration. Considering the complexity of the events related to the chondrogenesis and cartilage repair, it can be concluded that the road ahead is still long, and that further studies are needed.

  16. Regenerative Potential of D-δ-Tocotrienol Rich Fraction on Crushed Skeletal Muscle of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Bijo Elsy

    2017-06-01

    Full Text Available Background: Delayed muscle growth and regeneration of skeletal muscle in diabetics is believed to be due to diabetic myopathy because of alteration in the skeletal muscle homeostatis. Since vitamin E is a natural antioxidant and is also important for the integrity of sarcolemma, the present study was designed to explore the muscle regenerative potency of d-δ-tocotrienol-rich fraction (d-δ-TRF on crushed skeletal muscle in healthy and diabetic rats. Materials and Methods: Diabetes was induced through single subcutaneous injection of alloxan (100 mg/kg. Twenty-four albino rats were divided into four groups; healthy control, diabetic control, healthy treated, and diabetic treated. Treated groups received injections orally, daily (200 mg/kg for 3 weeks. A horizontal skin incision was made on the shaved right mid-thigh region, by splitting the fascia between gluteus maximus and tensor fascia lata, and gluteus maximus was crushed with Kocher’s forceps. Skin wound was closed with an absorbable suture. The crushed muscle changes were studied by assessing the histopathological features, histomorphological measurements, and biochemical analyses on 3rd week following induction of injury. One-way “ANOVA” followed by Tukey’s test and Student t-test were used for statistical analysis of data. Results: Results obtained through various methods indicate that the d-δ-TRF treated groups have controlled glycemic status, improved antioxidant capacity, faster revascularization, re-innervation, regeneration of myofibers, and connective tissue remodeling. Conclusion: It is, therefore, concluded that the d-δ-TRF is a beneficial nutritional adjuvant for skeletal muscles’ structural and functional recovery after crushed injury in both healthy and diabetics. [J Interdiscipl Histopathol 2017; 5(2.000: 36-42

  17. Vitamin D and bone health: potential mechanisms.

    Science.gov (United States)

    Laird, Eamon; Ward, Mary; McSorley, Emeir; Strain, J J; Wallace, Julie

    2010-07-01

    Osteoporosis is associated with increased morbidity, mortality and significant economic and health costs. Vitamin D is a secosteriod hormone essential for calcium absorption and bone mineralization which is positively associated with bone mineral density [BMD]. It is well-established that prolonged and severe vitamin D deficiency leads to rickets in children and osteomalacia in adults. Sub-optimal vitamin D status has been reported in many populations but it is a particular concern in older people; thus there is clearly a need for effective strategies to optimise bone health. A number of recent studies have suggested that the role of vitamin D in preventing fractures may be via its mediating effects on muscle function (a defect in muscle function is one of the classical signs of rickets) and inflammation. Studies have demonstrated that vitamin D supplementation can improve muscle strength which in turn contributes to a decrease in incidence of falls, one of the largest contributors to fracture incidence. Osteoporosis is often considered to be an inflammatory condition and pro-inflammatory cytokines have been associated with increased bone metabolism. The immunoregulatory mechanisms of vitamin D may thus modulate the effect of these cytokines on bone health and subsequent fracture risk. Vitamin D, therefore, may influence fracture risk via a number of different mechanisms.

  18. Vitamin D and Bone Health; Potential Mechanisms

    Directory of Open Access Journals (Sweden)

    J.J. Strain

    2010-07-01

    Full Text Available Osteoporosis is associated with increased morbidity, mortality and significant economic and health costs. Vitamin D is a secosteriod hormone essential for calcium absorption and bone mineralization which is positively associated with bone mineral density [BMD]. It is well-established that prolonged and severe vitamin D deficiency leads to rickets in children and osteomalacia in adults. Sub-optimal vitamin D status has been reported in many populations but it is a particular concern in older people; thus there is clearly a need for effective strategies to optimise bone health. A number of recent studies have suggested that the role of vitamin D in preventing fractures may be via its mediating effects on muscle function (a defect in muscle function is one of the classical signs of rickets and inflammation. Studies have demonstrated that vitamin D supplementation can improve muscle strength which in turn contributes to a decrease in incidence of falls, one of the largest contributors to fracture incidence. Osteoporosis is often considered to be an inflammatory condition and pro-inflammatory cytokines have been associated with increased bone metabolism. The immunoregulatory mechanisms of vitamin D may thus modulate the effect of these cytokines on bone health and subsequent fracture risk. Vitamin D, therefore, may influence fracture risk via a number of different mechanisms.

  19. Regenerative endodontics.

    Science.gov (United States)

    Simon, S; Smith, A J

    2014-03-01

    Significant advances in our understanding of the biological processes involved in tooth development and repair at the cellular and molecular levels have underpinned the newly emerging area of regenerative endodontics. Development of treatment protocols based on exploiting the natural wound healing properties of the dental pulp and applying tissue engineering principles has allowed reporting of case series showing preservation of tissue vitality and apexogenesis. To review current case series reporting regenerative endodontics. Current treatment approaches tend to stimulate more reparative than regenerative responses in respect of the new tissue generated, which often does not closely resemble the physiological structure of dentine-pulp. However, despite these biological limitations, such techniques appear to offer significant promise for improved treatment outcomes. Improved biological outcomes will likely emerge from the many experimental studies being reported and will further contribute to improvements in clinical treatment protocols.

  20. Regenerative Endodontics.

    Science.gov (United States)

    Feigin, Kristina; Shope, Bonnie

    2017-09-01

    Regenerative endodontics has been defined as "biologically based procedure designed to replace damaged structures, including dentin and root structures, as well as cells of the pulp-dentin complex." This is an exciting and rapidly evolving field of human endodontics for the treatment of immature permanent teeth with infected root canal systems. These procedures have shown to be able not only to resolve pain and apical periodontitis but continued root development, thus increasing the thickness and strength of the previously thin and fracture-prone roots. In the last decade, over 80 case reports, numerous animal studies, and series of regenerative endodontic cases have been published. However, even with multiple successful case reports, there are still some remaining questions regarding terminology, patient selection, and procedural details. Regenerative endodontics provides the hope of converting a nonvital tooth into vital one once again.

  1. Potential Osteoporosis Recovery by Deep Sea Water through Bone Regeneration in SAMP8 Mice

    Directory of Open Access Journals (Sweden)

    Hen-Yu Liu

    2013-01-01

    Full Text Available The aim of this study is to examine the therapeutic potential of deep sea water (DSW on osteoporosis. Previously, we have established the ovariectomized senescence-accelerated mice (OVX-SAMP8 and demonstrated strong recovery of osteoporosis by stem cell and platelet-rich plasma (PRP. Deep sea water at hardness (HD 1000 showed significant increase in proliferation of osteoblastic cell (MC3T3 by MTT assay. For in vivo animal study, bone mineral density (BMD was strongly enhanced followed by the significantly increased trabecular numbers through micro-CT examination after a 4-month deep sea water treatment, and biochemistry analysis showed that serum alkaline phosphatase (ALP activity was decreased. For stage-specific osteogenesis, bone marrow-derived stromal cells (BMSCs were harvested and examined. Deep sea water-treated BMSCs showed stronger osteogenic differentiation such as BMP2, RUNX2, OPN, and OCN, and enhanced colony forming abilities, compared to the control group. Interestingly, most untreated OVX-SAMP8 mice died around 10 months; however, approximately 57% of DSW-treated groups lived up to 16.6 months, a life expectancy similar to the previously reported life expectancy for SAMR1 24 months. The results demonstrated the regenerative potentials of deep sea water on osteogenesis, showing that deep sea water could potentially be applied in osteoporosis therapy as a complementary and alternative medicine (CAM.

  2. Instrumentation for Investigating the Regenerative Potential of Bone-Tissue-Engineered Scaffolds

    Science.gov (United States)

    2015-05-12

    threshold value, the droplet elongates, the electrostatic force between the needle and the collector plate overcomes the surface tension , and a streaming...the droplet elongates, the electrostatic force between the needle and the collector plate overcomes the surface tension , and a streaming jet of the...17 kV) from a high voltage electrical field are induced on the liquid droplet held by its surface tension . This is done by connecting one electrode

  3. Osteogenesis and angiogenesis: The potential for engineering bone

    Directory of Open Access Journals (Sweden)

    JM Kanczler

    2008-05-01

    Full Text Available The repair of large bone defects remains a major clinical orthopaedic challenge. Bone is a highly vascularised tissue reliant on the close spatial and temporal connection between blood vessels and bone cells to maintain skeletal integrity. Angiogenesis thus plays a pivotal role in skeletal development and bone fracture repair. Current procedures to repair bone defects and to provide structural and mechanical support include the use of grafts (autologous, allogeneic or implants (polymeric or metallic. These approaches face significant limitations due to insufficient supply, potential disease transmission, rejection, cost and the inability to integrate with the surrounding host tissue.The engineering of bone tissue offers new therapeutic strategies to aid musculoskeletal healing. Various scaffold constructs have been employed in the development of tissue-engineered bone; however, an active blood vessel network is an essential pre-requisite for these to survive and integrate with existing host tissue. Combination therapies of stem cells and polymeric growth factor release scaffolds tailored to promote angiogenesis and osteogenesis are under evaluation and development actively to stimulate bone regeneration. An understanding of the cellular and molecular interactions of blood vessels and bone cells will enhance and aid the successful development of future vascularised bone scaffold constructs, enabling survival and integration of bioengineered bone with the host tissue. The role of angiogenic and osteogenic factors in the adaptive response and interaction of osteoblasts and endothelial cells during the multi step process of bone development and repair will be highlighted in this review, with consideration of how some of these key mechanisms can be combined with new developments in tissue engineering to enable repair and growth of skeletal fractures. Elucidation of the processes of angiogenesis, osteogenesis and tissue engineering strategies offer

  4. Mobilization of endogenous bone marrow derived endothelial progenitor cells and therapeutic potential of parathyroid hormone after ischemic stroke in mice.

    Directory of Open Access Journals (Sweden)

    Li-Li Wang

    Full Text Available Stroke is a major neurovascular disorder threatening human life and health. Very limited clinical treatments are currently available for stroke patients. Stem cell transplantation has shown promising potential as a regenerative treatment after ischemic stroke. The present investigation explores a new concept of mobilizing endogenous stem cells/progenitor cells from the bone marrow using a parathyroid hormone (PTH therapy after ischemic stroke in adult mice. PTH 1-34 (80 µg/kg, i.p. was administered 1 hour after focal ischemia and then daily for 6 consecutive days. After 6 days of PTH treatment, there was a significant increase in bone marrow derived CD-34/Fetal liver kinase-1 (Flk-1 positive endothelial progenitor cells (EPCs in the peripheral blood. PTH treatment significantly increased the expression of trophic/regenerative factors including VEGF, SDF-1, BDNF and Tie-1 in the brain peri-infarct region. Angiogenesis, assessed by co-labeled Glut-1 and BrdU vessels, was significantly increased in PTH-treated ischemic brain compared to vehicle controls. PTH treatment also promoted neuroblast migration from the subventricular zone (SVZ and increased the number of newly formed neurons in the peri-infarct cortex. PTH-treated mice showed significantly better sensorimotor functional recovery compared to stroke controls. Our data suggests that PTH therapy improves endogenous repair mechanisms after ischemic stroke with functional benefits. Mobilizing endogenous bone marrow-derived stem cells/progenitor cells using PTH and other mobilizers appears an effective and feasible regenerative treatment after ischemic stroke.

  5. The bone regenerative effect of platelet-rich plasma in combination with an osteoconductive material in rat cranial defects.

    NARCIS (Netherlands)

    Plachokova, A.S.; Dolder, J. van den; Stoelinga, P.J.W.; Jansen, J.A.

    2006-01-01

    The effect of platelet-rich plasma (PRP) on bone regeneration, in combination with an osteoconductive material, was evaluated in a rat model. Cranial defects, 6.2 mm in diameter, were filled with HA/beta-TCP particles, HA/beta-TCP particles combined with PRP and HA/beta-TCP particles combined with P

  6. Comparison of the regenerative potential of an allograft used alone and that in conjunction with an immunosuppressive drug in the treatment of human periodontal infrabony defects: A clinical and radiological study

    Directory of Open Access Journals (Sweden)

    Dhawan Shivani

    2010-01-01

    Full Text Available Background: Experimentation confirmed the conclusion that bone allografts, like other tissue and organ allografts, are immunogenic. These immune responses cause resorption of allograft, thus lowering the bone formation capacity of the graft. An attempt has been made in this study to prevent immune reactions and achieve enhanced regeneration of allograft-demineralized freeze-dried bone matrix by incorporating it with an immunosuppressive drug Cyclosporine-A (CsA in the treatment of human periodontal infrabony defects. Materials and Methods: Fifteen patients showing clinical evidence of almost bilateral infrabony defects requiring bone grafting procedures were selected. In each patient, the infrabony defect of one side of the arch was designated as Group A (control site and the infrabony defect of the contralateral side of the same arch was designated as Group B (test site. Results: On comparative evaluation of the two groups (by Student t-test, the mean values of reduction in probing depth (P=0.81 NS and gain in clinical attachment level (P=1.00 NS of Group B were found to be greater than that of Group-A, but the differences were statistically non-significant. The mean linear bone fill (P=0.010 FNx08 of Group B was also detected to be higher than that of Group A, and the difference was found to be statistically significant. Conclusion: Increase in linear bone fill in Group B signifies the role of CsA in augmenting the regenerative potential of allograft by eliminating immune reactions.

  7. Cellular development of the human cochlea and the regenerative potential of hair follicle bulge stem cells

    OpenAIRE

    2015-01-01

    The embryonic development of the human cochlea (the organ of hearing) has been investigated for over one hundred years. However, little is still known about the development on a cellular and protein level, which is important to better understand etiologies and pathologies of various types of sensorineural hearing loss. Knowledge of the normal gene expression patterns and cell fate specification in the human cochlea has therefore the potential to aid in the development of gene and cell-based t...

  8. Regenerative medicine using adult neural stem cells: the potential for diabetes therapy and other pharmaceutical applications

    Institute of Scientific and Technical Information of China (English)

    Tomoko Kuwabara; Makoto Asashima

    2012-01-01

    Neural stem cells (NSCs),which are responsible for continuous neurogenesis during the adult stage,are present in human adults.The typical neurogenic regions are the hippocampus and the subventricular zone; recent studies have revealed that NSCs also exist in the olfactory bulb.Olfactory bulb-derived neural stem cells (OB NSCs) have the potential to be used in therapeutic applications and can be easily harvested without harm to the patient.Through the combined influence of extrinsic cues and innate programming,adult neurogenesis is a finely regulated process occurring in a specialized cellular environment,a niche.Understanding the regulatory mechanisms of adult NSCs and their cellular niche is not only important to understand the physiological roles of neurogenesis in adulthood,but also to provide the knowledge necessary for developing new therapeutic applications using adult NSCs in other organs with similar regulatory environments.Diabetes is a devastating disease affecting more than 200 million people worldwide.Numerous diabetic patients suffer increased symptom severity after the onset,involving complications such as retinopathy and nephropathy.Therefore,the development of treatments for fundamental diabetes is important.The utilization of autologous cells from patients with diabetes may address challenges regarding the compatibility of donor tissues as well as provide the means to naturally and safely restore function,reducing future risks while also providing a long-term cure.Here,we review recent findings regarding the use of adult OB NSCs as a potential diabetes cure,and discuss the potential of OB NSC-based pharmaceutical applications for neuronal diseases and mental disorders.

  9. Probing regenerative potential of Moringa oleifera aqueous extracts using In vitro cellular assays

    Directory of Open Access Journals (Sweden)

    Evangeline E Fernandes

    2016-01-01

    Full Text Available Background: Molecules stimulating regeneration and proliferation of cells are of significance in combating ailments caused due to tissue injury, inflammation, and degenerative disorders. Moringa oleifera is one of the most valued food plants having the profile of important nutrients and impressive range of medicinal uses. Objective: To evaluate the potential of M. oleifera aqueous leaf and flower extracts to promote the proliferation of cells and explore their effect on cancer cell lines for assessment of safety. Materials and Methods: Aqueous leaf and flower extracts of M. oleifera were investigated for effect on rat-derived primary fibroblast, mesenchymal stem cells (MSCs, and cancer cell lines using cell proliferation assay. They were also tested and compared for wound healing, angiogenesis, and hepatoprotective effect using in vitro assays. Results: Statistically significant increase in the proliferation of primary rat fibroblast, MSCs, and angiogenesis was observed after treatment with aqueous flower extract. The aqueous leaf extract determined a comparatively moderate increment in the proliferation of MSCs and angiogenesis. It however showed prominent cytotoxicity to cancer cell lines and a significant hepatoprotective effect. Conclusion: A very clear difference in response of the two extracts to different types of cells was detected in this study. The aqueous flower extract exhibited a higher potential to stimulate cell proliferation while not exerting the same effect on cancer cell lines. The leaf extract on the other hand, had a prominent antitumor and hepatoptotective effects.

  10. The Design and Use of Animal Models for Translational Research in Bone Tissue Engineering and Regenerative Medicine

    Science.gov (United States)

    2010-01-07

    repair,40,41 evaluation of the differential effects of marrow-derived and periosteal - derived cell populations,42 and in screening for the effects of cell...defect or gap in bone (caused by either tissue loss or distraction maintained by internal or external fixation), local tissue loss (particularly periosteal ...as an excel- lent resource. Critical defects are defined as ‘‘a defect that will not heal without intervention.’’ The femur and tibial diaphysis tend

  11. Protecting the delivery of heart failure: Regenerative Medicine/Stem Cell Therapeutics: Potential protections afforded by the Department of Health and Human Services and Health Resources Service Administration's Bureau of Special Programs

    Institute of Scientific and Technical Information of China (English)

    Gary S Friedman; John S. Tomicki; Neil Cohen; Robert Marshall; Philip Lowry; Jeffrey Warsh

    2006-01-01

    Advances in stem cell science and potential clinical applications have brought clinical medicine closer to the actualization of Regenerative Medicine-an extension of transplantation of organs and cells and implantation of bioprosthetics and biodevices. The goal of such therapeutics will be intervention prior to onset of severe individual disability, enhance organ function and enhance patient performance status without incurring the economic impacts of standard organ transplantation. Regenerative Medicine is already demonstrating proof of principle or efficacy in restoration of myocardial contractility, joint mobility and function, immune competence, pulmonary function, immunologic selftolerance, motor function and normal hemoglobin production with the next targets--diabetes mellitus (type Ⅰ and type Ⅱ),neurologic injury, hepatic dysfunction preparing to enter trials.Expenditures on health care needs of an aging U.S. citizenry approximate 20-25% ($3 trillion) of U.S. GDP currently and may to grow to 40% of U.S. GDP by 2025. As the potential of Regenerative Medicine is clinically realized, the societal impact and economic benefits will be disproportionately magnified in the economies of industrialized nations. The experience of the Department of Health and Human Services (HHS), United Network for Organ Sharing (UNOS), the National Bone Marrow Donor Registry (NBMDR), and the National Vaccine Injury Compensation Programs (NVICP) can help ensure that as Regenerative Medicine strives to achieve clinical benefits while avoiding decimation of therapeutic options by product liability and medical malpractice concerns-concerns that crippled the U.S. vaccine manufacturing industry until the creation of the NVICP.The first 50 years of organ/cell/tissue transplantation demonstrates that clinical reality of allogeneic and autologous transplantation can antedate complete understanding of the basic science underlying successful transplantation. Product liability and medical

  12. Potential cellular and regenerative approaches for the treatment of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Emma L Lane

    2008-08-01

    Full Text Available Emma L Lane, Olivia J Handley, Anne E Rosser, Stephen B DunnettBrain Repair Group, School of Biosciences, Cardiff University, CF10 3US, UKAbstract: Parkinson’s disease is most commonly treated with a range of pharmacotherapeutics, with the more recent introduction of surgical techniques including deep-brain stimulation. These have limited capabilities to improve symptoms of the disease in more advanced stages, thus new therapeutic strategies including the use of viral vectors and stem cells are in development. Providing a continuous supply of dopamine to the striatum in an attempt to improve the treatment of motor symptoms using enzymes in the dopamine synthesis and machinery is one approach. Alternatively, there are tools which may serve to both protect and encourage outgrowth of surviving neurons using growth factors or to directly replace lost innervation by transplantation of primary tissue or stem cell-derived dopaminergic neurons. We summarize some of the potential therapeutic approaches and also consider the recent EU directives on practical aspects of handling viral vectors, cells and tissues, and in the running of clinical trials in Europe which impact on their development.Keywords: transplantation, viral vector, stem cells, ethics, European Union directive

  13. Platelet-Rich Fibrin (PRF) in Implants Dentistry in Combination with New Bone Regenerative Flapless Technique: Evolution of the Technique and Final Results.

    Science.gov (United States)

    Cortese, Antonio; Pantaleo, Giuseppe; Amato, Massimo; Howard, Candace M; Pedicini, Lorenzo; Claudio, Pier Paolo

    2017-01-01

    Most common techniques for alveolar bone augmentation are guided bone regeneration (GBR) and autologous bone grafting. GBR studies demonstrated long-term reabsorption using heterologous bone graft. A general consensus has been achieved in implant surgery for a minimal amount of 2 mm of healthy bone around the implant. A current height loss of about 3-4 mm will result in proper deeper implant insertion when alveolar bone expansion is not planned because of the dome shape of the alveolar crest. To manage this situation a split crest technique has been proposed for alveolar bone expansion and the implants' insertion in one stage surgery. Platelet-rich fibrin (PRF) is a healing biomaterial with a great potential for bone and soft tissue regeneration without inflammatory reactions, and may be used alone or in combination with bone grafts, promoting hemostasis, bone growth, and maturation. The aim of this study was to demonstrate the clinical effectiveness of PRF combined with a new split crest flapless modified technique in 5 patients vs. 5 control patients. Ten patients with horizontal alveolar crests deficiency were treated in this study, divided into 2 groups: Group 1 (test) of 5 patients treated by the flapless split crest new procedure; Group 2 (control) of 5 patients treated by traditional technique with deeper insertion of smaller implants without split crest. The follow-up was performed with x-ray orthopantomography and intraoral radiographs at T0 (before surgery), T1 (operation time), T2 (3 months) and T3 (6 months) post-operation. All cases were successful; there were no problems at surgery and post-operative times. All implants succeeded osteointegration and all patients underwent uneventful prosthetic rehabilitation. Mean height bone loss was 1 mm, measured as bone-implant most coronal contact (Δ-BIC), and occurred at immediate T2 post-operative time (3 months). No alveolar bone height loss was detected at implant insertion time, which was instead

  14. Potential Strategies to Address the Major Clinical Hurdles Facing Stem Cell Regenerative Therapy for Cardiovascular Disease: A Review

    Science.gov (United States)

    Nguyen, Patricia K.; Neofytou, Evgenios; Rhee, June-Wha; Wu, Joseph C.

    2017-01-01

    Importance While progress continues to be made in the field of stem cell regenerative medicine for the treatment of cardiovascular disease, significant barriers to clinical translation still exist that have thwarted the delivery of cell therapy to the bedside. Objective The purpose of this review is to summarize the major current hurdles for the clinical implementation of stem cell therapy and discuss potential strategies to overcome them. Evidence Review Information for this review was obtained through a search of PubMed and the Cochrane database for English language studies published between January 1, 2000 and June 15, 2016. Ten randomized clinical trials and eight systematic reviews were included in this review. Findings One of the major clinical hurdles facing the routine implementation of stem cell therapy is the limited and inconsistent benefit observed thus far. Reasons for this are unclear but may be due to poor cell retention and survival, as suggested by numerous preclinical studies and a handful of human studies incorporating cell fate imaging. Additional cell fate imaging studies in humans are needed to determine how these factors contribute to limited efficacy. Treatment strategies to address poor cell retention and survival are under investigation and include the following: 1) co-administering of immunosuppressive and pro-survival agents, 2) delivering cardioprotective factors packaged in exosomes rather than the cells themselves, and 3) using tissue engineering strategies to provide structural support for cells. If larger grafts are achieved using the aforementioned strategies, it will be imperative to carefully monitor the potential risks of tumorigenicity, immunogenicity, and arrhythmogenicity. Conclusions and Relevance Despite important achievements to date, stem cell therapy is not yet ready for routine clinical implementation. Significant research is still needed to address the clinical hurdles outlined herein before the next wave of large

  15. The Infrapatellar Fat Pad as a Source of Perivascular Stem Cells with Increased Chondrogenic Potential for Regenerative Medicine.

    Science.gov (United States)

    Hindle, Paul; Khan, Nusrat; Biant, Leela; Péault, Bruno

    2017-01-01

    Perivascular stem cells (PSCs) are the natural ancestors of mesenchymal stem cells (MSCs) and are the stem cells responsible for homeostasis and repair in vivo. Prospectively identified and isolated PSCs have demonstrated increased plasticity and osteogenic potential. Cells from the infrapatellar fat pad (IFP) have demonstrated increased chondrogenic potential compared with those from subcutaneous fat. This research assessed the chondrogenic potential of IFP PSCs compared with MSCs from the IFP and bone marrow. Immunohistochemistry demonstrated the location of perivascular markers (CD146, CD34, neural/glial antigen 2 [NG2], platelet-derived growth factor receptor-β [PDGFRβ], and α-smooth muscle actin [α-SMA]) in relation to endothelial markers (CD31, CD144, von Willebrand factor [vWF]). Pericytes and adventitial cells were isolated from the stromal vascular fraction (3.8% and 21.2%, respectively) using flow cytometry with a viability of 88%. The mean numbers of pericytes and adventitial cells isolated were 4.6 ± 2.2 × 10(4) and 16.2 ± 3.2 × 10(4) , respectively, equating to 7.9 ± 4.4 × 10(3) and 20.8 ± 4.3 × 10(3) cells per gram of harvested tissue. Fluorescence-activated cell sorting demonstrated that cultured PSCs were CD44+CD90+CD105+; polymerase chain reaction and immunocytochemistry demonstrated that pericytes retained their CD146+ phenotype and expressed the pericyte markers PDGFRβ and NG2. Differentiation was confirmed using histochemical stains and genetic expression. Using a pellet model, the IFP PSCs and the MSCs generated significantly more extracellular matrix than bone marrow MSCs (p stem cells compared with bone marrow. PSCs generated significantly more extracellular matrix than culture-derived MSCs. Stem Cells Translational Medicine 2017;6:77-87.

  16. Clinical evaluation of a combined regenerative technique with enamel matrix derivative, bone grafts, and guided tissue regeneration.

    Science.gov (United States)

    Harris, Randall J; Harris, Laura E; Harris, Christopher R; Harris, Anne J

    2007-04-01

    The goal of this study was to evaluate the clinical changes obtained when intra-bony defects were treated with an enamel matrix derivative (EMD), a bone graft, and guided tissue regeneration. Fifty patients with a periodontal defect not associated with a furcation and with an attachment loss of at least 7.0 mm were included in this study. Full-thickness flaps were reflected, the roots were planed, EMD was applied, a demineralized freeze-dried bone allograft combined with EMD was placed, a bioabsorbable membrane was placed, and more EMD was applied. The defect areas were then sutured. At a mean of 5.3 months after treatment, there was a mean increase in recession of 0.7 mm, a mean reduction in probing depth of 5.7 mm, and a mean gain in attachment level of 5.0 mm. In this study there was more recession in smokers than in nonsmokers and in defects associated with anterior teeth. Additionally, the deeper defects (those with greater probing depths and attachment level loss) had the greatest reductions in probing depth and gains in attachment level. Based on this study, this technique proved itself to be an effective method to improve the clinical situation when treating periodontal defects not involving furcations.

  17. Depth and activity of carious lesions as indicators for the regenerative potential of dental pulp after intervention.

    Science.gov (United States)

    Bjørndal, Lars; Demant, Sune; Dabelsteen, Sally

    2014-04-01

    Studies on dental regeneration involving interventions for pulp therapy such as regeneration and revascularization procedures are promising for the injured tooth; however, a complete replication of the original pulp tissue does not seem to take place. In cases in which we wish to preserve or maintain parts of the pulp during treatment, it is apparent that the effectiveness of healing or biological regeneration is dependent on the degree of inflammation of the pulp tissue. Thus, the control or prevention of a pulp infection is still a major issue for the clinicians. Data indicate that the typical reason for performing endodontic treatment is deep caries. The biological concept of vital pulp therapy associated with deep caries takes the treatment and evaluation of the unexposed as well as the exposed pulp into account. Interestingly, the clinical diagnosis is typically the same. Deep caries with reversible pulpitis may receive differing treatments such as excavation procedures aiming to avoid pulp exposure or more pulp invasive treatments such as pulp capping or pulpotomy. This should not be the case. Consequently, huge treatment variation is noted among clinicians based on the same caries diagnosis. Which treatment should be selected? High-quality trials are needed, and it is important to obtain information on the actual lesion depth and an estimate of the lesion activity before treatment. These may be basic indicators for the regenerative potential of dental pulp. Recent clinical trials dealing with the treatment of deep caries lesion are discussed, including pulp invasive and noninvasive concepts, to attempt to solve the task of getting the best clinical outcome for adult patients. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  18. Use of carboxymethyl cellulose and collagen carrier with equine bone lyophilisate suggests late onset bone regenerative effect in a humerus drill defect - a pilot study in six sheep

    DEFF Research Database (Denmark)

    Jensen, Jonas; Foldager, Casper Bindzus; Jakobsen, Thomas Vestergaard;

    2010-01-01

    in the other. The animals were divided into three groups of two animals and observed for 8, 12 and 16 weeks. Drill holes was evaluated using quantitative computed tomography (QCT), micro computed tomography (microCT) and histomorphometry. Mean total bone mineral density (BMD) of each implantation site...

  19. Multimodal Approaches for Regenerative Stroke Therapies: Combination of Granulocyte Colony-Stimulating Factor with Bone Marrow Mesenchymal Stem Cells is Not Superior to G-CSF Alone

    Directory of Open Access Journals (Sweden)

    Adrian Tudor Balseanu

    2014-06-01

    Full Text Available Attractive therapeutic strategies to enhance post-stroke recovery of aged brains include methods of cellular therapy that can enhance the endogenous restorative mechanisms of the injured brain. Since stroke afflicts mostly the elderly, it is highly desirable to test the efficacy of cell therapy in the microenvironment of aged brains that is generally refractory to regeneration. In particular, stem cells from the bone marrow allow an autologous transplantation approach that can be translated in the near future to the clinical practice. Such a bone marrow-derived therapy includes the grafting of stem cells as well as the delayed induction of endogenous stem cell mobilization and homing by the stem cell mobilizer granulocyte colony-stimulating factor (G-CSF. We tested the hypothesis that grafting of bone marrow-derived pre-differentiated mesenchymal cells (BM-MSCs in G-CSF-treated animals improves the long-term functional outcome in aged rodents. To this end, G-CSF alone (50 μg/kg or in combination with a single dose (106 cells of rat BM MSCs was administered intravenously to Sprague-Dawley rats at 6 h after transient occlusion (90 min of the middle cerebral artery. Infarct volume was measured by magnetic resonance imaging at 3 and 48 days post-stroke and additionally by immunhistochemistry at day 56. Functional recovery was tested during the entire post-stroke survival period of 56 days. Daily treatment for post-stroke aged rats with G-CSF led to a robust and consistent improvement of neurological function after 28 days. The combination therapy also led to robust angiogenesis in the formerly infarct core and beyond in the “islet of regeneration.” However, G-CSF + BM MSCs may not impact at all on the spatial reference-memory task or infarct volume and therefore did not further improve the post-stroke recovery. We suggest that in a real clinical practice involving older post-stroke patients, successful regenerative therapies

  20. MULTIMODAL APPROACHES FOR REGENERATIVE STROKE THERAPIES: COMBINATION OF GRANULOCYTE COLONY-STIMULATING FACTOR WITH BONE MARROW MESENCHYMAL STEM CELLS IS NOT SUPERIOR TO G-CSF ALONE

    Directory of Open Access Journals (Sweden)

    AurelPopa-Wagner

    1900-01-01

    Full Text Available Attractive therapeutic strategies to enhance post-stroke recovery of aged brains include methods of cellular therapy that can enhance the endogenous restorative mechanisms of the injured brain. Since stroke afflicts mostly the elderly, it is highly desirable to test the efficacy of cell therapy in the microenvironment of aged brains that is generally refractory to regeneration. In particular, stem cells from the bone marrow allow an autologous transplantation approach that can be translated in the near future to the clinical practice. Such a bone marrow-derived therapy includes the grafting of stem cells as well as the delayed induction of endogenous stem cell mobilisation and homing by the stem cell mobiliser Granulocyte-colony Stimulating Factor (G-CSF. We tested the hypothesis that grafting of bone marrow-derived pre-differentiated mesenchymal cells (BM MSCs in G-CSF-treated animals improves the long-term functional outcome in aged rodents. To this end, G-CSF alone (50 µg/kg or in combination with a single dose (106 cells of rat BM MSCs were administered intravenously to Sprague-Dawley rats at six hour safter transient occlusion (90 min of the middle cerebral artery. Infarct volume was measured by MRI at 3 and 48 days post-stroke and additionally by immunhistochemistry at day 56. Functional recovery was tested during the entire post-stroke survival period of 56 days. Daily treatment for post-stroke aged rats with G-CSF led to a robust and consistent improvement of neurological function after 28 days. The combination therapy also led to robust angiogenesis in the formerly infarct core and beyond in the “islet of regeneration”. However, G-CSF + BM MSCs may not impact at all on the spatial reference-memory task or infarct volume and therefore did not further improve the post-stroke recovery. We suggest that in a real clinical practice involving older post-stroke patients, successful regenerative therapies would have to be carried out for a

  1. Design, synthesis, and initial evaluation of D-glyceraldehyde crosslinked gelatin-hydroxyapatite as a potential bone graft substitute material

    Science.gov (United States)

    Florschutz, Anthony Vatroslav

    Utilization of bone grafts for the treatment of skeletal pathology is a common practice in orthopaedic, craniomaxillofacial, dental, and plastic surgery. Autogenous bone graft is the established archetype but has disadvantages including donor site morbidity, limited supply, and prolonging operative time. In order to avoid these and other issues, bone graft substitute materials are becoming increasingly prevalent among surgeons for reconstructing skeletal defects and arthrodesis applications. Bone graft substitutes are biomaterials, biologics, and guided tissue/bone regenerative devices that can be used alone or in combinations as supplements or alternatives to autogenous bone graft. There is a growing interest and trend to specialize graft substitutes for specific indications and although there is good rationale for this indication-specific approach, the development and utility of a more universal bone graft substitute may provide a better answer for patients and surgeons. The aim of the present research focuses on the design, synthesis, and initial evaluation of D-glyceraldehyde crosslinked gelatin-hydroxyapatite composites for potential use as a bone graft substitutes. After initial establishment of rational material design, gelatinhydroxyapatite scaffolds were fabricated with different gelatin:hydroxyapatite ratios and crosslinking concentrations. The synthesized scaffolds were subsequently evaluated on the basis of their swelling behavior, porosity, density, percent composition, mechanical properties, and morphology and further assessed with respect to cell-biomaterial interaction and biomineralization in vitro. Although none of the materials achieved mechanical properties suitable for structural graft applications, a reproducible material design and synthesis was achieved with properties recognized to facilitate bone formation. Select scaffold formulations as well as a subset of scaffolds loaded with recombinant human bone morphogenetic protein-2 were

  2. Demineralized Freeze-Dried Bovine Cortical Bone: Its Potential for Guided Bone Regeneration Membrane

    Directory of Open Access Journals (Sweden)

    David B. Kamadjaja

    2017-01-01

    Full Text Available Background. Bovine pericardium collagen membrane (BPCM had been widely used in guided bone regeneration (GBR whose manufacturing process usually required chemical cross-linking to prolong its biodegradation. However, cross-linking of collagen fibrils was associated with poorer tissue integration and delayed vascular invasion. Objective. This study evaluated the potential of bovine cortical bone collagen membrane for GBR by evaluating its antigenicity potential, cytotoxicity, immune and tissue response, and biodegradation behaviors. Material and Methods. Antigenicity potential of demineralized freeze-dried bovine cortical bone membrane (DFDBCBM was done with histology-based anticellularity evaluation, while cytotoxicity was analyzed using MTT Assay. Evaluation of immune response, tissue response, and biodegradation was done by randomly implanting DFDBCBM and BPCM in rat’s subcutaneous dorsum. Samples were collected at 2, 5, and 7 days and 7, 14, 21, and 28 days for biocompatibility and tissue response-biodegradation study, respectively. Result. DFDBCBM, histologically, showed no retained cells; however, it showed some level of in vitro cytotoxicity. In vivo study exhibited increased immune response to DFDBCBM in early healing phase; however, normal tissue response and degradation rate were observed up to 4 weeks after DFDBCBM implantation. Conclusion. Demineralized freeze-dried bovine cortical bone membrane showed potential for clinical application; however, it needs to be optimized in its biocompatibility to fulfill all requirements for GBR membrane.

  3. Regenerative engineering

    CERN Document Server

    Laurencin, Cato T

    2013-01-01

    Regenerative Engineering: The Future of Medicine Saadiq F. El-Amin III , MD , PhD; Joylene W.L. Thomas, MD ; Ugonna N. Ihekweazu, MD ; Mia D. Woods, MS; and Ashim Gupta, MSCell Biology Gloria Gronowicz, PhD and Karen Sagomonyants, DMDStem Cells and Tissue Regeneration Kristen Martins-Taylor, PhD; Xiaofang Wang, MD , PhD; Xue-Jun Li, PhD; and Ren-He Xu, MD , PhDIntroduction to Materials Science Sangamesh G. Kumbar, PhD and Cato T. Laurencin, MD , PhDBiomaterials A. Jon Goldberg, PhD and Liisa T. Kuhn, PhDIn Vitro Assessment of Cell-Biomaterial Interactions Yong Wang, PhDHost Response to Biomate

  4. Investigation of potential injectable polymeric biomaterials for bone regeneration.

    Science.gov (United States)

    Dreifke, Michael B; Ebraheim, Nabil A; Jayasuriya, Ambalangodage C

    2013-08-01

    This article reviews the potential injectable polymeric biomaterial scaffolds currently being investigated for application in bone tissue regeneration. Two types of injectable biomaterial scaffolds are focused in this review, including injectable microspheres and injectable gels. The injectable microspheres section covers several polymeric materials, including poly(L-lactide-co-glycolide)-PLGA, poly(propylene fumarate), and chitosan. The injectable gel section covers alginate gels, hyaluronan hydrogels, poly(ethylene-glycol)-PEG hydrogels, and PEG-PLGA copolymer hydrogels. This review focuses on the effect of cellular behavior in vitro and in vivo in terms of material properties of polymers, such as biodegradation, biocompatibility, porosity, microsphere size, and cross-linking nature. Injectable polymeric biomaterials offer a major advantage for orthopedic applications by allowing the ability to use noninvasive or minimally invasive treatment methods. Therefore, combining injectable polymeric biomaterial scaffolds with cells have a significant potential to treat orthopedic bone defects, including spine fusion, and craniofacial and periodontal defects.

  5. Regenerative strategies for craniofacial disorders

    Directory of Open Access Journals (Sweden)

    Catharine Bradford Garland

    2012-12-01

    Full Text Available Craniofacial disorders present markedly complicated problems in reconstruction because of the complex interactions of the multiple, simultaneously affected tissues. Regenerative medicine holds promise for new strategies to improve treatment of these disorders. This review addresses current areas of unmet need in craniofacial reconstruction and emphasizes how craniofacial tissues differ from their analogs elsewhere in the body. We present a problem-based approach to illustrate current treatment strategies for various craniofacial disorders, to highlight areas of need, and to suggest regenerative strategies for craniofacial bone, fat, muscle, nerve, and skin. For some tissues, current approaches offer excellent reconstructive solutions using autologous tissue or prosthetic materials. Thus, new regenerative approaches would need to offer major advantages in order to be adopted. In other tissues, the unmet need is great, and we suggest the greatest regenerative need is for muscle, skin, and nerve. The advent of composite facial tissue transplantation and the development of regenerative medicine are each likely to add important new paradigms to our treatment of craniofacial disorders.

  6. Influence of age on rat bone-marrow mesenchymal stem cells potential.

    Science.gov (United States)

    Fafián-Labora, J; Fernández-Pernas, P; Fuentes, I; De Toro, J; Oreiro, N; Sangiao-Alvarellos, S; Mateos, J; Arufe, M C

    2015-11-19

    Mesenchymal stem cells promising role in cell-based therapies and tissue engineering appears to be limited due to a decline of their regenerative potential with increasing donor age. Six age groups from bone marrow mesenchymal stem cells of Wistar rats were studied (newborn, infant, young, pre-pubertal, pubertal and adult). Quantitative proteomic assay was performance by iTRAQ using an 8-plex iTRAQ labeling and the proteins differentially expressed were grouped in pluripotency, proliferative and metabolism processes. Proliferation makers, CD117 and Ki67 were measure by flow cytometry assay. Real time polymerase chain reaction analysis of pluripotency markers Rex1, Oct4, Sox2 and Nanog were done. Biological differentiation was realized using specific mediums for 14 days to induce osteogenesis, adipogenesis or chondrogenesis and immunostain analysis of differentiated cell resulting were done. Enzimoimmunoassay analysis of several enzymes as L-lactate dehydrogenase and glucose-6-phosphate isomerase were also done to validate iTRAQ data. Taking together these results indicate for the first time that mesenchymal stem cells have significant differences in their proliferative, pluripotency and metabolism profiles and those differences are age depending.

  7. Isolation of human adipose-derived stromal cells using laser-assisted liposuction and their therapeutic potential in regenerative medicine.

    Science.gov (United States)

    Chung, Michael T; Zimmermann, Andrew S; Paik, Kevin J; Morrison, Shane D; Hyun, Jeong S; Lo, David D; McArdle, Adrian; Montoro, Daniel T; Walmsley, Graham G; Senarath-Yapa, Kshemendra; Sorkin, Michael; Rennert, Robert; Chen, Hsin-Han; Chung, Andrew S; Vistnes, Dean; Gurtner, Geoffrey C; Longaker, Michael T; Wan, Derrick C

    2013-10-01

    Harvesting adipose-derived stromal cells (ASCs) for tissue engineering is frequently done through liposuction. However, several different techniques exist. Although third-generation ultrasound-assisted liposuction has been shown to not have a negative effect on ASCs, the impact of laser-assisted liposuction on the quality and differentiation potential of ASCs has not been studied. Therefore, ASCs were harvested from laser-assisted lipoaspirate and suction-assisted lipoaspirate. Next, in vitro parameters of cell yield, cell viability and proliferation, surface marker phenotype, osteogenic differentiation, and adipogenic differentiation were performed. Finally, in vivo bone formation was assessed using a critical-sized cranial defect in athymic nude mice. Although ASCs isolated from suction-assisted lipoaspirate and laser-assisted lipoaspirate both successfully underwent osteogenic and adipogenic differentiation, the cell yield, viability, proliferation, and frequency of ASCs (CD34(+)CD31(-)CD45(-)) in the stromal vascular fraction were all significantly less with laser-assisted liposuction in vitro (p liposuction appears to negatively impact the biology of ASCs, cell harvest using suction-assisted liposuction is preferable for tissue-engineering purposes.

  8. Processing and characterization of diatom nanoparticles and microparticles as potential source of silicon for bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Le, Thi Duy Hanh [Department of Industrial Engineering, University of Trento, Trento (Italy); BIOtech Research Center and European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Trento (Italy); Bonani, Walter [Department of Industrial Engineering, University of Trento, Trento (Italy); BIOtech Research Center and European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Trento (Italy); Interuniversity Consortium for Science and Technology of Materials, Trento Research Unit, Trento (Italy); Speranza, Giorgio [Center for Materials and Microsystems, PAM-SE, Fondazione Bruno Kessler, Trento (Italy); Sglavo, Vincenzo; Ceccato, Riccardo [Department of Industrial Engineering, University of Trento, Trento (Italy); Maniglio, Devid; Motta, Antonella [Department of Industrial Engineering, University of Trento, Trento (Italy); BIOtech Research Center and European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Trento (Italy); Interuniversity Consortium for Science and Technology of Materials, Trento Research Unit, Trento (Italy); Migliaresi, Claudio, E-mail: claudio.migliaresi@unitn.it [Department of Industrial Engineering, University of Trento, Trento (Italy); BIOtech Research Center and European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Trento (Italy); Interuniversity Consortium for Science and Technology of Materials, Trento Research Unit, Trento (Italy)

    2016-02-01

    Silicon plays an important role in bone formation and maintenance, improving osteoblast cell function and inducing mineralization. Often, bone deformation and long bone abnormalities have been associated with silica/silicon deficiency. Diatomite, a natural deposit of diatom skeleton, is a cheap and abundant source of biogenic silica. The aim of the present study is to validate the potential of diatom particles derived from diatom skeletons as silicon-donor materials for bone tissue engineering applications. Raw diatomite (RD) and calcined diatomite (CD) powders were purified by acid treatments, and diatom microparticles (MPs) and nanoparticles (NPs) were produced by fragmentation of purified diatoms under alkaline conditions. The influence of processing on the surface chemical composition of purified diatomites was evaluated by X-ray photoelectron spectroscopy (XPS). Diatoms NPs were also characterized in terms of morphology and size distribution by transmission electron microscopy (TEM) and Dynamic light scattering (DLS), while diatom MPs morphology was analyzed by scanning electron microscopy (SEM). Surface area and microporosity of the diatom particles were evaluated by nitrogen physisorption methods. Release of silicon ions from diatom-derived particles was demonstrated using inductively coupled plasma optical emission spectrometry (ICP/OES); furthermore, silicon release kinetic was found to be influenced by diatomite purification method and particle size. Diatom-derived microparticles (MPs) and nanoparticles (NPs) showed limited or no cytotoxic effect in vitro depending on the administration conditions. - Highlights: • Diatomite is a natural source of silica and has a potential as silicon-donor for bone regenerative applications. • Diatom particles derived from purified diatom skeletons were prepared by fragmentation under extreme alkaline condition. • Dissolution of diatom particles derived from diatom skeletons in DI water depend on purification method

  9. Preparation of laponite bioceramics for potential bone tissue engineering applications.

    Directory of Open Access Journals (Sweden)

    Chuanshun Wang

    Full Text Available We report a facile approach to preparing laponite (LAP bioceramics via sintering LAP powder compacts for bone tissue engineering applications. The sintering behavior and mechanical properties of LAP compacts under different temperatures, heating rates, and soaking times were investigated. We show that LAP bioceramic with a smooth and porous surface can be formed at 800°C with a heating rate of 5°C/h for 6 h under air. The formed LAP bioceramic was systematically characterized via different methods. Our results reveal that the LAP bioceramic possesses an excellent surface hydrophilicity and serum absorption capacity, and good cytocompatibility and hemocompatibility as demonstrated by resazurin reduction assay of rat mesenchymal stem cells (rMSCs and hemolytic assay of pig red blood cells, respectively. The potential bone tissue engineering applicability of LAP bioceramic was explored by studying the surface mineralization behavior via soaking in simulated body fluid (SBF, as well as the surface cellular response of rMSCs. Our results suggest that LAP bioceramic is able to induce hydroxyapatite deposition on its surface when soaked in SBF and rMSCs can proliferate well on the LAP bioceramic surface. Most strikingly, alkaline phosphatase activity together with alizarin red staining results reveal that the produced LAP bioceramic is able to induce osteoblast differentiation of rMSCs in growth medium without any inducing factors. Finally, in vivo animal implantation, acute systemic toxicity test and hematoxylin and eosin (H&E-staining data demonstrate that the prepared LAP bioceramic displays an excellent biosafety and is able to heal the bone defect. Findings from this study suggest that the developed LAP bioceramic holds a great promise for treating bone defects in bone tissue engineering.

  10. Preparation of laponite bioceramics for potential bone tissue engineering applications.

    Science.gov (United States)

    Wang, Chuanshun; Wang, Shige; Li, Kai; Ju, Yaping; Li, Jipeng; Zhang, Yongxing; Li, Jinhua; Liu, Xuanyong; Shi, Xiangyang; Zhao, Qinghua

    2014-01-01

    We report a facile approach to preparing laponite (LAP) bioceramics via sintering LAP powder compacts for bone tissue engineering applications. The sintering behavior and mechanical properties of LAP compacts under different temperatures, heating rates, and soaking times were investigated. We show that LAP bioceramic with a smooth and porous surface can be formed at 800°C with a heating rate of 5°C/h for 6 h under air. The formed LAP bioceramic was systematically characterized via different methods. Our results reveal that the LAP bioceramic possesses an excellent surface hydrophilicity and serum absorption capacity, and good cytocompatibility and hemocompatibility as demonstrated by resazurin reduction assay of rat mesenchymal stem cells (rMSCs) and hemolytic assay of pig red blood cells, respectively. The potential bone tissue engineering applicability of LAP bioceramic was explored by studying the surface mineralization behavior via soaking in simulated body fluid (SBF), as well as the surface cellular response of rMSCs. Our results suggest that LAP bioceramic is able to induce hydroxyapatite deposition on its surface when soaked in SBF and rMSCs can proliferate well on the LAP bioceramic surface. Most strikingly, alkaline phosphatase activity together with alizarin red staining results reveal that the produced LAP bioceramic is able to induce osteoblast differentiation of rMSCs in growth medium without any inducing factors. Finally, in vivo animal implantation, acute systemic toxicity test and hematoxylin and eosin (H&E)-staining data demonstrate that the prepared LAP bioceramic displays an excellent biosafety and is able to heal the bone defect. Findings from this study suggest that the developed LAP bioceramic holds a great promise for treating bone defects in bone tissue engineering.

  11. Digital image processing of bone - Problems and potentials

    Science.gov (United States)

    Morey, E. R.; Wronski, T. J.

    1980-01-01

    The development of a digital image processing system for bone histomorphometry and fluorescent marker monitoring is discussed. The system in question is capable of making measurements of UV or light microscope features on a video screen with either video or computer-generated images, and comprises a microscope, low-light-level video camera, video digitizer and display terminal, color monitor, and PDP 11/34 computer. Capabilities demonstrated in the analysis of an undecalcified rat tibia include the measurement of perimeter and total bone area, and the generation of microscope images, false color images, digitized images and contoured images for further analysis. Software development will be based on an existing software library, specifically the mini-VICAR system developed at JPL. It is noted that the potentials of the system in terms of speed and reliability far exceed any problems associated with hardware and software development.

  12. Cytomics in regenerative medicine

    Science.gov (United States)

    Tárnok, Attila; Pierzchalski, Arkadiusz

    2008-02-01

    Cytomics is the high-content analysis of cell-systems [6, 78]. The area of Cytomics and Systems Biology received great attention during the last years as it harbours the promise to substantially impact on various fields of biomedicine, drug discovery, predictive medicine [6] and may have major potential for regenerative medicine. In regenerative medicine Cytomics includes process control of cell preparation and culturing using non-invasive detection techniques, quality control and standardization for GMP and GLP conformity and even prediction of cell fate based on sophisticated data analysis. Cytomics requires quantitative and stoichiometric single cell analysis. In some areas the leading cytometric techniques represent the cutting edge today. Many different applications/variations of multicolour staining were developed for flow- or slide-based cytometry (SBC) analysis of suspensions and sections to whole animal analysis [78]. SBC has become an important analytical technology in drug discovery, diagnosis and research and is an emerging technology for systems analysis [78]. It enables high-content high-throughput measurement of cell suspensions, cell cultures and tissues. In the last years various commercial SBC instruments were launched principally enabling to perform similar tasks. Standardisation as well as comparability of different instruments is a major challenge. Hyperspectral optical imaging may be implemented in SBC analysis for label free cell detection based on cellular autofluorescence [3]. All of these developments push the systemic approach of the analysis of biological specimens to enhance the outcome of regenerative medicine.

  13. Comparison of 2 regenerative procedures--guided tissue regeneration and demineralized freeze-dried bone allograft--in the treatment of intrabony defects: a clinical and radiographic study.

    Science.gov (United States)

    Parashis, A; Andronikaki-Faldami, A; Tsiklakis, K

    1998-07-01

    The purpose of this study was to compare clinically and radiographically the effectiveness of guided tissue regeneration (GTR), using a bioabsorbable polylactic acid softened with citric acid ester barrier and commercially available demineralized freeze-dried bone allograft (DFDBA) in the treatment of 2- and 3-wall intrabony defects. Twelve patients each with one treated defect comprised each group. Conservative treatment was completed 2 to 4 months prior to surgery. Clinical measurements, plaque index, gingival index, probing depths (PD), clinical attachment levels (CAL) and recession (REC), were comparable in both groups at baseline. They were repeated at 12 months. Surgical measurements were also comparable at baseline in both groups. In the GTR group, at baseline the mean distance between the cemento-enamel junction (CEJ) and base of the defect was 12.3 +/- 2.9 mm and in the DFDBA group 11.3 +/- 1.8 mm. The defect depth was 6.3 +/- 2.0 mm and 5.4 +/- 1.3 mm, respectively. Radiographs were taken at baseline and 12 months later and compared using non-standardized digital subtraction radiography. In the GTR group, mean PD decreased from 7.9 +/- 2.5 mm to 3.5 +/- 1.4 mm and mean CAL from 10.8 +/- 2.8 mm to 7.0 +/- 1.6 mm, the differences being statistically significant (P = 0.002), while REC increased from 2.9 +/- 1.2 mm to 3.5 +/- 1.1 mm. In the DFDBA group, mean PD decreased from 7.1 +/- 1.1 mm to 3.5 +/- 1.1 mm and mean CAL from 9.8 +/- 1.5 mm to 6.6 +/- 1.7 mm (P = 0.002), while REC increased from 2.8 +/- 1.0 mm to 3.1 +/- 1.2 mm. No significant differences were found when the clinical results of the 2 groups were compared. Radiographic differences between the baseline and reconstructed images 12 months later were observed in both groups. Mean crestal bone resorption was 15.3 +/- 22.5% in the GTR group and 10.4 +/- 31.8% in the DFDBA group, and mean improvement in the distance between the CEJ and the base of the defect was 22.8 +/- 18.1% in the GTR group and 15

  14. Intranasal delivery of hypoxia-preconditioned bone marrow-derived mesenchymal stem cells enhanced regenerative effects after intracerebral hemorrhagic stroke in mice.

    Science.gov (United States)

    Sun, Jinmei; Wei, Zheng Zachory; Gu, Xiaohuan; Zhang, James Ya; Zhang, Yongbo; Li, Jimei; Wei, Ling

    2015-10-01

    Intracerebral hemorrhagic stroke (ICH) causes high mortality and morbidity with very limited treatment options. Cell-based therapy has emerged as a novel approach to replace damaged brain tissues and promote regenerative processes. In this study we tested the hypothesis that intranasally delivered hypoxia-preconditioned BMSCs could reach the brain, promote tissue repair and improve functional recovery after ICH. Hemorrhagic stroke was induced in adult C57/B6 mice by injection of collagenase IV into the striatum. Animals were randomly divided into three groups: sham group, intranasal BMSC treatment group, and vehicle treatment group. BMSCs were pre-treated with hypoxic preconditioning (HP) and pre-labeled with Hoechst before transplantation. Behavior tests, including the mNSS score, rotarod test, adhesive removal test, and locomotor function evaluation were performed at varying days, up to 21days, after ICH to evaluate the therapeutic effects of BMSC transplantation. Western blots and immunohistochemistry were performed to analyze the neurotrophic effects. Intranasally delivered HP-BMSCs were identified in peri-injury regions. NeuN+/BrdU+ co-labeled cells were markedly increased around the hematoma region, and growth factors, including BDNF, GDNF, and VEGF were significantly upregulated in the ICH brain after BMSC treatment. The BMSC treatment group showed significant improvement in behavioral performance compared with the vehicle group. Our data also showed that intranasally delivered HP-BMSCs migrated to peri-injury regions and provided growth factors to increase neurogenesis after ICH. We conclude that intranasal administration of BMSC is an effective treatment for ICH, and that it enhanced neuroregenerative effects and promoted neurological functional recovery after ICH. Overall, the investigation supports the potential therapeutic strategy for BMSC transplantation therapy against hemorrhagic stroke. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Space Nutrition: Effects on Bone and Potential Nutrition Countermeasures

    Science.gov (United States)

    Smith, Scott M.

    2008-01-01

    Optimal nutrition will be critical for crew members who embark on space exploration missions. Nutritional assessment provides an opportunity to ensure that crewmembers begin their missions in optimal nutritional status, to document changes during a mission and , if necessary, to provide intervention to maintain that status throughout the mission, and to assesses changes after landing in order to facilitate the return to their normal status as soon as possible after landing. We report here the findings from our nutritional assessment of the US astronauts who participated in the first eight International Space Station (ISS) missions. Bone loss during space flight remains one of the most critical challenges to astronaut health on space exploration missions. An increase in bone resorption of ISS crew members after flight was indicated by several markers. Vitamin D status also remains a challenge for long-duration space travelers, who lack ultraviolet light exposure in the shielded craft. Many nutrients affect bone, including calcium, protein, fatty acids, sodium, and others. Data supporting their potential as countermeasures for space flight, as published in many papers, will be reviewed in this presentation. Defining nutrient requirements, and being able to provide and maintain those nutrients on exploration missions, will be critical for maintaining crew member health. Please note, this abstract is not required for the meeting. A presentation on the topics described above will be given. This abstract is for travel documentation only.

  16. Long-term stability of surgical bone regenerative procedures of peri-implantitis lesions in a prospective case-control study over three years

    OpenAIRE

    2011-01-01

    Abstract Objectives: To evaluate the extent of bone fill over three years following surgical treatment of peri-implantitis with bone grafting with or without a membrane. Material & Methods: In a non-submerged wound healing mode, 15 subjects with 27 implants were treated with a bone substitute (Algipore?) alone, and 17 subjects with 29 implants were treated with the bone substitute and a resorbable membrane (Osseoquest?). Implants with radiographic bone loss ?1.8 mm following the...

  17. Interleukin-10 Inhibits Bone Resorption: A Potential Therapeutic Strategy in Periodontitis and Other Bone Loss Diseases

    Science.gov (United States)

    Guo, Jianbin; Zhu, Xiaofeng; Ma, Shouzhi; Yang, Wenrong

    2014-01-01

    Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on long-term medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy. PMID:24696846

  18. Two sides of the same coin: stem cells in cancer and regenerative medicine.

    Science.gov (United States)

    Ilmer, Matthias; Vykoukal, Jody; Recio Boiles, Alejandro; Coleman, Michael; Alt, Eckhard

    2014-07-01

    Multipotent stromal cells (MSCs) derived from bone marrow, adipose tissue, cord blood, and other origins have recently received much attention as potential therapeutic agents with beneficial immunomodulatory and regenerative properties. In their native tissue environment, however, such cells also appear to have essential functions in building and supporting tumor microenvironments, providing metastatic niches, and maintaining cancer hallmarks. Here, we consider the varied roles of these tissue-resident stroma-associated cells, synthesize recent and emerging discoveries, and discuss the role, potential, and clinical applications of MSCs in cancer and regenerative medicine.-Ilmer, M., Vykoukal, J., Recio Boiles, A., Coleman, M., Alt, E. Two sides of the same coin: stem cells in cancer and regenerative medicine.

  19. Regenerative Perspective in Modern Dentistry

    Directory of Open Access Journals (Sweden)

    Mihnea Ioan Nicolescu

    2016-04-01

    Full Text Available This review aims to trace the contour lines of regenerative dentistry, to offer an introductory overview on this emerging field to both dental students and practitioners. The crystallized depiction of the concept is a translational approach, connecting dental academics to scientific research and clinical utility. Therefore, this review begins by presenting the general features of regenerative medicine, and then gradually introduces the specific aspects of major dental subdomains, highlighting the progress achieved during the last years by scientific research and, in some cases, which has already been translated into clinical results. The distinct characteristics of stem cells and their microenvironment, together with their diversity in the oral cavity, are put into the context of research and clinical use. Examples of regenerative studies regarding endodontic and periodontal compartments, as well as hard (alveolar bone and soft (salivary glands related tissues, are presented to make the reader further acquainted with the topic. Instead of providing a conclusion, we will emphasize the importance for all dental community members, from young students to experienced dentists, of an early awareness rising regarding biomedical research progress in general and regenerative dentistry in particular.

  20. Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials.

    Science.gov (United States)

    Kawasaki, Haruhisa; Guan, Jianjun; Tamama, Kenichi

    2010-07-02

    Cell therapy with bone marrow multipotential stromal cells/mesenchymal stem cells (MSCs) represents a promising approach in the field of regenerative medicine. Low frequency of MSCs in adult bone marrow necessitates ex vivo expansion of MSCs after harvest; however, such a manipulation causes cellular senescence with loss of differentiation, proliferative, and therapeutic potentials of MSCs. Hydrogen molecules have been shown to exert organ protective effects through selective reduction of hydroxyl radicals. As oxidative stress is one of the key insults promoting cell senescence in vivo as well as in vitro, we hypothesized that hydrogen molecules prevent senescent process during MSC expansion. Addition of 3% hydrogen gas enhanced preservation of colony forming early progenitor cells within MSC preparation and prolonged the in vitro replicative lifespan of MSCs without losing differentiation potentials and paracrine capabilities. Interestingly, 3% hydrogen gas treatment did not decrease hydroxyl radical, protein carbonyl, and 8-hydroxydeoxyguanosine, suggesting that scavenging hydroxyl radical might not be responsible for these effects of hydrogen gas in this study.

  1. Cellular cardiac regenerative therapy in which patients?

    Science.gov (United States)

    Chachques, Juan C

    2009-08-01

    Cell-based myocardial regenerative therapy is undergoing experimental and clinical trials in order to limit the consequences of decreased contractile function and compliance of damaged ventricles owing to ischemic and nonischemic myocardial diseases. A variety of myogenic and angiogenic cell types have been proposed, such as skeletal myoblasts, mononuclear and mesenchymal bone marrow cells, circulating blood-derived progenitors, adipose-derived stromal cells, induced pluripotent stem cells, umbilical cord cells, endometrial mesenchymal stem cells, adult testis pluripotent stem cells and embryonic cells. Current indications for stem cell therapy concern patients who have had a left- or right-ventricular infarction or idiopathic dilated cardiomyopathies. Other indications and potential applications include patients with diabetic cardiomyopathy, Chagas heart disease (American trypanosomiasis), ischemic mitral regurgitation, left ventricular noncompacted myocardium and pediatric cardiomyopathy. Suitable sources of cells for cardiac implant will depend on the types of diseases to be treated. For acute myocardial infarction, a cell that reduces myocardial necrosis and augments vascular blood flow will be desirable. For heart failure, cells that replace or promote myogenesis, reverse apoptopic mechanisms and reactivate dormant cell processes will be useful. It is important to note that stem cells are not an alternative to heart transplantation; selected patients should be in an early stage of heart failure as the goal of this regenerative approach is to avoid or delay organ transplantation. Since the cell niche provides crucial support needed for stem cell maintenance, the most interesting and realistic perspectives include the association of intramyocardial cell transplantation with tissue-engineered scaffolds and multisite cardiac pacing in order to transform a passive regenerative approach into a 'dynamic cellular support', a promising method for the creation of

  2. Regenerative Endodontics for Adult Patients.

    Science.gov (United States)

    He, Ling; Kim, Sahng G; Gong, Qimei; Zhong, Juan; Wang, Sainan; Zhou, Xuedong; Ye, Ling; Ling, Junqi; Mao, Jeremy J

    2017-09-01

    The goal of endodontics is to save teeth. Since inception, endodontic treatments are performed to obturate disinfected root canals with inert materials such as gutta-percha. Although teeth can be saved after successful endodontic treatments, they are devitalized and therefore susceptible to reinfections and fractures. The American Association of Endodontists (AAE) has made a tremendous effort to revitalize disinfected immature permanent teeth in children and adolescents with diagnoses including pulp necrosis or apical periodontitis. The American Dental Association (ADA) in 2011 issued several clinical codes for regenerative endodontic procedures or apical revascularization in necrotic immature permanent teeth in children and adolescents. These AAE and ADA initiatives have stimulated robust interest in devising a multitude of tissue engineering approaches for dental pulp and dentin regeneration. Can the concept of regenerative endodontics be extended to revitalize mature permanent teeth with diagnoses including irreversible pulpitis and/or pulp necrosis in adults? The present article was written not only to summarize emerging findings to revitalize mature permanent teeth in adult patients but also to identify challenges and strategies that focus on realizing the goal of regenerative endodontics in adults. We further present clinical cases and describe the biological basis of potential regenerative endodontic procedures in adults. This article explores the frequently asked question if regenerative endodontic therapies should be developed for dental pulp and/or dentin regeneration in adults, who consist of the great majority of endodontic patients. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  3. [Regenerative approach for COPD].

    Science.gov (United States)

    Kubo, Hiroshi

    2011-10-01

    No treatment to cure of chronic obstructive pulmonary disease (COPD) is available. Regenerative medicine is one of promising areas for this intractable disease. Several reagents and growth factors are known to promote lung regeneration in small animal models. However, regenerative medicines for human lungs are not achieved yet. Recent advances in stem cell biology and tissue engineering have expanded our understanding of lung endogenous stem cells, and this new knowledge provides us with new ideas for future regenerative therapy for lung diseases. Although lungs are the most challenging organ for regenerative medicine, our cumulative knowledge of lung regeneration and of endogenous progenitor cells makes clear the possibilities for regenerative approach to COPD.

  4. Functional tooth regenerative therapy: tooth tissue regeneration and whole-tooth replacement.

    Science.gov (United States)

    Oshima, Masamitsu; Tsuji, Takashi

    2014-07-01

    Oral and general health is compromised by irreversible dental problems, including dental caries, periodontal disease and tooth injury. Regenerative therapy for tooth tissue repair and whole-tooth replacement is currently considered a novel therapeutic concept with the potential for the full recovery of tooth function. Several types of stem cells and cell-activating cytokines have been identified in oral tissues. These cells are thought to be candidate cell sources for tooth tissue regenerative therapies because they have the ability to differentiate into tooth tissues in vitro and in vivo. Whole-tooth replacement therapy is regarded as an important model for the development of an organ regenerative concept. A novel three-dimensional cell-manipulation method, designated the organ germ method, has been developed to recapitulate organogenesis. This method involves compartmentalisation of epithelial and mesenchymal cells at a high cell density to mimic multicellular assembly conditions and epithelial-mesenchymal interactions. A bioengineered tooth germ can generate a structurally correct tooth in vitro and erupt successfully with the correct tooth structure when transplanted into the oral cavity. We have ectopically generated a bioengineered tooth unit composed of a mature tooth, periodontal ligament and alveolar bone, and that tooth unit was successfully engrafted into an adult jawbone through bone integration. Such bioengineered teeth were able to perform normal physiological tooth functions, such as developing a masticatory potential in response to mechanical stress and a perceptive potential for noxious stimuli. In this review, we describe recent findings and technologies underpinning tooth regenerative therapy.

  5. Functional tooth regeneration using a bioengineered tooth unit as a mature organ replacement regenerative therapy.

    Science.gov (United States)

    Oshima, Masamitsu; Mizuno, Mitsumasa; Imamura, Aya; Ogawa, Miho; Yasukawa, Masato; Yamazaki, Hiromichi; Morita, Ritsuko; Ikeda, Etsuko; Nakao, Kazuhisa; Takano-Yamamoto, Teruko; Kasugai, Shohei; Saito, Masahiro; Tsuji, Takashi

    2011-01-01

    Donor organ transplantation is currently an essential therapeutic approach to the replacement of a dysfunctional organ as a result of disease, injury or aging in vivo. Recent progress in the area of regenerative therapy has the potential to lead to bioengineered mature organ replacement in the future. In this proof of concept study, we here report a further development in this regard in which a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone, was successfully transplanted into a properly-sized bony hole in the alveolar bone through bone integration by recipient bone remodeling in a murine transplantation model system. The bioengineered tooth unit restored enough the alveolar bone in a vertical direction into an extensive bone defect of murine lower jaw. Engrafted bioengineered tooth displayed physiological tooth functions such as mastication, periodontal ligament function for bone remodeling and responsiveness to noxious stimulations. This study thus represents a substantial advance and demonstrates the real potential for bioengineered mature organ replacement as a next generation regenerative therapy.

  6. Uso de terapia regenerativa com células-tronco da medula óssea em doenças cardiovasculares: perspectiva do hematologista Regenerative therapy using bone marrow stem cells in cardiovascular diseases: the perspective of the hematologist

    Directory of Open Access Journals (Sweden)

    Augusto C. A. Mota

    2005-06-01

    Full Text Available O desenvolvimento de técnicas de transplante de órgãos sólidos e de medula óssea foi um dos mais fascinantes avanços da medicina no século XX. A virada do século XXI testemunha um desdobramento também fascinante e promissor desta modalidade terapêutica: o uso de células-tronco para regenerar tecidos lesados outrora considerados irreparáveis. Resultados encorajadores de inúmeros estudos com animais de experimentação impulsionaram grupos de diversos centros no mundo a iniciar estudos clínicos com transplante de células-tronco em várias doenças, particularmente as doenças cardiovasculares e neurológicas. Embora ainda estejamos algo distante de entender o mecanismo preciso pelo qual as células-tronco regeneram órgãos lesados, os estudos publicados até o presente momento, incluindo vários estudos envolvendo seres humanos, sugerem haver um benefício real com esta terapia. O presente artigo pretende abordar os aspectos relevantes da terapia celular em doenças cardiovasculares, incluindo conceitos básicos sobre células-tronco, e os principais estudos de animais de experimentação e clínicos publicados até o presente.Solid organ and bone marrow transplantation were two of the most fascinating treatment modalities developed in the second half of the past century. At the turn of the 21st century the use of stem cells emerge as a potential therapeutic option for diseases previously thought to be irreversible. The promising results of animal studies paved the way for several groups all around the world to investigate the role of stem cell therapy in the clinical setting. The results of these clinical trials have been published over the last couple of years, most of which dealing with cardiovascular and neurological disorders. The results of the trials published thus far are encouraging (both animal and clinical and suggest that there may be a real benefit with this therapy, yet we are still considerably distant from a

  7. New Insights into Osteogenic and Chondrogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells and Their Potential Clinical Applications for Bone Regeneration in Pediatric Orthopaedics

    Directory of Open Access Journals (Sweden)

    Nicola Giuliani

    2013-01-01

    Full Text Available Human mesenchymal stem cells (hMSCs are pluripotent adult stem cells capable of being differentiated into osteoblasts, adipocytes, and chondrocytes. The osteogenic differentiation of hMSCs is regulated either by systemic hormones or by local growth factors able to induce specific intracellular signal pathways that modify the expression and activity of several transcription factors. Runt-related transcription factor 2 (Runx2 and Wnt signaling-related molecules are the major factors critically involved in the osteogenic differentiation process by hMSCs, and SRY-related high-mobility-group (HMG box transcription factor 9 (SOX9 is involved in the chondrogenic one. hMSCs have generated a great interest in the field of regenerative medicine, particularly in bone regeneration. In this paper, we focused our attention on the molecular mechanisms involved in osteogenic and chondrogenic differentiation of hMSC, and the potential clinical use of hMSCs in osteoarticular pediatric disease characterized by fracture nonunion and pseudarthrosis.

  8. New Insights into Osteogenic and Chondrogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells and Their Potential Clinical Applications for Bone Regeneration in Pediatric Orthopaedics

    Science.gov (United States)

    Giuliani, Nicola; Lisignoli, Gina; Magnani, Marina; Racano, Costantina; Dalla Palma, Benedetta; Spolzino, Angelica; Manferdini, Cristina; Abati, Caterina; Toscani, Denise; Facchini, Andrea; Aversa, Franco

    2013-01-01

    Human mesenchymal stem cells (hMSCs) are pluripotent adult stem cells capable of being differentiated into osteoblasts, adipocytes, and chondrocytes. The osteogenic differentiation of hMSCs is regulated either by systemic hormones or by local growth factors able to induce specific intracellular signal pathways that modify the expression and activity of several transcription factors. Runt-related transcription factor 2 (Runx2) and Wnt signaling-related molecules are the major factors critically involved in the osteogenic differentiation process by hMSCs, and SRY-related high-mobility-group (HMG) box transcription factor 9 (SOX9) is involved in the chondrogenic one. hMSCs have generated a great interest in the field of regenerative medicine, particularly in bone regeneration. In this paper, we focused our attention on the molecular mechanisms involved in osteogenic and chondrogenic differentiation of hMSC, and the potential clinical use of hMSCs in osteoarticular pediatric disease characterized by fracture nonunion and pseudarthrosis. PMID:23766767

  9. Adipose Tissue-Derived Stem Cells in Regenerative Medicine.

    Science.gov (United States)

    Frese, Laura; Dijkman, Petra E; Hoerstrup, Simon P

    2016-07-01

    In regenerative medicine, adult stem cells are the most promising cell types for cell-based therapies. As a new source for multipotent stem cells, human adipose tissue has been introduced. These so called adipose tissue-derived stem cells (ADSCs) are considered to be ideal for application in regenerative therapies. Their main advantage over mesenchymal stem cells derived from other sources, e.g. from bone marrow, is that they can be easily and repeatable harvested using minimally invasive techniques with low morbidity. ADSCs are multipotent and can differentiate into various cell types of the tri-germ lineages, including e.g. osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic β-cells, and hepatocytes. Interestingly, ADSCs are characterized by immunosuppressive properties and low immunogenicity. Their secretion of trophic factors enforces the therapeutic and regenerative outcome in a wide range of applications. Taken together, these particular attributes of ADSCs make them highly relevant for clinical applications. Consequently, the therapeutic potential of ADSCs is enormous. Therefore, this review will provide a brief overview of the possible therapeutic applications of ADSCs with regard to their differentiation potential into the tri-germ lineages. Moreover, the relevant advancements made in the field, regulatory aspects as well as other challenges and obstacles will be highlighted.

  10. NOTCH-Mediated Maintenance and Expansion of Human Bone Marrow Stromal/Stem Cells: A Technology Designed for Orthopedic Regenerative Medicine.

    Science.gov (United States)

    Dong, Yufeng; Long, Teng; Wang, Cuicui; Mirando, Anthony J; Chen, Jianquan; O'Keefe, Regis J; Hilton, Matthew J

    2014-12-01

    Human bone marrow-derived stromal/stem cells (BMSCs) have great therapeutic potential for treating skeletal disease and facilitating skeletal repair, although maintaining their multipotency and expanding these cells ex vivo have proven difficult. Because most stem cell-based applications to skeletal regeneration and repair in the clinic would require large numbers of functional BMSCs, recent research has focused on methods for the appropriate selection, expansion, and maintenance of BMSC populations during long-term culture. We describe here a novel biological method that entails selection of human BMSCs based on NOTCH2 expression and activation of the NOTCH signaling pathway in cultured BMSCs via a tissue culture plate coated with recombinant human JAGGED1 (JAG1) ligand. We demonstrate that transient JAG1-mediated NOTCH signaling promotes human BMSC maintenance and expansion while increasing their skeletogenic differentiation capacity, both ex vivo and in vivo. This study is the first of its kind to describe a NOTCH-mediated methodology for the maintenance and expansion of human BMSCs and will serve as a platform for future clinical or translational studies aimed at skeletal regeneration and repair.

  11. Regenerative cell therapy and pharmacotherapeutic intervention in heart failure Part 2 : Pharmacological targets, agents and intervention perspectives

    NARCIS (Netherlands)

    Qian, C.; Schoemaker, R. G.; van Gilst, W. H.; Yu, B.; Roks, A. J. M.

    2008-01-01

    Regenerative medicine represents a promising perspective on therapeutic angiogenesis in patients with cardiovascular disease, including heart failure. However, previous or ongoing clinical trials show ambiguous outcomes with respect to the benefit of regenerative therapy by means of bone marrow stem

  12. Regenerative cell therapy and pharmacotherapeutic intervention in heart failure Part 2 : Pharmacological targets, agents and intervention perspectives

    NARCIS (Netherlands)

    Qian, C.; Schoemaker, R. G.; van Gilst, W. H.; Yu, B.; Roks, A. J. M.

    2008-01-01

    Regenerative medicine represents a promising perspective on therapeutic angiogenesis in patients with cardiovascular disease, including heart failure. However, previous or ongoing clinical trials show ambiguous outcomes with respect to the benefit of regenerative therapy by means of bone marrow stem

  13. Exploration of electric properties of bone compared to cement: streaming potential and piezoelectirc properties

    Science.gov (United States)

    Dry, Carolyn

    2015-03-01

    Bone is a material after which to model construction materials for many reasons, including its great strength, toughness, and adaptability. This paper focuses on bone's intrinsic ability to adapt to its environment, namely loading conditions. Research on bone's electrical properties reveals that two phenomena occur in bone to allow it to adapt to environmental changes; they are the inherent piezoelectric property of bone and the streaming potential of bone [1]. Together they create charge differences that attract ions to specific regions of the bone, namely those under greatest stress, in order to build up the region to handle the applied load. Research on the utilization of these properties in cement in order to increase adaptability was studied along with 1) the inherent electric properties of the cement itself and 2) considered the introduction of a different polymer or ceramic within the cement to impart piezoelectricity and streaming potential.

  14. Dexamethasone Regulates EphA5, a Potential Inhibitory Factor with Osteogenic Capability of Human Bone Marrow Stromal Cells

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Yamada

    2016-01-01

    Full Text Available We previously demonstrated the importance of quality management procedures for the handling of human bone marrow stromal cells (hBMSCs and provided evidence for the existence of osteogenic inhibitor molecules in BMSCs. One candidate inhibitor is the ephrin type-A receptor 5 (EphA5, which is expressed in hBMSCs and upregulated during long-term culture. In this study, forced expression of EphA5 diminished the expression of osteoblast phenotypic markers. Downregulation of endogenous EphA5 by dexamethasone treatment promoted osteoblast marker expression. EphA5 could be involved in the normal growth regulation of BMSCs and could be a potential marker for replicative senescence. Although Eph forward signaling stimulated by ephrin-B-Fc promoted the expression of ALP mRNA in BMSCs, exogenous addition of EphA5-Fc did not affect the ALP level. The mechanism underlying the silencing of EphA5 in early cultures remains unclear. EphA5 promoter was barely methylated in hBMSCs while histone deacetylation could partially suppress EphA5 expression in early-passage cultures. In repeatedly passaged cultures, the upregulation of EphA5 independent of methylation could competitively inhibit osteogenic signal transduction pathways such as EphB forward signaling. Elucidation of the potential inhibitory function of EphA5 in hBMSCs may provide an alternative approach for lineage differentiation in cell therapy strategies and regenerative medicine.

  15. Regeneration of a Compromized Masticatory Unit in a Large Mandibular Defect Caused by a Huge Solitary Bone Cyst: A Case Report and Review of the Regenerative Literature.

    Science.gov (United States)

    Muhammad, Joseph Kamal; Akhtar, Shakeel; Abu Al Nassar, Hiba; Al Khoury, Nabil

    2016-07-01

    The reconstructive options for large expansive cystic lesion affecting the jaws are many. The first stage of treatment may involve enucleation or marsupialization of the cyst. Attempted reconstruction of large osseous defects arising from the destruction of local tissue can present formidable challenges. The literature reports the use of bone grafts, free tissue transfer, bone morphogenic protein and reconstruction plates to assist in the healing and rehabilitation process. The management of huge mandibular cysts needs to take into account the preservation of existing intact structures, removal of the pathology and the reconstructive objectives which focus both on aesthetic and functional rehabilitation. The planning and execution of such treatment requires not only the compliance of the patient and family but also their assent as customers with a voice in determining their surgical destiny. The authors would like to report a unique case of a huge solitary bone cyst that had reduced the ramus, angle and part of the body of one side of the mandible to a pencil-thin-like strut of bone. A combination of decompression through marsupialization, serial packing, and the fabrication of a custom made obturator facilitated the regeneration of the myo-osseous components of the masticatory unit of this patient. Serial CT scans showed evidence of concurrent periosteal and endosteal bone formation and, quite elegantly, the regeneration of the first branchial arch components of the right myo-osseous masticatory complex. The microenvironmental factors that may have favored regeneration of these complex structures are discussed.

  16. Stromal cell-derived factor-1 potentiates bone morphogenetic protein-2 induced bone formation.

    Science.gov (United States)

    Higashino, Kosaku; Viggeswarapu, Manjula; Bargouti, Maggie; Liu, Hui; Titus, Louisa; Boden, Scott D

    2011-02-01

    The mechanisms driving bone marrow stem cell mobilization are poorly understood. A recent murine study found that circulating bone marrow-derived osteoprogenitor cells (MOPCs) were recruited to the site of recombinant human bone morphogenetic protein-2 (BMP-2)-induced bone formation. Stromal cell-derived factor-1α (SDF-1α) and its cellular receptor CXCR4 have been shown to mediate the homing of stem cells to injured tissues. We hypothesized that chemokines, such as SDF-1, are also involved with mobilization of bone marrow cells. The CD45(-) fraction is a major source of MOPCs. In this report we determined that the addition of BMP-2 or SDF-1 to collagen implants increased the number of MOPCs in the peripheral blood. BMP-2-induced mobilization was blocked by CXCR4 antibody, confirming the role of SDF-1 in mobilization. We determined for the first time that addition of SDF-1 to implants containing BMP-2 enhances mobilization, homing of MOPCs to the implant, and ectopic bone formation induced by suboptimal BMP-2 doses. These results suggest that SDF-1 increases the number of osteoprogenitor cells that are mobilized from the bone marrow and then home to the implant. Thus, addition of SDF-1 to BMP-2 may improve the efficiency of BMPs in vivo, making their routine use for orthopaedic applications more affordable and available to more patients.

  17. The current status of iPS cells in cardiac research and their potential for tissue engineering and regenerative medicine.

    Science.gov (United States)

    Martins, Ana M; Vunjak-Novakovic, Gordana; Reis, Rui L

    2014-04-01

    The recent availability of human cardiomyocytes derived from induced pluripotent stem (iPS) cells opens new opportunities to build in vitro models of cardiac disease, screening for new drugs, and patient-specific cardiac therapy. Notably, the use of iPS cells enables studies in the wide pool of genotypes and phenotypes. We describe progress in reprogramming of induced pluripotent stem (iPS) cells towards the cardiac lineage/differentiation. The focus is on challenges of cardiac disease modeling using iPS cells and their potential to produce safe, effective and affordable therapies/applications with the emphasis of cardiac tissue engineering. We also discuss implications of human iPS cells to biological research and some of the future needs.

  18. Applications of regenerative medicine in organ transplantation

    Directory of Open Access Journals (Sweden)

    Aditya Jain

    2015-01-01

    Full Text Available A worldwide shortage of organs for clinical implantation establishes the need to bring forward and test new technologies that will help in solving the problem. The concepts of regenerative medicine hold the potential for augmenting organ function or repairing damaged organ or allowing regeneration of deteriorated organs and tissue. Researchers are exploring possible regenerative medicine applications in organ transplantation so that coming together of the two fields can benefit each other. The present review discusses the strategies that are being implemented to regenerate or bio-engineer human organs for clinical purposes. It also highlights the limitations of the regenerative medicine that needs to be addressed to explore full potential of the field. A web-based research on MEDLINE was done using keywords "regenerative medicine," "tissue-engineering," "bio-engineered organs," "decellularized scaffold" and "three-dimensional printing." This review screened about 170 articles to get the desired knowledge update.

  19. Ephrin-A2 and-A3 are negative regulators of the regenerative potential of Müller cells

    Institute of Scientific and Technical Information of China (English)

    Zhu Ruilin; Cho Kin-Sang; Chen Dong Feng; Yang Liu

    2014-01-01

    Background In a previous study,we demonstrated that ephrin-A2 and-A3 negatively regulate the growth of neural progenitor cells in the central nervous system.Adult mice deficient in ephrin-A2 and-A3 (A2-/-A3-/-) displayed active ongoing neurogenesis throughout the brain,and mice deficient in ephrin-A3 alone showed increased proliferation of ciliary epithelium derived retinal stem cells.This study aimed to detect that the increase in proliferation and neurogenic potential of Müller cells is influenced by the absence of ephrin-A2 and-A3.Methods We assessed the retinal and Müller cell expression of ephrin-As and their receptor and neural progenitor cell markers by immunostaining and real-time PCR.We cultured purified primary Müller cells derived from wild-type and A2-/-A3-/-mice in a defined culture medium that enables trans-differentiation of Müller cells into retinal neurons.To evaluate proliferating Müller cells in vivo,we injected 5'-ethylnyl-2'-deoxiuridine (EdU) intraperitoneally to adult mice.Results Expression of ephrin-A2/A3 and their receptor EphA4 were detected in the retinas of adult mice,with EphA4 expression particularly enriched in Müller cells.Müller cells of A2-/-A3-/-mice exhibited significantly elevated expression of retinal progenitor cell markers,Pax6 and Chx10,when compared with those from wild-type mice.Moreover,a higher percentage of Müller cells of A2-/-A3-/-mice trans-differentiated and became recoverin+ and β-Ⅲ-tublin+ in the culture than those from wild type mice.Strikingly,an increased number of EdU+ retinal cells was detected in the retinas of adult A2-/-A3-/-mice as compared with wild-type mice.Conclusions Ephrin-A2 and-A3 are negative regulators of the proliferative and neurogenic potentials of Müller cells.Manipulating ephrin-A signaling may thus represent a novel strategy for stimulating neuroregeneration from endogenous progenitors to participate in retinal repair in case of disease or damage.

  20. Ethylene oxide gas sterilization does not reduce the osteoinductive potential of demineralized bone in rats

    DEFF Research Database (Denmark)

    Solheim, E; Pinholt, E M; Bang, G

    1995-01-01

    It has been shown that different sterilization procedures of demineralized bone may influence its osteoinductive properties. The aim of this study was to evaluate the effect of ethylene oxide sterilization for 1, 3, and 6 hours on the osteoinductive potential of allogeneic demineralized bone...... without prior sterilization of the material, whereas the demineralized bone implanted in Groups B, C, and D had been sterilized in ethylene oxide gas for 1, 3, or 6 hours, respectively, and aerated for 48 hours. At 4 weeks postoperatively, bone formation was evaluated quantitatively by strontium 85 uptake...

  1. Regenerative nanomedicine: current perspectives and future directions

    Directory of Open Access Journals (Sweden)

    Chaudhury K

    2014-09-01

    Full Text Available Koel Chaudhury, Vishu Kumar, Jayaprakash Kandasamy, Sourav RoyChoudhurySchool of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, IndiaAbstract: Nanotechnology has considerably accelerated the growth of regenerative medicine in recent years. Application of nanotechnology in regenerative medicine has revolutionized the designing of grafts and scaffolds which has resulted in new grafts/scaffold systems having significantly enhanced cellular and tissue regenerative properties. Since the cell–cell and cell-matrix interaction in biological systems takes place at the nanoscale level, the application of nanotechnology gives an edge in modifying the cellular function and/or matrix function in a more desired way to mimic the native tissue/organ. In this review, we focus on the nanotechnology-based recent advances and trends in regenerative medicine and discussed under individual organ systems including bone, cartilage, nerve, skin, teeth, myocardium, liver and eye. Recent studies that are related to the design of various types of nanostructured scaffolds and incorporation of nanomaterials into the matrices are reported. We have also documented reports where these materials and matrices have been compared for their better biocompatibility and efficacy in supporting the damaged tissue. In addition to the recent developments, future directions and possible challenges in translating the findings from bench to bedside are outlined.Keywords: regenerative medicine, nanomedicine, nanotechnology

  2. AST-induced bone loss in men with prostate cancer: exercise as a potential countermeasure.

    Science.gov (United States)

    Bolam, K A; Galvão, D A; Spry, N; Newton, R U; Taaffe, D R

    2012-12-01

    Androgen suppression treatment (AST) for men with prostate cancer is associated with a number of treatment-related side effects including an accelerated rate of bone loss. This loss of bone is greatest within the first year of AST and increases the risk for fracture. Pharmaceutical treatment in the form of bisphosphonates is currently used to counter the effects of hormone suppression on bone but is costly and associated with potential adverse effects. Recently, exercise has been shown to be an important adjuvant therapy to manage a range of treatment-related toxicities and enhance aspects of quality of life for men receiving AST. We propose that physical exercise may also have an important role in not only attenuating the bone loss associated with AST but in improving bone health and reducing fracture risk. In this review, the rationale underlying exercise as a countermeasure to AST-induced bone loss is provided.

  3. A potential mechanism for allometric trabecular bone scaling in terrestrial mammals.

    Science.gov (United States)

    Christen, Patrik; Ito, Keita; van Rietbergen, Bert

    2015-03-01

    Trabecular bone microstructural parameters, including trabecular thickness, spacing, and number, have been reported to scale with animal size with negative allometry, whereas bone volume fraction is animal size-invariant in terrestrial mammals. As for the majority of scaling patterns described in animals, its underlying mechanism is unknown. However, it has also been found that osteocyte density is inversely related to animal size, possibly adapted to metabolic rate, which shows a negative relationship as well. In addition, the signalling reach of osteocytes is limited by the extent of the lacuno-canalicular network, depending on trabecular dimensions and thus also on animal size. Here we propose animal size-dependent variations in osteocyte density and their signalling influence distance as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. Using an established and tested computational model of bone modelling and remodelling, we run simulations with different osteocyte densities and influence distances mimicking six terrestrial mammals covering a large range of body masses. Simulated trabecular structures revealed negative allometric scaling for trabecular thickness, spacing, and number, constant bone volume fraction, and bone turnover rates inversely related to animal size. These results are in agreement with previous observations supporting our proposal of osteocyte density and influence distance variation as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. The inverse relationship between bone turnover rates and animal size further indicates that trabecular bone scaling may be linked to metabolic rather than mechanical adaptations. © 2015 Anatomical Society.

  4. Regenerative Hydride Heat Pump

    Science.gov (United States)

    Jones, Jack A.

    1992-01-01

    Hydride heat pump features regenerative heating and single circulation loop. Counterflow heat exchangers accommodate different temperatures of FeTi and LaNi4.7Al0.3 subloops. Heating scheme increases efficiency.

  5. Regenerative Hydride Heat Pump

    Science.gov (United States)

    Jones, Jack A.

    1992-01-01

    Hydride heat pump features regenerative heating and single circulation loop. Counterflow heat exchangers accommodate different temperatures of FeTi and LaNi4.7Al0.3 subloops. Heating scheme increases efficiency.

  6. Bone marrow concentrate for autologous transplantation in minipigs. Characterization and osteogenic potential of mesenchymal stem cells.

    Science.gov (United States)

    Herten, M; Grassmann, J P; Sager, M; Benga, L; Fischer, J C; Jäger, M; Betsch, M; Wild, M; Hakimi, M; Jungbluth, P

    2013-01-01

    Autologous bone marrow plays an increasing role in the treatment of bone, cartilage and tendon healing disorders. Cell-based therapies display promising results in the support of local regeneration, especially therapies using intra-operative one-step treatments with autologous progenitor cells. In the present study, bone marrow-derived cells were concentrated in a point-of-care device and investigated for their mesenchymal stem cell (MSC) characteristics and their osteogenic potential. Bone marrow was harvested from the iliac crest of 16 minipigs. The mononucleated cells (MNC) were concentrated by gradient density centrifugation, cultivated, characterized by flow cytometry and stimulated into osteoblasts, adipocytes, and chondrocytes. Cell differentiation was investigated by histological and immunohistological staining of relevant lineage markers. The proliferation capacity was determined via colony forming units of fibroblast and of osteogenic alkaline-phosphatase-positive-cells. The MNC could be enriched 3.5-fold in nucleated cell concentrate in comparison to bone marrow. Flow cytometry analysis revealed a positive signal for the MSC markers. Cells could be differentiated into the three lines confirming the MSC character. The cellular osteogenic potential correlated significantly with the percentage of newly formed bone in vivo in a porcine metaphyseal long-bone defect model. This study demonstrates that bone marrow concentrate from minipigs display cells with MSC character and their osteogenic differentiation potential can be used for osseous defect repair in autologous transplantations.

  7. Advances in Regenerative medicine

    OpenAIRE

    2011-01-01

    PREFACE In order to better introduce this book, it is important to define regenerative medicine as this field is built through a combination of multiple elements including living cells, matrix to support the living cells (i.e. a scaffold), and cell communicators (or signaling systems) to stimulate the cells, and their surrounding environment to grow and develop into new tissue or organ. Indeed, regenerative medicine is an emerging multidisciplinary field involving biology, medicine, and ...

  8. Bone Marrow Stem Cell as a Potential Treatment for Diabetes

    Directory of Open Access Journals (Sweden)

    Ming Li

    2013-01-01

    Full Text Available Diabetes mellitus (DM is a group of metabolic diseases in which a person has high blood glucose levels resulting from defects in insulin secretion and insulin action. The chronic hyperglycemia damages the eyes, kidneys, nerves, heart, and blood vessels. Curative therapies mainly include diet, insulin, and oral hypoglycemic agents. However, these therapies fail to maintain blood glucose levels in the normal range all the time. Although pancreas or islet-cell transplantation achieves better glucose control, a major obstacle is the shortage of donor organs. Recently, research has focused on stem cells which can be classified into embryonic stem cells (ESCs and tissue stem cells (TSCs to generate functional β cells. TSCs include the bone-marrow-, liver-, and pancreas-derived stem cells. In this review, we focus on treatment using bone marrow stem cells for type 1 and 2 DM.

  9. Factors that influence Greeks' decision to register as potential bone marrow donors.

    Science.gov (United States)

    Galanis, P A; Sparos, L D; Katostaras, T; Velonakis, E; Kalokerinou, A

    2008-06-01

    Hemopoietic stem cells can be used from bone marrow or blood or umbilical cord blood of matched siblings or appropriately matched unrelated volunteers. Today, large bone marrow registries have been established to help identify volunteer unrelated bone marrow donors for patients lacking a family donor. Despite there being almost 10 million registered potential bone marrow donors (PBMD) worldwide, only 50% of white patients have a suitable bone marrow match. Growth in the number of PBMD increases the likelihood of finding a compatible donor for a patient. The attitudes and knowledge of 250 registered PBMD and 315 not registered PBMD toward bone marrow donation, tissues and organs donation, and blood donation were surveyed, using a questionnaire with 27 items. Multivariate logistic regression identified gender (females more often than males), regular blood donation, having a relative or a friend who has already been registered as PBMD, having a relative or a friend who needs bone marrow transplantation, family discussion about tissue and organ donation, knowledge about bone marrow transplantation, information about bone marrow transplantation, and trust in health professionals were independent predictive factors influencing people's decision to register as PBMD. Knowledge of these factors is important to target recruitment efforts.

  10. Immature muscular tissue differentiation into bone-like tissue by bone morphogenetic proteins in vitro, with ossification potential in vivo.

    Science.gov (United States)

    Hayashi, Tatsuhide; Kobayashi, Syuichiro; Asakura, Masaki; Kawase, Mayu; Ueno, Atsuko; Uematsu, Yasuaki; Kawai, Tatsushi

    2014-09-01

    The objective of this study was to induce bone formation from immature muscular tissue (IMT) in vitro, using bone morphogenetic proteins (BMPs) as a cytokine source and an expanded polytetrafluoroethylene (ePTFE) scaffold. In addition, cultured IMTs were implanted subcutaneously into Sprague-Dawley (SD) rats to determine their in vivo ossification potential. BMPs, extracted from bovine cortical bones, were applied to embryonic SD rat IMT cultures, before 2 weeks culture on ePTFE scaffolds. Osteoblast-like cells and osteoid tissues were partially identified by hematoxylin-eosin staining 2 weeks after culture. Collagen type I (Col-I), osteopontin (OP), and osteocalcin (OC) were detected in the osteoid tissues by immunohistochemical staining. OC gene expression remained low, but OP and Col-I were upregulated during the culture period. In vivo implanted IMTs showed slight radiopacity 1 week after implantation and strong radiopacity 2 and 3 weeks after implantation. One week after implantation, migration of numerous capillaries was observed and ossification was detected after 2 weeks by histological observation. These results suggest that IMTs are able to differentiate into bone-like tissue in vitro, with an ossification potential after implantation in vivo.

  11. Refinement of the $n-\\alpha$ and $p-\\alpha$ fish-bone potential

    CERN Document Server

    Smith, E; Papp, Z

    2012-01-01

    The fishbone potential of composite particles simulates the Pauli effect by nonlocal terms. We determine the $n-\\alpha$ and $p-\\alpha$ fish-bone potential by simultaneously fitting to the experimental phase shifts. We found that with a double Gaussian parametrization of the local potential can describe the $n-\\alpha$ and $p-\\alpha$ phase shifts for all partial waves.

  12. Biomaterials in periodontal regenerative surgery: effects of cryopreserved bone, commercially available coral, demineralized freeze-dried dentin, and cementum on periodontal ligament fibroblasts and osteoblasts.

    Science.gov (United States)

    Devecioğlu, Didem; Tözüm, Tolga F; Sengün, Dilek; Nohutcu, Rahime M

    2004-10-01

    The ultimate goal of periodontal therapy is to achieve successful periodontal regeneration. The effects of different biomaterials, allogenic and alloplastic, used in periodontal surgeries to achieve regeneration have been studied in vitro on periodontal ligament (PDL) cells and MC3T3-E1 cells. The materials tested included cryopreserved bone allograft (CBA), coralline hydroxyapatite (CH), demineralized freeze-dried dentin (DFDD), and cementum. CBA and CH revealed an increase in initial PDL cell attachment, whereas CH resulted in an increase in long-term PDL cell attachment. Mineral-like nodule formation was observed significantly higher in DFDD compared to other materials tested for osteoblasts. Based on the results of this in vitro study, we conclude that the materials used are all biocompatible with human PDL cells and osteoblasts, which have pivotal importance in periodontal regeneration.

  13. Improving Recovery from Catastrophic Bone Injuries: An Animal Model for Assessing the Bone Reparative Potential of Progenitor Cell Therapy

    Science.gov (United States)

    2009-08-01

    Liu, Y. Strecker, S., Wang, L., Kronenberg , M., Kalajzic, I. and Rowe, D. Characterizing the Osteogenic Potential of Mesenchymal Stem Cells and...Their Immediate Cellular Derivatives. J. Bone. Min. Res. 24: Suppl 1, Abst SA0220, 2009. 3. Kronenberg , M., Harrison, J., Ravi, N., Shin, D. and Rowe, D...Abst SA0227, 2009. 4. Harrison, J., Kronenberg , M. and Rowe, D. Tracking Expression of a Smooth Muscle Alpha- Actin-Red Fluorescent Protein (SMAA-RFP

  14. Bone

    Science.gov (United States)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  15. Three-dimensional bioprinting in tissue engineering and regenerative medicine.

    Science.gov (United States)

    Gao, Guifang; Cui, Xiaofeng

    2016-02-01

    With the advances of stem cell research, development of intelligent biomaterials and three-dimensional biofabrication strategies, highly mimicked tissue or organs can be engineered. Among all the biofabrication approaches, bioprinting based on inkjet printing technology has the promises to deliver and create biomimicked tissue with high throughput, digital control, and the capacity of single cell manipulation. Therefore, this enabling technology has great potential in regenerative medicine and translational applications. The most current advances in organ and tissue bioprinting based on the thermal inkjet printing technology are described in this review, including vasculature, muscle, cartilage, and bone. In addition, the benign side effect of bioprinting to the printed mammalian cells can be utilized for gene or drug delivery, which can be achieved conveniently during precise cell placement for tissue construction. With layer-by-layer assembly, three-dimensional tissues with complex structures can be printed using converted medical images. Therefore, bioprinting based on thermal inkjet is so far the most optimal solution to engineer vascular system to the thick and complex tissues. Collectively, bioprinting has great potential and broad applications in tissue engineering and regenerative medicine. The future advances of bioprinting include the integration of different printing mechanisms to engineer biphasic or triphasic tissues with optimized scaffolds and further understanding of stem cell biology.

  16. Minerals and vitamins in bone health: the potential value of dietary enhancement.

    Science.gov (United States)

    Bonjour, Jean-Philippe; Guéguen, Léon; Palacios, Cristina; Shearer, Martin J; Weaver, Connie M

    2009-06-01

    Nutrition is important to bone health, and a number of minerals and vitamins have been identified as playing a potential role in the prevention of bone diseases, particularly osteoporosis. Despite this, there is currently no consensus on maximum levels to allow in food or as dietary supplements. The benefits of supplementation of populations at risk of osteoporosis with Ca and vitamin D are well established. Prolonged supplementation of Ca and vitamin D in elderly has been shown to prevent bone loss, and in some intervention studies to prevent fragility fractures. Although P is essential to bone health, the average intake is considered to be more than sufficient and supplementation could raise intake to adverse levels. The role of vitamin K in bone health is less well defined, though it may enhance the actions of Ca and vitamin D. Sr administered in pharmacological doses as the ranelate salt was shown to prevent fragility fractures in postmenopausal osteoporosis. However, there is no hard evidence that supplementation with Sr salts would be beneficial in the general population. Mg is a nutrient implicated in bone quality, but the benefit of supplementation via foodstuffs remains to be established. A consensus on dietary supplementation for bone health should balance the risks, for example, exposure of vulnerable populations to values close to maximal tolerated doses, against evidence for benefits from randomised clinical trials, such as those for Ca and vitamin D. Feedback from community studies should direct further investigations and help formulate a consensus on dietary supplementation for bone health.

  17. Potential of targeted drug delivery system for the treatment of bone metastasis.

    Science.gov (United States)

    Vinay, Raichur; KusumDevi, V

    2016-01-01

    Bone metastasis is a devastating complication of cancer that requires an immediate attention. Although our understanding of the metastatic process has improved over the years, yet a number of questions still remain unanswered, and more research is required for complete understanding of the skeletal consequences of metastasis. Furthermore, as no effective treatments are available for some of the most common skeleton disorders such as arthritis, osteoarthritis, osteosarcoma and metastatic bone cancer, there is an urgent need to develop new drugs and drug delivery systems for safe and efficient clinical treatments. Hence this article describes the potential of targeted delivery platforms aimed specifically at bone metastasized tumors. The review gives a brief understanding of the proposed mechanisms of metastasis and focuses primarily on the targeting moieties such as bisphosphonates, which represent the current gold standard in bone metastasis therapies. Special focus has been given to the targeted nanoparticulate systems for treating bone metastasis and its future. Also highlighted are some of the therapeutic targets that can be exploited for designing therapies for bone metastasis. Some of the patented molecules for bone metastasis prevention and treatment have also been discussed. Recently proposed HIFU-CHEM, which utilizes High Intensity Focused ultrasound (HIFU) guided by MRI in combination with temperature-sensitive nanomedicines has also been briefed. The study has been concluded with a focus on the innovations requiring an immediate attention that could improve the treatment modality of bone metastasis.

  18. Summary of: Regenerative endodontics.

    Science.gov (United States)

    Clark, Stephen J

    2014-03-01

    Significant advances in our understanding of the biological processes involved in tooth development and repair at the cellular and molecular levels have underpinned the newly emerging area of regenerative endodontics. Development of treatment protocols based on exploiting the natural wound healing properties of the dental pulp and applying tissue engineering principles has allowed reporting of case series showing preservation of tissue vitality and apexogenesis. To review current case series reporting regenerative endodontics. Current treatment approaches tend to stimulate more reparative than regenerative responses in respect of the new tissue generated, which often does not closely resemble the physiological structure of dentine-pulp. However, despite these biological limitations, such techniques appear to offer significant promise for improved treatment outcomes. Improved biological outcomes will likely emerge from the many experimental studies being reported and will further contribute to improvements in clinical treatment protocols.

  19. Regenerative similariton laser

    Directory of Open Access Journals (Sweden)

    Thibault North

    2016-05-01

    Full Text Available Self-pulsating lasers based on cascaded reshaping and reamplification (2R are capable of initiating ultrashort pulses despite the accumulation of large amounts of nonlinearities in all-fiber resonators. The spectral properties of pulses in self-similar propagation are compatible with cascaded 2R regeneration by offset filtering, making parabolic pulses suitable for the design of a laser of this recently introduced class. A new type of regenerative laser giving birth to similaritons is numerically investigated and shows that this laser is the analog of regenerative sources based solely on self-phase modulation and offset filtering. The regenerative similariton laser does not suffer from instabilities due to excessive nonlinearities and enables ultrashort pulse generation in a simple cavity configuration.

  20. A regenerative approach towards mucosal fenestration closure.

    Science.gov (United States)

    Gandi, Padma; Anumala, Naveen; Reddy, Amarender; Chandra, Rampalli Viswa

    2013-06-06

    Mucosal fenestration is an opening or an interstice through the oral mucosa. A lesion which occurs with greater frequency than generally realised, its occurrence is attributed to a myriad of causes. Mucogingival procedures including connective tissue grafts, free gingival grafts and lateral pedicle grafts are generally considered to be the treatment of choice in the closure of a mucosal fenestration. More often, these procedures are performed in conjunction with other procedures such as periradicular surgery and with bone grafts. However, the concomitant use of gingival grafts and bone grafts in mucosal fenestrations secondary to infections in sites exhibiting severe bone loss is highly debatable. In this article, we report two cases of mucosal fenestrations secondary to trauma and their management by regenerative periodontal surgery with the placement of guided tissue regeneration membrane and bone graft. The final outcome was a complete closure of the fenestration in both the cases.

  1. Heating or freezing bone. Effects on angiogenesis induction and growth potential in mice.

    Science.gov (United States)

    Leunig, M; Yuan, F; Berk, D A; Gerweck, L E; Jain, R K

    1996-08-01

    We have characterized the effect of bone graft treatment by heating or freezing (with or without dimethyl sulfoxide (DMSO)). Tissue culture and dorsal skin-fold chambers in mice were used as sites to quantify the effect on angiogenesis, growth and calcification of neonatal femora. Fresh femora increased in both length and cartilage diameter (calcification in vivo only), but cryopreservation or heating abolished the increase in femoral dimensions. In vivo, femora of all experimental groups elicited an angiogenic response from the host tissue, which was most pronounced for fresh femora, weaker for DMSO-preserved frozen bone and poor for unprotected frozen bone and boiled femora. Freezing in the presence of a cryopreservative (DMSO) was found to preserve the angiogenic potential of frozen bone, whereas unprotected heating or freezing significantly impaired angiogenesis induction and growth potential.

  2. Platelet rich fibrin - a novel acumen into regenerative endodontic therapy

    Directory of Open Access Journals (Sweden)

    Kavita Hotwani

    2014-02-01

    Full Text Available Research into regenerative dentistry has added impetus onto the field of molecular biology. It can be documented as a prototype shift in the therapeutic armamentarium for dental disease. Regenerative endodontic procedures are widely being added to the current armamentarium of pulp therapy procedures. The regenerative potential of platelets has been deliberated. A new family of platelet concentrates called the platelet rich fibrin (PRF has been recently used by several investigators and has shown application in diverse disciplines of dentistry. This paper is intended to add light on the various prospects of PRF and clinical insights to regenerative endodontic therapy.

  3. Platelet rich fibrin - a novel acumen into regenerative endodontic therapy.

    Science.gov (United States)

    Hotwani, Kavita; Sharma, Krishna

    2014-02-01

    Research into regenerative dentistry has added impetus onto the field of molecular biology. It can be documented as a prototype shift in the therapeutic armamentarium for dental disease. Regenerative endodontic procedures are widely being added to the current armamentarium of pulp therapy procedures. The regenerative potential of platelets has been deliberated. A new family of platelet concentrates called the platelet rich fibrin (PRF) has been recently used by several investigators and has shown application in diverse disciplines of dentistry. This paper is intended to add light on the various prospects of PRF and clinical insights to regenerative endodontic therapy.

  4. A comparative study of the regenerative effect of sinus bone grafting with platelet-rich fibrin-mixed Bio-Oss® and commercial fibrin-mixed Bio-Oss®: an experimental study.

    Science.gov (United States)

    Xuan, Feng; Lee, Chun-Ui; Son, Jeong-Seog; Jeong, Seung-Mi; Choi, Byung-Ho

    2014-06-01

    Anorganic bovine bone (Bio-Oss®) particles are one of the most popular grafting materials. The particles are often mixed with platelet-rich fibrin (PRF) or a commercial fibrin (Tisseel®) to form a mouldable graft material. The objective of this study was to compare the potentials of PRF-mixed Bio-Oss® and Tisseel®-mixed Bio-Oss® to enhance bone regeneration in a canine sinus model. Six mongrel dogs were used in this study. After elevating the sinus membrane in both maxillary sinus cavities, an implant was placed into the sinus cavity. In one of the sinus cavities, the PRF/Bio-Oss® composite was grafted, and the Tisseel®/Bio-Oss® composite was grafted in the other sinus cavity. After a 6 month healing period, bone formation in the graft sites and bone-implant contact were evaluated. The mean osseointegration rate was 43.5 ± 12.4% and new bone formation rate 41.8 ± 5.9% in the PRF/Bio-Oss® composite sites. In the Tisseel®/Bio-Oss® composite sites they were 30.7 ± 7.9% and 31.3 ± 6.4%. There were statistically significant differences between the groups. The findings from this study suggest that when platelet-rich fibrin is used as an adjunct to Bio-Oss® particles for bone augmentation in the maxillary sinus, bone formation in the graft sites is significantly greater than when Tisseel® is used.

  5. Cryogenic regenerative heat exchangers

    CERN Document Server

    Ackermann, Robert A

    1997-01-01

    An in-depth survey of regenerative heat exchangers, this book chronicles the development and recent commercialization of regenerative devices for cryogenic applications. Chapters cover historical background, concepts, practical applications, design data, and numerical solutions, providing the latest information for engineers to develop advanced cryogenic machines. The discussions include insights into the operation of a regenerator; descriptions of the cyclic and fluid temperature distributions in a regenerator; data for various matrix geometries and materials, including coarse and fine bronze, stainless steel-woven wire mesh screens, and lead spheres; and unique operating features of cryocoolers that produce deviations from ideal regenerator theory.

  6. [Therapeutic potential of bone marrow stem cells in cerebral infarction].

    Science.gov (United States)

    Sánchez-Cruz, Gilberto; Milián-Rodríguez, Lismary

    2015-05-16

    Introduccion. Las celulas madre constituyen una alternativa terapeutica que se encuentra en fase de experimentacion para el infarto cerebral. Objetivo. Mostrar la evidencia cientifica existente sobre el potencial terapeutico de las celulas madre de la medula osea en esta enfermedad. Desarrollo. El infarto cerebral representa el 80% de las enfermedades cerebrovasculares. La trombolisis constituye la unica terapia aprobada, pero, por su estrecha ventana terapeutica, solo se aplica a un bajo porcentaje de los pacientes. De manera alternativa, los tratamientos neurorrestauradores, como el de celulas madre, pueden aplicarse en periodos mas prolongados. Por esta razon se efectuo una busqueda bibliografica en PubMed con el empleo de las palabras clave 'stem cells', 'bone marrow derived mononuclear cells' y 'stroke'. Se encontraron evidencias de seguridad y eficacia de dichas celulas en diferentes momentos evolutivos del infarto cerebral. Se identificaron estudios que en clinica y preclinica las recolectaron por puncion medular y en sangre periferica, y las trasplantaron directamente en el area infartada o por via intravascular. El efecto terapeutico se relaciona con sus propiedades de plasticidad celular y liberacion de factores troficos. Conclusiones. El concentrado de celulas mononucleares autologas, obtenido en sangre periferica o por puncion de la medula osea, y trasplantado por via intravenosa, es una factible opcion metodologica que permitira rapidamente incrementar el numero de ensayos clinicos en diferentes etapas evolutivas del infarto cerebral. Esta terapia muestra seguridad y eficacia; sin embargo, deben ampliarse las evidencias que avalen su generalizacion en humanos.

  7. Perfluorodecalin and bone regeneration

    Directory of Open Access Journals (Sweden)

    F Tamimi

    2013-01-01

    Full Text Available Perfluorodecalin (PFD is a chemically and biologically inert biomaterial and, as many perfluorocarbons, is also hydrophobic, radiopaque and has a high solute capacity for gases such as oxygen. In this article we have demonstrated, both in vitro and in vivo, that PFD may significantly enhance bone regeneration. Firstly, the potential benefit of PFD was demonstrated by prolonging the survival of bone marrow cells cultured in anaerobic conditions. These findings translated in vivo, where PFD incorporated into bone-marrow-loaded 3D-printed scaffolds substantially improved their capacity to regenerate bone. Secondly, in addition to biological applications, we have also shown that PFD improves the radiopacity of bone regeneration biomaterials, a key feature required for the visualisation of biomaterials during and after surgical implantation. Finally, we have shown how the extreme hydrophobicity of PFD enables the fabrication of highly cohesive self-setting injectable biomaterials for bone regeneration. In conclusion, perfluorocarbons would appear to be highly beneficial additives to a number of regenerative biomaterials, especially those for bone regeneration.

  8. Bioprinting in Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Manuela Monti

    2016-02-01

    Full Text Available Prof. Turksen is a very well known scientist in the stem cell biology field and he is also internationally known for his fundamental studies on claudin-6. In addition to his research activity he is editor for the Stem Cell Biology and Regenerative Medicine series (Humana Press and editor-in-chief of Stem Cell Reviews and Reports.....

  9. Osteogenic potential of the human bone morphogenetic protein 2 gene activated nanobone putty

    Institute of Scientific and Technical Information of China (English)

    TIAN Xiao-bin; SUN Li; YANG Shu-hua; ZHANG Yu-kun; HU Ru-yin; FU De-hao

    2008-01-01

    Background Nanobone putty is an injectable and bioresorbable bone substitute. The neutral-pH putty resembles hard bone tissue, does not contain polymers or plasticizers, and is self-setting and nearly isothermic, properties which are helpful for the adhesion, proliferation, and function of bone cells. The aim of this study was to investigate the osteogenic potential of human bone morphogenetic protein 2(hBMP2)gene activated nanobone putty in inducing ectopic bone formation, and the effects of the hBMP2 gene activated nanobone putry on repairing bone defects. Methods Twenty four Kunming mice were randomly divided into two groups. The nanobone putty+hBMP2 plasmid was injected into the right thigh muscle pouches of the mice(experiment side). The nanobone putty+blank plasmid or nanobone putty was injected into the left thigh muscle pouches of the group 1(control side 1)or group 2(control side 2), respectively. The effects of ectopic bone formation were evaluated by radiography, histology, and molecular biology analysis at 2 and 4 weeks after operation. Bilateral 15 mm radial defects were made in forty-eight rabbits. These rabbits were randomly divided into three groups: Group A, nanobone putty+hBMP2 plasmid;Group B, putty+blank plasmid; Group C, nanobone putty only. Six rabbits with left radial defects served as blank controls. The effect of bone repairing was evaluated by radiography, histology, molecular biology, and biomechanical analysis at 4, 8, and 12 weeks after operation. Results The tissue from the experimental side of the mice expressed hBMP2. Obvious cartilage and island-distributed immature bone formation in implants of the experiment side were observed at 2 weeks after operation, and massive mature bone observed at 4 weeks. No bone formation was observed in the control side of the mice. The ALP activity in the experiment side of the mice was higher than that in the control side. The tissue of Group A rabbits expressed hBMP2 protein and higher ALP level

  10. Artificial Cell Microencapsulated Stem Cells in Regenerative Medicine, Tissue Engineering and Cell Therapy

    Science.gov (United States)

    Liu, Zun Chang; Chang, Thomas Ming Swi

    2012-01-01

    Adult stem cells, especially isolated from bone marrow, have been extensively investigated in recent years. Studies focus on their multiple plasticity of transdifferentiating into various cell lineages and on their potential in cellular therapy in regenerative medicine. In many cases, there is the need for tissue engineering manipulation. Among the different approaches of stem cells tissue engineering, microencapsulation can immobilize stem cells to provide a favorable microenvironment for stem cells survival and functioning. Furthermore, microencapsulated stem cells are immunoisolated after transplantation. We show that one intraperitoneal injection of microencapsulated bone marrow stem cells can prolong the survival of liver failure rat models with 90% of the liver removed surgically. In addition to transdifferentiation, bone marrow stem cells can act as feeder cells. For example, when coencapsulated with hepatocytes, stem cells can increase the viability and function of the hepatocytes in vitro and in vivo. PMID:20384219

  11. PLATELET RICH FIBRIN: A PROMISING INNOVATION IN REGENERATIVE THERAPY

    Directory of Open Access Journals (Sweden)

    Arun

    2015-04-01

    Full Text Available Platelets can play a crucial role in regenerative therapy as they are reservoirs of growth factors and cytokines which are the key factors for regeneration of the bone and maturation of the soft tissue. Platelet - rich fibr in (PRF was first described by Choukroun et al. in France. It has been referred to as a second - generation platelet concentrate, which has been shown to have several advantages over traditionally prepared PRP. Platelet - rich fibrin (PRF is autologous plate let concentrates prepared from patient’s own blood. It is a natural fibrin - based biomaterial prepared from an anticoagulant - free blood harvest without any artificial biochemical modification that allows obtaining fibrin membranes enriched with platelets a nd growth factors. Evidence from the literature suggests the potential role of PRF in regeneration and tissue engineering. The slow polymerisation during centrifugation and fibrin - based structure makes PRF a better healing biomaterial than PRP and other fi brin adhesives. The purpose of this review article is to describe the novel second - generation platelet concentrate PRF, which is an improvement over the traditionally prepared PRP for use in regenerative dentistry.

  12. Implications of mesenchymal stem cells in regenerative medicine.

    Science.gov (United States)

    Kariminekoo, Saber; Movassaghpour, Aliakbar; Rahimzadeh, Amirbahman; Talebi, Mehdi; Shamsasenjan, Karim; Akbarzadeh, Abolfazl

    2016-05-01

    Mesenchymal stem cells (MSCs) are a population of multipotent progenitors which reside in bone marrow, fat, and some other tissues and can be isolated from various adult and fetal tissues. Self-renewal potential and multipotency are MSC's hallmarks. They have the capacity of proliferation and differentiation into a variety of cell lineages like osteoblasts, condrocytes, adipocytes, fibroblasts, cardiomyocytes. MSCs can be identified by expression of some surface molecules like CD73, CD90, CD105, and lack of hematopoietic specific markers including CD34, CD45, and HLA-DR. They are hopeful tools for regenerative medicine for repairing injured tissues. Many studies have focused on two significant features of MSC therapy: (I) systemically administered MSCs home to sites of ischemia or injury, and (II) MSCs can modulate T-cell-mediated immunological responses. MSCs express chemokine receptors and ligands involved in cells migration and homing process. MSCs induce immunomedulatory effects on the innate (dendritic cells, monocyte, natural killer cells, and neutrophils) and the adaptive immune system cells (T helper-1, cytotoxic T lymphocyte, and B lymphocyte) by secreting soluble factors like TGF-β, IL-10, IDO, PGE-2, sHLA-G5, or by cell-cell interaction. In this review, we discuss the main applications of mesenchymal stem in Regenerative Medicine and known mechanisms of homing and Immunomodulation of MSCs.

  13. The hematopoietic system in the context of regenerative medicine.

    Science.gov (United States)

    Porada, Christopher D; Atala, Anthony J; Almeida-Porada, Graça

    2016-04-15

    Hematopoietic stem cells (HSC) represent the prototype stem cell within the body. Since their discovery, HSC have been the focus of intensive research, and have proven invaluable clinically to restore hematopoiesis following inadvertent radiation exposure and following radio/chemotherapy to eliminate hematologic tumors. While they were originally discovered in the bone marrow, HSC can also be isolated from umbilical cord blood and can be "mobilized" peripheral blood, making them readily available in relatively large quantities. While their ability to repopulate the entire hematopoietic system would already guarantee HSC a valuable place in regenerative medicine, the finding that hematopoietic chimerism can induce immunological tolerance to solid organs and correct autoimmune diseases has dramatically broadened their clinical utility. The demonstration that these cells, through a variety of mechanisms, can also promote repair/regeneration of non-hematopoietic tissues as diverse as liver, heart, and brain has further increased their clinical value. The goal of this review is to provide the reader with a brief glimpse into the remarkable potential HSC possess, and to highlight their tremendous value as therapeutics in regenerative medicine.

  14. Stem Cells Applications in Regenerative Medicine and Disease Therapeutics.

    Science.gov (United States)

    Mahla, Ranjeet Singh

    2016-01-01

    Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation.

  15. Improving Soldier Recovery from Catastrophic Bone Injuries: Developing an Animal Model for Standarizing the Bone Reparative Potential of Emerging Progenitor Cell Therapies

    Science.gov (United States)

    2008-08-01

    Injuries: Developing an animal model for standarizing the bone reparative potential of emerging progenitor cell therapies PRINCIPAL...osteogenesis in the surrounding host bone. Helos is a collagen fiber, hydroxyapatite composite that has sufficient structure to make inoculation with donor...adjacent to tubular green structures (muscular vessels). Although myofibroblastic like green cells are also present, they do not appear to

  16. Perspectives and challenges in regenerative medicine using plasma rich in growth factors.

    Science.gov (United States)

    Anitua, Eduardo; Alkhraisat, Mohammad H; Orive, Gorka

    2012-01-10

    Plasma rich in growth factors (PRGF-Endoret) is an endogenous therapeutic technology that is gaining interest in regenerative medicine due to its potential to stimulate and accelerate tissue healing and bone regeneration. This autologous biotechnology is designed for the in situ delivery of multiple cellular modulators and the formation of a fibrin scaffold, thereby providing different formulations that can be widely used in numerous medical and scientific fields including dentistry, oral implantology, orthopedics, ulcer treatment and tissue engineering among others. Here we discuss the important progress that has been accomplished in this field. Furthermore, a comprehensive outlook of the intriguing therapeutic applications of this technology is presented.

  17. The imperative for regenerative agriculture.

    Science.gov (United States)

    Rhodes, Christopher J

    2017-03-01

    A review is made of the current state of agriculture, emphasising issues of soil erosion and dependence on fossil fuels, in regard to achieving food security for a relentlessly enlarging global population. Soil has been described as "the fragile, living skin of the Earth", and yet both its aliveness and fragility have all too often been ignored in the expansion of agriculture across the face of the globe. Since it is a pivotal component in a global nexus of soil-water-air-energy, how we treat the soil can impact massively on climate change - with either beneficial or detrimental consequences, depending on whether the soil is preserved or degraded. Regenerative agriculture has at its core the intention to improve the health of soil or to restore highly degraded soil, which symbiotically enhances the quality of water, vegetation and land-productivity. By using methods of regenerative agriculture, it is possible not only to increase the amount of soil organic carbon (SOC) in existing soils, but to build new soil. This has the effect of drawing down carbon from the atmosphere, while simultaneously improving soil structure and soil health, soil fertility and crop yields, water retention and aquifer recharge - thus ameliorating both flooding and drought, and also the erosion of further soil, since runoff is reduced. Since food production on a more local scale is found to preserve the soil and its quality, urban food production should be seen as a significant potential contributor to regenerative agriculture in the future, so long as the methods employed are themselves 'regenerative'. If localisation is to become a dominant strategy for dealing with a vastly reduced use of fossil fuels, and preserving soil quality - with increased food production in towns and cities - it will be necessary to incorporate integrated ('systems') design approaches such as permaculture and the circular economy (which minimise and repurpose 'waste') within the existing urban infrastructure. In

  18. A novel calcium phosphate ceramic-magnetic nanoparticle composite as a potential bone substitute.

    Science.gov (United States)

    Wu, Yao; Jiang, Wen; Wen, Xiantao; He, Bin; Zeng, Xiaobo; Wang, Gang; Gu, Zhongwei

    2010-02-01

    A magnetic field has been applied to accelerate bone healing for a long time. In this study, in order to combine the bone repair capability of calcium phosphate (CaP) ceramics with the magnetic field, a novel CaP ceramic-magnetic nanoparticle (CaP-MNP) composite was fabricated through integrating the superparamagnetic nanoparticles into the CaP ceramics. Two kinds of CaP ceramics were chosen: hydroxyapatite (HA) and HA/tricalcium phosphate (65/35, HT). The samples were cultured with Ros17/2.8 and MG63 cells respectively in vitro to evaluate the cell proliferation and differentiation via MTT and alkaline phosphatase activity tests. In order to find the influence of the magnetic materials on the expression of the bone morphological protein (BMP), the samples composited with BMP-2 were implanted subcutaneously in the fasciae of rat back muscles for 30 days. Compared with ordinary CaP ceramics, the results indicated that the CaP-MNP composite had good biocompatibility and was able to promote cell proliferation and differentiation significantly. The in vivo test showed that the expression of BMP-2 would be accelerated by HT composited with MNPs, and new bone-like tissue formation could be observed. Accordingly, it might be expected that this CaP-MNP composite could become a potential bone substitute or bone tissue engineering scaffold.

  19. Graded porous polyurethane foam: A potential scaffold for oro-maxillary bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Giannitelli, S.M. [Department of Engineering, Tissue Engineering Unit, Università Campus Bio-Medico di Roma, Rome (Italy); Basoli, F. [Department of Chemical Science and Technology, University of Rome “Tor Vergata”, Rome (Italy); Mozetic, P. [Department of Engineering, Tissue Engineering Unit, Università Campus Bio-Medico di Roma, Rome (Italy); Piva, P.; Bartuli, F.N.; Luciani, F. [University of Rome “Tor Vergata”, Rome (Italy); Arcuri, C. [Department of Periodontics, University of Rome “Tor Vergata”, Rome (Italy); U.O.C.C. Odontostomatology, “S. Giovanni Calibita, Fatebenefratelli” Hospital, Rome (Italy); Trombetta, M. [Department of Engineering, Tissue Engineering Unit, Università Campus Bio-Medico di Roma, Rome (Italy); Rainer, A., E-mail: a.rainer@unicampus.it [Department of Engineering, Tissue Engineering Unit, Università Campus Bio-Medico di Roma, Rome (Italy); Licoccia, S. [Department of Chemical Science and Technology, University of Rome “Tor Vergata”, Rome (Italy)

    2015-06-01

    Bone tissue engineering applications demand for biomaterials offering a substrate for cell adhesion, migration, and proliferation, while inferring suitable mechanical properties to the construct. In the present study, polyurethane (PU) foams were synthesized to develop a graded porous material—characterized by a dense shell and a porous core—for the treatment of oro-maxillary bone defects. Foam was synthesized via a one-pot reaction starting from a polyisocyanate and a biocompatible polyester diol, using water as a foaming agent. Different foaming conditions were examined, with the aim of creating a dense/porous functional graded material that would perform at the same time as an osteoconductive scaffold for bone defect regeneration and as a membrane-barrier to gingival tissue ingrowth. The obtained PU was characterized in terms of morphological and mechanical properties. Biocompatibility assessment was performed in combination with bone-marrow-derived human mesenchymal stromal cells (hBMSCs). Our findings confirm that the material is potentially suitable for guided bone regeneration applications. - Highlights: • Graded porous polyurethane foams were synthesized via a one-pot foaming reaction. • The inner porous core might act as a scaffold for guided bone regeneration. • A dense outer shell was introduced to act as a barrier to gingival tissue ingrowth. • The synthesized foams were non-toxic and supportive of hBMSC adhesion.

  20. State of the art: stem cells in equine regenerative medicine.

    Science.gov (United States)

    Lopez, M J; Jarazo, J

    2015-03-01

    According to Greek mythology, Prometheus' liver grew back nightly after it was removed each day by an eagle as punishment for giving mankind fire. Hence, contrary to popular belief, the concept of tissue and organ regeneration is not new. In the early 20th century, cell culture and ex vivo organ preservation studies by Alexis Carrel, some with famed aviator Charles Lindbergh, established a foundation for much of modern regenerative medicine. While early beliefs and discoveries foreshadowed significant accomplishments in regenerative medicine, advances in knowledge within numerous scientific disciplines, as well as nano- and micromolecular level imaging and detection technologies, have contributed to explosive advances over the last 20 years. Virtually limitless preparations, combinations and applications of the 3 major components of regenerative medicine, namely cells, biomaterials and bioactive molecules, have created a new paradigm of future therapeutic options for most species. It is increasingly clear, however, that despite significant parallels among and within species, there is no 'one-size-fits-all' regenerative therapy. Likewise, a panacea has yet to be discovered that completely reverses the consequences of time, trauma and disease. Nonetheless, there is no question that the promise and potential of regenerative medicine have forever altered medical practices. The horse is a relative newcomer to regenerative medicine applications, yet there is already a large body of work to incorporate novel regenerative therapies into standard care. This review focuses on the current state and potential future of stem cells in equine regenerative medicine.

  1. Regenerative photonic therapy: Review

    Science.gov (United States)

    Salansky, Natasha; Salansky, Norman

    2012-09-01

    After four decades of research of photobiomodulation phenomena in mammals in vitro and in vivo, a solid foundation is created for the use of photobiomodulation in regenerative medicine. Significant accomplishments are achieved in animal models that demonstrate opportunities for photo-regeneration of injured or pathological tissues: skin, muscles and nerves. However, the use of photobiomodulation in clinical studies leads to controversial results while negative or marginal clinical efficacy is reported along with positive findings. A thor ough analysis of requirements to the optical parameters (dosimetry) for high efficacy in photobimodulation led us to the conclusion that there are several misconceptions in the clinical applications of low level laser therapy (LLLT). We present a novel appr oach of regenerative photonic therapy (RPT) for tissue healing and regeneration that overcomes major drawbacks of LLLT. Encouraging clinical results on RPT efficacy are presented. Requirements for RPT approach and vision for its future development for tissue regeneration is discussed.

  2. Regenerative Endodontics: Burning Questions.

    Science.gov (United States)

    Smith, Anthony J; Cooper, Paul R

    2017-09-01

    Pulp regeneration and its clinical translation into regenerative endodontic procedures are receiving increasing research attention, leading to significant growth of the published scientific and clinical literature within these areas. Development of research strategies, which consider patient-, clinician-, and scientist-based outcomes, will allow greater focus on key research questions driving more rapid clinical translation. Three key areas of focus for these research questions should include cells, signaling, and infection/inflammation. A translational pathway is envisaged in which clinical approaches are increasingly refined to provide regenerative endodontic protocols that are based on a robust understanding of the physiological processes and events responsible for the normal secretion, structure, and biological behavior of pulpal tissue. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  3. Regenerative feedback resonant circuit

    Science.gov (United States)

    Jones, A. Mark; Kelly, James F.; McCloy, John S.; McMakin, Douglas L.

    2014-09-02

    A regenerative feedback resonant circuit for measuring a transient response in a loop is disclosed. The circuit includes an amplifier for generating a signal in the loop. The circuit further includes a resonator having a resonant cavity and a material located within the cavity. The signal sent into the resonator produces a resonant frequency. A variation of the resonant frequency due to perturbations in electromagnetic properties of the material is measured.

  4. Operculum bone carp (cyprinus carprio sp.) scaffold is a new potential xenograft material: a preliminary study

    Science.gov (United States)

    Kartiwa, A.; Abbas, B.; Pandansari, P.; Prahasta, A.; Nandini, M.; Fadhlillah, M.; Subroto, T.; Panigoro, R.

    2017-02-01

    Orbital floor fracture with extensive bone loss, would cause herniation of the orbital tissue into the maxillary sinus. Graft implantation should be done on the orbital fracture with extensive bone loss. Different types of grafts have their own characteristics and advantages. Xenograft has been widely studied for use in bone defects. This study was to investigate cyprinus carprio sp. opercula bone as a potential xenograft. The aim of this study was to investigate based on EDS chemical analysis using a ZAF Standardless Method of Quantitative Analysis (Oxide) and SEM examination conducted in the laboratory of Mathematics, Institute of Technology Bandung. Particularly the mass ratio of Ca and P (5.8/3:47), the result is 1.67. This is equivalent to the stoichiometric Hydroxyapatite (HA) (Aoki H, 1991, Science and medical applications of hydroxyapatite, Tokyo: Institute for Medical and Engineering, Tokyo Medical and Dental University). C N O that there is an element of protein/amino acid collagen compound, serves as a matrix together with HA. As shown in the SEM analysis that the matrix is a porous sheet-shaped (oval) that interconnect with each other, which is good scaffold. The pore is composed of large pores >200 microns and smaller pores between the large pores with a size smaller or equal to 10 microns that can serve for the attachment of osteoblast cell. In conclusion, Opercula bone carp (cyprinus carprio sp.) scaffold could be a new potential xenograft material.

  5. Assessment of bone ingrowth potential of biomimetic hydroxyapatite and brushite coated porous E-beam structures

    NARCIS (Netherlands)

    Biemond, J.E.; Eufrasio, T.S.; Hannink, G.J.; Verdonschot, N.J.J.; Buma, P.

    2011-01-01

    The bone ingrowth potential of biomimetic hydroxyapatite and brushite coatings applied on porous E-beam structure was examined in goats and compared to a similar uncoated porous structure and a conventional titanium plasma spray coating. Specimens were implanted in the iliac crest of goats for a per

  6. Human adipose tissue possesses a unique population of pluripotent stem cells with nontumorigenic and low telomerase activities: potential implications in regenerative medicine.

    Science.gov (United States)

    Ogura, Fumitaka; Wakao, Shohei; Kuroda, Yasumasa; Tsuchiyama, Kenichiro; Bagheri, Mozhdeh; Heneidi, Saleh; Chazenbalk, Gregorio; Aiba, Setsuya; Dezawa, Mari

    2014-04-01

    In this study, we demonstrate that a small population of pluripotent stem cells, termed adipose multilineage-differentiating stress-enduring (adipose-Muse) cells, exist in adult human adipose tissue and adipose-derived mesenchymal stem cells (adipose-MSCs). They can be identified as cells positive for both MSC markers (CD105 and CD90) and human pluripotent stem cell marker SSEA-3. They intrinsically retain lineage plasticity and the ability to self-renew. They spontaneously generate cells representative of all three germ layers from a single cell and successfully differentiate into targeted cells by cytokine induction. Cells other than adipose-Muse cells exist in adipose-MSCs, however, do not exhibit these properties and are unable to cross the boundaries from mesodermal to ectodermal or endodermal lineages even under cytokine inductions. Importantly, adipose-Muse cells demonstrate low telomerase activity and transplants do not promote teratogenesis in vivo. When compared with bone marrow (BM)- and dermal-Muse cells, adipose-Muse cells have the tendency to exhibit higher expression in mesodermal lineage markers, while BM- and dermal-Muse cells were generally higher in those of ectodermal and endodermal lineages. Adipose-Muse cells distinguish themselves as both easily obtainable and versatile in their capacity for differentiation, while low telomerase activity and lack of teratoma formation make these cells a practical cell source for potential stem cell therapies. Further, they will promote the effectiveness of currently performed adipose-MSC transplantation, particularly for ectodermal and endodermal tissues where transplanted cells need to differentiate across the lineage from mesodermal to ectodermal or endodermal in order to replenish lost cells for tissue repair.

  7. Safety and Potential Effect of a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy

    DEFF Research Database (Denmark)

    Haahr, Martha Kirstine; Jensen, Charlotte Harken; Toyserkani, Navid Mohamadpour

    2016-01-01

    and this condition presents an unmet medical need. Preclinical studies using adipose-derived stem cells to treat ED have shown promising results. Herein, we report the results of a human phase 1 trial with autologous adipose-derived regenerative cells (ADRCs) freshly isolated after a liposuction. METHODS: Seventeen...... men suffering from post RP ED, with no recovery using conventional therapy, were enrolled in a prospective phase 1 open-label and single-arm study. All subjects had RP performed 5-18 months before enrolment, and were followed for 6 months after intracavernosal transplantation. ADRCs were analyzed...... for the presence of stem cell surface markers, viability and ability to differentiate. Primary endpoint was the safety and tolerance of the cell therapy while the secondary outcome was improvement of erectile function. Any adverse events were reported and erectile function was assessed by IIEF-5 scores. The study...

  8. Specific enhancement of vascular endothelial growth factor (VEGF) production in ischemic region by alprostadil--potential therapeutic application in pharmaceutical regenerative medicine.

    Science.gov (United States)

    Inoue, Hajime; Aihara, Masaki; Tomioka, Miyuki; Watabe, Yu-ichi

    2013-01-01

    Alprostadil (lipo-PGE1) is a drug delivery system preparation. This preparation is applied to treat refractory skin ulcers and arteriosclerosis obliterans. We investigated the effects of alprostadil by using the earflap ischemic model. The following results were obtained: 1) Treatment with alprostadil significantly increased the VEGF contents in an ischemic ear; 2) Treatment with alprostadil resulted in strongly expressed VEGF levels only in the ischemic region; 3) Image analysis revealed a significant increase in the number of vessel bypasses and paths after flap creation with alprostadil administration compared to the vehicle-treated ears. The results suggest that it may be possible to apply alprostadil as one device for regenerative medical technology.

  9. Emdogain in regenerative periodontal therapy. A review of the literature.

    NARCIS (Netherlands)

    Sculean, A.; Windisch, P.; Dori, F.; Keglevich, T.; Molnar, B.; Gera, I.

    2007-01-01

    The goal of regenerative periodontal therapy is the reconstitution of the lost periodontal structures (i.e. the new formation of root cementum, periodontal ligament and alveolar bone). Results from basic research have pointed to the important role of the enamel matrix protein derivative (EMD) in the

  10. Regenerative Periodontal Therapy: History and Prospects

    Directory of Open Access Journals (Sweden)

    Arasay Calzada Bandomo

    2013-10-01

    Full Text Available Within the field of tissue engineering, in the area of periodontics, the use of matrices for guiding tissue proliferation has included the guided tissue regeneration procedures, which aims at new bone, cementum and desmodontium formation. The present literature review was conducted in order to provide a general and updated overview on the use of these procedures in periodontal therapy. It was concluded that guided tissue regeneration improve the periodontal therapeutic spectrum; that scientific literature supports its choice and, specially the use of membranes to facilitate the regenerative processes of the anomalies caused by periodontal disease and its sequelae.

  11. Crosstalk between bone niche and immune system: osteoimmunology signaling as a potential target for cancer treatment.

    Science.gov (United States)

    Criscitiello, Carmen; Viale, Giulia; Gelao, Lucia; Esposito, Angela; De Laurentiis, Michele; De Placido, Sabino; Santangelo, Michele; Goldhirsch, Aron; Curigliano, Giuseppe

    2015-02-01

    There is a well recognized link between the bone and the immune system and in recent years there has been a major effort to elucidate the multiple functions of the molecules expressed in both bone and immune cells. Several molecules that were initially identified and studied in the immune system have been shown to have essential functions also in the bone. An interdisciplinary field embracing immune and bone biology has been brought together and called "osteoimmunology". The co-regulation of the skeletal and immune systems strikingly exemplifies the extreme complexity of such an interaction. Their interdependency must be considered in designing therapeutic approaches for either of the two systems. In other words, it is necessary to think of the osteoimmune system as a complex physiological unit. Denosumab was originally introduced to specifically target bone resorption, but it is now under evaluation for its effect on the long term immune response. Similarly, our current and still growing knowledge of the intimate link between the immune system and bone will be beneficial for the safety of drugs targeting either of these integrated systems. Given the large number of molecules exerting functions on both the skeletal and immune systems, osteoimmunological understanding is becoming increasingly important. Both bone and immune systems are frequently disrupted in cancer; and they may be crucial in regulating tumor growth and progression. Some therapies - such as bisphosphonates and receptor activator of NF-κB ligand (RANKL) targeted drugs - that aim at reducing pathologic osteolysis in cancer may interact with the immune system, thus providing potential favorable effects on survival.

  12. Potential synergistic implications for stromal-targeted radiopharmaceuticals in bone-metastatic prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Oliver Sartor

    2011-01-01

    Genetic heterogeneity and chemotherapy-resistant 'stem cells' represent two of the most pressing issues in devising new strategies for the treatment of advanced prostate cancer. Though curative strategies have long been present for men with localized disease, metastatic prostate cancer is currently incurable. Though substantial improvements in outcomes are now possible through the utilization of newly approved therapies, novel combinations are clearly needed. Herein we describe potentially synergistic interactions between bone stromal-targeted radiopharmaceuticals and other therapies for treatment of bone-metastatic prostate cancer. Radiation has long been known to synergize with cytotoxic chemotherapies and recent data also suggest the possibility of synergy when combining radiation and immune-based strategies. Combination therapies will be required to substantially improve survival for men with castrate-resistant metastatic prostate cancer and we hypothesize that bone-targeted radiopharmaceuticals will play an important role in this process.

  13. Applications of regenerative medicine in organ transplantation

    Science.gov (United States)

    Jain, Aditya; Bansal, Ramta

    2015-01-01

    A worldwide shortage of organs for clinical implantation establishes the need to bring forward and test new technologies that will help in solving the problem. The concepts of regenerative medicine hold the potential for augmenting organ function or repairing damaged organ or allowing regeneration of deteriorated organs and tissue. Researchers are exploring possible regenerative medicine applications in organ transplantation so that coming together of the two fields can benefit each other. The present review discusses the strategies that are being implemented to regenerate or bio-engineer human organs for clinical purposes. It also highlights the limitations of the regenerative medicine that needs to be addressed to explore full potential of the field. A web-based research on MEDLINE was done using keywords “regenerative medicine,” “tissue-engineering,” “bio-engineered organs,” “decellularized scaffold” and “three-dimensional printing.” This review screened about 170 articles to get the desired knowledge update. PMID:26229352

  14. Graded porous polyurethane foam: a potential scaffold for oro-maxillary bone regeneration.

    Science.gov (United States)

    Giannitelli, S M; Basoli, F; Mozetic, P; Piva, P; Bartuli, F N; Luciani, F; Arcuri, C; Trombetta, M; Rainer, A; Licoccia, S

    2015-06-01

    Bone tissue engineering applications demand for biomaterials offering a substrate for cell adhesion, migration, and proliferation, while inferring suitable mechanical properties to the construct. In the present study, polyurethane (PU) foams were synthesized to develop a graded porous material-characterized by a dense shell and a porous core-for the treatment of oro-maxillary bone defects. Foam was synthesized via a one-pot reaction starting from a polyisocyanate and a biocompatible polyester diol, using water as a foaming agent. Different foaming conditions were examined, with the aim of creating a dense/porous functional graded material that would perform at the same time as an osteoconductive scaffold for bone defect regeneration and as a membrane-barrier to gingival tissue ingrowth. The obtained PU was characterized in terms of morphological and mechanical properties. Biocompatibility assessment was performed in combination with bone-marrow-derived human mesenchymal stromal cells (hBMSCs). Our findings confirm that the material is potentially suitable for guided bone regeneration applications.

  15. Potential of mesenchymal stem cells by adenovirus-mediated erythropoietin gene therapy approaches for bone defect.

    Science.gov (United States)

    Li, Chen; Ding, Jian; Jiang, Liming; Shi, Ce; Ni, Shilei; Jin, Han; Li, Daowei; Sun, Hongchen

    2014-11-01

    Regeneration of large bone defects is a common clinical problem. Recent studies have shown that mesenchymal stem cells (MSCs) have emerged as a promising alternative to traditional surgical techniques. However, it is still a key question how to enhance the osteogenic potential of MSCs for possible clinical trials. The aim of the present study was to investigate the effect of adenovirus-mediated erythropoietin (Ad-EPO) transfer on BMSCs, we performed extensive in vitro/in vivo assays in this study. Flow cytometry analysis and the result of MTT showed that EPO could promote BMSCs proliferation. QPCR data demonstrated that EPO increased expressions of Runx2, Sp7, and Col1 in osteoblast at various time points and also increased alkaline phosphatase activity and the calcium deposition. These results indicate that EPO can increase the differentiation of osteoblast. Importantly, in vivo assays clearly demonstrate that EPO can efficiently induce new bone formation in the bone defect model. Our results strongly suggest that EPO can affect osteoblast differentiation and play important roles in bone regeneration leading to an increase in bone formation.

  16. BMI and BMD: The Potential Interplay between Obesity and Bone Fragility

    Directory of Open Access Journals (Sweden)

    Andrea Palermo

    2016-05-01

    Full Text Available Recent evidence demonstrating an increased fracture risk among obese individuals suggests that adipose tissue may negatively impact bone health, challenging the traditional paradigm of fat mass playing a protective role towards bone health. White adipose tissue, far from being a mere energy depot, is a dynamic tissue actively implicated in metabolic reactions, and in fact secretes several hormones called adipokines and inflammatory factors that may in turn promote bone resorption. More specifically, Visceral Adipose Tissue (VAT may potentially prove detrimental. It is widely acknowledged that obesity is positively associated to many chronic disorders such as metabolic syndrome, dyslipidemia and type 2 diabetes, conditions that could themselves affect bone health. Although aging is largely known to decrease bone strength, little is yet known on the mechanisms via which obesity and its comorbidities may contribute to such damage. Given the exponentially growing obesity rate in recent years and the increased life expectancy of western countries it appears of utmost importance to timely focus on this topic.

  17. BMI and BMD: The Potential Interplay between Obesity and Bone Fragility.

    Science.gov (United States)

    Palermo, Andrea; Tuccinardi, Dario; Defeudis, Giuseppe; Watanabe, Mikiko; D'Onofrio, Luca; Lauria Pantano, Angelo; Napoli, Nicola; Pozzilli, Paolo; Manfrini, Silvia

    2016-05-28

    Recent evidence demonstrating an increased fracture risk among obese individuals suggests that adipose tissue may negatively impact bone health, challenging the traditional paradigm of fat mass playing a protective role towards bone health. White adipose tissue, far from being a mere energy depot, is a dynamic tissue actively implicated in metabolic reactions, and in fact secretes several hormones called adipokines and inflammatory factors that may in turn promote bone resorption. More specifically, Visceral Adipose Tissue (VAT) may potentially prove detrimental. It is widely acknowledged that obesity is positively associated to many chronic disorders such as metabolic syndrome, dyslipidemia and type 2 diabetes, conditions that could themselves affect bone health. Although aging is largely known to decrease bone strength, little is yet known on the mechanisms via which obesity and its comorbidities may contribute to such damage. Given the exponentially growing obesity rate in recent years and the increased life expectancy of western countries it appears of utmost importance to timely focus on this topic.

  18. Dialkyl bisphosphonate platinum(II) complex as a potential drug for metastatic bone tumor.

    Science.gov (United States)

    Nakatake, Hidetoshi; Ekimoto, Hisao; Aso, Mariko; Ogawa, Atsushi; Yamaguchi, Asami; Suemune, Hiroshi

    2011-01-01

    Bisphosphonates have high affinity for hydroxyapatite (HA), which is abundantly present in bone. Also, platinum complexes are known that have a wide spectrum of antitumor activities. The conjugate of bisphosphonate and a platinum complex might have HA affinity and antitumor activity, and become a drug for metastatic bone tumor. In this study, the authors synthesized platinum complexes that had dialkyl bisphosphonic acid as a ligand, and evaluated the possibility of the synthesized complexes as a drug for metastatic bone tumor. The synthesized dialkyl bisphosphonate platinum(II) complex was characterized, and its stability in an aqueous solution was also confirmed. The synthesized platinum complex showed higher HA affinity than other platinum complexes such as cisplatin and carboplatin in an experiment of adsorption to HA. In vitro, the platinum complex showed tumor growth inhibitory effect stronger than or equal to cisplatin, which is the most commonly used antitumor agent. Moreover, the platinum complex showed a bone absorption inhibitory effect on the osteoclast. These results suggest potential of dialkyl bisphosphonate platinum(II) complexes as a drug for metastatic bone tumor.

  19. Regenerative Medicine for Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Dong-Hyuk Park

    2010-01-01

    Full Text Available The annual meeting of the American Society for Neural Therapy and Repair (ASNTR has always introduced us to top-notch and up-to-date approaches for regenerative medicine related to neuroscience, ranging from stem cell–based therapy to novel drugs. The 16th ASNTR meeting focused on a variety of different topics, including the unknown pathogenesis or mechanisms of specific neurodegenerative diseases, stem cell biology, and development of novel alternative medicines or devices. Newly developed stem cells, such as amniotic epithelial stem cells and induced pluripotent stem cells, as well as well-known traditional stem cells, such as neural, embryonic, bone marrow mesenchymal, and human umbilical cord blood–derived stem cells, were reported. A number of commercialized stem cells were also covered at this meeting. Fetal neural tissues, such as ventral mesencephalon, striatum, and Schwann cells, were investigated for neurodegenerative diseases or spinal cord injury. A number of studies focused on novel methods for drug monitoring or graft tracking, and combination therapy with stem cells and medicine, such as cytokines or trophic factors. Finally, the National Institutes of Health guidelines for human stem cell research, clinical trials of commercialized stem cells without larger animal testing, and prohibition of medical tourism were big controversial issues that led to heated discussion.

  20. Regenerative Medicine Build-Out

    OpenAIRE

    Terzic, Andre; Pfenning, Michael A.; Gregory J Gores; Harper, C. Michel

    2015-01-01

    Summary Regenerative technologies strive to boost innate repair processes and restitute normative impact. Deployment of regenerative principles into practice is poised to usher in a new era in health care, driving radical innovation in patient management to address the needs of an aging population challenged by escalating chronic diseases. There is urgency to design, execute, and validate viable paradigms for translating and implementing the science of regenerative medicine into tangible heal...

  1. Sclerostin antibody stimulates bone regeneration after experimental periodontitis.

    Science.gov (United States)

    Taut, Andrei D; Jin, Qiming; Chung, Jong-Hyuk; Galindo-Moreno, Pablo; Yi, Erica S; Sugai, James V; Ke, Hua Z; Liu, Min; Giannobile, William V

    2013-11-01

    The reconstruction of large osseous defects due to periodontitis is a challenge in regenerative therapy. Sclerostin, secreted by osteocytes, is a key physiological inhibitor of osteogenesis. Pharmacologic inhibition of sclerostin using sclerostin-neutralizing monoclonal antibody (Scl-Ab) thus increases bone formation, bone mass and bone strength in models of osteopenia and fracture repair. This study assessed the therapeutic potential of Scl-Ab to stimulate alveolar bone regeneration following experimental periodontitis (EP). Ligature-induced EP was induced in rats to generate localized alveolar bone defects. Following 4 weeks of disease induction, Scl-Ab (+EP) or vehicle (+/- EP) were systemically delivered, twice weekly for up to 6 wks to determine the ability of Scl-Ab to regenerate bone around tooth-supporting osseous defects. 3 and 6 wks after the initiation of Scl-Ab or vehicle treatment, femur and maxillary jawbones were harvested for histology, histomorphometry, and micro-computed tomography (micro-CT) of linear alveolar bone loss (ABL) and volumetric measures of bone support, including bone volume fraction (BVF) and tissue mineral density (TMD). Serum was analyzed to examine bone turnover markers during disease and regenerative therapy. Vehicle + EP animals exhibited maxillary bone loss (BVF, TMD and ABL) at ligature removal and thereafter. 6 weeks of Scl-Ab significantly improved maxillary bone healing, as measured by BVF, TMD and ABL, when compared to vehicle + EP. After 6 weeks of treatment, BVF and TMD values in the Scl-Ab + EP group were similar to those of healthy controls. Serum analysis demonstrated higher levels of bone formation markers osteocalcin and PINP in Scl-Ab treatment groups. Scl-Ab restored alveolar bone mass following experimental periodontitis. These findings warrant further exploration of Scl-Ab therapy in this and other oral bone defect disease scenarios.

  2. Center for Neuroscience & Regenerative Medicine

    Data.gov (United States)

    Federal Laboratory Consortium — The Center for Neuroscience and Regenerative Medicine (CNRM) was established as a collaborative intramural federal program involving the U.S. Department of Defense...

  3. Initiation of limb regeneration: the critical steps for regenerative capacity.

    Science.gov (United States)

    Yokoyama, Hitoshi

    2008-01-01

    While urodele amphibians (newts and salamanders) can regenerate limbs as adults, other tetrapods (reptiles, birds and mammals) cannot and just undergo wound healing. In adult mammals such as mice and humans, the wound heals and a scar is formed after injury, while wound healing is completed without scarring in an embryonic mouse. Completion of regeneration and wound healing takes a long time in regenerative and non-regenerative limbs, respectively. However, it is the early steps that are critical for determining the extent of regenerative response after limb amputation, ranging from wound healing with scar formation, scar-free wound healing, hypomorphic limb regeneration to complete limb regeneration. In addition to the accumulation of information on gene expression during limb regeneration, functional analysis of signaling molecules has recently shown important roles of fibroblast growth factor (FGF), Wnt/beta-catenin and bone morphogenic protein (BMP)/Msx signaling. Here, the routine steps of wound healing/limb regeneration and signaling molecules specifically involved in limb regeneration are summarized. Regeneration of embryonic mouse digit tips and anuran amphibian (Xenopus) limbs shows intermediate regenerative responses between the two extremes, those of adult mammals (least regenerative) and urodele amphibians (more regenerative), providing a range of models to study the various abilities of limbs to regenerate.

  4. Regenerative adsorbent heat pump

    Science.gov (United States)

    Jones, Jack A. (Inventor)

    1991-01-01

    A regenerative adsorbent heat pump process and system is provided which can regenerate a high percentage of the sensible heat of the system and at least a portion of the heat of adsorption. A series of at least four compressors containing an adsorbent is provided. A large amount of heat is transferred from compressor to compressor so that heat is regenerated. The process and system are useful for air conditioning rooms, providing room heat in the winter or for hot water heating throughout the year, and, in general, for pumping heat from a lower temperature to a higher temperature.

  5. REGENERATIVE TRANSISTOR AMPLIFIER

    Science.gov (United States)

    Kabell, L.J.

    1958-11-25

    Electrical circults for use in computers and the like are described. particularly a regenerative bistable transistor amplifler which is iurned on by a clock signal when an information signal permits and is turned off by the clock signal. The amplifier porforms the above function with reduced power requirements for the clock signal and circuit operation. The power requirements are reduced in one way by employing transformer coupling which increases the collector circuit efficiency by eliminating the loss of power in the collector load resistor.

  6. Regenerative adsorption distillation system

    KAUST Repository

    Ng, Kim Choon

    2013-12-26

    There is provided a regenerative adsorption distillation system comprising a train of distillation effects in fluid communication with each other. The train of distillation effects comprises at least one intermediate effect between the first and last distillation effects of the train, each effect comprising a vessel and a condensing tube for flow of a fluid therein. The system further comprises a pair of adsorption-desorption beds in vapour communication with the last effect and at least one intermediate effect, wherein the beds contain an adsorbent that adsorbs vapour from the last effect and transmits desorbed vapour into at least one of the intermediate effect.

  7. Murine metapodophalangeal sesamoid bones: morphology and potential means of mineralization underlying function.

    Science.gov (United States)

    Doherty, Alison H; Lowder, Elizabeth M; Jacquet, Robin D; Landis, William J

    2010-05-01

    Normal murine metapodophalangeal sesamoid bones, closely associated with tendons, were examined in terms of their structure and mineralization with reference to their potential function following crystal deposition. This study utilized radiography, whole mount staining, histology, and conventional electron microscopy to establish a maturation timeline of mineral formation in 1- to 6-week-old metapodophalangeal sesamoids from CD-1 mice. An intimate cellular and structural relationship was documented in more detail than previously described between the sesamoid bone, tendon, and fibrocartilage enthesis at the metapodophalangeal joint. Sesamoid calcification began in 1-week lateral sesamoids of the murine metacarpophalangeal joint of the second digit. All sesamoids were completely calcified by 4 weeks. Transmission electron microscopy of 2-week metacarpophalangeal sesamoids revealed extensive Type I collagen in the associated tendon and fibrocartilage insertion sites and Type II collagen and proteoglycan networks in the interior of the sesamoid. No extracellular matrix vesicles were documented. The results demonstrate that murine sesamoid bones consist of cartilage elaborated by chondrocytes that predominantly synthesize and secrete Type II collagen and proteoglycan. Type II collagen and proteoglycans appear responsible for the onset and progression of mineral formation in this tissue. These data contribute to new understanding of the biochemistry, ultrastructure, and mineralization of sesamoids in relation to other bones and calcifying cartilage and tendon of vertebrates. They also reflect on the potentially important but currently uncertain function of sesamoids as serving as a fulcrum point along a tendon, foreshortening its length and altering advantageously its biomechanical properties with respect to tendon-muscle interaction.

  8. In vitro osteoinductive potential of porous monetite for bone tissue engineering.

    Science.gov (United States)

    Idowu, Bernadine; Cama, Giuseppe; Deb, Sanjukta; Di Silvio, Lucy

    2014-01-01

    Tissue engineering-based bone grafts are emerging as a viable alternative treatment modality to repair and regenerate tissues damaged as a result of disease or injury. The choice of the biomaterial component is a critical determinant of the success of the graft or scaffold; essentially, it must induce and allow native tissue integration, and most importantly mimic the hierarchical structure of the native bone. Calcium phosphate bioceramics are widely used in orthopaedics and dentistry applications due to their similarity to bone mineral and their ability to induce a favourable biological response. One such material is monetite, which is biocompatible, osteoconductive and has the ability to be resorbed under physiological conditions. The osteoinductive properties of monetite in vivo are known; however, little is known of the direct effect on osteoinduction of human mesenchymal stem cells in vitro. In this study, we evaluated the potential of monetite to induce and sustain human mesenchymal stem cells towards osteogenic differentiation. Human mesenchymal stem cells were seeded on the monetite scaffold in the absence of differentiating factors for up to 28 days. The gene expression profile of bone-specific markers in cells on monetite scaffold was compared to the control material hydroxyapatite. At day 14, we observed a marked increase in alkaline phosphatase, osteocalcin and osteonectin expressions. This study provides evidence of a suitable material that has potential properties to be used as a tissue engineering scaffold.

  9. In vitro osteoinductive potential of porous monetite for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Bernadine Idowu

    2014-05-01

    Full Text Available Tissue engineering–based bone grafts are emerging as a viable alternative treatment modality to repair and regenerate tissues damaged as a result of disease or injury. The choice of the biomaterial component is a critical determinant of the success of the graft or scaffold; essentially, it must induce and allow native tissue integration, and most importantly mimic the hierarchical structure of the native bone. Calcium phosphate bioceramics are widely used in orthopaedics and dentistry applications due to their similarity to bone mineral and their ability to induce a favourable biological response. One such material is monetite, which is biocompatible, osteoconductive and has the ability to be resorbed under physiological conditions. The osteoinductive properties of monetite in vivo are known; however, little is known of the direct effect on osteoinduction of human mesenchymal stem cells in vitro. In this study, we evaluated the potential of monetite to induce and sustain human mesenchymal stem cells towards osteogenic differentiation. Human mesenchymal stem cells were seeded on the monetite scaffold in the absence of differentiating factors for up to 28 days. The gene expression profile of bone-specific markers in cells on monetite scaffold was compared to the control material hydroxyapatite. At day 14, we observed a marked increase in alkaline phosphatase, osteocalcin and osteonectin expressions. This study provides evidence of a suitable material that has potential properties to be used as a tissue engineering scaffold.

  10. Nature's Electric Potential: A Systematic Review of the Role of Bioelectricity in Wound Healing and Regenerative Processes in Animals, Humans, and Plants

    Directory of Open Access Journals (Sweden)

    Sheena E. B. Tyler

    2017-09-01

    Full Text Available Natural endogenous voltage gradients not only predict and correlate with growth and development but also drive wound healing and regeneration processes. This review summarizes the existing literature for the nature, sources, and transmission of information-bearing bioelectric signals involved in controlling wound healing and regeneration in animals, humans, and plants. It emerges that some bioelectric characteristics occur ubiquitously in a range of animal and plant species. However, the limits of similarities are probed to give a realistic assessment of future areas to be explored. Major gaps remain in our knowledge of the mechanistic basis for these processes, on which regenerative therapies ultimately depend. In relation to this, it is concluded that the mapping of voltage patterns and the processes generating them is a promising future research focus, to probe three aspects: the role of wound/regeneration currents in relation to morphology; the role of endogenous flux changes in driving wound healing and regeneration; and the mapping of patterns in organisms of extreme longevity, in contrast with the aberrant voltage patterns underlying impaired healing, to inform interventions aimed at restoring them.

  11. Nanostructured polymeric scaffolds for orthopaedic regenerative engineering.

    Science.gov (United States)

    Deng, Meng; James, Roshan; Laurencin, Cato T; Kumbar, Sangamesh G

    2012-03-01

    Successful regeneration necessitates the development of three-dimensional (3-D) tissue-inducing scaffolds that mimic the hierarchical architecture of native tissue extracellular matrix (ECM). Cells in nature recognize and interact with the surface topography they are exposed to via ECM proteins. The interaction of cells with nanotopographical features such as pores, ridges, groves, fibers, nodes, and their combinations has proven to be an important signaling modality in controlling cellular processes. Integrating nanotopographical cues is especially important in engineering complex tissues that have multiple cell types and require precisely defined cell-cell and cell-matrix interactions on the nanoscale. Thus, in a regenerative engineering approach, nanoscale materials/scaffolds play a paramount role in controlling cell fate and the consequent regenerative capacity. Advances in nanotechnology have generated a new toolbox for the fabrication of tissue-specific nanostructured scaffolds. For example, biodegradable polymers such as polyesters, polyphosphazenes, polymer blends and composites can be electrospun into ECM-mimicking matrices composed of nanofibers, which provide high surface area for cell attachment, growth, and differentiation. This review provides the fundamental guidelines for the design and development of nanostructured scaffolds for the regeneration of various tissue types in human upper and lower extremities such as skin, ligament, tendon, and bone. Examples focusing on the collective work of our laboratory in those areas are discussed to demonstrate the regenerative efficacy of this approach. Furthermore, preliminary strategies and significant challenges to integrate these individual tissues into one complex organ through regenerative engineering-based integrated graft systems are also discussed.

  12. Regenerative Medicine Build-Out.

    Science.gov (United States)

    Terzic, Andre; Pfenning, Michael A; Gores, Gregory J; Harper, C Michel

    2015-12-01

    Regenerative technologies strive to boost innate repair processes and restitute normative impact. Deployment of regenerative principles into practice is poised to usher in a new era in health care, driving radical innovation in patient management to address the needs of an aging population challenged by escalating chronic diseases. There is urgency to design, execute, and validate viable paradigms for translating and implementing the science of regenerative medicine into tangible health benefits that provide value to stakeholders. A regenerative medicine model of care would entail scalable production and standardized application of clinical grade biotherapies supported by comprehensive supply chain capabilities that integrate sourcing and manufacturing with care delivery. Mayo Clinic has rolled out a blueprint for discovery, translation, and application of regenerative medicine therapies for accelerated adoption into the standard of care. To establish regenerative medical and surgical service lines, the Mayo Clinic model incorporates patient access, enabling platforms and delivery. Access is coordinated through a designated portal, the Regenerative Medicine Consult Service, serving to facilitate patient/provider education, procurement of biomaterials, referral to specialty services, and/or regenerative interventions, often in clinical trials. Platforms include the Regenerative Medicine Biotrust and Good Manufacturing Practice facilities for manufacture of clinical grade products for cell-based, acellular, and/or biomaterial applications. Care delivery leverages dedicated interventional suites for provision of regenerative services. Performance is tracked using a scorecard system to inform decision making. The Mayo Clinic roadmap exemplifies an integrated organization in the discovery, development, and delivery of regenerative medicine within a growing community of practice at the core of modern health care. Regenerative medicine is at the vanguard of health care

  13. Regenerative Medicine Build-Out

    Science.gov (United States)

    Pfenning, Michael A.; Gores, Gregory J.; Harper, C. Michel

    2015-01-01

    Summary Regenerative technologies strive to boost innate repair processes and restitute normative impact. Deployment of regenerative principles into practice is poised to usher in a new era in health care, driving radical innovation in patient management to address the needs of an aging population challenged by escalating chronic diseases. There is urgency to design, execute, and validate viable paradigms for translating and implementing the science of regenerative medicine into tangible health benefits that provide value to stakeholders. A regenerative medicine model of care would entail scalable production and standardized application of clinical grade biotherapies supported by comprehensive supply chain capabilities that integrate sourcing and manufacturing with care delivery. Mayo Clinic has rolled out a blueprint for discovery, translation, and application of regenerative medicine therapies for accelerated adoption into the standard of care. To establish regenerative medical and surgical service lines, the Mayo Clinic model incorporates patient access, enabling platforms and delivery. Access is coordinated through a designated portal, the Regenerative Medicine Consult Service, serving to facilitate patient/provider education, procurement of biomaterials, referral to specialty services, and/or regenerative interventions, often in clinical trials. Platforms include the Regenerative Medicine Biotrust and Good Manufacturing Practice facilities for manufacture of clinical grade products for cell-based, acellular, and/or biomaterial applications. Care delivery leverages dedicated interventional suites for provision of regenerative services. Performance is tracked using a scorecard system to inform decision making. The Mayo Clinic roadmap exemplifies an integrated organization in the discovery, development, and delivery of regenerative medicine within a growing community of practice at the core of modern health care. Significance Regenerative medicine is at the

  14. Esophagus and regenerative medicine

    Institute of Scientific and Technical Information of China (English)

    Ricardo Londono; Blair A Jobe; Toshitaka Hoppo; Stephen F Badylak

    2012-01-01

    In addition to squamous cell carcinoma,the incidence of Barrett's esophagus with high-grade dysplasia and esophageal adenocarcinoma is rapidly increasing worldwide.Unfortunately,the current standard of care for esophageal pathology involves resection of the affected tissue,sometimes involving radical esophagectomy.Without exception,these procedures are associated with a high morbidity,compromised quality of life,and unacceptable mortality rates.Regenerative medicine approaches to functional tissue replacement include the use of biological and synthetic scaffolds to promote tissue remodeling and growth.In the case of esophageal repair,extracellular matrix (ECM) scaffolds have proven to be effective for the reconstruction of small patch defects,anastomosis reinforcement,and the prevention of stricture formation after endomucosal resection (EMR).More so,esophageal cancer patients treated with ECM scaffolds have shown complete restoration of a normal,functional,and disease-free epithelium after EMR.These studies provide evidence that a regenerative medicine approach may enable aggressive resection of neoplastic tissue without the need for radical esophagectomy and its associated complications.

  15. Morphological and mechanical characterization of chitosan-calcium phosphate composites for potential application as bone-graft substitutes

    Directory of Open Access Journals (Sweden)

    Guilherme Maia Mulder van de Graaf

    Full Text Available Introduction: Bone diseases, aging and traumas can cause bone loss and lead to bone defects. Treatment of bone defects is challenging, requiring chirurgical procedures. Bone grafts are widely used for bone replacement, but they are limited and expensive. Due to bone graft limitations, natural, semi-synthetic, synthetic and composite materials have been studied as potential bone-graft substitutes. Desirable characteristics of bone-graft substitutes are high osteoinductive and angiogenic potentials, biological safety, biodegradability, bone-like mechanical properties, and reasonable cost. Herein, we prepared and characterized potential bone-graft substitutes composed of calcium phosphate (CP - a component of natural bone, and chitosan (CS - a biocompatible biopolymer. Methods CP-CS composites were synthetized, molded, dried and characterized. The effect of drying temperatures (38 and 60 °C on the morphology, porosity and chemical composition of the composites was evaluated. As well, the effects of drying temperature and period of drying (3, 24, 48 and 72 hours on the mechanical properties - compressive strength, modulus of elasticity and relative deformation-of the demolded samples were investigated. Results Scanning electron microscopy and gas adsorption-desorption analyses of the CS-CP composites showed interconnected pores, indicating that the drying temperature played an important role on pores size and distribution. In addition, drying temperature have altered the color (brownish at 60 °C due to Maillard reaction and the chemical composition of the samples, confirmed by FTIR. Conclusion Particularly, prolonged period of drying have improved mechanical properties of the CS-CP composites dried at 38 °C, which can be designed according to the mechanical needs of the replaceable bone.

  16. MRI tracking of SPIO labelled stem cells in a true regenerative environment, the regenerating limb of the axolotl

    DEFF Research Database (Denmark)

    Lauridsen, Henrik; Foldager, Casper Bindzus; Hagensen, Mette

    are generally restricted by their limited regenerative potential. Conversely, excellent animal models for regenerative studies exist in lower vertebrates such as the urodele amphibians (salamanders and newts), exemplified in the iconic Mexican axolotl (Ambystoma mexicanum) capable of regenerating whole limbs...

  17. Aarhus Regenerative Orthopaedics Symposium (AROS)

    DEFF Research Database (Denmark)

    Foldager, Casper B.; Bendtsen, Michael; Berg, Lise C.

    2016-01-01

    to musculoskeletal pain and disability. The Aarhus Regenerative Orthopaedics Symposium (AROS) 2015 was motivated by the need to address regenerative challenges in an ageing population by engaging clinicians, basic scientists, and engineers. In this position paper, we review our contemporary understanding of societal...

  18. Low-intensity pulsed ultrasound therapy: a potential strategy to stimulate tendon-bone junction healing

    Institute of Scientific and Technical Information of China (English)

    Zhi-min YING; Tiao LIN; Shi-gui YAN

    2012-01-01

    Incorporation of a tendon graft within the bone tunnel represents a challenging clinical problem.Successful anterior cruciate ligament (ACL) reconstruction requires solid healing of the tendon graft in the bone tunnel.Enhancement of graft healing to bone is important to facilitate early aggressive rehabilitation and a rapid return to pre-injury activity levels.No convenient,effective or inexpensive procedures exist to enhance tendon-bone (T-B) healing after surgery.Low-intensity pulsed ultrasound (LIPUS) improves local blood perfusion and angiogenesis,stimulates cartilage maturation,enhances differentiation and proliferation of osteoblasts,and motivates osteogenic differentiation of mesenchymal stem cells (MSCs),and therefore,appears to be a potential non-invasive tool for T-B healing in early stage of rehabilitation of ACL reconstruction.It is conceivable that LIPUS could be used to stimulate T-B tunnel healing in the home,with the aim of accelerating rehabilitation and an earlier return to normal activities in the near future.The purpose of this review is to demonstrate how LIPUS stimulates T-B healing at the cellular and molecular levels,describe studies in animal models,and provide a future direction for research.

  19. Potential uses of bone scintiscanning in the maxillofacial region. Moeglichkeiten der Knochenszintigraphie im Kiefer-Gesichtsbereich

    Energy Technology Data Exchange (ETDEWEB)

    Goebel, V.

    1985-05-15

    Bone scintigrams obtained from a large cohort of patients were first divided into wholebody and cranial recordings and subsequently contrasted with X-ray findings in order to gain data on their diagnostic value and scope of potential uses. In the fields of odontology and orthodontology the scintigrams provided additional information that helped to elucidate doubtful radiological results in osteomyelitis, primary and metastic tumours, in supposed skeletal diseases by confirming or disproving any incipient pathological changes, in disturbed bone metabolism, fractures, osteotomy, osteosynthesis, bone chip grafts and during follow-up observations of the therapeutic strategy and healing success. One important use of skeletal scintiscans is the in assessment of metaplastic bone processes at an early stage and the procurement of a reliable and sensitive overall picture. The risks from radiation are kept to a minimum and no greater than those associated with X-rays taken to diagnose neoplastic changes. A combination of both methods will mostly lead to the best results and the order in which they are used should be determined by the condition of the patient, the urgency of the examination and the extent of the health risks involved. (TRV).

  20. Active Magnetic Regenerative Liquefier

    Energy Technology Data Exchange (ETDEWEB)

    Barclay, John A. [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Oseen-Send, Kathryn [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Ferguson, Luke [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Pouresfandiary, Jamshid [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Cousins, Anand [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Ralph, Heather [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Hampto, Tom [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States)

    2016-01-12

    This final report for the DOE Project entitled Active Magnetic Regenerative Liquefier (AMRL) funded under Grant DE-FG36-08GO18064 to Heracles Energy Corporation d.b.a. Prometheus Energy (Heracles/Prometheus) describes an active magnetic regenerative refrigerator (AMRR) prototype designed and built during the period from July 2008 through May 2011. The primary goal of this project was to make significant technical advances toward highly efficient liquefaction of hydrogen. Conventional hydrogen liquefiers at any scale have a maximum FOM of ~0.35 due primarily to the intrinsic difficulty of rapid, efficient compression of either hydrogen or helium working gases. Numerical simulation modeling of high performance AMRL designs indicates certain designs have promise to increase thermodynamic efficiency from a FOM of ~0.35 toward ~0.5 to ~0.6. The technical approach was the use of solid magnetic working refrigerants cycled in and out of high magnetic fields to build an efficient active regenerative magnetic refrigeration module providing cooling power for AMRL. A single-stage reciprocating AMRR with a design temperature span from ~290 K to ~120 K was built and tested with dual magnetic regenerators moving in and out of the conductively-cooled superconducting magnet subsystem. The heat transfer fluid (helium) was coupled to the process stream (refrigeration/liquefaction load) via high performance heat exchangers. In order to maximize AMRR efficiency a helium bypass loop with adjustable flow was incorporated in the design because the thermal mass of magnetic refrigerants is higher in low magnetic field than in high magnetic field. Heracles/Prometheus designed experiments to measure AMRR performance under a variety of different operational parameters such as cycle frequency, magnetic field strength, heat transfer fluid flow rate, amount of bypass flow of the heat transfer fluid while measuring work input, temperature span, cooling capability as a function of cold temperature

  1. Regenerative cells for transplantation in hepatic failure.

    Science.gov (United States)

    Ishikawa, Tetsuya; Banas, Agnieszka; Teratani, Takumi; Iwaguro, Hideki; Ochiya, Takahiro

    2012-01-01

    Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have an enormous potential; however, their potential clinical application is being arrested due to various limitations such as teratoma formation followed by tumorigenesis, emergent usage, and the quality control of cells, as well as safety issues regarding long-term culture are also delaying their clinical application. In addition, human ES cells have two crucial issues: immunogenicity and ethical issues associated with their clinical application. The efficient generation of human iPS cells requires gene transfer, yet the mechanism underlying pluripotent stem cell induction has not yet been fully elucidated. Otherwise, although human adult regenerative cells including mesenchymal stem cells have a limited capacity for differentiation, they are nevertheless promising candidates for tissue regeneration in a clinical setting. This review highlights the use of regenerative cells for transplantation in hepatic failure.

  2. Endometrial stem cells in regenerative medicine.

    Science.gov (United States)

    Verdi, Javad; Tan, Aaron; Shoae-Hassani, Alireza; Seifalian, Alexander M

    2014-01-01

    First described in 2004, endometrial stem cells (EnSCs) are adult stem cells isolated from the endometrial tissue. EnSCs comprise of a population of epithelial stem cells, mesenchymal stem cells, and side population stem cells. When secreted in the menstrual blood, they are termed menstrual stem cells or endometrial regenerative cells. Mounting evidence suggests that EnSCs can be utilized in regenerative medicine. EnSCs can be used as immuno-modulatory agents to attenuate inflammation, are implicated in angiogenesis and vascularization during tissue regeneration, and can also be reprogrammed into induced pluripotent stem cells. Furthermore, EnSCs can be used in tissue engineering applications and there are several clinical trials currently in place to ascertain the therapeutic potential of EnSCs. This review highlights the progress made in EnSC research, describing their mesodermal, ectodermal, and endodermal potentials both in vitro and in vivo.

  3. Osteogenic potential of icariin compared with recombinant human bone morphogenetic protein 2 in vitro: a preliminary study

    NARCIS (Netherlands)

    Zhang, X.; Liu, T.; Huang, Y.; Zheng, Y.; Liu, T.; Wismeijer, D.; Liu, Y.

    2015-01-01

    Icariin, the primary active ingredient of Herba Epimedii which has been used for decades to treat bone related maladies in China, has the ability to support bone regeneration. In this study, we investigated icariin's potential to stimulate osteogenesis using an in vitro studies to compare icariin's

  4. Regenerative strategies for the treatment of knee joint disabilities

    CERN Document Server

    Reis, Rui

    2017-01-01

    This book presents regenerative strategies for the treatment of knee joint disabilities. The book is composed of four main sections totaling 19 chapters which review the current knowledge on the clinical management and preclinical regenerative strategies. It examines the role of different natural-based biomaterials as scaffolds and implants for addressing different tissue lesions in the knee joint. Section one provides an updated and comprehensive discussion on articular cartilage tissue regeneration. Section two focuses on the important contributions for bone and osteochondral tissue engineering. Section three overview the recent advances on meniscus repair/regeneration strategies. Finally, section four further discusses the current strategies for treatment of ligament lesions. Each chapter is prepared by world know expert on their fields, so we do firmly believe that the proposed book will be a reference in the area of biomaterials for regenerative medicine.

  5. [The prospects for the development of regenerative physical therapy].

    Science.gov (United States)

    Konchugova, T V; Bobrovnitskiĭ, I P; Orekhova, É M; Puzyreva, G A

    2014-01-01

    The review is concerned with the investigations into the influence of physiotherapeutic factors on the regeneration of the muscular, nervous, bone, and epidermal tissues; also, it analyses the publications pertaining to the influence of low-intensive physiotherapeutic modalities on the migration rate, proliferative activity, and differentiation of stem cells as well as physiological stability and viability of these cells following their transplantation. The currently available data give evidence of the possibility in principle of the combined application of physiotherapeutic factors and cellular technologies in regenerative medicine and the prospects opening for the development of the new direction of research in modern biomedicine, namely regenerative physical therapy. The importance of interdisciplinary basic and clinical investigations in this direction becomes especially evident in the light of the recent achievements and rapid progress in the development of modern regenerative medicine.

  6. Potential Use of Bacterial Community Succession in Decaying Human Bone for Estimating Postmortem Interval.

    Science.gov (United States)

    Damann, Franklin E; Williams, Daniel E; Layton, Alice C

    2015-07-01

    Bacteria are taphonomic agents of human decomposition, potentially useful for estimating postmortem interval (PMI) in late-stage decomposition. Bone samples from 12 individuals and three soil samples were analyzed to assess the effects of decomposition and advancing time on bacterial communities. Results indicated that partially skeletonized remains maintained a presence of bacteria associated with the human gut, whereas bacterial composition of dry skeletal remains maintained a community profile similar to soil communities. Variation in the UniFrac distances was significantly greater between groups than within groups (p < 0.001) for the unweighted metric and not the weighted metric. The members of the bacterial communities were more similar within than between decomposition stages. The oligotrophic environment of bone relative to soft tissue and the physical protection of organic substrates may preclude bacterial blooms during the first years of skeletonization. Therefore, community membership (unweighted) may be better for estimating PMI from skeletonized remains than community structure (weighted).

  7. Periosteum derived stem cells for regenerative medicine proposals: boosting current knowledge

    Institute of Scientific and Technical Information of China (English)

    Concetta; Ferretti; Monica; Mattioli-Belmonte

    2014-01-01

    Periosteum is a thin fibrous layer that covers most bones. It resides in a dynamic mechanically loaded environment and provides a niche for pluripotent cells and a source for molecular factors that modulate cell behaviour. Elucidating periosteum regenerative poten-tial has become a hot topic in orthopaedics. This review discusses the state of the art of osteochondral tissue engineering rested on periosteum derived progenitor cells(PDPCs) and suggests upcoming research direc-tions. Periosteal cells isolation, characterization and migration in the site of injury, as well as their differen-tiation, are analysed. Moreover, the role of cell mecha-nosensing and its contribution to matrix organization, bone microarchitecture and bone stenght is examined. In this regard the role of periostin and its upregulation under mechanical stress in order to preserve PDPC sur-vival and bone tissue integrity is contemplated. The re-view also summarized the role of the periosteum in the field of dentistry and maxillofacial reconstruction. The involvement of microRNAs in osteoblast differentiation and in endogenous tissue repair is explored as well. Fi-nally the novel concept of a guided bone regenerationbased on the use of periosteum itself as a smart mate-rial and the realization of constructs able to mimic the extracellular matrix features is talked out. Additionally, since periosteum can differentiate into insulin produc-ing cells it could be a suitable source in allogenic trans-plantations. That innovative applications would takeadvantage from investigations aimed to assess PDPCimmune privilege.

  8. The pharmacology of regenerative medicine.

    Science.gov (United States)

    Christ, George J; Saul, Justin M; Furth, Mark E; Andersson, Karl-Erik

    2013-07-01

    Regenerative medicine is a rapidly evolving multidisciplinary, translational research enterprise whose explicit purpose is to advance technologies for the repair and replacement of damaged cells, tissues, and organs. Scientific progress in the field has been steady and expectations for its robust clinical application continue to rise. The major thesis of this review is that the pharmacological sciences will contribute critically to the accelerated translational progress and clinical utility of regenerative medicine technologies. In 2007, we coined the phrase "regenerative pharmacology" to describe the enormous possibilities that could occur at the interface between pharmacology, regenerative medicine, and tissue engineering. The operational definition of regenerative pharmacology is "the application of pharmacological sciences to accelerate, optimize, and characterize (either in vitro or in vivo) the development, maturation, and function of bioengineered and regenerating tissues." As such, regenerative pharmacology seeks to cure disease through restoration of tissue/organ function. This strategy is distinct from standard pharmacotherapy, which is often limited to the amelioration of symptoms. Our goal here is to get pharmacologists more involved in this field of research by exposing them to the tools, opportunities, challenges, and interdisciplinary expertise that will be required to ensure awareness and galvanize involvement. To this end, we illustrate ways in which the pharmacological sciences can drive future innovations in regenerative medicine and tissue engineering and thus help to revolutionize the discovery of curative therapeutics. Hopefully, the broad foundational knowledge provided herein will spark sustained conversations among experts in diverse fields of scientific research to the benefit of all.

  9. Regenerative Therapy for Retinal Disorders

    Directory of Open Access Journals (Sweden)

    Narsis Daftarian

    2010-01-01

    Full Text Available Major advances in various disciplines of basic sciences including embryology, molecular and cell biology, genetics, and nanotechnology, as well as stem cell biology have opened new horizons for regenerative therapy. The unique characteristics of stem cells prompt a sound understanding for their use in modern regenerative therapies. This review article discusses stem cells, developmental stages of the eye field, eye field transcriptional factors, and endogenous and exogenous sources of stem cells. Recent studies and challenges in the application of stem cells for retinal pigment epithelial degeneration models will be summarized followed by obstacles facing regenerative therapy.

  10. Osteogenic potential of bone marrow stromal cells on smooth, roughened, and tricalcium phosphate-modified titanium alloy surfaces.

    LENUS (Irish Health Repository)

    Colombo, John S

    2012-09-01

    This study investigated the influence of smooth, roughened, and tricalcium phosphate (TCP)-coated roughened titanium-aluminum-vanadium (Ti-6Al-4V) surfaces on the osteogenic potential of rat bone marrow stromal cells (BMSCs).

  11. [Progress in stem cells and regenerative medicine].

    Science.gov (United States)

    Wang, Libin; Zhu, He; Hao, Jie; Zhou, Qi

    2015-06-01

    Stem cells have the ability to differentiate into all types of cells in the body and therefore have great application potential in regenerative medicine, in vitro disease modelling and drug screening. In recent years, stem cell technology has made great progress, and induced pluripotent stem cell technology revolutionizes the whole stem cell field. At the same time, stem cell research in our country has also achieved great progress and becomes an indispensable power in the worldwide stem cell research field. This review mainly focuses on the research progress in stem cells and regenerative medicine in our country since the advent of induced pluripotent stem cell technology, including induced pluripotent stem cells, transdifferentiation, haploid stem cells, and new gene editing tools.

  12. Regenerative Endodontics: A Road Less Travelled

    Science.gov (United States)

    Bansal, Ramta; Mittal, Sunandan; Kumar, Tarun; Kaur, Dilpreet

    2014-01-01

    Although traditional approaches like root canal therapy and apexification procedures have been successful in treating diseased or infected root canals, but these modalities fail to re-establish healthy pulp tissue in treated teeth. Regeneration-based approaches aims to offer high levels of success by replacing diseased or necrotic pulp tissues with healthy pulp tissue to revitalize teeth. The applications of regenerative approaches in dental clinics have potential to dramatically improve patients’ quality of life. This review article offers a detailed overview of present regenerative endodontic approaches aiming to revitalize teeth and also outlines the problems to be dealt before this emerging field contributes to clinical treatment protocols. It conjointly covers the basic trilogy elements of tissue engineering. PMID:25478476

  13. Regenerative endodontics: a road less travelled.

    Science.gov (United States)

    Bansal, Ramta; Jain, Aditya; Mittal, Sunandan; Kumar, Tarun; Kaur, Dilpreet

    2014-10-01

    Although traditional approaches like root canal therapy and apexification procedures have been successful in treating diseased or infected root canals, but these modalities fail to re-establish healthy pulp tissue in treated teeth. Regeneration-based approaches aims to offer high levels of success by replacing diseased or necrotic pulp tissues with healthy pulp tissue to revitalize teeth. The applications of regenerative approaches in dental clinics have potential to dramatically improve patients' quality of life. This review article offers a detailed overview of present regenerative endodontic approaches aiming to revitalize teeth and also outlines the problems to be dealt before this emerging field contributes to clinical treatment protocols. It conjointly covers the basic trilogy elements of tissue engineering.

  14. Bimix antimicrobial scaffolds for regenerative endodontics.

    Science.gov (United States)

    Palasuk, Jadesada; Kamocki, Krzysztof; Hippenmeyer, Lauren; Platt, Jeffrey A; Spolnik, Kenneth J; Gregory, Richard L; Bottino, Marco C

    2014-11-01

    Eliminating and/or inhibiting bacterial growth within the root canal system has been shown to play a key role in the regenerative outcome. The aim of this study was to synthesize and determine in vitro both the antimicrobial effectiveness and cytocompatibility of bimix antibiotic-containing polydioxanone-based polymer scaffolds. Antibiotic-containing (metronidazole [MET] and ciprofloxacin [CIP]) polymer solutions (distinct antibiotic weight ratios) were spun into fibers as a potential mimic to the double antibiotic paste (DAP, a MET/CIP mixture). Fiber morphology, chemical characteristics, and tensile strength were evaluated by scanning electron microscopy, Fourier transform infrared spectroscopy, and tensile testing, respectively. Antimicrobial efficacy was tested over time (aliquot collection) against Enterococcus faecalis (Ef), Porphyromonas gingivalis (Pg), and Fusobacterium nucleatum (Fn). Similarly, cytotoxicity was evaluated in human dental pulp stem cells. Data were statistically analyzed (P regenerative endodontics. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  15. Diatomite reinforced chitosan composite membrane as potential scaffold for guided bone regeneration.

    Science.gov (United States)

    Tamburaci, Sedef; Tihminlioglu, Funda

    2017-11-01

    In this study, natural silica source, diatomite, incorporated novel chitosan based composite membranes were fabricated and characterized for bone tissue engineering applications as possible bone regeneration membrane. The effect of diatomite loading on the mechanical, morphological, chemical, thermal and surface properties, wettability and in vitro cytotoxicity and cell proliferation on of composite membranes were investigated and observed by tensile test, atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), protein adsorption assay, air/water contact angle analysis and WST-1 respectively. Swelling studies were also performed by water absorption capacity determination. Results showed that incorporation of diatomite to the chitosan matrix increased the surface roughness, swelling capacity and tensile modulus of membranes. An increase of about 52% in Young's modulus was achieved for 10wt% diatomite composite membranes compared with chitosan membranes. High cell viability results were obtained with indirect extraction method. Besides, in vitro cell proliferation and ALP activity results showed that diatom incorporation significantly increased the ALP activity of Saos-2 cells cultured on chitosan membranes. The novel composite membranes prepared in the present study with tunable properties can be considered as a potential candidate as a scaffold in view of its enhanced physical & chemical properties as well as biological activities for bone tissue engineering applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Combination of hydroxyapatite, platelet rich fibrin and amnion membrane as a novel therapeutic option in regenerative periapical endodontic surgery: Case series.

    Science.gov (United States)

    Uppada, Uday Kiran; Kalakonda, Butchibabu; Koppolu, Pradeep; Varma, Narendra; Palakurthy, Kiran; Manchikanti, Venkatesh; Prasad, Shilpa; Samar, Shereen; Swapna, Lingam Amara

    2017-01-01

    Periapical surgery is the last resort in the arsenal of an endodontist to effectively deal with periapical lesions that result from necrosis of the pulp. Bone grafts, growth factors and membranes form an array of regenerative materials that influence the healing outcome of periapical surgery. The main purpose of the two cases reported here was to assess the potential benefits of a combination of bone graft, platelet-rich fibrin (PRF) and amnion membrane in terms of reduced post-operative discomfort, radiographic evidence of accelerated periapical bone healing and present a novel therapeutic option in the management of large periapical lesions. Two cases of radicular cysts were treated through a combined regenerative approachof Bio-Gen mix(®), PRF and amnion membrane. The patients were assessed for discomfort immediate post-operatively and after a week. The patients were recalled every month for the next 6 months for radiographic assessment of the periapical healing. Literature is replete with articles that have substantiated the role of demineralized bone matrix comprising a mixture of cancellous and cortical bone graft particles in enhancing regeneration. To the best of our knowledge, there has been no evidence related to the application of a human placental membrane in periapical surgery. Hence, the rationale of using a combined approach of Bio-Gen mix(®), PRF and amnion membrane was to combine the individual advantages of these materials to enhance clinical and radiographic healing outcomes. Our present case reports provide an insight into this novel therapeutic option. The results of this case seriessubstantiatesthe credibility of using a combination ofamnion membrane with a bone graft and PRF to enhance radiographic healing outcome with decreased post-operative discomfort and present a viable regenerative treatment modality in periapical surgery. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Inactivation of the Progesterone Receptor in Mx1+ Cells Potentiates Osteogenesis in Calvaria but Not in Long Bone.

    Directory of Open Access Journals (Sweden)

    Zhendong A Zhong

    Full Text Available The effect of progesterone on bone remains elusive. We previously reported that global progesterone receptor (PR knockout mice displayed high bone mass phenotype, suggesting that PR influences bone growth and modeling. Recently, Mx1+ cells were characterized to be mesenchymal stem cell-like pluripotent Cells. The aim of this study was to evaluate whether the PR in Mx1+ cells regulates osteogenesis. Using the Mx1-Cre;mT/mG reporter mouse model, we found that the calvarial cells exhibited minimal background Mx1-Cre activity prior to Cre activation by IFNα treatment as compared to the bone marrow stromal cells. IFNα treatment significantly activated Mx1-Cre in the calvarial cells. When the PR gene was deleted in the Mx1-Cre;PR-flox calvarial cells in vitro, significantly higher levels of expression of osteoblast maturation marker genes (RUNX2, Osteocalcin, and Dmp1 and osteogenic potential were detected. The PR-deficient calvariae exhibited greater bone volume, especially in the males. Although Mx1-Cre activity could be induced on the bone surface in vivo, the Mx1+ cells did not differentiate into osteocytes in long bones. Bone volumes at the distal femurs and the bone turnover marker serum Osteocalcin were similar between the Mx1-Cre;PR-flox mutant mice and the corresponding wild types in both sexes. In conclusion, our data demonstrates that blocking progesterone signaling via PRs in calvarial Mx1+ cells promoted osteoblast differentiation in the calvaria. Mx1+ was expressed by heterogeneous cells in bone marrow and did not differentiate into osteocyte during long bone development in vivo. Selectively inactivating the PR gene in Mx1+ cells affected the membrane bone formation but did not affect peripheral skeletal homeostasis.

  18. Inactivation of the Progesterone Receptor in Mx1+ Cells Potentiates Osteogenesis in Calvaria but Not in Long Bone.

    Science.gov (United States)

    Zhong, Zhendong A; Sun, Weihua; Chen, Haiyan; Zhang, Hongliang; Lane, Nancy E; Yao, Wei

    2015-01-01

    The effect of progesterone on bone remains elusive. We previously reported that global progesterone receptor (PR) knockout mice displayed high bone mass phenotype, suggesting that PR influences bone growth and modeling. Recently, Mx1+ cells were characterized to be mesenchymal stem cell-like pluripotent Cells. The aim of this study was to evaluate whether the PR in Mx1+ cells regulates osteogenesis. Using the Mx1-Cre;mT/mG reporter mouse model, we found that the calvarial cells exhibited minimal background Mx1-Cre activity prior to Cre activation by IFNα treatment as compared to the bone marrow stromal cells. IFNα treatment significantly activated Mx1-Cre in the calvarial cells. When the PR gene was deleted in the Mx1-Cre;PR-flox calvarial cells in vitro, significantly higher levels of expression of osteoblast maturation marker genes (RUNX2, Osteocalcin, and Dmp1) and osteogenic potential were detected. The PR-deficient calvariae exhibited greater bone volume, especially in the males. Although Mx1-Cre activity could be induced on the bone surface in vivo, the Mx1+ cells did not differentiate into osteocytes in long bones. Bone volumes at the distal femurs and the bone turnover marker serum Osteocalcin were similar between the Mx1-Cre;PR-flox mutant mice and the corresponding wild types in both sexes. In conclusion, our data demonstrates that blocking progesterone signaling via PRs in calvarial Mx1+ cells promoted osteoblast differentiation in the calvaria. Mx1+ was expressed by heterogeneous cells in bone marrow and did not differentiate into osteocyte during long bone development in vivo. Selectively inactivating the PR gene in Mx1+ cells affected the membrane bone formation but did not affect peripheral skeletal homeostasis.

  19. Perivascular cells for regenerative medicine

    NARCIS (Netherlands)

    M. Crisan (Mihaela); M. Corselli (Mirko); W.C. Chen (William); B. Péault (Bruno)

    2012-01-01

    textabstractMesenchymal stem/stromal cells (MSC) are currently the best candidate therapeutic cells for regenerative medicine related to osteoarticular, muscular, vascular and inflammatory diseases, although these cells remain heterogeneous and necessitate a better biological characterization. We an

  20. STEM CELLS IN REGENERATIVE ENDODONTICS

    National Research Council Canada - National Science Library

    T Nivethithan; Manish Ranjan

    2017-01-01

    Endodontic treatment is helpful in saving millions of teeth each year, but at present the focus has shifted towards regenerative approaches as an ideal form of therapy to treat diseased or necrotic pulp tissues...

  1. Clastogenic potential of Ruta graveolens extract and a homeopathic preparation in mouse bone marrow cells.

    Science.gov (United States)

    Preethi, Korengath C; Nair, Cherappally K K; Kuttan, Ramadasan

    2008-01-01

    Ruta graveolens belonging to family Rutaceae has long been traditionally used as a medicinal plant as well as a flavoring agent in food. However, very little data are available on the toxicity of the plant. This report presents evidence on the genotoxic and clastogenic potential of an extract of Ruta graveolens and Ruta 200C, a homeopathic preparation. Various types of chromosomal aberrations were noted in bone marrow cells after treatment. The percentage of aberrated cells in the 400mg/kgb.wt extract administered group was found to be 21% and with 1,000 mg/kg.b.wt it was 31%. The value for the Ruta 200C treated group was also elevated to 23% as compared to the 3%for untreated animals. In addition, bone marrow cells had higher incidence of micronuclei induction when treated with the extract (400 mg and 1,000 mg/kg body weight) and Ruta 200C for 30 days. Administration of the extract (1,000 mg/kg.b.wt) over a period of 30 days also resulted in damage to cellular DNA as evidenced by comet formation where the comet parameters such as percentage DNA in tail, tail length, tail moment of the bone marrow cells were increased several fold over control values. The comet tail moment of the bone marrow cells increased from 4.5 to 50.2 after the extract treatment. Administration of Ruta 200C for 5 consecutive days increased the tail moment to 11.7. These results indicate that Ruta graveolens and Ruta 200C may induce genotoxicity in animals.

  2. Antlerogenic stem cells: molecular features and potential in rabbit bone regeneration.

    Science.gov (United States)

    Dąbrowska, Natalia; Kiełbowicz, Zdzisław; Nowacki, Wojciech; Bajzert, Joanna; Reichert, Paweł; Bieżyński, Janusz; Zebrowski, Jacek; Haczkiewicz, Katarzyna; Cegielski, Marek

    2016-11-01

    (i) To assess the expression profiles of stem cell-associated markers including Oct4, Sox2, Klf4, Nanog, C-myc, Stat3 and Cd9, (ii) analyze the nanotopography of the MIC-1 stem cells and (iii) evaluate the efficiency of live stem cell implants and stem cell culture derivatives on the regeneration of bone deficiencies in rabbit mandibles. The expression profiles of stem cell-associated genes, including Oct4, Sox2, Klf4, Nanog, C-myc, Stat3 and CD9 were assessed using reverse transcription polymerase chain reaction and flow cytometry. Nanotopography of the antlerogenic MIC-1 cell lineage was analyzed using atomic force microscopy. The effect of MIC-1 stem cells, their homogenate and supernatant on the regeneration of bone deficiencies in rabbit mandibles was evaluated using histological analysis. The effect of MIC-1 stem cells and stem cell-based derivatives on the immune responses of the animals was assessed by analyses of acute phase protein levels (haptoglobin and fibrinogen). We found that the MIC-1 cells isolated from the apical regions of growing antlers exhibited molecular features that were characteristics of pluripotent stem cells. Using atomic force microscopy, we determined the details of the cell surface morphologies with a particular emphasis on the patterns of formation of plasma extensions for interlinking adjacent cells. We also demonstrated that not only implanted stem cells but also cell homogenates and cell post-culture supernatants have potential in the regeneration of bone deficiencies in the rabbit mandible. Our findings indicate that the use of both antlerogenic stem cell implants and the preparations derived from the cells offer alternative approaches to those based on autologous stem cells in the biological stimulation of osteogenesis and in bone regeneration.

  3. Personalized Regenerative Medicine.

    Science.gov (United States)

    Arjmand, Babak; Goodarzi, Parisa; Mohamadi-Jahani, Fereshteh; Falahzadeh, Khadijeh; Larijani, Bagher

    2017-03-01

    Personalized medicine as a novel field of medicine refers to the prescription of specific therapeutics procedure for an individual. This approach has established based on pharmacogenetic and pharmacogenomic information and data. The terms precision and personalized medicines are sometimes applied interchangeably. However, there has been a shift from "personalized medicine" towards "precision medicine". Although personalized medicine emerged from pharmacogenetics, nowadays it covers many fields of healthcare. Accordingly, regenerative medicine and cellular therapy as the new fields of medicine use cell-based products in order to develop personalized treatments. Different sources of stem cells including mesenchymal stem cells, embryonic stem cells and induced pluripotent stem cells (iPSCs) have been considered in targeted therapies which could give many advantages. iPSCs as the novel and individual pluripotent stem cells have been introduced as the appropriate candidates for personalized cell therapies. Cellular therapies can provide a personalized approach. Because of person-to-person and population differences in the result of stem cell therapy, individualized cellular therapy must be adjusted according to the patient specific profile, in order to achieve best therapeutic results and outcomes. Several factors should be considered to achieve personalized stem cells therapy such as, recipient factors, donor factors, and the overall body environment in which the stem cells could be active and functional. In addition to these factors, the source of stem cells must be carefully chosen based on functional and physical criteria that lead to optimal outcomes.

  4. Thermally regenerative fuel cells

    Science.gov (United States)

    Ludwig, F. A.; Kindler, A.; McHardy, J.

    1991-10-01

    The three phase project was undertaken to investigate solventless ionic liquids as possible working fluids for a new type of thermally regenerative fuel cell (TRFC). The heart of the new device, invented at Hughes Aircraft Company in 1983, is an electrochemical concentration cell where acid and base streams react to produce electrical energy. Thermal energy is then used to decompose the resulting salts and regenerate the cell reactants. In principle, a TRFC can be matched to any source of thermal energy simply by selecting working fluids with the appropriate regeneration temperature. However, aqueous working fluids (the focus of previous studies) impose limitations on both the operating temperatures and the achievable energy densities. It was the need to overcome these limitations that prompted the present investigation. Specific aims were to identify possible working fluids for TRFC systems with both low and high regeneration temperatures. A major advantage of our aqueous-fluid TRFC systems has been the ability to use hydrogen electrodes. The low activation and mass transfer losses of these electrodes contribute substantially to overall system efficiency.

  5. Biological Evaluation of Flexible Polyurethane/Poly l-Lactic Acid Composite Scaffold as a Potential Filler for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Yuk Fai Lui

    2017-09-01

    Full Text Available Degradable bone graft substitute for large-volume bone defects is a continuously developing field in orthopedics. With the advance in biomaterial in past decades, a wide range of new materials has been investigated for their potential in this application. When compared to common biopolymers within the field such as PLA or PCL, elastomers such as polyurethane offer some unique advantages in terms of flexibility. In cases of bone defect treatments, a flexible soft filler can help to establish an intimate contact with surrounding bones to provide a stable bone-material interface for cell proliferation and ingrowth of tissue. In this study, a porous filler based on segmented polyurethane incorporated with poly l-lactic acid was synthesized by a phase inverse salt leaching method. The filler was put through in vitro and in vivo tests to evaluate its potential in acting as a bone graft substitute for critical-sized bone defects. In vitro results indicated there was a major improvement in biological response, including cell attachment, proliferation and alkaline phosphatase expression for osteoblast-like cells when seeded on the composite material compared to unmodified polyurethane. In vivo evaluation on a critical-sized defect model of New Zealand White (NZW rabbit indicated there was bone ingrowth along the defect area with the introduction of the new filler. A tight interface formed between bone and filler, with osteogenic cells proliferating on the surface. The result suggested polyurethane/poly l-lactic acid composite is a material with the potential to act as a bone graft substitute for orthopedics application.

  6. Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis.

    Science.gov (United States)

    Langdahl, Bente; Ferrari, Serge; Dempster, David W

    2016-12-01

    The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20-30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that

  7. Clinical concepts for regenerative therapy in furcations.

    Science.gov (United States)

    Sanz, Mariano; Jepsen, Karin; Eickholz, Peter; Jepsen, Søren

    2015-06-01

    Furcation involvements present one of the greatest challenges in periodontal therapy because furcation-involved molar teeth respond less favorably to conventional periodontal therapy compared with noninvolved molar or nonmolar teeth. Various regenerative procedures have been proposed and applied with the aim of eliminating the furcation defect or reducing the furcation depth. An abundance of studies and several systematic reviews have established the effectiveness of membrane therapy (guided tissue regeneration) for buccal Class II furcation involvement of mandibular and maxillary molars compared with open flap surgery. Bone grafts/substitutes may enhance the results of guided tissue regeneration. However, complete furcation closure is not a predictable outcome. Limited data and no meta-analyses are available on the effects of enamel matrix proteins for furcation regeneration. Enamel matrix protein therapy has demonstrated clinical improvements in the treatment of buccal Class II furcation defects in mandibular molars; however, complete closure of the furcation lesion is achieved only in a minority of cases. Neither guided tissue regeneration nor enamel matrix protein therapy have demonstrated predictable results for approximal Class II and for Class III furcations. Promising preclinical data from furcation regeneration studies in experimental animals is available for growth factor- and differentiation factor-based technologies, but very limited data are available from human clinical studies. Although cell-based therapies have received considerable attention in regenerative medicine, their experimental evaluation in the treatment of periodontal furcation lesions is at a very early stage of development. In summary, the indications and the limitations for currently available treatment modalities for furcation defects are well established. New regenerative treatments are clearly needed to improve the predictability of a complete resolution of furcation defects.

  8. Short communication: Effect of commercial or depurinized milk diet on plasma advanced oxidation protein products, cardiovascular markers, and bone marrow CD34+ stem cell potential in rat experimental hyperuricemia.

    Science.gov (United States)

    Kocic, Gordana; Sokolovic, Dusan; Jevtovic, Tatjana; Cvetkovic, Tatjana; Veljkovic, Andrej; Kocic, Hristina; Stojanovic, Svetlana; Jovanovic, Aneta; Jovanovic, Jelena; Zivkovic, Petar

    2014-11-01

    Cardiovascular repair and myocardial contractility may be improved by migration of bone marrow stem cells (BMSC) and their delivery to the site of injury, a process known as BMSC homing. The aim of our study was to examine the dietary effect of a newly patented depurinized milk (DP) that is almost free of uric acid and purine and pyrimidine compounds compared with a standard commercial 1.5% fat UHT milk diet or allopurinol therapy in rat experimental hyperuricemia. Bone marrow stem cell potential (BMCD34(+), CD34-postive bone marrow cells), plasma oxidative stress parameters [advanced oxidation protein products, AOPP) and thiobarbituric acid reactive substances (TBARS)], myocardial damage markers [creatine phosphokinase (CPK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)], plasma cholesterol, and high-density lipoprotein cholesterol were investigated. The DP milk diet significantly increased the number of BMCD34(+) stem cells compared with commercial UHT milk. Allopurinol given alone also increased the number of BMCD34(+). Hyperuricemia caused a significant increase in all plasma enzyme markers for myocardial damage (CPK, LDH, and AST). A cardioprotective effect was achieved with allopurinol but almost equally with DP milk and more than with commercial milk. Regarding plasma AOPP, TBARS, and cholesterol levels, the most effective treatment was DP milk. In conclusion, the protective role of a milk diet on cardiovascular function may be enhanced through the new depurinized milk diet, which may improve cardiovascular system function via increased bone marrow stem cell regenerative potential, decreased plasma oxidative stress parameters, and decreased levels of myocardial damage markers and cholesterol. New dairy technology strategies focused on eliminating harmful milk compounds should be completely nontoxic. Novel milk products should be tested for their ability to improve tissue repair and function.

  9. Disc distraction shows evidence of regenerative potential in degenerated intervertebral discs as evaluated by protein expression, magnetic resonance imaging, and messenger ribonucleic acid expression analysis.

    Science.gov (United States)

    Guehring, Thorsten; Omlor, Georg W; Lorenz, Helga; Engelleiter, Karl; Richter, Wiltrud; Carstens, Claus; Kroeber, Markus

    2006-07-01

    An animal model of degeneration was used to determine the effects of disc distraction, and was evaluated with magnetic resonance imaging (MRI) as well as gene and protein expression levels. To investigate gene expression and MRI effects of distraction. Disc degeneration can result from hyper-physiologic loading. Distracted discs with degeneration showed histologic signs of tissue recovery. There were 18 rabbits that underwent 28 days of compression (200 N) to induce moderate disc degeneration followed by 28 days of distraction (120 N; attached and loaded distraction device) or sham distraction (attached but unloaded distraction device). Comparison was performed with 56 days of compressed discs without distraction. Quantitative outcome measures were MRI signal intensity and gene expression analysis to determine: messenger ribonucleic acid levels for extracellular matrix genes, including collagen 1, collagen 2, biglycan, decorin, aggrecan, fibromodulin, and osteonectin; and matrix-regulative genes, including matrix metalloproteinase-13, tissue-inhibitor of matrix metalloproteinase-1, and bone morphogenetic protein (BMP)-2. Immunohistology was performed for collagen 2 and BMP-2 to label cells semiquantitatively by staining of the cell-surrounding matrix. A total of 28 days of compression decreased signal intensity. Distraction over the same period reestablished physiologic signal intensity, however, a persistent reduction was found in sham distraction. Distraction resulted in gene expression up-regulation of collagen 1 (5.4-fold), collagen 2 (5.5-fold), biglycan (7.7-fold), and decorin (3.4-fold), while expression of fibromodulin (0.16-fold), tissue-inhibitor of matrix metalloproteinase-1 (0.05-fold), and BMP-2 (0.15-fold) was decreased, as compared with 56 days compression. Distracted discs showed more BMP-2 (19.67 vs. 3.67 in 56 days compression) and collagen 2 (18.67 vs. 11.33 in 56 days compression) positive cells per field. Distraction results in disc rehydration

  10. A regenerative elastocaloric heat pump

    Science.gov (United States)

    Tušek, Jaka; Engelbrecht, Kurt; Eriksen, Dan; Dall'Olio, Stefano; Tušek, Janez; Pryds, Nini

    2016-10-01

    A large fraction of global energy use is for refrigeration and air-conditioning, which could be decarbonized if efficient renewable energy technologies could be found. Vapour-compression technology remains the most widely used system to move heat up the temperature scale after more than 100 years; however, caloric-based technologies (those using the magnetocaloric, electrocaloric, barocaloric or elastocaloric effect) have recently shown a significant potential as alternatives to replace this technology due to high efficiency and the use of green solid-state refrigerants. Here, we report a regenerative elastocaloric heat pump that exhibits a temperature span of 15.3 K on the water side with a corresponding specific heating power up to 800 W kg-1 and maximum COP (coefficient-of-performance) values of up to 7. The efficiency and specific heating power of this device exceeds those of other devices based on caloric effects. These results open up the possibility of using the elastocaloric effect in various cooling and heat-pumping applications.

  11. Regenerative endodontics--Creating new horizons.

    Science.gov (United States)

    Dhillon, Harnoor; Kaushik, Mamta; Sharma, Roshni

    2016-05-01

    Trauma to the dental pulp, physical or microbiologic, can lead to inflammation of the pulp followed by necrosis. The current treatment modality for such cases is non-surgical root canal treatment. The damaged tissue is extirpated and the root canal system prepared. It is then obturated with an inert material such a gutta percha. In spite of advances in techniques and materials, 10%-15% of the cases may end in failure of treatment. Regenerative endodontics combines principles of endodontics, cell biology, and tissue engineering to provide an ideal treatment for inflamed and necrotic pulp. It utilizes mesenchymal stem cells, growth factors, and organ tissue culture to provide treatment. Potential treatment modalities include induction of blood clot for pulp revascularization, scaffold aided regeneration, and pulp implantation. Although in its infancy, successful treatment of damaged pulp tissue has been performed using principles of regenerative endodontics. This field is dynamic and exciting with the ability to shape the future of endodontics. This article highlights the fundamental concepts, protocol for treatment, and possible avenues for research in regenerative endodontics. © 2015 Wiley Periodicals, Inc.

  12. Osteogenic potential: comparison between bone marrow and adipose-derived mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Han-Tsung; Liao; Chien-Tzung; Chen

    2014-01-01

    Bone tissue engineering(BTE) is now a promising re-search issue to improve the drawbacks from traditional bone grafting procedure such as limited donor sources and possible complications. Stem cells are one of the major factors in BTE due to the capability of self re-newal and multi-lineage differentiation. Unlike embry-onic stem cells, which are more controversial in ethical problem, adult mesenchymal stem cells are considered to be a more appropriate cell source for BTE. Bone marrow mesenchymal stem cells(BMSCs) are the ear-liest-discovered and well-known stem cell source using in BTE. However, the low stem cell yield requiring long expansion time in vitro, pain and possible morbidities during bone marrow aspiration and poor proliferation and osteogenic ability at old age impede its’ clinical ap-plication. Afterwards, a new stem cell source coming from adipose tissue, so-called adipose-derived stemcells(ASCs), is found to be more suitable in clinical ap-plication because of high stem cells yield from lipoaspi-rates, faster cell proliferation and less discomfort and morbidities during harvesting procedure. However, the osteogenic capacity of ASCs is now still debated be-cause most papers described the inferior osteogenesis of ASCs than BMSCs. A better understanding of the osteogenic differences between ASCs and BMSCs is crucial for future selection of cells in clinical application for BTE. In this review, we describe the commonality and difference between BMSCs and ASCs by cell yield, cell surface markers and multiple-differentiation poten-tial. Then we compare the osteogenic capacity in vitro and bone regeneration ability in vivo between BMSCs and ASCs based on the literatures which utilized both BMSCs and ASCs simultaneously in their articles. The outcome indicated both BMSCs and ASCs exhibited the osteogenic ability to a certain extent both in-vitro and in-vivo. However, most in-vitro study papers verified the inferior osteogenesis of ASCs; conversely, in

  13. A new take on an old story: chick limb organ culture for skeletal niche development and regenerative medicine evaluation

    Directory of Open Access Journals (Sweden)

    EL Smith

    2013-09-01

    Full Text Available Scientific research and progress, particularly in the drug discovery and regenerative medicine fields, is typically dependent on suitable animal models to develop new and improved clinical therapies for injuries and diseases. In vivo model systems are frequently utilised, but these models are expensive, highly complex and pose a number of ethical considerations leading to the development and use of a number of alternative ex vivo model systems. The ex vivo embryonic chick long bone and limb bud models have been utilised in the scientific research field as a model to understand skeletal development for over eighty years. The rapid development of avian skeletal tissues, coupled with the ease of experimental manipulation, availability of genome sequence and the presence of multiple cell and tissue types has seen such model systems gain significant research interest in the last few years in the tissue engineering field. The models have been explored both as systems for understanding the developmental bone niche and as potential testing tools for tissue engineering strategies for bone repair and regeneration. This review details the evolution of the chick limb organ culture system and presents recent innovative developments and emerging techniques and technologies applied to these models that are aiding our understanding of skeletal developmental and regenerative medicine research and application.

  14. Nanocomposite Membranes Enhance Bone Regeneration Through Restoring Physiological Electric Microenvironment.

    Science.gov (United States)

    Zhang, Xuehui; Zhang, Chenguang; Lin, Yuanhua; Hu, Penghao; Shen, Yang; Wang, Ke; Meng, Song; Chai, Yuan; Dai, Xiaohan; Liu, Xing; Liu, Yun; Mo, Xiaoju; Cao, Cen; Li, Shue; Deng, Xuliang; Chen, Lili

    2016-08-23

    Physiological electric potential is well-known for its indispensable role in maintaining bone volume and quality. Although implanted biomaterials simulating structural, morphological, mechanical, and chemical properties of natural tissue or organ has been introduced in the field of bone regeneration, the concept of restoring physiological electric microenvironment remains ignored in biomaterials design. In this work, a flexible nanocomposite membrane mimicking the endogenous electric potential is fabricated to explore its bone defect repair efficiency. BaTiO3 nanoparticles (BTO NPs) were first coated with polydopamine. Then the composite membranes are fabricated with homogeneous distribution of Dopa@BTO NPs in poly(vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix. The surface potential of the nanocomposite membranes could be tuned up to -76.8 mV by optimizing the composition ratio and corona poling treatment, which conform to the level of endogenous biopotential. Remarkably, the surface potential of polarized nanocomposite membranes exhibited a dramatic stability with more than half of original surface potential remained up to 12 weeks in the condition of bone defect. In vitro, the membranes encouraged bone marrow mesenchymal stem cells (BM-MSCs) activity and osteogenic differentiation. In vivo, the membranes sustainably maintained the electric microenvironment giving rise to rapid bone regeneration and complete mature bone-structure formation. Our findings evidence that physiological electric potential repair should be paid sufficient attention in biomaterials design, and this concept might provide an innovative and well-suited strategy for bone regenerative therapies.

  15. Nanotechnology in bone tissue engineering.

    Science.gov (United States)

    Walmsley, Graham G; McArdle, Adrian; Tevlin, Ruth; Momeni, Arash; Atashroo, David; Hu, Michael S; Feroze, Abdullah H; Wong, Victor W; Lorenz, Peter H; Longaker, Michael T; Wan, Derrick C

    2015-07-01

    Nanotechnology represents a major frontier with potential to significantly advance the field of bone tissue engineering. Current limitations in regenerative strategies include impaired cellular proliferation and differentiation, insufficient mechanical strength of scaffolds, and inadequate production of extrinsic factors necessary for efficient osteogenesis. Here we review several major areas of research in nanotechnology with potential implications in bone regeneration: 1) nanoparticle-based methods for delivery of bioactive molecules, growth factors, and genetic material, 2) nanoparticle-mediated cell labeling and targeting, and 3) nano-based scaffold construction and modification to enhance physicochemical interactions, biocompatibility, mechanical stability, and cellular attachment/survival. As these technologies continue to evolve, ultimate translation to the clinical environment may allow for improved therapeutic outcomes in patients with large bone deficits and osteodegenerative diseases. Traditionally, the reconstruction of bony defects has relied on the use of bone grafts. With advances in nanotechnology, there has been significant development of synthetic biomaterials. In this article, the authors provided a comprehensive review on current research in nanoparticle-based therapies for bone tissue engineering, which should be useful reading for clinicians as well as researchers in this field. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Genetic engineering for skeletal regenerative medicine.

    Science.gov (United States)

    Gersbach, Charles A; Phillips, Jennifer E; García, Andrés J

    2007-01-01

    The clinical challenges of skeletal regenerative medicine have motivated significant advances in cellular and tissue engineering in recent years. In particular, advances in molecular biology have provided the tools necessary for the design of gene-based strategies for skeletal tissue repair. Consequently, genetic engineering has emerged as a promising method to address the need for sustained and robust cellular differentiation and extracellular matrix production. As a result, gene therapy has been established as a conventional approach to enhance cellular activities for skeletal tissue repair. Recent literature clearly demonstrates that genetic engineering is a principal factor in constructing effective methods for tissue engineering approaches to bone, cartilage, and connective tissue regeneration. This review highlights this literature, including advances in the development of efficacious gene carriers, novel cell sources, successful delivery strategies, and optimal target genes. The current status of the field and the challenges impeding the clinical realization of these approaches are also discussed.

  17. Therapeutic potential of bone marrow-derived mesenchymal stem cells in cutaneous wound healing

    Directory of Open Access Journals (Sweden)

    Jerry S Chen

    2012-07-01

    Full Text Available Despite advances in wound care, many wounds never heal and become chronic problems that result in significant morbidity and mortality to the patient. Cellular therapy for cutaneous wounds has recently come under investigation as a potential treatment modality for impaired wound healing. Bone marrow-derived mesenchymal stem cells (MSCs are a promising source of adult progenitor cells for cytotherapy as they are easy to isolate and expand and have been shown to differentiate into various cell lineages. Early studies have demonstrated that MSCs may enhance epithelialization, granulation tissue formation, and neovascularization resulting in accelerated wound closure. It is currently unclear if these effects are mediated through cellular differentiation or by secretion of cytokines and growth factors. This review discusses the proposed biological contributions of MSCs to cutaneous repair and their clinical potential in cell-based therapies.

  18. The Pharmacology of Regenerative Medicine

    Science.gov (United States)

    Saul, Justin M.; Furth, Mark E.; Andersson, Karl-Erik

    2013-01-01

    Regenerative medicine is a rapidly evolving multidisciplinary, translational research enterprise whose explicit purpose is to advance technologies for the repair and replacement of damaged cells, tissues, and organs. Scientific progress in the field has been steady and expectations for its robust clinical application continue to rise. The major thesis of this review is that the pharmacological sciences will contribute critically to the accelerated translational progress and clinical utility of regenerative medicine technologies. In 2007, we coined the phrase “regenerative pharmacology” to describe the enormous possibilities that could occur at the interface between pharmacology, regenerative medicine, and tissue engineering. The operational definition of regenerative pharmacology is “the application of pharmacological sciences to accelerate, optimize, and characterize (either in vitro or in vivo) the development, maturation, and function of bioengineered and regenerating tissues.” As such, regenerative pharmacology seeks to cure disease through restoration of tissue/organ function. This strategy is distinct from standard pharmacotherapy, which is often limited to the amelioration of symptoms. Our goal here is to get pharmacologists more involved in this field of research by exposing them to the tools, opportunities, challenges, and interdisciplinary expertise that will be required to ensure awareness and galvanize involvement. To this end, we illustrate ways in which the pharmacological sciences can drive future innovations in regenerative medicine and tissue engineering and thus help to revolutionize the discovery of curative therapeutics. Hopefully, the broad foundational knowledge provided herein will spark sustained conversations among experts in diverse fields of scientific research to the benefit of all. PMID:23818131

  19. Endothelial cells influence the osteogenic potential of bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    Arvidson Kristina

    2009-11-01

    Full Text Available Abstract Background Improved understanding of the interactions between bone cells and endothelial cells involved in osteogenesis should aid the development of new strategies for bone tissue engineering. The aim of the present study was to determine whether direct communication between bone marrow stromal cells (MSC and human umbilical vein endothelial cells (EC could influence the osteogenic potential of MSC in osteogenic factor-free medium. Methods After adding EC to MSC in a direct-contact system, cell viability and morphology were investigated with the WST assay and immnostaining. The effects on osteogenic differentiation of adding EC to MSC was systematically tested by the using Superarray assay and results were confirmed with real-time PCR. Results Five days after the addition of EC to MSC in a ratio of 1:5 (EC/MSC significant increases in cell proliferation and cellular bridges between the two cell types were detected, as well as increased mRNA expression of alkaline phosphatase (ALP. This effect was greater than that seen with addition of osteogenic factors such as dexamethasone, ascorbic acid and β-glycerophosphate to the culture medium. The expression of transcription factor Runx2 was enhanced in MSC incubated with osteogenic stimulatory medium, but was not influenced by induction with EC. The expression of Collagen type I was not influenced by EC but the cells grown in the osteogenic factor-free medium exhibited higher expression than those cultured with osteogenic stimulatory medium. Conclusion These results show that co-culturing of EC and MSC for 5 days influences osteogenic differentiation of MSC, an effect that might be independent of Runx2, and enhances the production of ALP by MSC.

  20. One-year clinical study of NeuroRegen scaffold implantation following scar resection in complete chronic spinal cord injury patients.

    Science.gov (United States)

    Xiao, Zhifeng; Tang, Fengwu; Tang, Jiaguang; Yang, Huilin; Zhao, Yannan; Chen, Bing; Han, Sufang; Wang, Nuo; Li, Xing; Cheng, Shixiang; Han, Guang; Zhao, Changyu; Yang, Xiaoxiong; Chen, Yumei; Shi, Qin; Hou, Shuxun; Zhang, Sai; Dai, Jianwu

    2016-07-01

    The objective of this clinical study was to assess the safety and feasibility of the collagen scaffold, NeuroRegen scaffold, one year after scar tissue resection and implantation. Scar tissue is a physical and chemical barrier that prevents neural regeneration. However, identification of scar tissue is still a major challenge. In this study, the nerve electrophysiology method was used to distinguish scar tissue from normal neural tissue, and then different lengths of scars ranging from 0.5-4.5 cm were surgically resected in five complete chronic spinal cord injury (SCI) patients. The NeuroRegen scaffold along with autologous bone marrow mononuclear cells (BMMCs), which have been proven to promote neural regeneration and SCI recovery in animal models, were transplanted into the gap in the spinal cord following scar tissue resection. No obvious adverse effects related to scar resection or NeuroRegen scaffold transplantation were observed immediately after surgery or at the 12-month follow-up. In addition, patients showed partially autonomic nervous function improvement, and the recovery of somatosensory evoked potentials (SSEP) from the lower limbs was also detected. The results indicate that scar resection and NeuroRegen scaffold transplantation could be a promising clinical approach to treating SCI.

  1. Carboxymethyl cellulose enables silk fibroin nanofibrous scaffold with enhanced biomimetic potential for bone tissue engineering application.

    Science.gov (United States)

    Singh, B N; Panda, N N; Mund, R; Pramanik, K

    2016-10-20

    Novel silk fibroin (SF) and carboxymethyl cellulose (CMC) composite nanofibrous scaffold (SFC) were developed to investigate their ability to nucleate bioactive nanosized calcium phosphate (Ca/P) by biomineralization for bone tissue engineering application. The composite nanofibrous scaffold was prepared by free liquid surface electrospinning method. The developed composite nanofibrous scaffold was observed to control the size of Ca/P particle (≤100nm) as well as uniform nucleation of Ca/P over the surface. The obtained nanofibrous scaffolds were fully characterized for their functional, structural and mechanical property. The XRD and EDX analysis depicted the development of apatite like crystals over SFC scaffolds of nanospherical in morphology and distributed uniformly throughout the surface of scaffold. Additionally, hydrophilicity as a measure of contact angle and water uptake capacity is higher than pure SF scaffold representing the superior cell supporting property of the SF/CMC scaffold. The effect of biomimetic Ca/P on osteogenic differentiation of umbilical cord blood derived human mesenchymal stem cells (hMSCs) studied in early and late stage of differentiation shows the improved osteoblastic differentiation capability as compared to pure silk fibroin. The obtained result confirms the positive correlation of alkaline phosphatase activity, alizarin staining and expression of runt-related transcription factor 2, osteocalcin and type1 collagen representing the biomimetic property of the scaffolds. Thus, the developed composite has been demonstrated to be a potential scaffold for bone tissue engineering application.

  2. Preparation of collagen/hydroxyapatite/alendronate hybrid hydrogels as potential scaffolds for bone regeneration.

    Science.gov (United States)

    Ma, Xin; He, Zhiwei; Han, Fengxuan; Zhong, Zhiyuan; Chen, Liang; Li, Bin

    2016-07-01

    Development of biomimetic scaffolds represents a promising direction in bone tissue engineering. In this study, we designed a two-step process to prepare a type of biomimetic hybrid hydrogels that were composed of collagen, hydroxyapatite (HAP) and alendronate (ALN), an anti-osteoporosis drug. First, water-soluble ALN-conjugated HAP (HAP-ALN) containing 4.0wt.% of ALN was synthesized by treating HAP particles with ALN. Hydrogels were then formed from HAP-ALN conjugate and collagen under physiological conditions using genipin (GNP) as the crosslinker. Depending on the ALN/collagen molar ratio and GNP concentration, the gelation time of hydrogels ranged from 5 to 37min. Notably, these hybrid hydrogels exhibited markedly improved mechanical property (storage modulus G'=38-187kPa), higher gel contents, and lower swelling ratios compared to the hydrogels prepared from collagen alone under similar conditions. Moreover, they showed tunable degradation behaviors against collagenase. The collagen/HAP-ALN hybrid hydrogels supported the adhesion and growth of murine MC3T3-E1 osteoblastic cells well. Such tough yet enzymatically degradable hybrid hydrogels hold potential as scaffolds for bone tissue engineering.

  3. Regenerative medicine in China: main progress in different fields.

    Science.gov (United States)

    Cheng, Biao; Lu, Shu-Liang; Fu, Xiao-Bing

    2016-01-01

    Regenerative medicine (RM) is an emerging interdisciplinary field of research and China has developed the research quickly and impressed the world with numerous research findings in stem cells, tissue engineering, active molecules and gene therapy. Important directions are induced differentiation of induced pluripotent stem and embryo stem cells as well as somatic stem cell differentiation potential and their application in trauma, burns, diseases of aging and nerve regeneration. The products ActivSkin and bone repair scaffolds have been approved and are applied in the clinic, and similar products are being studied. About 10 engineered growth-factor drugs for repair and regeneration have been approved and are used in the clinic. Gene therapy, therapeutic cloning and xenotransplantation are some of the strategies being studied. However, China needs to develop standards, regulations and management practices suitable for the healthy development of RM. Aspects that should be strengthened include sound administrative systems, laws, and technical specifications and guidelines; conservation of stem cell resources; emphasis on training and retention of talented stem cell researchers; and reasonable allocation of resources, diversification of investment and breakthroughs in key areas. Finally, broad and deep international cooperation is necessary.

  4. Preclinical investigation of an innovative magnesium-based bone graft substitute for potential orthopaedic applications

    Directory of Open Access Journals (Sweden)

    Chen Liu

    2014-07-01

    Full Text Available Degradable or corrosive biometal is an attractive research and development (R&D area in clinical orthopaedics. This study was designed to investigate biomechanical and biological properties of magnesium (Mg and strontium (Sr with a focus on Mg-based metals, including pure Mg and Mg–xwt% Sr (x = 0.25, x = 1.0, x = 1.5, x = 2.5 alloys, as potential bone graft substitutes in respect to their mechanical strength, corrosion resistance, and cytocompatibility for further optimization and establishing indications for relevant in vivo applications. Our data showed that the tensile and compressive strength increased with addition of Sr because of the Mg17Sr2 precipitation strengthen. Compared with commercially used bone graft substitutes, the mechanical properties of Mg–Sr alloys were close to those of cortical bone, and the compressive strength could reach 300 MPa, suggesting its potential application for load-bearing bone as bone defect filler. The corrosion rates of Mg–xwt% Sr alloys were controlled in the range of 0.05–0.07 mm/y, indicating feasibility of bone grafting and the in situ bone repair process. Moreover, Mg–Sr alloys also exhibit good cytocompatibility and antibacterial properties. Our innovation presented in this work supported in vivo clinical indication-based assessment of biodegradable Mg-based metals that could be potential candidates for bone graft substitutes for future orthopaedic applications.

  5. The species-specific regenerative effects of notochordal cell-conditioned medium on chondrocyte-like cells derived from degenerated human intervertebral discs

    NARCIS (Netherlands)

    Bach, F C; de Vries, S A; Krouwels, A; Creemers, L B; Ito, K; Meij, B P; Tryfonidou, M A

    2015-01-01

    During intervertebral disc (IVD) maturation, the main cell type shifts from notochordal cells (NCs) to chondrocyte-like cells (CLCs). NCs secrete factors with regenerative potential, making them an interesting focus for regenerative treatments. During initial development, these strategies preferably

  6. The species-specific regenerative effects of notochordal cell-conditioned medium on chondrocyte-like cells derived from degenerated human intervertebral discs.

    NARCIS (Netherlands)

    Bach, FC; de Vries, S A H; Krouwels, A; Creemers, L B; Ito, K; Meij, B P; Tryfonidou, M A

    2015-01-01

    During intervertebral disc (IVD) maturation, the main cell type shifts from notochordal cells (NCs) to chondrocyte-like cells (CLCs). NCs secrete factors with regenerative potential, making them an interesting focus for regenerative treatments. During initial development, these strategies preferably

  7. Perspectives in regenerative medicine

    CERN Document Server

    Ray Banerjee, Ena

    2014-01-01

    The information given in this book tries to capture the essence of the sheer dynamicity of the cell along with useful tips on how to address critical rate limiting steps in the process of exploration and investigation of its capacity to regenerate, rebuild and replenish from within. The definitions of stem cells, stemness, and the niche concept continue to undergo revisions. In adult vertebrates, hematopoietic and some non-hematopoietic progenitors are synthesized within specialized niches of bone marrow. They migrate to designated tissues, and are either trans-differentiated or become quiescent and settle down. These form the stem cell niche reservoir in all tissues. Not only the primary hematopoietic tissue but all organs and tissues are also capable of generating progenitors which are either synthesized from these migrants or are direct recruits from other tissues. In the niches, the cells settle down and await their turn to either make more clones like themselves or differentiate and mobilize in an exigen...

  8. Regenerative Endodontics by Cell Homing.

    Science.gov (United States)

    He, Ling; Zhong, Juan; Gong, Qimei; Cheng, Bin; Kim, Sahng G; Ling, Junqi; Mao, Jeremy J

    2017-01-01

    Apical revascularization (AR) and platelet-rich plasma have been used to restore dental pulp vitality in infected immature permanent teeth. Two regenerative therapies are cell transplantation and cell homing. This article updates and benchmarks these therapies with cell homing. A case report concluded that AR increased root length; however, quantitative and statistical assessments disproved this. Regenerative endodontic therapies require prospective clinical trials demonstrating safety and efficacy. These therapies are intrinsically susceptible to procedural and patient variations. Cell homing uses novel molecules that drive therapeutic efficacy, and may be less sensitive to procedural and patient variations. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Optical techniques in regenerative medicine

    CERN Document Server

    Morgan, Stephen P

    2013-01-01

    In regenerative medicine, tissue engineers largely rely on destructive and time-consuming techniques that do not allow in situ and spatial monitoring of tissue growth. Furthermore, once the therapy is implanted in the patient, clinicians are often unable to monitor what is happening in the body. To tackle these barriers, optical techniques have been developed to image and characterize many tissue properties, fabricate tissue engineering scaffolds, and characterize the properties of the scaffolds. Optical Techniques in Regenerative Medicine illustrates how to use optical imaging techniques and

  10. Regeneratively Cooled Porous Media Jacket

    Science.gov (United States)

    Mungas, Greg (Inventor); Fisher, David J. (Inventor); London, Adam Pollok (Inventor); Fryer, Jack Merrill (Inventor)

    2013-01-01

    The fluid and heat transfer theory for regenerative cooling of a rocket combustion chamber with a porous media coolant jacket is presented. This model is used to design a regeneratively cooled rocket or other high temperature engine cooling jacket. Cooling jackets comprising impermeable inner and outer walls, and porous media channels are disclosed. Also disclosed are porous media coolant jackets with additional structures designed to transfer heat directly from the inner wall to the outer wall, and structures designed to direct movement of the coolant fluid from the inner wall to the outer wall. Methods of making such jackets are also disclosed.

  11. Biomaterials and Stem Cells in Regenerative Medicine

    CERN Document Server

    Ramalingam, Murugan; Best, Serena

    2012-01-01

    Work in the area of biomaterials and stem cell therapy has revealed great potential for many applications, from the treatment of localized defects and diseases to the repair and replacement of whole organs. Researchers have also begun to develop a better understanding of the cellular environment needed for optimal tissue repair and regeneration. Biomaterials and Stem Cells in Regenerative Medicine explores a range of applications for biomaterials and stem cell therapy and describes recent research on suitable cell scaffolds and substrates for tissue repair and reconstruction. Featuring contrib

  12. Micro-computed tomography (CT) based assessment of dental regenerative therapy in the canine mandible model

    Science.gov (United States)

    Khobragade, P.; Jain, A.; Setlur Nagesh, S. V.; Andreana, S.; Dziak, R.; Sunkara, S. K.; Sunkara, S.; Bednarek, D. R.; Rudin, S.; Ionita, C. N.

    2015-03-01

    High-resolution 3D bone-tissue structure measurements may provide information critical to the understanding of the bone regeneration processes and to the bone strength assessment. Tissue engineering studies rely on such nondestructive measurements to monitor bone graft regeneration area. In this study, we measured bone yield, fractal dimension and trabecular thickness through micro-CT slices for different grafts and controls. Eight canines underwent surgery to remove a bone volume (defect) in the canine's jaw at a total of 44 different locations. We kept 11 defects empty for control and filled the remaining ones with three regenerative materials; NanoGen (NG), a FDA-approved material (n=11), a novel NanoCalcium Sulfate (NCS) material (n=11) and NCS alginate (NCS+alg) material (n=11). After a minimum of four and eight weeks, the canines were sacrificed and the jaw samples were extracted. We used a custombuilt micro-CT system to acquire the data volume and developed software to measure the bone yield, fractal dimension and trabecular thickness. The software used a segmentation algorithm based on histograms derived from volumes of interest indicated by the operator. Using bone yield and fractal dimension as indices we are able to differentiate between the control and regenerative material (pprocess and quality of bone were dependent upon the position of defect and time period of healing. This study presents one of the first quantitative comparisons using non-destructive Micro-CT analysis for bone regenerative material in a large animal with a critical defect model. Our results indicate that Micro-CT measurement could be used to monitor invivo bone regeneration studies for greater regenerative process understanding.

  13. Maximum Safety Regenerative Power Tracking for DC Traction Power Systems

    Directory of Open Access Journals (Sweden)

    Guifu Du

    2017-02-01

    Full Text Available Direct current (DC traction power systems are widely used in metro transport systems, with running rails usually being used as return conductors. When traction current flows through the running rails, a potential voltage known as “rail potential” is generated between the rails and ground. Currently, abnormal rises of rail potential exist in many railway lines during the operation of railway systems. Excessively high rail potentials pose a threat to human life and to devices connected to the rails. In this paper, the effect of regenerative power distribution on rail potential is analyzed. Maximum safety regenerative power tracking is proposed for the control of maximum absolute rail potential and energy consumption during the operation of DC traction power systems. The dwell time of multiple trains at each station and the trigger voltage of the regenerative energy absorbing device (READ are optimized based on an improved particle swarm optimization (PSO algorithm to manage the distribution of regenerative power. In this way, the maximum absolute rail potential and energy consumption of DC traction power systems can be reduced. The operation data of Guangzhou Metro Line 2 are used in the simulations, and the results show that the scheme can reduce the maximum absolute rail potential and energy consumption effectively and guarantee the safety in energy saving of DC traction power systems.

  14. Stem Cells Applications in Regenerative Medicine and Disease Therapeutics

    Directory of Open Access Journals (Sweden)

    Ranjeet Singh Mahla

    2016-01-01

    Full Text Available Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation.

  15. Regenerative Electrode Interfaces for Neural Prostheses.

    Science.gov (United States)

    Thompson, Cort H; Zoratti, Marissa J; Langhals, Nicholas B; Purcell, Erin K

    2016-04-01

    Neural prostheses are electrode arrays implanted in the nervous system that record or stimulate electrical activity in neurons. Rapid growth in the use of neural prostheses in research and clinical applications has occurred in recent years, but instability and poor patency in the tissue-electrode interface undermines the longevity and performance of these devices. The application of tissue engineering strategies to the device interface is a promising approach to improve connectivity and communication between implanted electrodes and local neurons, and several research groups have developed new and innovative modifications to neural prostheses with the goal of seamless device-tissue integration. These approaches can be broadly categorized based on the strategy used to maintain and regenerate neurons at the device interface: (1) redesign of the prosthesis architecture to include finer-scale geometries and/or provide topographical cues to guide regenerating neural outgrowth, (2) incorporation of material coatings and bioactive molecules on the prosthesis to improve neuronal growth, viability, and adhesion, and (3) inclusion of cellular grafts to replenish the local neuron population or provide a target site for reinnervation (biohybrid devices). In addition to stabilizing the contact between neurons and electrodes, the potential to selectively interface specific subpopulations of neurons with individual electrode sites is a key advantage of regenerative interfaces. In this study, we review the development of regenerative interfaces for applications in both the peripheral and central nervous system. Current and future development of regenerative interfaces has the potential to improve the stability and selectivity of neural prostheses, improving the patency and resolution of information transfer between neurons and implanted electrodes.

  16. A bioresorbable polylactide implant used in bone cyst filling.

    Science.gov (United States)

    Ficek, Krzysztof; Filipek, Jolanta; Wojciechowski, Piotr; Kopec, Konrad; Ewa, Stodolak-Zych; Blazewicz, Stanislaw

    2016-02-01

    The aims in treating patients diagnosed with critical-sized bone defects resulting from bone cysts are to replace the lost bone mass after its removal and to restore function. The standard treatment is autologous or allogeneic bone transplantation, notwithstanding the known consequences and risks due to possible bone infection, donor site morbidity, bleeding and nerve injury and possible undesirable immune reactions. Additionally, allogeneic grafts are inhomogeneous, with a mosaic of components with difficult-to-predict regenerative potential, because they consist of cancellous bone obtained from different bones from various cadavers. In the present study, a 22-year-old patient with a history of right humerus fracture due to bone cysts was diagnosed with recurrent cystic lesions based on X-ray results. The patient qualified for an experimental program, in which he was treated with the application of a bioresorbable polylactide hybrid sponge filled with autologous platelet-rich plasma. Computed tomography and magnetic resonance imaging performed 3, 6, and 36 months after surgery showed progressive ossification and bone formation inside the defect cavity in the humerus. Three years after treatment with the bone substitute, the patient is pain free, and the cystic lesions have not reoccurred.

  17. Mesenchymal stem cells from reaming material possess high osteogenic potential and react sensitively to bone morphogenetic protein 7.

    Science.gov (United States)

    Hoellig, Melanie; Westhauser, Fabian; Kornienko, Kira; Xiao, Kai; Schmidmaier, Gerhard; Moghaddam, Arash

    2017-01-26

    Femoral material harvested using the Reamer-Irrigator-Aspirator (RIA) system is an alternative source for autogenous bone material in the treatment of non-unions, especially in combination with bone morphogenetic proteins (BMP). So far, there is no in vivo evidence of BMP-7 interacting with mesenchymal stem cells (MSCs) from RIA material (RIA-MSCs) and iliac crest autogenous bone (BMSCs). The aim of this study was to compare their osteogenic potential when stimulated with BMP-7 in vivo. RIA-MSC and BMSC from 11 donors were isolated and the character of MSCs was investigated in vitro. Constructs consisting of MSC, β-tricalcium phosphate and 2 concentrations of BMP-7 (0.1 µg/mL and 1 µg/mL) were implanted in mice for 8 weeks. Bone formation in the constructs was analyzed quantitatively and qualitatively. All cell populations used were determined to be MSCs. The qualitative in vivo analysis showed formation of bone tissue. With regard to quantity, bone formation was significantly higher in RIA constructs without or with stimulation with 0.1 µg/mL BMP-7, compared with BMSC constructs. We found no significant differences between constructs stimulated with 1 µg/mL BMP-7. In the RIA group, we observed a significant increase in bone formation after stimulation with 0.1 µg/mL BMP-7. No significant change could be found using a higher concentration. In the BMSC group, we detected a significant increase when using 0.1 µg/mL and 1 µg/mL BMP-7. RIA material is a source of MSCs with high osteogenic potential. Our results showed that stimulation by BMP-7 leads to an increased osteogenic potential of MSCs. In this respect, RIA-MSCs reacted more sensitively than BMSCs.

  18. [Bone tissue engineering. Reconstruction of critical sized segmental bone defects in the ovine tibia].

    Science.gov (United States)

    Reichert, J C; Epari, D R; Wullschleger, M E; Berner, A; Saifzadeh, S; Nöth, U; Dickinson, I C; Schuetz, M A; Hutmacher, D W

    2012-04-01

    Well-established therapies for bone defects are restricted to bone grafts which face significant disadvantages (limited availability, donor site morbidity, insufficient integration). Therefore, the objective was to develop an alternative approach investigating the regenerative potential of medical grade polycaprolactone-tricalcium phosphate (mPCL-TCP) and silk-hydroxyapatite (silk-HA) scaffolds.Critical sized ovine tibial defects were created and stabilized. Defects were left untreated, reconstructed with autologous bone grafts (ABG) and mPCL-TCP or silk-HA scaffolds. Animals were observed for 12 weeks. X-ray analysis, torsion testing and quantitative computed tomography (CT) analyses were performed. Radiological analysis confirmed the critical nature of the defects. Full defect bridging occurred in the autograft and partial bridging in the mPCL-TCP group. Only little bone formation was observed with silk-HA scaffolds. Biomechanical testing revealed a higher torsional moment/stiffness (p CT analysis a significantly higher amount of bone formation for the ABG group when compared to the silk-HA group. No significant difference was determined between the ABG and mPCL-TCP groups. The results of this study suggest that mPCL-TCP scaffolds combined can serve as an alternative to autologous bone grafting in long bone defect regeneration. The combination of mPCL-TCP with osteogenic cells or growth factors represents an attractive means to further enhance bone formation.

  19. Clinical Application of Vascular Regenerative Therapy for Peripheral Artery Disease

    Directory of Open Access Journals (Sweden)

    Hiroshi Suzuki

    2013-01-01

    Full Text Available Prognosis of peripheral artery disease (PAD, especially critical limb ischemia, is very poor despite the development of endovascular therapy and bypass surgery. Many patients result in leg amputation and, therefore, vascular regenerative therapy is expected in this field. Gene therapy using vascular endothelial growth factor is the first step of vascular regenerative therapy, but did not confirm effectiveness in a large-scale randomized comparative study. Based on animal experiments, bone marrow mononuclear cells (MNCs, peripheral blood MNCs were used as the cell source for regenerative therapy. Those cells were confirmed to be effective to decrease rest pain and ulcer size, but its effect was not fully satisfied. Mesenchymal stem cells (MSCs are expected as an effective cell source for vascular regeneration and clinical studies are ongoing, because the cells are able to differentiate into various cell types and produce a significant amount of vascular growth factors. Of vascular regeneration therapy, peripheral MNCs and bone marrow MNCs were recognized as advanced medical technology but do not attain to the standard therapy. However, clinical use of MSCs have already started, and induced pluripotent stem cells are surely promising tool for vascular regeneration therapy although further basic studies are required for clinical application.

  20. Long-term potentiation in bone – a role for glutamate in strain-induced cellular memory?

    Directory of Open Access Journals (Sweden)

    Genever Paul G

    2003-07-01

    Full Text Available Abstract Background The adaptive response of bone cells to mechanical strain is a primary determinant of skeletal architecture and bone mass. In vivo mechanical loading induces new bone formation and increases bone mineral density whereas disuse, immobilisation and weightlessness induce bone loss. The potency of mechanical strain is such that a single brief period of loading at physiological strain magnitude is able to induce a long-lasting osteogenic response that lasts for days. Although the process of mechanotransduction in bone is incompletely understood, observations that responses to mechanical strain outlast the duration of stimulation necessitate the existence of a form of cellular memory through which transient strain episodes are recorded, interpreted and remembered by bone cells. Recent evidence supports the existence of a complex multicellular glutamate-signalling network in bone that shares functional similarities to glutamatergic neurotransmission in the central nervous system. In neurones, these signalling molecules coordinate synaptic communication required to support learning and memory formation, through a complex process of long-term potentiation. Presentation of the hypothesis We hypothesise that osteoblasts use a cellular mechanism similar or identical to neuronal long-term potentiation in the central nervous system to mediate long-lasting changes in osteogenesis following brief periods of mechanical strain. Testing the hypothesis N-methyl-D-aspartate (NMDA receptor antagonism should inhibit the saturating response of mechanical strain and reduce the enhanced osteogenicity of segregated loading to that of an equivalent period of uninterrupted loading. Changes in α-amino-3-hydroxy-5-methyl-isoxazole propionate (AMPA receptor expression, localisation and electrophysiological responses should be induced by mechanical strain and inhibited by modulators of neuronal long-term potentiation. Implications of the hypothesis If true

  1. Saccular function in otosclerosis patients: bone conducted-vestibular evoked myogenic potential analysis.

    Directory of Open Access Journals (Sweden)

    Amin Amali

    2014-02-01

    Full Text Available Vestibular involvements have long been observed in otosclerotic patients. Among vestibular structures saccule has the closest anatomical proximity to the sclerotic foci, so it is the most prone vestibular structure to be affected during the otosclerosis process. The aim of this study was to investigate the saccular function in patients suffering from otosclerosis, by means of Vestibular Evoked Myogenic Potential (VEMP. The material consisted of 30 otosclerosis patients and 20 control subjects. All participants underwent audiometric and VEMP testing. Analysis of tests results revealed that the mean values of Air-Conducted Pure Tone Average (AC-PTA and Bone-Conducted Pure Tone Average (BC-PTA in patients were 45.28 ± 15.57 and 19.68 ± 10.91, respectively and calculated 4 frequencies Air Bone Gap (ABG was 25.64 ± 9.95. The VEMP response was absent in 14 (28.57% otosclerotic ears. A statistically significant increase in latency of the p13 was found in the affected ears (P=0.004, differences in n23 latency did not reach a statistically significant level (P=0.112. Disparities in amplitude of p13-n23 in between two study groups was statistically meaningful (P=0.009, indicating that the patients with otosclerosis had lower amplitudes. This study tends to suggest that due to the direct biotoxic effect of the materials released from the otosclerosis foci on saccular receptors, there might be a possibility of vestibular dysfunction in otosclerotic patients.

  2. Stem cells:Sources, and regenerative therapies in dental research and practice

    Institute of Scientific and Technical Information of China (English)

    Lobna; Abdel; Aziz; Aly

    2015-01-01

    Stem cells are considered to be among the principle scientific breakthroughs of the twentieth century for the future of medicine, and considered to be an important weapon to fight against diseases, particularly those that have resisted the efforts of science for a long time. Human dental tissues have limited potentials to regenerate but the discovery of dental stem cells have developed new and surprising scenario in regenerative dentistry. Stem cell treatments are one example of thepossibility using adult cells sourced from patients’ own bodies’ means that it can be expected that in the near future such treatments may become routine at dental practices. The hope is that it will become possible to regenerate bone and dental tissues including the periodontal ligament, dental pulp and enamel, and that the creation of new teeth may also become feasible. In view of this possibility of achieving restoration with regenerative medicine, it can be considered that a new era of dentistry is beginning. Thus the aim of this review is to give dental professionals a brief overview of different stem cells sources and the latest findings and their implications for improving oral health and treating certain conditions of the human mouth and face.

  3. Biomimetic microenvironments for regenerative endodontics.

    Science.gov (United States)

    Kaushik, Sagar N; Kim, Bogeun; Walma, Alexander M Cruz; Choi, Sung Chul; Wu, Hui; Mao, Jeremy J; Jun, Ho-Wook; Cheon, Kyounga

    2016-01-01

    Regenerative endodontics has been proposed to replace damaged and underdeveloped tooth structures with normal pulp-dentin tissue by providing a natural extracellular matrix (ECM) mimicking environment; stem cells, signaling molecules, and scaffolds. In addition, clinical success of the regenerative endodontic treatments can be evidenced by absence of signs and symptoms; no bony pathology, a disinfected pulp, and the maturation of root dentin in length and thickness. In spite of the various approaches of regenerative endodontics, there are several major challenges that remain to be improved: a) the endodontic root canal is a strong harbor of the endodontic bacterial biofilm and the fundamental etiologic factors of recurrent endodontic diseases, (b) tooth discolorations are caused by antibiotics and filling materials, (c) cervical root fractures are caused by endodontic medicaments, (d) pulp tissue is not vascularized nor innervated, and (e) the dentin matrix is not developed with adequate root thickness and length. Generally, current clinical protocols and recent studies have shown a limited success of the pulp-dentin tissue regeneration. Throughout the various approaches, the construction of biomimetic microenvironments of pulp-dentin tissue is a key concept of the tissue engineering based regenerative endodontics. The biomimetic microenvironments are composed of a synthetic nano-scaled polymeric fiber structure that mimics native pulp ECM and functions as a scaffold of the pulp-dentin tissue complex. They will provide a framework of the pulp ECM, can deliver selective bioactive molecules, and may recruit pluripotent stem cells from the vicinity of the pulp apex. The polymeric nanofibers are produced by methods of self-assembly, electrospinning, and phase separation. In order to be applied to biomedical use, the polymeric nanofibers require biocompatibility, stability, and biodegradability. Therefore, this review focuses on the development and application of the

  4. Concise Review: Parthenote Stem Cells for Regenerative Medicine: Genetic, Epigenetic, and Developmental Features

    OpenAIRE

    Daughtry, Brittany; Mitalipov, Shoukhrat

    2014-01-01

    It has been observed that embryonic stem cells have the potential to provide unlimited cells and tissues for regenerative medicine. This review suggests potential advantages and limitations of embryonic stem cells derived from parthenogenetic embryos for cell-based therapies.

  5. Advances in regenerative orthopedics.

    Science.gov (United States)

    Evans, Christopher H

    2013-11-01

    Orthopedic injuries are common and a source of much misery and economic stress. Several relevant tissues, such as cartilage, meniscus, and intra-articular ligaments, do not heal. And even bone, which normally regenerates spontaneously, can fail to mend. The regeneration of orthopedic tissues requires 4 key components: cells, morphogenetic signals, scaffolds, and an appropriate mechanical environment. Although differentiated cells from the tissue in question can be used, most cellular research focuses on the use of mesenchymal stem cells. These can be retrieved from many different tissues, and one unresolved question is the degree to which the origin of the cells matters. Embryonic and induced pluripotent stem cells are also under investigation. Morphogenetic signals are most frequently supplied by individual recombinant growth factors or native mixtures provided by, for example, platelet-rich plasma; mesenchymal stem cells are also a rich source of trophic factors. Obstacles to the sustained delivery of individual growth factors can be addressed by gene transfer or smart scaffolds, but we still lack detailed, necessary information on which delivery profiles are needed. Scaffolds may be based on natural products, synthetic materials, or devitalized extracellular matrix. Strategies to combine these components to regenerate tissue can follow traditional tissue engineering practices, but these are costly, cumbersome, and not well suited to treating large numbers of individuals. More expeditious approaches make full use of intrinsic biological processes in vivo to avoid the need for ex vivo expansion of autologous cells and multiple procedures. Clinical translation remains a bottleneck. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  6. Potential of bone marrow mesenchymal stem cells in management of Alzheimer's disease in female rats.

    Science.gov (United States)

    Salem, Ahmed M; Ahmed, Hanaa H; Atta, Hazem M; Ghazy, Mohamed A; Aglan, Hadeer A

    2014-12-01

    Alzheimer's disease (AD) has been called the disease of the century with significant clinical and socioeconomic impacts. Pharmacological treatment has limited efficacy and only provides symptomatic relief without long-term cure. Accordingly, there is an urgent need to develop novel and effective medications for AD. Stem cell-based therapy is a promising approach to handling neurodegenerative diseases. Therefore, the current study aimed to explore the possible therapeutic role of single intravenous injection of bone marrow derived mesenchymal stem cells (BM-MSCs) after 4 months in management of AD in the experimental model. The work also extended to compare the therapeutic potential of BM-MSCs with 2 conventional therapies of AD; rivastigmine and cerebrolysin administered daily. BM-MSCs were able to home at the injured brains and produced significant increases in the number of positive cells for choline acetyltransferase (ChAT) and survivin expression, as well as selective AD indicator-1 (seladin-1) and nestin gene expression. Histopathological examination indicated that BM-MSCs could remove beta-amyloid plaques from hippocampus. Significant improvement in these biomarkers was similar to or better sometimes than the reference drugs, clearly showing the potential therapeutic role of BM-MSCs against AD through their anti-apoptotic, neurogenic and immunomodulatory properties. © 2014 International Federation for Cell Biology.

  7. BMI and BMD: The Potential Interplay between Obesity and Bone Fragility

    OpenAIRE

    Andrea Palermo; Dario Tuccinardi; Giuseppe Defeudis; Mikiko Watanabe; Luca D’Onofrio; Angelo Lauria Pantano; Nicola Napoli; Paolo Pozzilli; Silvia Manfrini

    2016-01-01

    Recent evidence demonstrating an increased fracture risk among obese individuals suggests that adipose tissue may negatively impact bone health, challenging the traditional paradigm of fat mass playing a protective role towards bone health. White adipose tissue, far from being a mere energy depot, is a dynamic tissue actively implicated in metabolic reactions, and in fact secretes several hormones called adipokines and inflammatory factors that may in turn promote bone resorption. More specif...

  8. Rethinking Regenerative Medicine: A Macrophage-Centered Approach

    Directory of Open Access Journals (Sweden)

    Bryan N Brown

    2014-11-01

    Full Text Available Regenerative medicine, a multi-disciplinary approach that seeks to restore form and function to damaged or diseased tissues and organs, has evolved significantly during the past decade. By adapting and integrating fundamental knowledge from cell biology, polymer science, and engineering, coupled with an increasing understanding of the mechanisms which underlie the pathogenesis of specific diseases, regenerative medicine has the potential for innovative and transformative therapies for heretofore unmet medical needs. However, the translation of novel technologies from the benchtop to animal models and clinical settings is non-trivial and requires an understanding of the mechanisms by which the host will respond to these novel therapeutic approaches. The role of the innate immune system, especially the role of macrophages, in the host response to regenerative medicine based strategies has recently received considerable attention. Macrophage phenotype and function have been suggested as critical and determinant factors in downstream functional outcomes. The constructive and regulatory, and in fact essential, role of macrophages in positive outcomes represents a significant departure from the classical paradigms of host-biomaterial interactions, which typically consider activation of the host immune system as undesirable. It appears desirable that emerging regenerative medicine approaches should not only accommodate, but promote, the involvement of the immune system to facilitate positive outcomes. Herein, we describe the current understanding of macrophage phenotype as it pertains to regenerative medicine and suggest that improvement of our understanding of context-dependent macrophage polarization will lead to concurrent improvement in outcomes.

  9. Osteoinductive potential of demineralized rat bone increases with increasing donor age from birth to adulthood

    DEFF Research Database (Denmark)

    Pinholt, E M; Solheim, E

    1998-01-01

    quantitatively, by uptake of strontium 85, the osteoinductive effect of demineralized bone matrix from newborn, 8-week-old (adolescent), and 8-month-old (adult) male Wistar rats implanted in the abdominal muscles of 8-week-old male Wistar rats. The osteoinductive response increased significantly with increasing......Demineralized allogenic bone implanted in the subcutis or muscle of rodents causes formation of heterotopic bone by osteoinduction. The osteoinductive response may be weaker in primates than in rodents. It was suggested that the osteoinductive response of demineralized bone for clinical use could...

  10. Gene delivery in tissue engineering and regenerative medicine.

    Science.gov (United States)

    Fang, Y L; Chen, X G; W T, Godbey

    2015-11-01

    As a promising strategy to aid or replace tissue/organ transplantation, gene delivery has been used for regenerative medicine applications to create or restore normal function at the cell and tissue levels. Gene delivery has been successfully performed ex vivo and in vivo in these applications. Excellent proliferation capabilities and differentiation potentials render certain cells as excellent candidates for ex vivo gene delivery for regenerative medicine applications, which is why multipotent and pluripotent cells have been intensely studied in this vein. In this review, gene delivery is discussed in detail, along with its applications to tissue engineering and regenerative medicine. A definition of a stem cell is compared to a definition of a stem property, and both provide the foundation for an in-depth look at gene delivery investigations from a germ lineage angle.

  11. Potential Spermatogenesis Recovery with Bone Marrow Mesenchymal Stem Cells in an Azoospermic Rat Model

    Directory of Open Access Journals (Sweden)

    Deying Zhang

    2014-07-01

    Full Text Available Non-obstructive azoospermia is the most challenging type of male infertility. Stem cell based therapy provides the potential to enhance the recovery of spermatogenesis following cancer therapy. Bone marrow-derived mesenchymal stem cells (BMSCs possess the potential to differentiate or trans-differentiate into multi-lineage cells, secrete paracrine factors to recruit the resident stem cells to participate in tissue regeneration, or fuse with the local cells in the affected region. In this study, we tested whether spermatogenically-induced BMSCs can restore spermatogenesis after administration of an anticancer drug. Allogeneic BMSCs were co-cultured in conditioned media derived from cultured testicular Sertoli cells in vitro, and then induced stem cells were transplanted into the seminiferous tubules of a busulfan-induced azoospermatic rat model for 8 weeks. The in vitro induced BMSCs exhibited specific spermatogonic gene and protein markers, and after implantation the donor cells survived and located at the basement membranes of the recipient seminiferous tubules, in accordance with what are considered the unique biological characteristics of spermatogenic stem cells. Molecular markers of spermatogonial stem cells and spermatogonia (Vasa, Stella, SMAD1, Dazl, GCNF, HSP90α, integrinβ1, and c-kit were expressed in the recipient testis tissue. No tumor mass, immune response, or inflammatory reaction developed. In conclusion, BMSCs might provide the potential to trans-differentiate into spermatogenic-like-cells, enhancing endogenous fertility recovery. The present study indicates that BMSCs might offer alternative treatment for the patients with azoospermatic infertility after cancer chemotherapy.

  12. Multiple regenerative techniques for class II furcation defect

    Directory of Open Access Journals (Sweden)

    Pushpendra Kumar Verma

    2012-01-01

    Full Text Available Regeneration of the periodontium is a major goal in the treatment of teeth affected by periodontitis. Periodontal regeneration is quite challenging, especially when it is in the furcation area. There are several techniques used alone or in combination, considered to achieve periodontal regeneration, including bone grafts or substitutes, guided tissue regeneration, root surface modification, and biological mediators. Many factors may account for variability in the response to regenerative therapy in class II furcation. This case report describes the management of a buccal class II furcation defect, with the help of surgical intervention, including the guided tissue regeneration (GTR membrane and bone graft materials. This combined treatment resulted in a healthy periodontium, with radiographic evidence of alveolar bone gain. This case report demonstrates that proper diagnosis, followed by removal of the etiological factors and utilizing combined treatment modalities, restored health and function of the tooth with severe attachment loss, at the 18-month follow-up.

  13. Stem cell-mediated osteogenesis: therapeutic potential for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Neman J

    2012-03-01

    Full Text Available Josh Neman1, Amanda Hambrecht2, Cherie Cadry3, Rahul Jandial11Department of Neurosurgery, Beckman Research Institute, City of Hope National Cancer Center, Duarte, 2Department of Biological Sciences, University of Southern California, Los Angeles, 3Department of Public Health Sciences, University of California, Irvine, California, USAAbstract: Intervertebral disc degeneration often requires bony spinal fusion for long-term relief. Current arthrodesis procedures use bone grafts from autogenous bone, allogenic backed bone, or synthetic materials. Autogenous bone grafts can result in donor site morbidity and pain at the donor site, while allogenic backed bone and synthetic materials have variable effectiveness. Given these limitations, researchers have focused on new treatments that will allow for safe and successful bone repair and regeneration. Mesenchymal stem cells have received attention for their ability to differentiate into osteoblasts, cells that synthesize new bone. With the recent advances in scaffold and biomaterial technology as well as stem cell manipulation and transplantation, stem cells and their scaffolds are uniquely positioned to bring about significant improvements in the treatment and outcomes of spinal fusion and other injuries.Keywords: mesenchymal stem cell, osteogenesis, scaffolds, bone morphogenetic protein, Wnt, autograft, osteoblast

  14. Relation between in vitro and in vivo osteogenic potential of cultured human bone marrow stromal cells

    NARCIS (Netherlands)

    Mendes, SC; Tibbe, JM; Veenhof, M; Both, S; Oner, FC; van Blitterswijk, CA; de Bruijn, Joost D.

    2004-01-01

    The use of cell therapies in bone reconstruction has been the subject of extensive research. It is known that human bone marrow stromal cell (HBMSC) cultures contain a population of progenitor cells capable of differentiation towards the osteogenic lineage. In the present study, the correlation betw

  15. The role of P2 purinergic receptores in bone metabolisme and their therapeutic potential

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Solgaard, M; Schwarz, P

    2006-01-01

    Abstract. The role of purinergic P2 receptors in bone biology has been evaluated over the last decade. These receptors have proven to be an interesting target for new pharmacological agents with the ability to regulate bone metabolism. As the prevalence of osteoporosis increases new efficient age...... drugs, which can be used for treatment of metabolic bone diseases, including osteoporosis. This article is reviewing the studies documenting the effects of nucleotides and P2 receptors in bone and bone cells.......Abstract. The role of purinergic P2 receptors in bone biology has been evaluated over the last decade. These receptors have proven to be an interesting target for new pharmacological agents with the ability to regulate bone metabolism. As the prevalence of osteoporosis increases new efficient...... agents to treat the disease are sought for. The P2 receptors are activated by nucleotides and recently, studies have shown a possible role for these in bone turnover and metabolism. P2 receptors can be divided further into P2X and P2Y subtypes with strikingly different mechanisms of action...

  16. Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    John G. Hardy

    2016-07-01

    Full Text Available Materials based on biodegradable polyesters, such as poly(butylene terephthalate (PBT or poly(butylene terephthalate-co-poly(alkylene glycol terephthalate (PBTAT, have potential application as pro-regenerative scaffolds for bone tissue engineering. Herein, the preparation of films composed of PBT or PBTAT and an engineered spider silk protein, (eADF4(C16, that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported. Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering.

  17. Regenerative Endodontic Procedures: Clinical Outcomes.

    Science.gov (United States)

    Diogenes, Anibal; Ruparel, Nikita B

    2017-01-01

    Immature teeth are at risk for pulp necrosis, resulting in arrested root development and poor long-term prognosis. There is growing evidence that regenerative endodontic procedures promote desirable clinical outcomes. Despite significant advances in the field of regenerative endodontics and acceptable clinical outcomes, current evidence suggests that the tissues formed following currently used procedures do not completely recapitulate the former pulp-dentin complex. Further research is needed to identify prognostic factors and predictors of successful outcomes and to develop different treatment strategies to better predictably achieve all identified clinical outcomes, while favoring tissue formation that more closely resembles the pulp-dentin complex. Copyright © 2016. Published by Elsevier Inc.

  18. Bone-targeted acid-sensitive doxorubicin conjugate micelles as potential osteosarcoma therapeutics.

    Science.gov (United States)

    Low, Stewart A; Yang, Jiyuan; Kopeček, Jindřich

    2014-11-19

    Osteosarcoma is a malignancy of the bone that primarily affects adolescents. Current treatments retain mortality rates, which are higher than average cancer mortality rates for the adolescent age group. We designed a micellar delivery system with the aim to increase drug accumulation in the tumor and potentially reduce side effects associated with chemotherapy. The design features are the use of the hydrophilic D-aspartic acid octapeptide as both the effective targeting agent as well as the hydrophilic micelle corona. Micelle stabilization was accomplished by binding of model drug (doxorubicin) via an acid-sensitive hydrazone bond and incorporating one to four 11-aminoundecanoic acid (AUA) moieties to manipulate the hydrophobic/hydrophilic ratio. Four micelle-forming unimers have been synthesized and their self-assembly into micelles was evaluated. Size of the micelles could be modified by changing the architecture of the unimers from linear to branched. The stability of the micelles increased with increasing content of AUA moieties. Adsorption of all micelles to hydroxyapatite occurred rapidly. Doxorubicin release occurred at pH 5.5, whereas no release was detected at pH 7.4. Cytotoxicity toward human osteosarcoma Saos-2 cells correlated with drug release data.

  19. Engineering growth factors for regenerative medicine applications.

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, Aaron C.; Briquez, Priscilla S.; Hubbell, Jeffrey A.; Cochran, Jennifer R.

    2016-01-15

    Growth factors are important morphogenetic proteins that instruct cell behavior and guide tissue repair and renewal. Although their therapeutic potential holds great promise in regenerative medicine applications, translation of growth factors into clinical treatments has been hindered by limitations including poor protein stability, low recombinant expression yield, and suboptimal efficacy. This review highlights current tools, technologies, and approaches to design integrated and effective growth factor-based therapies for regenerative medicine applications. The first section describes rational and combinatorial protein engineering approaches that have been utilized to improve growth factor stability, expression yield, biodistribution, and serum half-life, or alter their cell trafficking behavior or receptor binding affinity. The second section highlights elegant biomaterial-based systems, inspired by the natural extracellular matrix milieu, that have been developed for effective spatial and temporal delivery of growth factors to cell surface receptors. Although appearing distinct, these two approaches are highly complementary and involve principles of molecular design and engineering to be considered in parallel when developing optimal materials for clinical applications.

  20. Integrated regenerative fuel cell experimental evaluation

    Science.gov (United States)

    Martin, Ronald E.

    1990-01-01

    An experimental test program was conducted to investigate the performance characteristics of an integrated regenerative fuel cell (IRFC) concept. The IRFC consists of a separate fuel cell unit and electrolysis cell unit in the same structure, with internal storage of fuel cell product water and external storage of electrolysis cell produced hydrogen and oxygen. The fuel cell unit incorporates an enhanced Orbiter-type cell capable of improved performance at reduced weight. The electrolysis cell features a NiCo2O4 catalyst oxygen evolution eletrode with a porous Teflon cover to retard electrolyte loss. Six complete IRFC assemblies were assembled and performance tested at an operating temperature of 200 F (93.3 C) and reactant pressures up to 170 psia (117.2 n/cu cm) on IRFC No. 4. Anomalous pressure charge/discharge characteristics were encountered during performance evaluation. A reversible fuel cell incorporating a proprietary bi-functional oxygen electrode operated satisfactory at 200 F (93.3 C) at reactant pressures up to 50 psia (41.4 n/cu cm) as a regenerative fuel cell for one cycle, before developing an electrical short in the fuel cell mode. Electrolysis cell 300-hour endurance tests demonstrated the electrolyte retention capability of the electrode Teflon cover and the performance stability of the bi-functional oxygen electrode at high potential.

  1. Regenerative endodontics: A way forward.

    Science.gov (United States)

    Diogenes, Anibal; Ruparel, Nikita B; Shiloah, Yoav; Hargreaves, Kenneth M

    2016-05-01

    Immature teeth are susceptible to infections due to trauma, anatomic anomalies, and caries. Traditional endodontic therapies for immature teeth, such as apexification procedures, promote resolution of the disease and prevent future infections. However, these procedures fail to promote continued root development, leaving teeth susceptible to fractures. Regenerative endodontic procedures (REPs) have evolved in the past decade, being incorporated into endodontic practice and becoming a viable treatment alternative for immature teeth. The authors have summarized the status of regenerative endodontics on the basis of the available published studies and provide insight into the different levels of clinical outcomes expected from these procedures. Substantial advances in regenerative endodontics are allowing a better understanding of a multitude of factors that govern stem cell-mediated regeneration and repair of the damaged pulp-dentin complex. REPs promote healing of apical periodontitis, continued radiographic root development, and, in certain cases, vitality responses. Despite the clinical success of these procedures, they appear to promote a guided endodontic repair process rather than a true regeneration of physiological-like tissue. Immature teeth with pulpal necrosis with otherwise poor prognosis can be treated with REPs. These procedures do not preclude the possibility of apexification procedures if attempts are unsuccessful. Therefore, REPs may be considered first treatment options for immature teeth with pulpal necrosis. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

  2. Regenerative endodontics: regeneration or repair?

    Science.gov (United States)

    Simon, Stéphane R J; Tomson, Phillip L; Berdal, Ariane

    2014-04-01

    Recent advances in biotechnology and translational research have made it possible to provide treatment modalities that protect the vital pulp, allow manipulation of reactionary and reparative dentinogenesis, and, more recently, permit revascularization of an infected root canal space. These approaches are referred to as regenerative procedures. The method currently used to determine the origin of the tissue secreted during the repair/regeneration process is largely based on the identification of cellular markers (usually proteins) left by cells that were responsible for this tissue production. The presence of these proteins in conjunction with other indicators of cellular behavior (especially biomineralization) and analysis of the structure of the newly generated tissue allow conclusions to be made of how it was formed. Thus far, it has not been possible to truly establish the biological mechanism controlling tertiary dentinogenesis. This article considers current therapeutic techniques to treat the dentin-pulp complex and contextualize them in terms of reparative and regenerative processes. Although it may be considered a semantic argument rather than a biological one, the definitions of regeneration and repair are explored to clarify our position in this era of regenerative endodontics. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  3. Sustained release of bone morphogenetic protein 2 via coacervate improves the osteogenic potential of muscle-derived stem cells.

    Science.gov (United States)

    Li, Hongshuai; Johnson, Noah Ray; Usas, Arvydas; Lu, Aiping; Poddar, Minakshi; Wang, Yadong; Huard, Johnny

    2013-09-01

    Muscle-derived stem cells (MDSCs) isolated from mouse skeletal muscle by a modified preplate technique exhibit long-term proliferation, high self-renewal, and multipotent differentiation capabilities in vitro. MDSCs retrovirally transduced to express bone morphogenetic proteins (BMPs) can differentiate into osteocytes and chondrocytes and enhance bone and articular cartilage repair in vivo, a feature that is not observed with nontransduced MDSCs. These results emphasize that MDSCs require prolonged exposure to BMPs to undergo osteogenic and chondrogenic differentiation. A sustained BMP protein delivery approach provides a viable and potentially more clinically translatable alternative to genetic manipulation of the cells. A unique growth factor delivery platform comprised of native heparin and a synthetic polycation, poly(ethylene argininylaspartate diglyceride) (PEAD), was used to bind, protect, and sustain the release of bone morphogenetic protein-2 (BMP2) in a temporally and spatially controlled manner. Prolonged exposure to BMP2 released by the PEAD:heparin delivery system promoted the differentiation of MDSCs to an osteogenic lineage in vitro and induced the formation of viable bone at an ectopic site in vivo. This new strategy represents an alternative approach for bone repair mediated by MDSCs while bypassing the need for gene therapy.

  4. Multifunctional nano-hydroxyapatite and alginate/gelatin based sticky gel composites for potential bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Yurong; Yu, Juhong [The Key Laboratory of Advanced Textile Materials and Manufacturing Technology of Ministry of Education, National Engineering Lab of Textile Fiber Materials & Processing Technology, College of Materials and Textile, Zhejiang Sci-Tech University, Hangzhou 310018 (China); Kundu, Subhas C. [Department of Biotechnology, Indian Institute of Technology (IIT) Kharagpur, West Bengal 721302 (India); Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714 (Korea, Republic of); Yao, Juming, E-mail: yaoj@zstu.edu.cn [The Key Laboratory of Advanced Textile Materials and Manufacturing Technology of Ministry of Education, National Engineering Lab of Textile Fiber Materials & Processing Technology, College of Materials and Textile, Zhejiang Sci-Tech University, Hangzhou 310018 (China)

    2016-09-15

    To improve the fixations of the implant and implant-bone integration after joint arthroplasty from locally preventing inflammation and promoting the bone regeneration, we design a multifunctional biomaterial consisting of recombinant human bone morphogenetic protein 2 (rhBMP-2) and antibiotic loaded nano-hydroxyapatite with an alginate/gelatin sticky gel. We investigate its role for the prevention of the inflammation and possibility of inducing a new bone growth along with its adhesive ability. The stickiness exists in the composite, which may help to fix itself on the bone fracture surface. The composite sustains the antibacterial effect and promotes the proliferation and differentiation of MG63 cells in vitro. In vivo experimentation also shows that the composite gel has a role for the reduction of inflammation. It enhances the formation of new bone and blood vessels compared to both the sole rhBMP-2 and non-rhBMP-2/antibiotic loaded composite gels. The multifunctional composite provides a promising material for the prosthetic and bone tissue regeneration. - Highlights: • Multifunctional nanohydroxyapatite composite is fabricated. • The composite consists of nHAP, growth factor, antibiotic and alginate/gelatin gel. • The composite shows antibacterial effect and good cytocompatibility. • No adverse effect to the cells tested in vitro and in vivo.

  5. Electrospinning of polysaccharides for regenerative medicine.

    Science.gov (United States)

    Lee, Kuen Yong; Jeong, Lim; Kang, Yun Ok; Lee, Seung Jin; Park, Won Ho

    2009-10-05

    Electrospinning techniques enable the production of continuous fibers with dimensions on the scale of nanometers from a wide range of natural and synthetic polymers. The number of recent studies regarding electrospun polysaccharides and their derivatives, which are potentially useful for regenerative medicine, is increasing dramatically. However, difficulties regarding the processibility of the polysaccharides (e.g., poor solubility and high surface tension) have limited their application. In this review, we summarize the characteristics of various polysaccharides such as alginate, cellulose, chitin, chitosan, hyaluronic acid, starch, dextran, and heparin, which are either currently being used or have potential to be used for electrospinning. The recent progress of nanofiber matrices electrospun from polysaccharides and their biomedical applications in tissue engineering, wound dressings, drug delivery, and enzyme immobilization are discussed.

  6. Moderate alcohol consumption and increased bone mineral density: potential ethanol and non-ethanol mechanisms.

    Science.gov (United States)

    Jugdaohsingh, R; O'Connell, M A; Sripanyakorn, S; Powell, J J

    2006-08-01

    Mounting epidemiological evidence indicates an association between the moderate ingestion of alcoholic beverages and higher bone mineral density (v. abstainers). More limited findings provide some evidence for translation of this association into reduced fracture risk, but further studies are required. Here, these data are reviewed and caveats in their assimilation, comparison and interpretation as well as in the use and application of bone health indices are discussed. Whilst it is concluded that evidence is now strong for the moderate alcohol-bone health association, at least in relation to bone mineral density, mechanisms are less clear. Both ethanol and non-ethanol components have been implicated as factors that positively affect bone health in the light of moderate consumption of alcoholic beverages, and four particular areas are discussed. First, recent findings suggest that moderate ethanol consumption acutely inhibits bone resorption, in a non-parathyroid hormone- and non-calcitonin-dependent fashion, which can only partly be attributed to an energy effect. Second, critical review of the literature does not support a role for moderate ethanol consumption affecting oestrogen status and leading to a knock-on effect on bone. Third, Si is present at high levels in certain alcoholic beverages, especially beer, and may have a measurable role in promoting bone formation. Fourth, a large body of work indicates that phytochemicals (e.g. polyphenols) from alcoholic beverages could influence bone health, but human data are lacking. With further work it is hoped to be able to model epidemiological observations and provide a clear pathway between the magnitude of association and the relative contribution of these mechanisms for the major classes of alcoholic beverage.

  7. The application of an enamel matrix protein derivative (Emdogain) in regenerative periodontal therapy: a review.

    NARCIS (Netherlands)

    Sculean, A.; Schwarz, F.; Becker, J.; Brecx, M.

    2007-01-01

    Regenerative periodontal therapy aims at reconstitution of the lost periodontal structures such as new formation of root cementum, periodontal ligament and alveolar bone. Findings from basic research indicate that enamel matrix protein derivative (EMD) has a key role in periodontal wound healing. Hi

  8. The promise of perfect adult tissue repair and regeneration in mammals: Learning from regenerative amphibians and fish.

    Science.gov (United States)

    Godwin, James

    2014-09-01

    Regenerative medicine promises to greatly impact on human health by improving repair outcomes in a range of tissues and injury contexts. Successful therapies will rely on identifying both intrinsic and extrinsic biological circuits that control wound healing, proliferation, cell survival, and developmental cell fate. Animals such as the zebrafish and the salamander display powerful examples of near-perfect regeneration and scar-free healing in a range of injury contexts not attained in mammals. By studying regeneration in a range of highly regenerative species that maintain regenerative potential throughout life, many instructive and permissive factors have been identified that could assist in the development of regenerative therapies. This review highlights some of the recent observations in immune regulation, epigenetic regulation, stem cell mobilization, and regenerative signatures that have improved our understanding of the regenerative process. Potential opportunities in harnessing this knowledge for future translation into the clinic are discussed.

  9. In vitro osteoinductive potential of porous monetite for bone tissue engineering

    OpenAIRE

    2014-01-01

    Tissue engineering–based bone grafts are emerging as a viable alternative treatment modality to repair and regenerate tissues damaged as a result of disease or injury. The choice of the biomaterial component is a critical determinant of the success of the graft or scaffold; essentially, it must induce and allow native tissue integration, and most importantly mimic the hierarchical structure of the native bone. Calcium ...

  10. Comparative assessment of bone regeneration by histometry and a histological scoring system / Evaluarea comparativă a regenerării osoase utilizând histometria și un scor de vindecare histologică

    Directory of Open Access Journals (Sweden)

    Lucaciu Ondine

    2015-03-01

    Full Text Available Obiective: Scopul studiului de față a constat în evaluarea valorii scorului de vindecare histologică, comparativ cu histometria în monitorizarea vindecării osose la nivelul calotei. Material și metodă: Am realizat un studiu cazcontrol cu un lot control și unul de studiu. La un număr de 60 de șoareci CD1 incluși în lotul de studiu am indus chirurgical un defect osos la nivelul calotei și am realizat reconstrucția defectului utilizând grefe obținute prin inginerie tisulară. Ingineria tisulară a grefonului osos s-a realizat utilizând celule stem embrionare poziționate pe suport matriceal -corn caduc de cerb, iar ca inductor al diferențierii am utilizat mediu osteogenetic bazal și complex. La cei 30 de șoareci CD1 incluși în lotul control am indus chirurgical același defect osos la nivelul calotei, dar nu am realizat reconstrucția osoasă a acestuia. Procesul de regenerare osoasă a fost evaluat la 2 și respectiv la 4 luni utilizând scorul de vindecare și histometria. Rezultate: Scorul de vindecare histologică s-a corelat statistic semnificativ cu dimeniunea defectului obtinută la histometrie (p<0.001. Evaluarea parametrilor în baza cărora s-a stabilit scorul de vindecare histologică indică regenerarea cea mai avansată la subiecții din lotul de studiu sacrificați la 4 luni, la care s-a utilizat pentru ingineria grefonului osos celule stem embrionare, suport matriceal corn caduc de cerb și mediu osteogenetic complex ca inductor. Concluzii: scorul de vindecare histologică este o metoda valoroasă de cuantificare a procesului de regenerare osoasă. Relevanță clinică: Acest studiu demonstrează că scorul de vindecare histologică prezentat este un instrument util pentru clinician în procesul de evaluare a regenerării osoase.

  11. Natural Products from Chinese Medicines with Potential Benefits to Bone Health

    Directory of Open Access Journals (Sweden)

    Chun-Tao Che

    2016-02-01

    Full Text Available Osteoporosis is a progressive, systemic bone disorder characterized by loss of bone mass and microstructure, leading to reduced bone strength and increased risk of fracture. It is often associated with reduced quality of life and other medical complications. The disease is common in the aging population, particularly among postmenopausal women and patients who receive long-term steroidal therapy. Given the rapid growth of the aging population, increasing life expectancy, the prevalence of bone loss, and financial burden to the healthcare system and individuals, demand for new therapeutic agents and nutritional supplements for the management and promotion of bone health is pressing. With the advent of global interest in complementary and alternative medicine and natural products, Chinese medicine serves as a viable source to offer benefits for the improvement and maintenance of bone health. This review summarizes the scientific information obtained from recent literatures on the chemical ingredients of Chinese medicinal plants that have been reported to possess osteoprotective and related properties in cell-based and/or animal models. Some of these natural products (or their derivatives may become promising leads for development into dietary supplements or therapeutic drugs.

  12. Investigating the Potential of Amnion-Based Scaffolds as a Barrier Membrane for Guided Bone Regeneration.

    Science.gov (United States)

    Li, Wuwei; Ma, Guowu; Brazile, Bryn; Li, Nan; Dai, Wei; Butler, J Ryan; Claude, Andrew A; Wertheim, Jason A; Liao, Jun; Wang, Bo

    2015-08-11

    Guided bone regeneration is a new concept of large bone defect therapy, which employs a barrier membrane to afford a protected room for osteogenesis and prevent the invasion of fibroblasts. In this study, we developed a novel barrier membrane made from lyophilized multilayered acellular human amnion membranes (AHAM). After decellularization, the AHAM preserved the structural and biomechanical integrity of the amnion extracellular matrix (ECM). The AHAM also showed minimal toxic effects when cocultured with mesenchymal stem cells (MSCs), as evidenced by high cell density, good cell viability, and efficient osteogenic differentiation after 21-day culturing. The effectiveness of the multilayered AHAM in guiding bone regeneration was evaluated using an in vivo rat tibia defect model. After 6 weeks of surgery, the multilayered AHAM showed great efficiency in acting as a shield to avoid the invasion of the fibrous tissues, stabilizing the bone grafts and inducing the massive bone growth. We hence concluded that the advantages of the lyophilized multilayered AHAM barrier membrane are as follows: preservation of the structural and mechanical properties of the amnion ECM, easiness for preparation and handling, flexibility in adjusting the thickness and mechanical properties to suit the application, and efficiency in inducing bone growth and avoiding fibrous tissues invasion.

  13. Osteostatin-coated porous titanium can improve early bone regeneration of cortical bone defects in rats

    NARCIS (Netherlands)

    Van Der Stok, Johan; Lozano, Daniel; Chai, Yoke Chin; Amin Yavari, Saber; Bastidas Coral, Angela P.; Verhaar, Jan A N; Gómez-Barrena, Enrique; Schrooten, Jan; Jahr, Holger; Zadpoor, Amir A.; Esbrit, Pedro; Weinans, Harrie

    2015-01-01

    A promising bone graft substitute is porous titanium. Porous titanium, produced by selective laser melting (SLM), can be made as a completely open porous and load-bearing scaffold that facilitates bone regeneration through osteoconduction. In this study, the bone regenerative capacity of porous tita

  14. Osteoinductive potential and bone-bonding ability of ProRoot MTA, MTA Plus and Biodentine in rabbit intramedullary model: Microchemical characterization and histological analysis.

    Science.gov (United States)

    Gandolfi, M G; Iezzi, G; Piattelli, A; Prati, C; Scarano, A

    2017-05-01

    To study the in vivo osteoinductive potential, bone-bonding ability (bioactivity) and bone biomineralization of current hydraulic calcium silicate cements used as graft materials and placed in contact with medullary bone. ProRoot MTA, MTA Plus and Biodentine were used to fill surgical bone defects (2-mm diameter through the entire cortical thickness to reach the medullary bone) in the tibia of mature male rabbits. Tibiae were retrieved after 30days and submitted to histological analysis and microchemical characterization using Optical Microscopy (OM) and Environmental Scanning Electron Microscopy with Energy Dispersive X-ray analysis (ESEM-EDX). Bone neoformation and histomorphometric evaluations, degree of mineralization (by Ca/P, Ca/N and P/N ratios) and the diffusion of material elements were studied. Bone neoformation was observed in response to all materials. No sign of necrosis were found on the walls of the pre-existing cortical bone. No osteoclasts and no formation of fibrous tissue were evident. Sign of angiogenesis were present. EDX (element content, line profile and element mapping) showed the increase in Ca and P and decrease in C, S and N from the mature bone towards the mineralizing interface. Ca/P, Ca/N and P/N ratios showed differences in the degree of mineralization/maturation stage of bone. MTA Plus and ProRoot MTA exhibited close contact with the pre-existing bone and good bone-bonding with neoformed bone juxtaposed on the medullary side of the materials without interposed connective tissue or resorption lacunae or gaps. The materials showed a dense appearance with 100% of residual materials and no colonization by fluids and cells. No migration of Bi or Al material elements to the newly formed bone was found. Biodentine showed newly formed trabecular bone with marrow spaces and sparse traces of residual material (≈9%). The in vivo osteoinductive properties with dynamic biomineralization processes around these calcium silicate materials extruded

  15. The potential of chitosan combined with chicken shank collagen as scaffold on bone defect regeneration process in Rattus norvegicus

    Directory of Open Access Journals (Sweden)

    Fitria Rahmitasari

    2016-12-01

    Full Text Available Background: In the field of dentistry, alveolar bone damage can be caused by periodontal disease, traumatic injury due to tooth extraction, cyst enucleation, and tumor surgery. One of the ways to regenerate the bone defect is using graft scaffold. Thus, combination of chitosan and collagen can stimulate osteogenesis. Purpose: The aim of this study was to examine the potential of chitosan combined with chicken shank collagen on bone defect regeneration process. Method: Twelve Rattus norvegicus were prepared as animal models in this research. A bone defect was intentionally created at both of the right and left femoral bones of the models. Next, 24 samples were divided into four groups, namely Group 1 using chitosan – collagen scaffold (50:50, Group 2 using chitosan collagen-scaffold (80:20, Group 3 using chitosan scaffold only, and Control Group using 3% CMC-Na. On 14th day, those animals were sacrificed, and histopathological anatomy examination was conducted to observe osteoclast cells. In addition, immunohistochemistry examination was also performed to observe RANKL expressions. Result: There was a significant difference in RANKL expressions among the groups, except between Group 3 using chitosan scaffold only and control group (p value > 0.05. The highest expression of RANKL was found in Group 1 with chitosan – collagen scaffold (50:50, followed by Group 2 with chitosan-collagen scaffold (80:20. Moreover, there was also a significant difference in osteoclast generation, except between Group 1 using chitosan – collagen scaffold (50:50 and Group 2 using chitosan-collagen scaffold (80:20, p value 0.05. Less osteoclast was found in the groups using chitosan – collagen scaffold (Group 1 and Group 2. Conclusion: Combination of chitosan and chicken shank collagen scaffold can improve regeneration process of bone defect in Rattus novergicus animals through increasing of RANKL expressions, and decreasing of osteoclast.

  16. Erythropoietin Modulates the Structure of Bone Morphogenetic Protein 2–Engineered Cranial Bone

    OpenAIRE

    Sun, Hongli; Jung, Younghun; Shiozawa, Yusuke; Taichman, Russell S.; Krebsbach, Paul H.

    2012-01-01

    The ideally engineered bone should have similar structural and functional properties to the native tissue. Although structural integrity is critical for functional bone regeneration, we know less about modulating the structural properties of the engineered bone elicited by bone morphogenetic protein (BMP) than efficacy and safety. Erythropoietin (Epo), a primary erythropoietic hormone, has been used to augment blood transfusion in orthopedic surgery. However, the effects of Epo on bone regene...

  17. Introduction to stem cells and regenerative medicine.

    Science.gov (United States)

    Kolios, George; Moodley, Yuben

    2013-01-01

    Stem cells are a population of undifferentiated cells characterized by the ability to extensively proliferate (self-renewal), usually arise from a single cell (clonal), and differentiate into different types of cells and tissue (potent). There are several sources of stem cells with varying potencies. Pluripotent cells are embryonic stem cells derived from the inner cell mass of the embryo and induced pluripotent cells are formed following reprogramming of somatic cells. Pluripotent cells can differentiate into tissue from all 3 germ layers (endoderm, mesoderm, and ectoderm). Multipotent stem cells may differentiate into tissue derived from a single germ layer such as mesenchymal stem cells which form adipose tissue, bone, and cartilage. Tissue-resident stem cells are oligopotent since they can form terminally differentiated cells of a specific tissue. Stem cells can be used in cellular therapy to replace damaged cells or to regenerate organs. In addition, stem cells have expanded our understanding of development as well as the pathogenesis of disease. Disease-specific cell lines can also be propagated and used in drug development. Despite the significant advances in stem cell biology, issues such as ethical controversies with embryonic stem cells, tumor formation, and rejection limit their utility. However, many of these limitations are being bypassed and this could lead to major advances in the management of disease. This review is an introduction to the world of stem cells and discusses their definition, origin, and classification, as well as applications of these cells in regenerative medicine.

  18. 3-dimensional analysis of regenerative endodontic treatment outcome.

    Science.gov (United States)

    EzEldeen, Mostafa; Van Gorp, Gertrude; Van Dessel, Jeroen; Vandermeulen, Dirk; Jacobs, Reinhilde

    2015-03-01

    A growing body of evidence supports the regeneration potential of dental tissues after regenerative endodontic treatment (RET). Nevertheless, a standard method for the evaluation of RET outcome is lacking. The aim of this study was to develop a standardized quantitative method for RET outcome analysis based on cone-beam computed tomographic (CBCT) volumetric measurements. Five human teeth embedded in mandibular bone samples were scanned using both an Accuitomo 170 CBCT machine (Morita, Kyoto, Japan) and a SkyScan 1174 micro-computed tomographic (μCT) system (SkyScan, Antwerp, Belgium). For subsequent clinical application, clinical data and low-dose CBCT scans (preoperatively and follow-up) from 5 immature permanent teeth treated with RET were retrieved. In vitro and clinical 3-dimensional image data sets were imported into a dedicated software tool. Two segmentation steps were applied to extract the teeth of interest from the surrounding tissue (livewire) and to separate tooth hard tissue and root canal space (level set methods). In vitro and clinical volumetric measurements were assessed separately for differences using Wilcoxon matched pairs test. Pearson correlation analysis and Bland-Altman plots were used to evaluate the relation and agreement between the segmented CBCT and μCT volumes. The results showed no statistical differences and strong agreement between CBCT and μCT volumetric measurements. Volumetric comparison of the root hard tissue showed significant hard tissue formation. (The mean volume of newly formed hard tissue was 27.9 [±10.5] mm(3) [P < .05]). Analysis of 3-dimensional data for teeth treated with RET offers valuable insights into the treatment outcome and patterns of hard tissue formation. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  19. Regenerative Braking Algorithm for an ISG HEV Based on Regenerative Torque Optimization

    Institute of Scientific and Technical Information of China (English)

    XIAO Wen-yong; WANG Feng; ZHUO Bin

    2008-01-01

    A novel regenerative braking algorithm based on regenerative torque optimization with emulate engine compression braking (EECB) was proposed to make effective and maximum use of brake energy in order to improve fuel economy. The actual brake oil pressure of driving wheel which is reduced by the amount of the regenerative braking force is supplied from the electronic hydraulic brake system. Regenerative torque optimization maximizes the actual regenerative power recuperation by energy storage component, and EECB is a useful extended type of regenerative braking. The simulation results show that actual regenerative power recuperation for the novel regenerative braking algorithm is more than using conventional one, and life-span of brake disks is prolonged for the novel algorithm.

  20. High frequency bone conduction auditory evoked potentials in the guinea pig: Assessing cochlear injury after ossicular chain manipulation.

    Science.gov (United States)

    Bergin, M J; Bird, P A; Vlajkovic, S M; Thorne, P R

    2015-12-01

    Permanent high frequency (>4 kHz) sensorineural hearing loss following middle ear surgery occurs in up to 25% of patients. The aetiology of this loss is poorly understood and may involve transmission of supra-physiological forces down the ossicular chain to the cochlea. Investigating the mechanisms of this injury using animal models is challenging, as evaluating cochlear function with evoked potentials is confounded when ossicular manipulation disrupts the normal air conduction (AC) pathway. Bone conduction (BC) using clinical bone vibrators in small animals is limited by poor transducer output at high frequencies sensitive to trauma. The objectives of the present study were firstly to evaluate a novel high frequency bone conduction transducer with evoked auditory potentials in a guinea pig model, and secondly to use this model to investigate the impact of middle ear surgical manipulation on cochlear function. We modified a magnetostrictive device as a high frequency BC transducer and evaluated its performance by comparison with a calibrated AC transducer at frequencies up to 32 kHz using the auditory brainstem response (ABR), compound action potential (CAP) and summating potential (SP). To mimic a middle ear traumatising stimulus, a rotating bur was brought in to contact with the incudomalleal complex and the effect on evoked cochlear potentials was observed. BC-evoked potentials followed the same input-output function pattern as AC potentials for all ABR frequencies. Deterioration in CAP and SP thresholds was observed after ossicular manipulation. It is possible to use high frequency BC to evoke responses from the injury sensitive basal region of the cochlea and so not rely on AC with the potential confounder of conductive hearing loss. Ongoing research explores how these findings evolve over time, and ways in which injury may be reduced and the cochlea protected during middle ear surgery.

  1. Spaceflight-relevant types of ionizing radiation and cortical bone: Potential LET effect?

    Science.gov (United States)

    Lloyd, Shane A.J.; Bandstra, Eric R.; Travis, Neil D.; Nelson, Gregory A.; Bourland, J. Daniel; Pecaut, Michael J.; Gridley, Daila S.; Willey, Jeffrey S.; Bateman, Ted A.

    2008-01-01

    Extended exposure to microgravity conditions results in significant bone loss. Coupled with radiation exposure, this phenomenon may place astronauts at a greater risk for mission-critical fractures. In a previous study, we identified a profound and prolonged loss of trabecular bone (29−39%) in mice following exposure to an acute, 2 Gy dose of radiation simulating both solar and cosmic sources. However, because skeletal strength depends on trabecular and cortical bone, accurate assessment of strength requires analysis of both bone compartments. The objective of the present study was to examine various properties of cortical bone in mice following exposure to multiple types of spaceflight-relevant radiation. Nine-week old, female C57BL/6 mice were sacrificed 110 days after exposure to a single, whole body, 2 Gy dose of gamma, proton, carbon, or iron radiation. Femora were evaluated with biomechanical testing, microcomputed tomography, quantitative histomorphometry, percent mineral content, and micro-hardness analysis. Compared to non-irradiated controls, there were significant differences compared to carbon or iron radiation for only fracture force, medullary area and mineral content. A greater differential effect based on linear energy transfer (LET) level may be present: high-LET (carbon or iron) particle irradiation was associated with a decline in structural properties (maximum force, fracture force, medullary area, and cortical porosity) and mineral composition compared to low-LET radiation (gamma and proton). Bone loss following irradiation appears to be largely specific to trabecular bone and may indicate unique biological microenvironments and microdosimetry conditions. However, the limited time points examined and non-haversian skeletal structure of the mice employed highlight the need for further investigation. PMID:19122806

  2. Evaluation of the regenerative potential of 25% doxycycline-loaded biodegradable membrane vs biodegradable membrane alone in the treatment of human periodontal infrabony defects: A clinical and radiological study

    Directory of Open Access Journals (Sweden)

    Chaturvedi Rashi

    2008-01-01

    Full Text Available Background: Microbial colonization of the barrier membranes used for guided tissue regeneration is inevitable and can lead to delayed healing. Aims: Antimicrobial coating of the membrane with 25% doxycycline paste has been attempted to prevent infection and achieve enhanced regeneration in periodontal infrabony defects. Materials and Methods: Twenty-four patients with 2-walled or 3-walled infrabony defects were selected and randomly divided into two equal groups. Infrabony defects of group A were treated with a biodegradable membrane coated with 25% doxycycline while those of group B were treated with membrane alone. Clinical assessment of probing depth and attachment level and radiographic evaluation of the defect depth was done preoperatively and at 12 and 24 weeks postoperatively. Statistical Analysis: The relative efficacy of the two treatment modalities were evaluated using the paired Student′s t- test and the comparative evaluation between the two groups was done using the independent Student′s t -test. Results: Both the groups exhibited a highly significant reduction in probing depth and gain in clinical attachment level and linear bone fill at the end of 24 weeks. Comparative evaluation between the two study groups revealed a significant reduction in probing depth ( P = 0.016 FNx01 and linear bone fill ( P = 0.02 FNx01 in group A as compared to group B. Mean gain in attachment level was greater for group A than for group B but the difference was statistically nonsignificant ( P = 0.065 NS . Conclusions: The results suggest that doxycycline is beneficial in reducing membrane-associated infection and can potentiate regeneration through host modulation.

  3. Regenerative medicine in dental and oral tissues: Dental pulp mesenchymal stem cell

    Directory of Open Access Journals (Sweden)

    Janti Sudiono

    2017-08-01

    Full Text Available Background. Regenerative medicine is a new therapeutic modality using cell, stem cell and tissue engineering technologies. Purpose. To describe the regenerative capacity of dental pulp mesenchymal stem cell. Review. In dentistry, stem cell and tissue engineering technologies develop incredibly and attract great interest, due to the capacity to facilitate innovation in dental material and regeneration of dental and oral tissues. Mesenchymal stem cells derived from dental pulp, periodontal ligament and dental follicle, can be isolated, cultured and differentiated into various cells, so that can be useful for regeneration of dental, nerves, periodontal and bone tissues. Tissue engineering is a technology in reconstructive biology, which utilizes mechanical, cellular, or biological mediators to facilitate regeneration or reconstruction of a particular tissue. The multipotency, high proliferation rates and accessibility, make dental pulp as an attractive source of mesenchymal stem cells for tissue regeneration. Revitalized dental pulp and continued root development is the focus of regenerative endodontic while biological techniques that can restore lost alveolar bone, periodontal ligament, and root cementum is the focus of regenerative periodontic. Conclucion. Dentin-derived morphogens such as BMP are known to be involved in the regulation of odontogenesis. The multipotency and angiogenic capacity of DPSCs as the regenerative capacity of human dentin / pulp complex indicated that dental pulp may contain progenitors that are responsible for dentin repair. The human periodontal ligament is a viable alternative source for possible primitive precursors to be used in stem cell therapy.

  4. Regenerative Engineering and Bionic Limbs

    Science.gov (United States)

    James, Roshan; Laurencin, Cato T.

    2015-01-01

    Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counselling. There is no prosthesis that allows the amputees near-normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities and international conflicts, there is a growing requirement for novel strategies and new discoveries. Advances have been made in technological, material and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and technologies to allow for the regeneration of injured tissues, recording on tissue signals and feed-back to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits and thumb in the upper extremity. Regenerative engineering focused on the regeneration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past thirty years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. The convergence of toolboxes crated within each discipline will allow interdisciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. Tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feed-back will be the important goals in regenerative engineering over the next

  5. Regenerative Engineering and Bionic Limbs.

    Science.gov (United States)

    James, Roshan; Laurencin, Cato T

    2015-03-01

    Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counselling. There is no prosthesis that allows the amputees near-normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities and international conflicts, there is a growing requirement for novel strategies and new discoveries. Advances have been made in technological, material and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and technologies to allow for the regeneration of injured tissues, recording on tissue signals and feed-back to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits and thumb in the upper extremity. Regenerative engineering focused on the regeneration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past thirty years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. The convergence of toolboxes crated within each discipline will allow interdisciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. Tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feed-back will be the important goals in regenerative engineering over the next

  6. Regenerative superheated steam turbine cycles

    Science.gov (United States)

    Fuller, L. C.; Stovall, T. K.

    1980-01-01

    PRESTO computer program was developed to analyze performance of wide range of steam turbine cycles with special attention given to regenerative superheated steam turbine cycles. It can be used to model standard turbine cycles, including such features as process steam extraction, induction and feedwater heating by external sources, peaking, and high back pressure. Expansion line efficiencies, exhaust loss, leakages, mechanical losses, and generator losses are used to calculate cycle heat rate and generator output. Program provides power engineer with flexible aid for design and analysis of steam turbine systems.

  7. Entropy Generation in Regenerative Systems

    Science.gov (United States)

    Kittel, Peter

    1995-01-01

    Heat exchange to the oscillating flows in regenerative coolers generates entropy. These flows are characterized by oscillating mass flows and oscillating temperatures. Heat is transferred between the flow and heat exchangers and regenerators. In the former case, there is a steady temperature difference between the flow and the heat exchangers. In the latter case, there is no mean temperature difference. In this paper a mathematical model of the entropy generated is developed for both cases. Estimates of the entropy generated by this process are given for oscillating flows in heat exchangers and in regenerators. The practical significance of this entropy is also discussed.

  8. Biomechanical aspects of bone microstructure in vertebrates: potential approach to palaeontological investigations

    Indian Academy of Sciences (India)

    S Mishra

    2009-11-01

    Biomechanical or biophysical principles can be applied to study biological structures in their modern or fossil form. Bone is an important tissue in paleontological studies as it is a commonly preserved element in most fossil vertebrates, and can often allow its microstructures such as lacuna and canaliculi to be studied in detail. In this context, the principles of Fluid Mechanics and Scaling Laws have been previously applied to enhance the understanding of bone microarchitecture and their implications for the evolution of hydraulic structures to transport fluid. It has been shown that the microstructure of bone has evolved to maintain efficient transport between the nutrient supply and cells, the living components of the tissue. Application of the principle of minimal expenditure of energy to this analysis shows that the path distance comprising five or six lamellar regions represents an effective limit for fluid and solute transport between the nutrient supply and cells; beyond this threshold, hydraulic resistance in the network increases and additional energy expenditure is necessary for further transportation. This suggests an optimization of the size of the bone’s building blocks (such as osteon or trabecular thickness) to meet the metabolic demand concomitant to minimal expenditure of energy. This biomechanical aspect of bone microstructure is corroborated from the ratio of osteon to Haversian canal diameters and scaling constants of several mammals considered in this study. This aspect of vertebrate bone microstructure and physiology may provide a basis of understanding of the form and function relationship in both extinct and extant taxa.

  9. Age-related decline in the osteogenic potential of human bone marrow cells cultured in three-dimensional collagen sponges.

    Science.gov (United States)

    Mueller, S M; Glowacki, J

    2001-01-01

    Studies with human and animal culture systems indicate that a sub-population of bone marrow stromal cells has the potential to differentiate into osteoblasts. There are conflicting reports on the effects of age on human marrow-derived osteogenic cells. In this study, we used a three dimensional (3D) culture system and quantitative RT-PCR methods to test the hypothesis that the osteogenic potential of human bone marrow stromal cells decreases with age. Marrow was obtained from 39 men aged 37 to 86 years, during the course of total hip arthroplasty. Low-density mononuclear cells were seeded onto 3D collagen sponges and cultured for 3 weeks. Histological sections of sponges were stained for alkaline phosphatase activity and were scored as positive or negative. In the group or = 60 years were positive (p = 0.0504). As revealed by RT-PCR, there was no expression of alkaline phosphatase or collagen type I mRNA before culture, however there were strong signals after 3 weeks, an indication of osteoblast differentiation in vitro. We performed a quantitative, competitive RT-PCR assay with 8 samples (age range 38-80) and showed that the group or = 60 years (p = 0.021). There was a significant decrease with age (r = - 0.78, p = 0.028). These molecular and histoenzymatic data indicate that the osteogenic potential of human bone marrow cells decreases with age.

  10. Surgical and immune reconstitution murine models in bone marrow research: Potential for exploring mechanisms in sepsis, trauma and allergy.

    Science.gov (United States)

    Xavier-Elsas, Pedro; Ferreira, Renato Nunes; Gaspar-Elsas, Maria Ignez C

    2017-08-20

    Bone marrow, the vital organ which maintains lifelong hemopoiesis, currently receives considerable attention, as a source of multiple cell types which may play important roles in repair at distant sites. This emerging function, distinct from, but closely related to, bone marrow roles in innate immunity and inflammation, has been characterized through a number of strategies. However, the use of surgical models in this endeavour has hitherto been limited. Surgical strategies allow the experimenter to predetermine the site, timing, severity and invasiveness of injury; to add or remove aggravating factors (such as infection and defects in immunity) in controlled ways; and to manipulate the context of repair, including reconstitution with selected immune cell subpopulations. This endows surgical models overall with great potential for exploring bone marrow responses to injury, inflammation and infection, and its roles in repair and regeneration. We review three different murine surgical models, which variously combine trauma with infection, antigenic stimulation, or immune reconstitution, thereby illuminating different aspects of the bone marrow response to systemic injury in sepsis, trauma and allergy. They are: (1) cecal ligation and puncture, a versatile model of polymicrobial sepsis; (2) egg white implant, an intriguing model of eosinophilia induced by a combination of trauma and sensitization to insoluble allergen; and (3) ectopic lung tissue transplantation, which allows us to dissect afferent and efferent mechanisms leading to accumulation of hemopoietic cells in the lungs. These models highlight the gain in analytical power provided by the association of surgical and immunological strategies.

  11. Processing and characterization of diatom nanoparticles and microparticles as potential source of silicon for bone tissue engineering.

    Science.gov (United States)

    Le, Thi Duy Hanh; Bonani, Walter; Speranza, Giorgio; Sglavo, Vincenzo; Ceccato, Riccardo; Maniglio, Devid; Motta, Antonella; Migliaresi, Claudio

    2016-02-01

    Silicon plays an important role in bone formation and maintenance, improving osteoblast cell function and inducing mineralization. Often, bone deformation and long bone abnormalities have been associated with silica/silicon deficiency. Diatomite, a natural deposit of diatom skeleton, is a cheap and abundant source of biogenic silica. The aim of the present study is to validate the potential of diatom particles derived from diatom skeletons as silicon-donor materials for bone tissue engineering applications. Raw diatomite (RD) and calcined diatomite (CD) powders were purified by acid treatments, and diatom microparticles (MPs) and nanoparticles (NPs) were produced by fragmentation of purified diatoms under alkaline conditions. The influence of processing on the surface chemical composition of purified diatomites was evaluated by X-ray photoelectron spectroscopy (XPS). Diatoms NPs were also characterized in terms of morphology and size distribution by transmission electron microscopy (TEM) and Dynamic light scattering (DLS), while diatom MPs morphology was analyzed by scanning electron microscopy (SEM). Surface area and microporosity of the diatom particles were evaluated by nitrogen physisorption methods. Release of silicon ions from diatom-derived particles was demonstrated using inductively coupled plasma optical emission spectrometry (ICP/OES); furthermore, silicon release kinetic was found to be influenced by diatomite purification method and particle size. Diatom-derived microparticles (MPs) and nanoparticles (NPs) showed limited or no cytotoxic effect in vitro depending on the administration conditions.

  12. MicroRNAs: Potential Biomarkers and Therapeutic Targets for Alveolar Bone Loss in Periodontal Disease

    Directory of Open Access Journals (Sweden)

    Tadayoshi Kagiya

    2016-08-01

    Full Text Available Periodontal disease is an inflammatory disease caused by bacterial infection of tooth-supporting structures, which results in the destruction of alveolar bone. Osteoclasts play a central role in bone destruction. Osteoclasts are tartrate-resistant acid phosphatase (TRAP-positive multinucleated giant cells derived from hematopoietic stem cells. Recently, we and other researchers revealed that microRNAs are involved in osteoclast differentiation. MicroRNAs are novel, single-stranded, non-coding, small (20–22 nucleotides RNAs that act in a sequence-specific manner to regulate gene expression at the post-transcriptional level through cleavage or translational repression of their target mRNAs. They regulate various biological activities such as cellular differentiation, apoptosis, cancer development, and inflammatory responses. In this review, the roles of microRNAs in osteoclast differentiation and function during alveolar bone destruction in periodontal disease are described.

  13. Potential therapeutic application of intravenous autologous bone marrow infusion in patients with alcoholic liver cirrhosis.

    Science.gov (United States)

    Saito, Takafumi; Okumoto, Kazuo; Haga, Hiroaki; Nishise, Yuko; Ishii, Rika; Sato, Chikako; Watanabe, Hisayoshi; Okada, Akio; Ikeda, Motoki; Togashi, Hitoshi; Ishikawa, Tsuyoshi; Terai, Shuji; Sakaida, Isao; Kawata, Sumio

    2011-09-01

    The present study was conducted to evaluate the application and efficacy of autologous bone marrow infusion (ABMi) for improvement of liver function in patients with alcoholic liver cirrhosis (ALC). Five subjects and 5 control patients with ALC who had abstained from alcohol intake for 24 weeks before the study were enrolled. Autologous bone marrow cells were washed and injected intravenously, and the changes in serum liver function parameters, and the level of the type IV collagen 7S domain as a marker of fibrosis, were monitored for 24 weeks. The distribution of activated bone marrow was assessed by indium-111-chloride bone marrow scintigraphy. The number of cells infused was 8.0±7.3×10(9) (mean±standard error). The serum levels of albumin and total protein and the prothrombin time were significantly higher during the follow-up period after ABMi than during the observation period in treated patients, whereas no such changes were observed in the controls. In the patients who received ABMi, the Child-Pugh score decreased in all 3 who were classified as class B; the serum levels of type IV collagen 7S domain improved in 4 of the 5 patients; and bone marrow scintigraphy demonstrated an increase of indium-111-chloride uptake in 3 of the 4 patients tested. ABMi for patients with ALC helps improve liver function parameters in comparison with observation during abstinence and ameliorates the degree of fibrosis in terms of serum markers and bone marrow activation in most cases.

  14. Sequential Treatment with SDF-1 and BMP-2 Potentiates Bone Formation in Calvarial Defects.

    Science.gov (United States)

    Hwang, Hee-Don; Lee, Jung-Tae; Koh, Jeong-Tae; Jung, Hong-Moon; Lee, Heon-Jin; Kwon, Tae-Geon

    2015-07-01

    Stromal cell-derived factor-1 (SDF-1) protein and its receptor, CXCR-4, play an important role in tissue repair and regeneration in various organs, including the bone. SDF-1 is indispensable for bone morphogenetic protein-2 (BMP-2)-induced osteogenic differentiation. However, SDF-1 is not needed after the osteogenic induction has been activated. Since the precise condition for the additive effects of combined DF-1 and BMP-2 in bone healing had not been fully investigated, we aimed to determine the optimal conditions for SDF-1- and BMP-2-mediated bone regeneration. We examined the in vitro osteoblastic differentiation and cell migration after sequential treatments with SDF-1 and BMP-2. Based on the in vitro additive effects of SDF-1 and BMP-2, the critical size defects of mice calvaria were treated with these cytokines in various sequences. Phosphate buffered saline (PBS)-, SDF-1-, or BMP-2-soaked collagen scaffolds were implanted into the calvarial defects (n=36). Periodic percutaneous injections of PBS or the cytokine SDF-1 and BMP-2 into the implanted scaffolds were performed on days 3 and 6, postoperatively. Six experimental groups were used according to the types and sequences of the cytokine treatments. After 28 days, the mice were euthanized and bone formation was evaluated with microcomputed tomography and histology. The molecular mechanism of the additive effect of SDF-1 and BMP-2 was evaluated by analyzing intracellular signal transduction through Smad and Erk phosphorylation. The in vitro experiments revealed that, among all the treatments, the treatment with BMP-2 after SDF-1 showed the strongest osteoblastic differentiation and enhanced cell migration. Similarly, in the animal model, the treatment with SDF-1 followed by BMP-2 treatment showed the highest degree of new bone regeneration than any other groups, including the one with continuous BMP-2 treatment. This new bone formation can be partially explained by the activation of Smad and Erk pathways

  15. Differentiation potentials of perivascular cells in the bone tissue remodeling zones under microgravity

    Science.gov (United States)

    Rodionova, Natalia; Katkova, Olena

    Adaptive remodeling processes in the skeleton bones occur in the close topographical interconnection with blood capillaries followed by perivascular cells. Radioautographic studies with 3Н- thymidine (Kimmel D.B., Fee W.S., 1980; Rodionova N.V., 1989, 2006) has shown that in osteogenesis zones there is sequential differentiation process of the perivascular cells into osteogenic ones. Using electron microscopy and cytochemistry we studied perivsacular cells in metaphysis of the rats femoral bones under conditions of modeling microgravity (28 days duration) and in femoral bonеs metaphyses of rats flown on board of the space laboratory (Spacelab - 2) It was revealed that population of the perivascular cells is not homogeneous in adaptive zones of the remodeling in both control and test groups (lowering support loading). This population comprises adjacent to endothelium little differentiated forms and isolated cells with differentiation features (specific volume of rough endoplasmic reticulum in cytoplasm is increased). Majority of the perivascular cells in the control group reveals reaction to alkaline phosphatase (marker of the osteogenic differentiation). In little differentiated cells this reaction is registered in nucleolus, nucleous and cytoplasm. In differentiating cells activity of the alkaline phosphatase is also detected on the outer surface of the cellular membrane. Unlike the control group in the bones of animals under microgravitaty reaction to the alkaline phosphatase is registered not for all cells of perivascular population. Part of the differentiating perivascular cells does not contain a product of the reaction. There is also visible trend of individual alkaline phosphatase containing perivascular cells amounts decrease (i.e. osteogenic cells-precursors). Under microgravity some little differentiated perivascular cells reveal destruction signs. Found decrease trend of the alkaline phosphatase containing cells (i.e. osteogenic cells) number in

  16. Estrogen inhibits Dlk1/FA1 production: A potential mechanism for estrogen effects on bone turnover

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Bay-Jensen, Anne-Christine; Srinivasan, Bhuma;

    2011-01-01

    We have recently identified delta-like 1/fetal antigen 1 (Dlk1/FA1) as a novel regulator of bone mass that functions to mediate bone loss under estrogen deficiency in mice. In this report, we investigated the effects of estrogen (E) deficiency and E replacement on serum (s) levels of Dlk1/FA1 (s...... estrogen-replacement therapy (ERT, n = 166). s-Dlk1/FA1 and s-CTX were elevated in postmenopausal E-deficient women compared with premenopausal E-replete women (both p ...

  17. Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells.

    Science.gov (United States)

    Wakao, Shohei; Kuroda, Yasumasa; Ogura, Fumitaka; Shigemoto, Taeko; Dezawa, Mari

    2012-11-08

    Mesenchymal stem cells (MSCs) are easily accessible and safe for regenerative medicine. MSCs exert trophic, immunomodulatory, anti-apoptotic, and tissue regeneration effects in a variety of tissues and organs, but their entity remains an enigma. Because MSCs are generally harvested from mesenchymal tissues, such as bone marrow, adipose tissue, or umbilical cord as adherent cells, MSCs comprise crude cell populations and are heterogeneous. The specific cells responsible for each effect have not been clarified. The most interesting property of MSCs is that, despite being adult stem cells that belong to the mesenchymal tissue lineage, they are able to differentiate into a broad spectrum of cells beyond the boundary of mesodermal lineage cells into ectodermal or endodermal lineages, and repair tissues. The broad spectrum of differentiation ability and tissue-repairing effects of MSCs might be mediated in part by the presence of a novel pluripotent stem cell type recently found in adult human mesenchymal tissues, termed multilineage-differentiating stress enduring (Muse) cells. Here we review recently updated studies of the regenerative effects of MSCs and discuss their potential in regenerative medicine.

  18. Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells

    Directory of Open Access Journals (Sweden)

    Mari Dezawa

    2012-11-01

    Full Text Available Mesenchymal stem cells (MSCs are easily accessible and safe for regenerative medicine. MSCs exert trophic, immunomodulatory, anti-apoptotic, and tissue regeneration effects in a variety of tissues and organs, but their entity remains an enigma. Because MSCs are generally harvested from mesenchymal tissues, such as bone marrow, adipose tissue, or umbilical cord as adherent cells, MSCs comprise crude cell populations and are heterogeneous. The specific cells responsible for each effect have not been clarified. The most interesting property of MSCs is that, despite being adult stem cells that belong to the mesenchymal tissue lineage, they are able to differentiate into a broad spectrum of cells beyond the boundary of mesodermal lineage cells into ectodermal or endodermal lineages, and repair tissues. The broad spectrum of differentiation ability and tissue-repairing effects of MSCs might be mediated in part by the presence of a novel pluripotent stem cell type recently found in adult human mesenchymal tissues, termed multilineage-differentiating stress enduring (Muse cells. Here we review recently updated studies of the regenerative effects of MSCs and discuss their potential in regenerative medicine.

  19. Optimal performance of regenerative cryocoolers

    Science.gov (United States)

    de Boer, P. C. T.

    2011-02-01

    The key component of a regenerative cryocooler is its regenerative heat exchanger. This device is subject to losses due to imperfect heat transfer between the regenerator material and the gas, as well as due to viscous dissipation. The relative magnitudes of these losses can be characterized by the ratio of the Stanton number St to the Fanning friction factor f. Using available data for the ratio St/ f, results are developed for the optimal cooling rate and Carnot efficiency. The variations of pressure and temperature are taken to be sinusoidal in time, and to have small amplitudes. The results are applied to the case of the Stirling cryocooler, with flow being generated by pistons at both sides of the regenerator. The performance is found to be close to optimal at large ratio of the warm space volume to the regenerator void volume. The results are also applied to the Orifice Pulse Tube Refrigerator. In this case, optimal performance additionally requires a large ratio of the regenerator void volume to the cold space volume.

  20. Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression

    Directory of Open Access Journals (Sweden)

    Montzka Katrin

    2009-03-01

    Full Text Available Abstract Background In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs are capable of transdifferentiating to neural cell types, effectively crossing normal lineage restriction boundaries. Such reports have been based on the detection of neural-related proteins by the differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in populations of non-differentiated MSCs obtained from 4 donors. Results The expression analysis revealed that several of the commonly used marker genes from other studies like nestin, Enolase2 and microtubule associated protein 1b (MAP1b are already expressed by undifferentiated human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL and MBP could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample revealed a unique expression pattern, demonstrating a significant variation of marker expression. Conclusion The present study highlights the existence of an inter-donor variability of expression of neural-related markers in human MSC samples that has not previously been described. This donor-related heterogeneity might influence the reproducibility of transdifferentiation protocols as

  1. Bone ingrowth potential of electron beam and selective laser melting produced trabecular-like implant surfaces with and without a biomimetic coating

    NARCIS (Netherlands)

    Biemond, J.E.; Hannink, G.J.; Verdonschot, N.J.; Buma, P.

    2013-01-01

    The bone ingrowth potential of trabecular-like implant surfaces produced by either selective laser melting (SLM) or electron beam melting (EBM), with or without a biomimetic calciumphosphate coating, was examined in goats. For histological analysis and histomorphometry of bone ingrowth depth and bon

  2. Bone ingrowth potential of electron beam and selective laser melting produced trabecular-like implant surfaces with and without a biomimetic coating

    NARCIS (Netherlands)

    Biemond, J.E.; Hannink, G.J.; Verdonschot, N.J.; Buma, P.

    2013-01-01

    The bone ingrowth potential of trabecular-like implant surfaces produced by either selective laser melting (SLM) or electron beam melting (EBM), with or without a biomimetic calciumphosphate coating, was examined in goats. For histological analysis and histomorphometry of bone ingrowth depth and

  3. The clinical use of regenerative therapy in COPD.

    Science.gov (United States)

    Lipsi, Roberto; Rogliani, Paola; Calzetta, Luigino; Segreti, Andrea; Cazzola, Mario

    2014-01-01

    Regenerative or stem cell therapy is an emerging field of treatment based on stimulation of endogenous resident stem cells or administration of exogenous stem cells to treat diseases or injury and to replace malfunctioning or damaged tissues. Current evidence suggests that in the lung, these cells may participate in tissue homeostasis and regeneration after injury. Animal and human studies have demonstrated that tissue-specific stem cells and bone marrow-derived cells contribute to lung tissue regeneration and protection, and thus administration of exogenous stem/progenitor cells or humoral factors responsible for the activation of endogenous stem/progenitor cells may be a potent next-generation therapy for chronic obstructive pulmonary disease. The use of bone marrow-derived stem cells could allow repairing and regenerate the damaged tissue present in chronic obstructive pulmonary disease by means of their engraftment into the lung. Another approach could be the stimulation of resident stem cells by means of humoral factors or photobiostimulation.

  4. A SQSTM1/p62 mutation linked to Paget’s disease increases the osteoclastogenic potential of the bone microenvironment

    Science.gov (United States)

    Hiruma, Yuko; Kurihara, Noriyoshi; Subler, Mark A.; Zhou, Hua; Boykin, Christina S.; Zhang, Heju; Ishizuka, Seiichi; Dempster, David W.; Roodman, G. David; Windle, Jolene J.

    2008-01-01

    Paget’s disease of bone (PDB) is the second most common bone disease and is characterized by focal bone lesions which contain large numbers of abnormal osteoclasts (OCLs) and very active normal osteoblasts in a highly osteoclastogenic marrow microenvironment. The etiology of PDB is not well understood and both environmental and genetic causes have been implicated in its pathogenesis. Mutations in the SQSTM1/p62 gene have been identified in up to 30% of Paget’s patients. To determine if p62 mutation is sufficient to induce PDB, we generated mice harboring a mutation causing a P-to-L (proline-to-leucine) substitution at residue 394 (the murine equivalent of human p62P392L, the most common PDB-associated mutation). Bone marrow cultures from p62P394L mice formed increased numbers of OCLs in response to receptor activator of NF-κB ligand (RANKL), tumor necrosis factor α (TNF-α) or 1α,25-(OH)2D3, similar to PDB patients. However, purified p62P394L OCL precursors depleted of stromal cells were no longer hyper-responsive to 1α,25-(OH)2D3, suggesting effects of the p62P394L mutation on the marrow microenvironment in addition to direct effects on OCLs. Co-cultures of purified p62P394L stromal cells with either wild-type (WT) or p62P394L OCL precursors formed more OCLs than co-cultures containing WT stromal cells due to increased RANKL production by the mutant stromal cells. However, despite the enhanced osteoclastogenic potential of both OCL precursors and marrow stromal cells, the p62P394L mice had histologically normal bones. These results indicate that this PDB-associated p62 mutation is not sufficient to induce PDB and suggest that additional factors acting together with p62 mutation are necessary for the development of PDB in vivo. PMID:18765443

  5. [The potential of cone beam computed tomography of the temporal bones in the patients presenting with otosclerosis].

    Science.gov (United States)

    Karpishchenko, S A; Zubareva, A A; Filimonov, V N; Shavgulidze, M A; Azovtseva, E A

    The objective of the present study was to analyze the potential of cone beam computed tomography of the temporal bones in the patients presenting with otosclerosis for the detection of surgically significant specific structural features of the labyrinth wall of the tympanic cavity. More than 400 tomograms of the temporal bones were obtained with the use of a cone beam tomographwere available for the investigation during the period from 2012 till 2016. The study was carried out in several steps, viz. the search for the optimal (for the given instrument) position of the patient, the experimental stage, the retrospective analysis of the tomograms and the comparison of the temporal bones of different types (pneumatic, mixed, and sclerotic) in individual patients, the comparison of the results of cone beam computed tomography (CBCT) with the intraoperative observations, and the modification of the algorithm for the analysis of temporal bone cone beam tomograms. The study included a total of 16 patients (15 women at the age from 32 to 56 years and one managed 58 years) presenting with the clinical diagnosis of otosclerosis. The results of the study were used to elaborate the algorithm for the analysis of cone beam tomograms of the temporal bones to be performed inthe stage by stage manner including the qualitative analysis of tomograms, evaluation of their quantitative parameters and additional characteristics to be taken into consideration when planning the surgical interventions on the labyrinth wall and the tympanic cavity as a preparation for the stapedoplastic treatment. The results of CBCT obtained in the present study were compared with the surgical observations. The diagnostic sensitivity and specificity of the method were estimated to be 100% and 83% respectively. It is concluded that cone beam computed tomography can be employed as a component of the diagnostic algorithm prior to the planning of surgical interventions onthe medial wall of the tympanic cavity

  6. The application of an enamel matrix protein derivative (Emdogain) in regenerative periodontal therapy: a review.

    Science.gov (United States)

    Sculean, Anton; Schwarz, Frank; Becker, Jurgen; Brecx, Michel

    2007-01-01

    Regenerative periodontal therapy aims at reconstitution of the lost periodontal structures such as new formation of root cementum, periodontal ligament and alveolar bone. Findings from basic research indicate that enamel matrix protein derivative (EMD) has a key role in periodontal wound healing. Histological results from animal and human studies have shown that treatment with EMD promotes periodontal regeneration. Moreover, clinical studies have indicated that treatment with EMD positively influences periodontal wound healing in humans. This review aims to present an overview of evidence-based clinical indications for regenerative therapy with EMD.

  7. PIEZOELECTRIC BONE SURGERY: A REVIEW OF THE LITERATURE AND POTENTIAL APPLICATIONS IN VETERINARY OROMAXILLOFACIAL SURGERY

    Directory of Open Access Journals (Sweden)

    Philippe eHENNET

    2015-05-01

    Full Text Available Piezoelectric bone surgery is a recent and innovative technology permitting a selective cut of mineralized tissue while sparing soft tissue. Similar to a dental scaler, a high frequency vibration, in the range of 25-35kHz, is transmitted to a metallic tip. However, the power of the piezosurgical instrument is 3 to 6 times higher than that of a dental scaler. The major advantages of this technology include high precision, a design that increases ease of curvilinear osteotomy, less trauma to soft tissue, preservation of neurological and vascular structures, reduced hemorrhage, minimal thermal damage to the bone as well as overall improvement of healing. The handpiece of the instrument is equipped with a sterile irrigation system and light-emitting diode (LED light, which improves visibility and overall safety. Piezoelectric surgery is particularly useful when performing delicate bone procedures such as periodontal or endodontic surgery. It is also indicated when performing more invasive bone surgery such as maxillectomy, mandibulectomy, and condylectomy, where preservation of neurovascular structures is important. Piezoelectric instruments are different from rotary instrumentation or oscillating saws, they require light pressure with constant motion of the tip. Training is required to master the technique.

  8. Silver nanoparticle based antibacterial methacrylate hydrogels potential for bone graft applications

    Science.gov (United States)

    González-Sánchez, M. Isabel; Perni, Stefano; Tommasi, Giacomo; Morris, Nathanael Glyn; Hawkins, Karl; López-Cabarcos, Enrique; Prokopovich, Polina

    2015-01-01

    Infections are frequent and very undesired occurrences after orthopedic procedures; furthermore, the growing concern caused by the rise in antibiotic resistance is progressively dwindling the efficacy of such drugs. Artificial bone graft materials could solve some of the problems associated with the gold standard use of natural bone graft such as limited bone material, pain at the donor site and rejections if donor tissue is used. We have previously described new acrylate base nanocomposite hydrogels as bone graft materials. In the present paper, we describe the integration of silver nanoparticles in the polymeric mineralized biomaterial to provide non-antibiotic antibacterial activity against Staphylococcus epidermidis and Methicillin-resistant Staphylococcus aureus. Two different crosslinking degrees were tested and the silver nanoparticles were integrated into the composite matrix by means of three different methods: entrapment in the polymeric hydrogel before the mineralization; diffusion during the process of calcium phosphate crystallization and adsorption post-mineralization. The latter being generally the most effective method of encapsulation; however, the adsorption of silver nanoparticles inside the pores of the biomaterial led to a decreasing antibacterial activity for adsorption time longer than 2 days. PMID:25746278

  9. Relation between in vitro and in vivo osteogenic potential of cultured human bone marrow stromal cells

    NARCIS (Netherlands)

    Mendes, S.C.; Mendes, Sandra C.; Reis, R L; Bovell, Yvonne P.; Cunha, A.M.; Both, Sanne Karijn; van Blitterswijk, Clemens; de Bruijn, Joost Dick

    2004-01-01

    This paper describes an extensive biocompatibility evaluation of biodegradable starch-based materials aimed at orthopaedic applications as temporary bone replacement/fixation implants. For that purpose, a polymer (starch/ethylene vinyl alcohol blend, SEVA-C) and a composite of SEVA-C reinforced with

  10. Icariin: does it have an osteoinductive potential for bone tissue engineering?

    NARCIS (Netherlands)

    X. Zhang; T. Liu; Y. Huang; D. Wismeijer; Y. Liu

    2014-01-01

    Traditional Chinese medicines have been recommended for bone regeneration and repair for thousands of years. Currently, the Herba Epimedii and its multi-component formulation are the attractive native herbs for the treatment of osteoporosis. Icariin, a typical flavonol glycoside, is considered to be

  11. Selection of phosphorus solubilizing bacteria with biocontrol potential for growth in phosphorus rich animal bone charcoal

    NARCIS (Netherlands)

    Postma, J.; Nijhuis, E.H.; Sommeus, E.

    2010-01-01

    Bacteria with the ability to solubilize phosphorus (P) and to improve plant health were selected and tested for growth and survival in P-rich animal bone charcoal (ABC). ABC is suggested to be suitable as a carrier for biocontrol agents, offering them a protected niche as well as delivering phosphat

  12. Silver nanoparticle based antibacterial methacrylate hydrogels potential for bone graft applications.

    Science.gov (United States)

    González-Sánchez, M Isabel; Perni, Stefano; Tommasi, Giacomo; Morris, Nathanael Glyn; Hawkins, Karl; López-Cabarcos, Enrique; Prokopovich, Polina

    2015-05-01

    Infections are frequent and very undesired occurrences after orthopedic procedures; furthermore, the growing concern caused by the rise in antibiotic resistance is progressively dwindling the efficacy of such drugs. Artificial bone graft materials could solve some of the problems associated with the gold standard use of natural bone graft such as limited bone material, pain at the donor site and rejections if donor tissue is used. We have previously described new acrylate base nanocomposite hydrogels as bone graft materials. In the present paper, we describe the integration of silver nanoparticles in the polymeric mineralized biomaterial to provide non-antibiotic antibacterial activity against Staphylococcus epidermidis and Methicillin-resistant Staphylococcus aureus. Two different crosslinking degrees were tested and the silver nanoparticles were integrated into the composite matrix by means of three different methods: entrapment in the polymeric hydrogel before the mineralization; diffusion during the process of calcium phosphate crystallization and adsorption post-mineralization. The latter being generally the most effective method of encapsulation; however, the adsorption of silver nanoparticles inside the pores of the biomaterial led to a decreasing antibacterial activity for adsorption time longer than 2 days.

  13. Gingiva as a new and the most accessible source of mesenchymal stem cells from the oral cavity to be used in regenerative therapies

    Directory of Open Access Journals (Sweden)

    Bartłomiej Górski

    2016-08-01

    Full Text Available Since the discovery of bone marrow mesenchymal stem cells (BMMSCs, many researchers have focused their attention on new sources of mesenchymal stem cells (MSCs. Consequently, MSCs that display self-renewal capacity, multidifferentiation potential and immunomodulatory properties have been isolated from human oral tissues, including tooth, periodontal ligament, and gingiva. Oral MSCs involve dental pulp stem cells (DPSCs, stem cells from exfoliated deciduous teeth (SHED, periodontal ligament stem cells (PDLSCs, dental follicle stem cells (DFCs, stem cells from apical papilla (SCAP and gingival stem cells (GMSCs. Current research on oral stem cells is expanding at an unprecedented rate. That being the case, a plethora of in vitro differentiation assays, immunodeficient animal transplantations and preclinical trials have demonstrated that these cells exhibit strong potential for both regenerative dentistry and medicine. Oral MSCs have proved their capability to repair cornea, dental pulp, periodontal, bone, cartilage, tendon, neural, muscle and endothelial tissues without neoplasm formation as well as to treat inflammatory diseases and immune disorders. This article describes the current understanding of oral MSCs and their prospective applications in cell-based therapy, tissue engineering and regenerative medicine. Special attention is placed on GMSCs as they are easily accessible and may be obtained in a convenient and minimally invasive way.

  14. Mesenchymal stem cells and their subpopulation, pluripotent muse cells, in basic research and regenerative medicine.

    Science.gov (United States)

    Kuroda, Yasumasa; Dezawa, Mari

    2014-01-01

    Mesenchymal stem cells (MSCs) have gained a great deal of attention for regenerative medicine because they can be obtained from easy accessible mesenchymal tissues, such as bone marrow, adipose tissue, and the umbilical cord, and have trophic and immunosuppressive effects to protect tissues. The most outstanding property of MSCs is their potential for differentiation into cells of all three germ layers. MSCs belong to the mesodermal lineage, but they are known to cross boundaries from mesodermal to ectodermal and endodermal lineages, and differentiate into a variety of cell types both in vitro and in vivo. Such behavior is exceptional for tissue stem cells. As observed with hematopoietic and neural stem cells, tissue stem cells usually generate cells that belong to the tissue in which they reside, and do not show triploblastic differentiation. However, the scientific basis for the broad multipotent differentiation of MSCs still remains an enigma. This review summarizes the properties of MSCs from representative mesenchymal tissues, including bone marrow, adipose tissue, and the umbilical cord, to demonstrate their similarities and differences. Finally, we introduce a novel type of pluripotent stem cell, multilineage-differentiating stress-enduring (Muse) cells, a small subpopulation of MSCs, which can explain the broad spectrum of differentiation ability in MSCs.

  15. Chondrogenic potential of bone marrow–derived mesenchymal stem cells on a novel, auricular-shaped, nanocomposite scaffold

    Directory of Open Access Journals (Sweden)

    Kavi H Patel

    2013-12-01

    Full Text Available Reconstruction of the human auricle remains a challenge to plastic surgeons, and current approaches are not ideal. Tissue engineering provides a promising alternative. This study aims to evaluate the chondrogenic potential of bone marrow–derived mesenchymal stem cells on a novel, auricular-shaped polymer. The proposed polyhedral oligomeric silsesquioxane-modified poly(hexanolactone/carbonateurethane/urea nanocomposite polymer has already been transplanted in patients as the world’s first synthetic trachea, tear duct and vascular bypass graft. The nanocomposite scaffold was fabricated via a coagulation/salt-leaching method and shaped into an auricle. Adult bone marrow–derived mesenchymal stem cells were isolated, cultured and seeded onto the scaffold. On day 21, samples were sent for scanning electron microscopy, histology and immunofluorescence to assess for neocartilage formation. Cell viability assay confirmed cytocompatability and normal patterns of cellular growth at 7, 14 and 21 days after culture. This study demonstrates the potential of a novel polyhedral oligomeric silsesquioxane-modified poly(hexanolactone/carbonateurethane/urea scaffold for culturing bone marrow–derived mesenchymal stem cells in chondrogenic medium to produce an auricular-shaped construct. This is supported by scanning electron microscopy, histological and immunofluorescence analysis revealing markers of chondrogenesis including collagen type II, SOX-9, glycosaminoglycan and elastin. To the best of our knowledge, this is the first report of stem cell application on an auricular-shaped scaffold for tissue engineering purposes. Although many obstacles remain in producing a functional auricle, this is a promising step forward.

  16. The clinical use of regenerative therapy in COPD

    Directory of Open Access Journals (Sweden)

    Lipsi R

    2014-12-01

    Full Text Available Roberto Lipsi,1 Paola Rogliani,1 Luigino Calzetta,2 Andrea Segreti,1 Mario Cazzola1 1Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; 2Department of Pulmonary Rehabilitation, San Raffaele Pisana Hospital, Istituti di Ricovero e Cura a Carattere Scientifico, Rome, Italy Abstract: Regenerative or stem cell therapy is an emerging field of treatment based on stimulation of endogenous resident stem cells or administration of exogenous stem cells to treat diseases or injury and to replace malfunctioning or damaged tissues. Current evidence suggests that in the lung, these cells may participate in tissue homeostasis and regeneration after injury. Animal and human studies have demonstrated that tissue-specific stem cells and bone marrow-derived cells contribute to lung tissue regeneration and protection, and thus administration of exogenous stem/progenitor cells or humoral factors responsible for the activation of endogenous stem/progenitor cells may be a potent next-generation therapy for chronic obstructive pulmonary disease. The use of bone marrow-derived stem cells could allow repairing and regenerate the damaged tissue present in chronic obstructive pulmonary disease by means of their engraftment into the lung. Another approach could be the stimulation of resident stem cells by means of humoral factors or photobiostimulation. Keywords: chronic obstructive pulmonary disease, stem cells, regenerative therapy, all-trans retinoic acid, photobiostimulation

  17. Emdogain in regenerative periodontal therapy. A review of the literature.

    Science.gov (United States)

    Sculean, Anton; Windisch, Péter; Döri, Ferenc; Keglevich, Tibor; Molnár, Balint; Gera, István

    2007-10-01

    The goal of regenerative periodontal therapy is the reconstitution of the lost periodontal structures (i.e. the new formation of root cementum, periodontal ligament and alveolar bone). Results from basic research have pointed to the important role of the enamel matrix protein derivative (EMD) in the periodontal wound healing. Histological results from animal and human studies have shown that treatment with EMD promotes periodontal regeneration. Moreover, clinical studies have indicated that treatment with EMD positively influences periodontal wound healing in humans. The goal of the current overview is to present, based on the existing evidence, the clinical indications for regenerative therapy with EMD. Surgical periodontal treatment of deep intrabony defects with EMD promotes periodontal regeneration. The application of EMD in the context of non-surgical periodontal therapy has failed to result in periodontal regeneration. Surgical periodontal therapy of deep intrabony defects with EMD may lead to significantly higher improvements of the clinical parameters than open flap debridement alone. The results obtained following treatment with EMD are comparable to those following treatment with GTR and can be maintained over a longer period. Treatment of intrabony defects with a combination of EMD + GTR does not seem to additionally improve the results compared to treatment with EMD alone or GTR alone. The combination of EMD and some types of bone grafts/bone substitutes may result in certain improvements in the soft and hard tissue parameters compared to treatment with EMD alone. Treatment of recession-type defects with coronally repositioned flaps and EMD may promote formation of cementum, periodontal ligament and bone, and may significantly increase the width of the keratinized tissue. Application of EMD seems to provide better long-term results than coronally repositioned flaps alone. Application of EMD may enhance periodontal regeneration in mandibular Class II

  18. Assessing the potential of colony morphology for dissecting the CFU-F population from human bone marrow stromal cells.

    Science.gov (United States)

    Gothard, D; Dawson, J I; Oreffo, R O C

    2013-05-01

    Mesenchymal stem cells (MSCs) provide an ideal cell source for bone tissue engineering strategies. However, bone marrow stromal cell (BMSC) populations that contain MSCs are highly heterogeneous expressing a wide variety of proliferative and differentiation potentials. Current MSC isolation methods employing magnetic-activated and fluorescent-activated cell sorting can be expensive and time consuming and, in the absence of specific MSC markers, fail to generate homogeneous populations. We have investigated the potential of various colony morphology descriptors to provide correlations with cell growth potential. Density-independent colony forming unit-fibroblastic (CFU-F) capacity is a MSC prerequisite and resultant colonies display an array of shapes and sizes that might be representative of cell function. Parent colonies were initially categorised according to their diameter and cell density and grouped before passage for the subsequent assessment of progeny colonies. Whereas significant morphological differences between distinct parent populations indicated a correlation with immunophenotype, enhanced CFU-F capacity was not observed when individual colonies were isolated according to these morphological parameters. Colony circularity, an alternative morphological measure, displayed a strong correlation with subsequent cell growth potential. The current study indicates the potential of morphological descriptors for predicting cell growth rate and suggests new directions for research into dissection of human BMSC CFU-F populations.

  19. Changes in Regenerative Capacity through Lifespan

    Directory of Open Access Journals (Sweden)

    Maximina H. Yun

    2015-10-01

    Full Text Available Most organisms experience changes in regenerative abilities through their lifespan. During aging, numerous tissues exhibit a progressive decline in homeostasis and regeneration that results in tissue degeneration, malfunction and pathology. The mechanisms responsible for this decay are both cell intrinsic, such as cellular senescence, as well as cell-extrinsic, such as changes in the regenerative environment. Understanding how these mechanisms impact on regenerative processes is essential to devise therapeutic approaches to improve tissue regeneration and extend healthspan. This review offers an overview of how regenerative abilities change through lifespan in various organisms, the factors that underlie such changes and the avenues for therapeutic intervention. It focuses on established models of mammalian regeneration as well as on models in which regenerative abilities do not decline with age, as these can deliver valuable insights for our understanding of the interplay between regeneration and aging.

  20. Tissue Engineering and Regenerative Medicine

    Science.gov (United States)

    2006-11-01

    Vessels - 5 years; Heart Valves – in progress Respiratory: Trachea – in progress Orthopedic : Cartilage, Bone, Skeletal Muscle, Digits Nephrology...interactions (bio-engineers) Small & large animal models (physiologists, biochemists, veterinarians ) Clinical trials (physicians, epidemiologists

  1. A combined regenerative approach for the treatment of aggressive periodontitis: long-term follow-up of a familial case.

    Science.gov (United States)

    Sant'Ana, Adriana Campos Passanezi; Passanezi, Euloir; Todescan, Sylvia Maria Correia; de Rezende, Maria Lúcia Rubo; Greghi, Sebastião Luiz Aguiar; Ribeiro, Mônica Garcia

    2009-02-01

    This article reports the longitudinal follow-up of a familial case of aggressive periodontitis treated by a combined regenerative approach that consisted of root conditioning, bone grafting, and membrane positioning. Treatment resulted in attachment level gain, reduction of probing depth, absence of bleeding on probing, and complete bone filling of the defect. The short-term results obtained after surgery were maintained after 6 years, suggesting that the combined regenerative approach is able to completely arrest the disease with long-term stability.

  2. Bone printing: new frontiers in the treatment of bone defects.

    Science.gov (United States)

    Arealis, Georgios; Nikolaou, Vasileios S

    2015-12-01

    Bone defects can be congenital or acquired resulting from trauma, infection, neoplasm and failed arthroplasty. The osseous reconstruction of these defects is challenging. Unfortunately, none of the current techniques for the repair of bone defects has proven to be fully satisfactory. Bone tissue engineering (BTE) is the field of regenerative medicine (RM) that focuses on alternative treatment options for bone defects that will ideally address all the issues of the traditional techniques in treating large bone defects. However, current techniques of BTE is laborious and have their own shortcomings. More recently, 2D and 3D bone printing has been introduced to overcome most of the limitations of bone grafts and BTE. So far, results are extremely promising, setting new frontiers in the management of bone defects.

  3. The roles of vascular endothelial growth factor in bone repair and regeneration.

    Science.gov (United States)

    Hu, Kai; Olsen, Bjorn R

    2016-10-01

    Vascular endothelial growth factor-A (VEGF) is one of the most important growth factors for regulation of vascular development and angiogenesis. Since bone is a highly vascularized organ and angiogenesis plays an important role in osteogenesis, VEGF also influences skeletal development and postnatal bone repair. Compromised bone repair and regeneration in many patients can be attributed to impaired blood supply; thus, modulation of VEGF levels in bones represents a potential strategy for treating compromised bone repair and improving bone regeneration. This review (i) summarizes the roles of VEGF at different stages of bone repair, including the phases of inflammation, endochondral ossification, intramembranous ossification during callus formation and bone remodeling; (ii) discusses different mechanisms underlying the effects of VEGF on osteoblast function, including paracrine, autocrine and intracrine signaling during bone repair; (iii) summarizes the role of VEGF in the bone regenerative procedure, distraction osteogenesis; and (iv) reviews evidence for the effects of VEGF in the context of repair and regeneration techniques involving the use of scaffolds, skeletal stem cells and growth factors. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. In vitro models for the evaluation of angiogenic potential in bone engineering

    Institute of Scientific and Technical Information of China (English)

    Elisabetta CENNI; Francesca PERUT; Nicola BALDIN

    2011-01-01

    Blood vessels have a fundamental role both in skeletal homeostasis and in bone repair. Angiogenesis is also important for a success-ful bone engineering. Therefore, scaffolds should be tested for their ability to favour endothelial cell adhesion, proliferation and func-tions. The type of endothelial cell to use for in vitro assays should be carefully considered, because the properties of these cells may depend on their source. Morphological and functional relationships between endothelial cells and osteoblasts are evaluated with co-cultures, but this model should still be standardized, particularly for distinguishing the two cell types. Platelet-rich plasma and recom-binant growth factors may be useful for stimulating angiogenesis.

  5. Regenerative Electroless Etching of Silicon.

    Science.gov (United States)

    Kolasinski, Kurt W; Gimbar, Nathan J; Yu, Haibo; Aindow, Mark; Mäkilä, Ermei; Salonen, Jarno

    2017-01-09

    Regenerative electroless etching (ReEtching), described herein for the first time, is a method of producing nanostructured semiconductors in which an oxidant (Ox1 ) is used as a catalytic agent to facilitate the reaction between a semiconductor and a second oxidant (Ox2 ) that would be unreactive in the primary reaction. Ox2 is used to regenerate Ox1 , which is capable of initiating etching by injecting holes into the semiconductor valence band. Therefore, the extent of reaction is controlled by the amount of Ox2 added, and the rate of reaction is controlled by the injection rate of Ox2 . This general strategy is demonstrated specifically for the production of highly luminescent, nanocrystalline porous Si from the reaction of V2 O5 in HF(aq) as Ox1 and H2 O2 (aq) as Ox2 with Si powder and wafers.

  6. Regenerative Therapies for Diabetic Microangiopathy

    Directory of Open Access Journals (Sweden)

    Roberto Bassi

    2012-01-01

    Full Text Available Hyperglycaemia occurring in diabetes is responsible for accelerated arterial remodeling and atherosclerosis, affecting the macro- and the microcirculatory system. Vessel injury is mainly related to deregulation of glucose homeostasis and insulin/insulin-precursors production, generation of advanced glycation end-products, reduction in nitric oxide synthesis, and oxidative and reductive stress. It occurs both at extracellular level with increased calcium and matrix proteins deposition and at intracellular level, with abnormalities of intracellular pathways and increased cell death. Peripheral arterial disease, coronary heart disease, and ischemic stroke are the main causes of morbidity/mortality in diabetic patients representing a major clinical and economic issue. Pharmacological therapies, administration of growth factors, and stem cellular strategies are the most effective approaches and will be discussed in depth in this comprehensive review covering the regenerative therapies of diabetic microangiopathy.

  7. Towards personalized regenerative cell therapy

    DEFF Research Database (Denmark)

    Lin, Lin; Bolund, Lars; Luo, Yonglun

    2015-01-01

    Mesenchymal stem cells (MSCs) are adult stem cells with the capacity of self-renewal and multilineage differentiation, and can be isolated from several adult tissues. However, isolating MSCs from adult tissues for cell therapy is hampered by the invasive procedure, the rarity of the cells...... and their attenuated proliferation capacity when cultivated and expanded in vitro. Human MSCs derived from induced pluripotent stem cells (iPSC-MSCs) have now evolved as a promising alternative cell source for MSCs and regenerative medicine. Several groups, including ours, have reported successful derivation...... of functional iPSC-MSCs and applied these cells in MSC-based therapeutic testing. Still, the current experience and understanding of iPSC-MSCs with respect to production methods, safety and efficacy are primitive. In this review, we highlight the methodological progress in iPSC-MSC research, describing...

  8. Regenerative medicine for diseases of the head and neck: principles of in vivo regeneration.

    Science.gov (United States)

    Löwenheim, H

    2003-09-01

    The application of endogenous regeneration in regenerative medicine is based on the concept of inducing regeneration of damaged or lost tissues from residual tissues in situ. Therefore, endogenous regeneration is also termed in vivo regeneration as opposed to mechanisms of ex vivo regeneration which are applied, for example, in the field of tissue engineering. The basic science foundation for mechanisms of endogenous regeneration is provided by the field of regenerative biology. The ambitious vision for the application of endogenous regeneration in regenerative medicine is stimulated by investigations in the model organisms of regenerative biology, most notably hydra, planarians and urodeles. These model organisms demonstrate remarkable regenerative capabilities, which appear to be conserved over large phylogenetical stretches with convincing evidence for a homologue origin of an endogenous regenerative capability. Although the elucidation of the molecular and cellular mechanisms of these endogenous regenerative phenomena is still in its beginning, there are indications that these processes have potential to become useful for human benefit. Such indications also exist for particular applications in diseases of the head and neck region. As such epimorphic regeneration without blastema formation may be relevant to regeneration of sensorineural epithelia of the inner ear or the olphactory epithelium. Complex tissue lesions of the head and neck as they occur after trauma or tumor resections may be approached on the basis of relevant mechanisms in epimorphic regeneration with blastema formation.

  9. Actinide(IV) Deposits on Bone: Potential Role of the Osteopontin-Thorium Complex.

    Science.gov (United States)

    Creff, Gaëlle; Safi, Samir; Roques, Jérôme; Michel, Hervé; Jeanson, Aurélie; Solari, Pier-Lorenzo; Basset, Christian; Simoni, Eric; Vidaud, Claude; Den Auwer, Christophe

    2016-01-04

    In case of a nuclear event, contamination (broad or limited) of the population or of specific workers might occur. In such a senario, the fate of actinide contaminants may be of first concern, in particular with regard to human target organs like the skeleton. To improve our understanding of the toxicological processes that might take place, a mechanistic approach is necessary. For instance, ∼50% of Pu(IV) is known from biokinetic data to accumulate in bone, but the underlining mechanisms are almost unknown. In this context, and to obtain a better description of the toxicological mechanisms associated with actinides(IV), we have undertaken the investigation, on a molecular scale, of the interaction of thorium(IV) with osteopontin (OPN) a hyperphosphorylated protein involved in bone turnover. Thorium is taken here as a simple model for actinide(IV) chemistry. In addition, we have selected a phosphorylated hexapeptide (His-pSer-Asp-Glu-pSer-Asp-Glu-Val) that is representative of the peptidic sequence involved in the bone interaction. For both the protein and the biomimetic peptide, we have determined the local environment of Th(IV) within the bioactinidic complex, combining isothermal titration calorimetry, attenuated total reflectance Fourier transform infrared spectroscopy, theoretical calculations with density functional theory, and extended X-ray absorption fine structure spectroscopy at the Th LIII edge. The results demonstrate a predominance of interaction of metal with the phosphate groups and confirmed the previous physiological studies that have highlighted a high affinity of Th(IV) for the bone matrix. Data are further compared with those of the uranyl case, representing the actinyl(V) and actinyl(VI) species. Last, our approach shows the importance of developing simplified systems [Th(IV)-peptide] that can serve as models for more biologically relevant systems.

  10. In vitro characterization of bone marrow stromal cells from osteoarthritic donors

    DEFF Research Database (Denmark)

    Stiehler, Maik; Rauh, Juliane; Bünger, Cody;

    2016-01-01

    BMSCs, also known as bone marrow-derived mesenchymal stem cells, provide an excellent source of progenitor cells for regenerative therapy. To assess whether osteoarthritis (OA) affects the regenerative potential of BMSCs we compared the proliferation and differentiation potential as well......-forming-units of fibroblastsmax (CFU-F) assay. Differentiation assays included immunohistology, cell-specific alkaline phosphatase (ALP) activity, and osteogenic, chondrogenic as well as adipogenic marker gene qRT-PCR. Expression of BMSC-associated surface markers was analyzed using flow cytometry. No significant intergroup...... differences were observed concerning the proliferation potential, cell-specific ALP activity as well as adipogenic and osteogenic differentiation marker gene expressions. Interestingly, SOX9 gene expression levels were significantly increased in OA-BMSCs after 14days of chondrogenic stimulation (p

  11. Osteogenic differentiation of amniotic fluid mesenchymalstromal cells and their bone regeneration potential

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    In orthopedics, tissue engineering approach usingstem cells is a valid line of treatment for patients withbone defects. In this context, mesenchymal stromalcells of various origins have been extensively studiedand continue to be a matter of debate. Although mesenchymalstromal cells from bone marrow are alreadyclinically applied, recent evidence suggests that one mayuse mesenchymal stromal cells from extra-embryonictissues, such as amniotic fluid, as an innovative andadvantageous resource for bone regeneration. Theuse of cells from amniotic fluid does not raise ethicalproblems and provides a sufficientnumber of cellswithout invasive procedures. Furthermore, they donot develop into teratomas when transplanted, aconsequence observed with pluripotent stem cells.In addition, their multipotent differentiation ability,low immunogenicity, and anti-inflammatory propertiesmake them ideal candidates for bone regenerativemedicine. We here present an overview of the featuresof amniotic fluid mesenchymal stromal cells and theirpotential in the osteogenic differentiation process.We have examined the papers actually availableonthis regard, with particular interest in the strategiesapplied to improve in vitro osteogenesis. Importantly, adetailed understanding of the behavior of amniotic fluidmesenchymal stromal cells and their osteogenic abilityis desirable considering a feasible application in boneregenerative medicine.

  12. Investigations of genotoxic potential of levamisole hydrochloride in bone marrow cells of Wistar rats

    Directory of Open Access Journals (Sweden)

    Kulić Milan

    2006-01-01

    Full Text Available An experiment was performed under in vivo conditions on bone marrow cells of Wistar rats. The following doses of levamisole hydrochloride were tested: a therapeutic dose of 2.2 mg/kg bm, a dose of 4.4 mg/kg bm, LD50 -25% mg/kg bm, and LD50 -75% mg/kg bm. We followed the effect of levamisole hydrochloride on kinetics of the cell cycle and the appearance of structural and numeric changes in chromosomes in bone marrow cells. The therapeutic dose of levamisole of 2.2 mg/kg bm exhibited a capability to increase mitotic activity in the observed cells, thus confirming knowledge of the immunostimulative effect of this dose of the medicine under in vivo conditions. The other tested doses of levamisole in this experiment, observed in comparison with the control group, had an opposite effect, namely, they caused a reduction in the mitotic activity of bone marrow cells. All the examined doses in vivo exhibited the ability to induce numeric (aneuploid and polyploid and structural (lesions, breaks and insertions chromosomal aberrations. It can be concluded on the grounds of these findings that the examined doses have a genotoxic effect.

  13. Stem Cell, Regenerative Medicine and Cancer | Center for Cancer Research

    Science.gov (United States)

    Of the estimated trillion cells that build up our bodies, only a little number can self-renew and give rise to many different cell types. These unspecialized cells are called stem cells. Stem cell division and differentiation is fundamental to the development of the mature organism. Stem cells have recently attracted significant attention largely due to their potential medical benefits in the fields of therapeutic cloning and regenerative medicine.

  14. Distance between implants has a potential impact of crestal bone resorption.

    Science.gov (United States)

    Danza, Matteo; Zollino, Ilaria; Avantaggiato, Anna; Lucchese, Alessandra; Carinci, Francesco

    2011-07-01

    Around dental implants exists a "biologic width" of few millimeters that have to be preserved in order to not have adverse effect on soft and hard tissues around implant. Because the minimum distance between adjacent implants has not been determined yet, we therefore, decided to perform a retrospective study on a series of spiral family implants (SFIs) to verify the minimum inter-implants' distance that has an impact on crestal bone resorption. Fifty-nine implants were investigated with a mean follow-up of 14 months. Implant diameter was 3.75, 4.2, 5 and 6 mm in 11 (18.6%), 29 (49.2%), 17 (28.8%) and 2 (3.4%) SFIs. Implant length was shorter than 13 mm, equal to 13 mm and 16 mm in 23 (39%), 23 (39%) and 13 (22%) SFIs. Implants were inserted to replace 13 incisors (22%), 7 cuspids (11.9%), 30 premolars (50.8%) and 9 molars (15.3%). Twenty-seven fixtures were inserted in post-extractive sockets and the remaining 32 in healed bone; 36 (61%) were immediately loaded. In addition to the above mentioned implant-related factors, several host- and surgery-factors were investigated. Independent samples T-test, univariate and multivariate analysis were used to detect those variables associated with the clinical outcome. Data were evaluated with a two steps statistical analysis (i.e. univariate and multivariate) after having grouped implants in two series: those with an implant-implant distance less of 1.8 mm and those with an implant-implants distance greater than 1.8 mm. In univariate analysis, post-extractive implants and number of prosthetic units were statistically significant. In multivariate analysis, only post-extractive implants have a significant adverse effect on crestal bone resorption. Adjacent implants inserted with a distance lower and higher than 1.8 mm have difference in crestal bone resorption but this difference is not statistically significant in a short period follow up. This could due to the specific implant used that has a reverse conical neck

  15. Increasing dietary phosphorus intake from food additives: potential for negative impact on bone health.

    Science.gov (United States)

    Takeda, Eiji; Yamamoto, Hironori; Yamanaka-Okumura, Hisami; Taketani, Yutaka

    2014-01-01

    It is important to consider whether habitual high phosphorus intake adversely affects bone health, because phosphorus intake has been increasing, whereas calcium intake has been decreasing in dietary patterns. A higher total habitual dietary phosphorus intake has been associated with higher serum parathyroid hormone (PTH) and lower serum calcium concentrations in healthy individuals. Higher serum PTH concentrations have been shown in those who consume foods with phosphorus additives. These findings suggest that long-term dietary phosphorus loads and long-term hyperphosphatemia may have important negative effects on bone health. In contrast, PTH concentrations did not increase as a result of high dietary phosphorus intake when phosphorus was provided with adequate amounts of calcium. Intake of foods with a ratio of calcium to phosphorus close to that found in dairy products led to positive effects on bone health. Several randomized controlled trials have shown positive relations between dairy intake and bone mineral density. In our loading test with a low-calcium, high-phosphorus lunch provided to healthy young men, serum PTH concentrations showed peaks at 1 and 6 h, and serum fibroblast growth factor 23 (FGF23) concentrations increased significantly at 8 h after the meal. In contrast, the high-calcium, high-phosphorus meal suppressed the second PTH and FGF23 elevations until 8 h after the meal. This implies that adequate dietary calcium intake is needed to overcome the interfering effects of high phosphorus intake on PTH and FGF23 secretion. FGF23 acts on the parathyroid gland to decrease PTH mRNA and PTH secretion in rats with normal kidney function. However, increased serum FGF23 is an early alteration of mineral metabolism in chronic kidney disease, causing secondary hyperthyroidism, and implying resistance of the parathyroid gland to the action of FGF23 in chronic kidney disease. These findings suggest that long-term high-phosphorus diets may impair bone health

  16. Dental pulp stem cells: function, isolation and applications in regenerative medicine.

    Science.gov (United States)

    Tatullo, Marco; Marrelli, Massimo; Shakesheff, Kevin M; White, Lisa J

    2015-11-01

    Dental pulp stem cells (DPSCs) are a promising source of cells for numerous and varied regenerative medicine applications. Their natural function in the production of odontoblasts to create reparative dentin support applications in dentistry in the regeneration of tooth structures. However, they are also being investigated for the repair of tissues outside of the tooth. The ease of isolation of DPSCs from discarded or removed teeth offers a promising source of autologous cells, and their similarities with bone marrow stromal cells (BMSCs) suggest applications in musculoskeletal regenerative medicine. DPSCs are derived from the neural crest and, therefore, have a different developmental origin to BMSCs. These differences from BMSCs in origin and phenotype are being exploited in neurological and other applications. This review briefly highlights the source and functions of DPSCs and then focuses on in vivo applications across the breadth of regenerative medicine.

  17. Bioinorganics: synthetic growth factors for bone regeneration

    NARCIS (Netherlands)

    Tahmasebi Birgani, Z.

    2016-01-01

    Bone tissue is naturally able to regenerate when damaged. However, in many large defects caused by fractures due to aging or osteoporosis, trauma, tumor removal, etc., the natural regenerative ability of bone is not sufficient to fully heal the defect. In such cases, a graft is required to support t

  18. Alkaline RFC Space Station prototype - 'Next step Space Station'. [Regenerative Fuel Cells

    Science.gov (United States)

    Hackler, I. M.

    1986-01-01

    The regenerative fuel cell, a candidate technology for the Space Station's energy storage system, is described. An advanced development program was initiated to design, manufacture, and integrate a regenerative fuel cell Space Station prototype (RFC SSP). The RFC SSP incorporates long-life fuel cell technology, increased cell area for the fuel cells, and high voltage cell stacks for both units. The RFC SSP's potential for integration with the Space Station's life support and propulsion systems is discussed.

  19. REGENERATIVE MEDICINE AS APPLIED TO GENERAL SURGERY

    Science.gov (United States)

    Orlando, Giuseppe; Wood, Kathryn J; De Coppi, Paolo; Baptista, Pedro M; Binder, Kyle W; Bitar, Khalil N; Breuer, Christopher; Burnett, Luke; Christ, George; Farney, Alan; Figliuzzi, Marina; Holmes, James H; Koch, Kenneth; Macchiarini, Paolo; Sani, Sayed-Hadi Mirmalek; Opara, Emmanuel; Remuzzi, Andrea; Rogers, Jeffrey; Saul, Justin M; Seliktar, Dror; Shapira-Schweitzer, Keren; Smith, Tom; Solomon, Daniel; Van Dyke, Mark; Yoo, James J; Zhang, Yuanyuan; Atala, Anthony; Stratta, Robert J; Soker, Shay

    2012-01-01

    The present review illustrates the state of the art of regenerative medicine (RM) as applied to surgical diseases and demonstrates that this field has the potential to address some of the unmet needs in surgery. RM is a multidisciplinary field whose purpose is to regenerate in vivo or ex vivo human cells, tissues or organs in order to restore or establish normal function through exploitation of the potential to regenerate, which is intrinsic to human cells, tissues and organs. RM uses cells and/or specially designed biomaterials to reach its goals and RM-based therapies are already in use in several clinical trials in most fields of surgery. The main challenges for investigators are threefold: Creation of an appropriate microenvironment ex vivo that is able to sustain cell physiology and function in order to generate the desired cells or body parts; identification and appropriate manipulation of cells that have the potential to generate parenchymal, stromal and vascular components on demand, both in vivo and ex vivo; and production of smart materials that are able to drive cell fate. PMID:22330032

  20. Platelet derivatives in regenerative medicine: an update.

    Science.gov (United States)

    De Pascale, Maria Rosaria; Sommese, Linda; Casamassimi, Amelia; Napoli, Claudio

    2015-01-01

    Prior preclinical and clinical studies support the use of platelet-derived products for the treatment of soft and hard tissue lesions. These regenerative effects are controlled by autocrine and paracrine biomolecules including growth factors and cytokines contained in platelet alpha granules. Each growth factor is involved in a phase of the healing process, such as inflammation, collagen synthesis, tissue granulation, and angiogenesis collectively promoting tissue restitution. Platelet derivatives have been prepared as platelet-rich plasma, platelet gel, platelet-rich fibrin, and platelet eye drops. These products vary in their structure, growth factors, composition, and cytokine concentrations. Here, we review the current use of platelet-derived biological products focusing on the rationale for their use and the main requirements for their preparation. Variation in the apparent therapeutic efficacy may have resulted from a lack of reproducible, standardized protocols for preparation. Despite several individual studies showing favorable treatment effects, some randomized controlled trials as well as meta-analyses have found no constant clinical benefit from the application of platelet-derived products for prevention of tissue lesions. Recently, 3 published studies in dentistry showed an improvement in bone density. Seven published studies showed positive results in joint regeneration. Five published studies demonstrated an improvement in the wound healing, and an improvement of eye epithelial healing was observed in 2 reports. Currently, at least 14 ongoing clinical trials in phase 3 or 4 have been designed with large groups of treated patients (n > 100). Because the rationale of the therapy with platelet-derived compounds is still debated, a definitive insight can be acquired only when these large randomized trials will be completed.

  1. ''Black Bone'' MRI: a potential alternative to CT with three-dimensional reconstruction of the craniofacial skeleton in the diagnosis of craniosynostosis

    Energy Technology Data Exchange (ETDEWEB)

    Eley, Karen A. [University of Oxford, John Radcliffe Hospital, Nuffield Department of Surgical Sciences, Oxford (United Kingdom); University of Cambridge, Addenbrookes Hospital, Department of Radiology, Cambridge (United Kingdom); Watt-Smith, Stephen R. [University of Oxford, John Radcliffe Hospital, Nuffield Department of Surgical Sciences, Oxford (United Kingdom); University College London, Eastman Dental Institute, London (United Kingdom); Sheerin, Fintan [University of Oxford, John Radcliffe Hospital, Nuffield Department of Surgical Sciences, Oxford (United Kingdom); Oxford University Hospitals NHS Trust, Oxford (United Kingdom); Golding, Stephen J. [University of Oxford, John Radcliffe Hospital, Nuffield Department of Surgical Sciences, Oxford (United Kingdom)

    2014-10-15

    To determine the potential of novel gradient echo parameters, ''Black Bone'' MRI as an alternative to CT in the identification of normal and prematurely fused cranial sutures both in 2D and 3D imaging. Thirteen children with a clinical diagnosis of craniosynostosis underwent ''Black Bone'' MRI in addition to routine cranial CT. ''Black Bone'' datasets were compared to CT and clinical findings. ''Black Bone'' imaging was subsequently used to develop 3D reformats of the craniofacial skeleton to enhance further visualisation of the cranial sutures. Patent cranial sutures were consistently identified on ''Black Bone'' MRI as areas of increased signal intensity. In children with craniosynostosis the affected suture was absent, whilst the remaining patent sutures could be visualised, consistent with CT and clinical findings. Segmentation of the ''Black Bone'' MRI datasets was successful with both threshold and volume rendering techniques. The cranial sutures, where patent, could be visualised throughout their path. Patent cranial sutures appear as areas of increased signal intensity on ''Black Bone'' MRI distinct from the cranial bone, demonstrating considerable clinical potential as a non-ionising alternative to CT in the diagnosis of craniosynostosis. (orig.)

  2. Diffusion of protease into meat & bone meal for solubility improvement and potential inactivation of the BSE prion.

    Directory of Open Access Journals (Sweden)

    Brian A Coll

    Full Text Available BACKGROUND: Government-imposed feed bans have created a need for new applications for meat & bone meal (MBM. Many potential new applications require MBM protein to be both soluble and free of infectious prion. Treatment with protease is generally effective in reducing insoluble, thermally-denatured proteins to soluble peptides. It has been reported in the literature that certain proteases, including Versazyme, are able to degrade infectious prions in a system where the prions are readily accessible to proteolytic attack. Prions distributed within MBM, however, may conceivably be protected from proteases. METHODOLOGY/PRINCIPAL FINDINGS: The overall rate of proteolytic MBM digestion depends greatly on whether the protease can penetrate deep within individual particles, or if the protease can only act near the surface of the particle. This research examined the barriers to the diffusion of Versazyme into particles of MBM. Confocal microscopy demonstrated differences in the density distributions between the bone and the soft tissue particles of MBM. By tracking the diffusion of fluorescently labeled Versazyme through individual particles, it was found that bone particles show full Versazyme penetration within 30 minutes, while penetration of soft tissue particles can take up to four hours, depending on the particle's diameter. From the variety of normal proteins comprising MBM, a specific protein was chosen to serve as a prion surrogate based on characteristics including size, solubility, distribution and abundance. This surrogate was used to measure the effect of several factors on Versazyme diffusion. CONCLUSIONS/SIGNIFICANCE: Results showed that surrogate distributed in bone particles was more susceptible to degradation than that in soft tissue particles. Three factors controllable by unit operations in an industrial-scale process were also tested. It was found that removing the lipid content and hydrating MBM prior to incubation both

  3. Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration.

    Science.gov (United States)

    Richardson, Stephen M; Kalamegam, Gauthaman; Pushparaj, Peter N; Matta, Csaba; Memic, Adnan; Khademhosseini, Ali; Mobasheri, Reza; Poletti, Fabian L; Hoyland, Judith A; Mobasheri, Ali

    2016-04-15

    Musculoskeletal disorders represent a major cause of disability and morbidity globally and result in enormous costs for health and social care systems. Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders. Novel biological therapies that can effectively treat joint and spine degeneration are high priorities in regenerative medicine. Mesenchymal stem cells (MSCs) isolated from bone marrow (BM-MSCs), adipose tissue (AD-MSCs) and umbilical cord (UC-MSCs) show considerable promise for use in cartilage and intervertebral disc (IVD) repair. This review article focuses on stem cell-based therapeutics for cartilage and IVD repair in the context of the rising global burden of musculoskeletal disorders. We discuss the biology MSCs and chondroprogenitor cells and specifically focus on umbilical cord/Wharton's jelly derived MSCs and examine their potential for regenerative applications. We also summarize key components of the molecular machinery and signaling pathways responsible for the control of chondrogenesis and explore biomimetic scaffolds and biomaterials for articular cartilage and IVD regeneration. This review explores the exciting opportunities afforded by MSCs and discusses the challenges associated with cartilage and IVD repair and regeneration. There are still many technical challenges associated with isolating, expanding, differentiating, and pre-conditioning MSCs for subsequent implantation into degenerate joints and the spine. However, the prospect of combining biomaterials and cell-based therapies that incorporate chondrocytes, chondroprogenitors and MSCs leads to the optimistic view that interdisciplinary approaches will lead to significant breakthroughs in regenerating musculoskeletal tissues, such as the joint and the spine in the near future.

  4. New Regenerative Cycle for Vapor Compression Refrigeration

    Energy Technology Data Exchange (ETDEWEB)

    Mark J. Bergander

    2005-08-29

    The main objective of this project is to confirm on a well-instrumented prototype the theoretically derived claims of higher efficiency and coefficient of performance for geothermal heat pumps based on a new regenerative thermodynamic cycle as comparing to existing technology. In order to demonstrate the improved performance of the prototype, it will be compared to published parameters of commercially available geothermal heat pumps manufactured by US and foreign companies. Other objectives are to optimize the design parameters and to determine the economic viability of the new technology. Background (as stated in the proposal): The proposed technology closely relates to EERE mission by improving energy efficiency, bringing clean, reliable and affordable heating and cooling to the residential and commercial buildings and reducing greenhouse gases emission. It can provide the same amount of heating and cooling with considerably less use of electrical energy and consequently has a potential of reducing our nations dependence on foreign oil. The theoretical basis for the proposed thermodynamic cycle was previously developed and was originally called a dynamic equilibrium method. This theory considers the dynamic equations of state of the working fluid and proposes the methods for modification of T-S trajectories of adiabatic transformation by changing dynamic properties of gas, such as flow rate, speed and acceleration. The substance of this proposal is a thermodynamic cycle characterized by the regenerative use of the potential energy of two-phase flow expansion, which in traditional systems is lost in expansion valves. The essential new features of the process are: (1) The application of two-step throttling of the working fluid and two-step compression of its vapor phase. (2) Use of a compressor as the initial step compression and a jet device as a second step, where throttling and compression are combined. (3) Controlled ratio of a working fluid at the first and

  5. Regenerative endodontics: a review of current status and a call for action.

    Science.gov (United States)

    Murray, Peter E; Garcia-Godoy, Franklin; Hargreaves, Kenneth M

    2007-04-01

    Millions of teeth are saved each year by root canal therapy. Although current treatment modalities offer high levels of success for many conditions, an ideal form of therapy might consist of regenerative approaches in which diseased or necrotic pulp tissues are removed and replaced with healthy pulp tissue to revitalize teeth. Researchers are working toward this objective. Regenerative endodontics is the creation and delivery of tissues to replace diseased, missing, and traumatized pulp. This review provides an overview of regenerative endodontics and its goals, and describes possible techniques that will allow regenerative endodontics to become a reality. These potential approaches include root-canal revascularization, postnatal (adult) stem cell therapy, pulp implant, scaffold implant, three-dimensional cell printing, injectable scaffolds, and gene therapy. These regenerative endodontic techniques will possibly involve some combination of disinfection or debridement of infected root canal systems with apical enlargement to permit revascularization and use of adult stem cells, scaffolds, and growth factors. Although the challenges of introducing endodontic tissue engineering therapies are substantial, the potential benefits to patients and the profession are equally ground breaking. Patient demand is staggering both in scope and cost, because tissue engineering therapy offers the possibility of restoring natural function instead of surgical placement of an artificial prosthesis. By providing an overview of the methodological issues required to develop potential regenerative endodontic therapies, we hope to present a call for action to develop these therapies for clinical use.

  6. Stem cell research and regenerative medicine in 2014: first year of regenerative medicine in Japan.

    Science.gov (United States)

    Okano, Hideyuki

    2014-09-15

    It is my great pleasure to announce that we were able to publish the Japan Issue in Stem Cells and Development, especially in this year 2014. This year, 2014, is said to be the First Year of Regenerative Medicine in Japan. This movement is likely to be based on the establishment of a new law system regarding regenerative medicine (an Act for Ensuring the Safety of Regenerative Medicine or the so-called Regenerative Medicine Law) and the partial revision of the Pharmaceutical Affairs Law (PAL). Both laws will come into effect in 2014 in this country. These new law systems are expected to have a great impact on the facilitation of R&D related to regenerative medicine and stem cell biology. In the present Japan Issue, some excellent stem cell research in this country will be introduced to celebrate the First Year of Regenerative Medicine in Japan.

  7. TLR Stimulation of Bone Marrow Lymphoid Precursors from Childhood Acute Leukemia Modifies Their Differentiation Potentials

    Directory of Open Access Journals (Sweden)

    Elisa Dorantes-Acosta

    2013-01-01

    Full Text Available Acute leukemias are the most frequent childhood malignancies worldwide and remain a leading cause of morbidity and mortality of relapsed patients. While remarkable progress has been made in characterizing genetic aberrations that may control these hematological disorders, it has also become clear that abnormalities in the bone marrow microenvironment might hit precursor cells and contribute to disease. However, responses of leukemic precursor cells to inflammatory conditions or microbial components upon infection are yet unexplored. Our previous work and increasing evidence indicate that Toll-like receptors (TLRs in the earliest stages of lymphoid development in mice and humans provide an important mechanism for producing cells of the innate immune system. Using highly controlled co-culture systems, we now show that lymphoid precursors from leukemic bone marrow express TLRs and respond to their ligation by changing cell differentiation patterns. While no apparent contribution of TLR signals to tumor progression was recorded for any of the investigated diseases, the replenishment of innate cells was consistently promoted upon in vitro TLR exposure, suggesting that early recognition of pathogen-associated molecules might be implicated in the regulation of hematopoietic cell fate decisions in childhood acute leukemia.

  8. Derivation and application of pluripotent stem cells for regenerative medicine.

    Science.gov (United States)

    Wang, Jiaqiang; Zhou, Qi

    2016-06-01

    Pluripotent stem cells (PSCs) are cells that can differentiate into any type of cells in the body, therefore have valuable promise in regenerative medicine of cell replacement therapies and tissue/organ engineering. PSCs can be derived either from early embryos or directly from somatic cells by epigenetic reprogramming that result in customized cells from patients. Here we summarize the methods of deriving PSCs, the various types of PSCs generated with different status, and their versatile applications in both clinical and embryonic development studies. We also discuss an intriguing potential application of PSCs in constructing tissues/organs in large animals by interspecies chimerism. All these emerging findings are likely to contribute to the breakthroughs in biological research and the prosperous prospects of regenerative medicine.

  9. Differentiation of pluripotent stem cells for regenerative medicine.

    Science.gov (United States)

    Li, Ke; Kong, Yan; Zhang, Mingliang; Xie, Fei; Liu, Peng; Xu, Shaohua

    2016-02-26

    A long-standing goal in regenerative medicine is to obtain scalable functional cells on demand to replenish cells lost in various conditions, including relevant diseases, injuries, and aging. As an unlimited cell source, pluripotent stem cells (PSCs) are invaluable for regenerative medicine, because they have the potential to give rise to any cell type in an organism. For therapeutic purposes, it is important to develop specific approach to directing PSC differentiation towards desired cell types efficiently. Through directed differentiation, PSCs could give rise to scalable, clinically relevant cells for in vivo transplantation, as well as for studying diseases in vitro and discovering drugs to treat them. Over the past few years, significant progress has been made in directing differentiation of PSCs into a variety of cell types. In this review, we discuss recent progress in directed differentiation of PSCs, clinical translation of PSC-based cell replacement therapies, and remaining challenges.

  10. Stem cells: a promising source for vascular regenerative medicine.

    Science.gov (United States)

    Rammal, Hassan; Harmouch, Chaza; Lataillade, Jean-Jacques; Laurent-Maquin, Dominique; Labrude, Pierre; Menu, Patrick; Kerdjoudj, Halima

    2014-12-15

    The rising and diversity of many human vascular diseases pose urgent needs for the development of novel therapeutics. Stem cell therapy represents a challenge in the medicine of the twenty-first century, an area where tissue engineering and regenerative medicine gather to provide promising treatments for a wide variety of diseases. Indeed, with their extensive regeneration potential and functional multilineage differentiation capacity, stem cells are now highlighted as promising cell sources for regenerative medicine. Their multilineage differentiation involves environmental factors such as biochemical, extracellular matrix coating, oxygen tension, and mechanical forces. In this review, we will focus on human stem cell sources and their applications in vascular regeneration. We will also discuss the different strategies used for their differentiation into both mature and functional smooth muscle and endothelial cells.

  11. Fusion and regenerative therapies: is immortality really recessive?

    Science.gov (United States)

    Stolzing, Alexandra; Hescheler, Jürgen; Sethe, Sebastian

    2007-12-01

    Harnessing cellular fusion as a potential tool for regenerative therapy has been under tentative investigation for decades. A look back the history of fusion experiments in gerontology reveals that whereas some studies indicate that aging-related changes are conserved in fused cells, others have demonstrated that fusion can be used as a tool to revoke cellular senescence and induce tissue regeneration. Recent findings about the role of fusion processes in tissue homeostasis, replenishment, and repair link insights from fusion studies of previous decades with modern developments in stem cell biology and regenerative medicine. We suggest that age-associated loss of regenerative capacity is associated with a decline of effectiveness in stem cell fusion. We project how studies into the fusion of stem cells with tissue cells, or the fusion between activator stem cells and patient cells might help in the development of applications that "rejuvenate" certain target cells, thereby strategically reinstating a regeneration cascade. The outlook is concluded with a discussion of the next research milestones and the potential hazards of fusion therapies.

  12. Extracellular matrix considerations for scar-free repair and regeneration: insights from regenerative diversity among vertebrates.

    Science.gov (United States)

    Godwin, James; Kuraitis, Drew; Rosenthal, Nadia

    2014-11-01

    The extracellular matrix (ECM) is an essential feature of development, tissue homeostasis and recovery from injury. How the ECM responds dynamically to cellular and soluble components to support the faithful repair of damaged tissues in some animals but leads to the formation of acellular fibrotic scar tissue in others has important clinical implications. Studies in highly regenerative organisms such as the zebrafish and the salamander have revealed a specialist formulation of ECM components that support repair and regeneration, while avoiding scar tissue formation. By comparing a range of different contexts that feature scar-less healing and full regeneration vs. scarring through fibrotic repair, regenerative therapies that incorporate ECM components could be significantly enhanced to improve both regenerative potential and functional outcomes. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation.

  13. Potencial terapêutico das células-tronco de medula óssea no tratamento da epilepsia Therapeutic potential of bone marrow stem cells in epilepsy treatment

    Directory of Open Access Journals (Sweden)

    Maria Julia M. Carrion

    2009-05-01

    is frequently irreversible, regenerative strategies could represent a new path towards better treatment options. In our laboratory, we have been studying the therapeutic potential of bone marrow stem cells in controlling recurrent spontaneous seizures associated to the pilocarpine model of epilepsy with excellent results. We are also running the first study using bone marrow stem cell transplantation in the treatment of epilepsy in humans.

  14. Hyperbaric Oxygen Promotes Proximal Bone Regeneration and Organized Collagen Composition during Digit Regeneration.

    Directory of Open Access Journals (Sweden)

    Mimi C Sammarco

    Full Text Available Oxygen is critical for optimal bone regeneration. While axolotls and salamanders have retained the ability to regenerate whole limbs, mammalian regeneration is restricted to the distal tip of the digit (P3 in mice, primates, and humans. Our previous study revealed the oxygen microenvironment during regeneration is dynamic and temporally influential in building and degrading bone. Given that regeneration is dependent on a dynamic and changing oxygen environment, a better understanding of the effects of oxygen during wounding, scarring, and regeneration, and better ways to artificially generate both hypoxic and oxygen replete microenvironments are essential to promote regeneration beyond wounding or scarring. To explore the influence of increased oxygen on digit regeneration in vivo daily treatments of hyperbaric oxygen were administered to mice during all phases of the entire regenerative process. Micro-Computed Tomography (μCT and histological analysis showed that the daily application of hyperbaric oxygen elicited the same enhanced bone degradation response as two individual pulses of oxygen applied during the blastema phase. We expand past these findings to show histologically that the continuous application of hyperbaric oxygen during digit regeneration results in delayed blastema formation at a much more proximal location after amputation, and the deposition of better organized collagen fibers during bone formation. The application of sustained hyperbaric oxygen also delays wound closure and enhances bone degradation after digit amputation. Thus, hyperbaric oxygen shows the potential for positive influential control on the various phases of an epimorphic regenerative response.

  15. Hyperbaric Oxygen Promotes Proximal Bone Regeneration and Organized Collagen Composition during Digit Regeneration.

    Science.gov (United States)

    Sammarco, Mimi C; Simkin, Jennifer; Cammack, Alexander J; Fassler, Danielle; Gossmann, Alexej; Marrero, Luis; Lacey, Michelle; Van Meter, Keith; Muneoka, Ken

    2015-01-01

    Oxygen is critical for optimal bone regeneration. While axolotls and salamanders have retained the ability to regenerate whole limbs, mammalian regeneration is restricted to the distal tip of the digit (P3) in mice, primates, and humans. Our previous study revealed the oxygen microenvironment during regeneration is dynamic and temporally influential in building and degrading bone. Given that regeneration is dependent on a dynamic and changing oxygen environment, a better understanding of the effects of oxygen during wounding, scarring, and regeneration, and better ways to artificially generate both hypoxic and oxygen replete microenvironments are essential to promote regeneration beyond wounding or scarring. To explore the influence of increased oxygen on digit regeneration in vivo daily treatments of hyperbaric oxygen were administered to mice during all phases of the entire regenerative process. Micro-Computed Tomography (μCT) and histological analysis showed that the daily application of hyperbaric oxygen elicited the same enhanced bone degradation response as two individual pulses of oxygen applied during the blastema phase. We expand past these findings to show histologically that the continuous application of hyperbaric oxygen during digit regeneration results in delayed blastema formation at a much more proximal location after amputation, and the deposition of better organized collagen fibers during bone formation. The application of sustained hyperbaric oxygen also delays wound closure and enhances bone degradation after digit amputation. Thus, hyperbaric oxygen shows the potential for positive influential control on the various phases of an epimorphic regenerative response.

  16. Potentiation of acute morphine-induced analgesia measured by a thermal test in bone cancer-bearing mice.

    Science.gov (United States)

    González-Rodríguez, Sara; Llames, Sara; Hidalgo, Agustín; Baamonde, Ana; Menéndez, Luis

    2012-06-01

    Agonists of μ-opioid receptors are currently used in the management of cancer pain. However, several data suggest that the analgesic effect of morphine can diminish during the development of experimental tumors. By using a thermal test, we have studied whether the analgesic effect evoked by morphine is altered in mice bearing two painful bone tumors. The analgesic effect evoked by systemic morphine remained unaltered after the intratibial inoculation of B16-F10 melanoma cells and was potentiated after the inoculation of NCTC 2472 osteosarcoma cells. Although the number of spinal μ-opioid receptors measured by western blot studies was not augmented in osteosarcoma-bearing mice, the analgesia evoked by intrathecal (i.t.) morphine was also enhanced. The analgesic response produced by the spinal administration of the Gi/o protein activator mastoparan was amplified, whereas the analgesic response evoked by the i.t. administration of the N-type calcium channel blocker ω-conotoxin remained unaltered. The efficacy of the GIRK channel blocker tertiapin-Q to antagonize the analgesic effect produced by a maximal dose of morphine was also increased in osteosarcoma-bearing mice. Our results seem to indicate that the analgesic effect of morphine on thermal nociception can be enhanced in response to the development of particular bone tumors in mice, being this potentiation probably related to a greater efficacy of the transduction system driven by Gi/o proteins and GIRK channels.

  17. 3D Biomaterial Microarrays for Regenerative Medicine

    DEFF Research Database (Denmark)

    Gaharwar, Akhilesh K.; Arpanaei, Ayyoob; Andresen, Thomas Lars;

    2015-01-01

    Three dimensional (3D) biomaterial microarrays hold enormous promise for regenerative medicine because of their ability to accelerate the design and fabrication of biomimetic materials. Such tissue-like biomaterials can provide an appropriate microenvironment for stimulating and controlling stem...

  18. Lattice Regenerative Cooling Methods (LRCM) Project

    Data.gov (United States)

    National Aeronautics and Space Administration — ORBITEC proposes to develop and demonstrate a novel cooling concept called Lattice Regenerative Cooling Methods (LRCM) for future high thrust in-space propulsion...

  19. Use of Pig as a Model for Mesenchymal Stem Cell Therapies for Bone Regeneration.

    Science.gov (United States)

    Rubessa, Marcello; Polkoff, Kathryn; Bionaz, Massimo; Monaco, Elisa; Milner, Derek J; Holllister, Scott J; Goldwasser, Michael S; Wheeler, Matthew B

    2017-03-07

    Bone is a plastic tissue with a large healing capability. However, extensive bone loss due to disease or trauma requires extreme therapy such as bone grafting or tissue-engineering applications. Presently, bone grafting is the gold standard for bone repair, but presents serious limitations including donor site morbidity, rejection, and limited tissue regeneration. The use of stem cells appears to be a means to overcome such limitations. Bone marrow mesenchymal stem cells (BMSC) have been the choice thus far for stem cell therapy for bone regeneration. However, adipose-derived stem cells (ASC) have similar immunophenotype, morphology, multilineage potential, and transcriptome compared to BMSC, and both types have demonstrated extensive osteogenic capacity both in vitro and in vivo in several species. The use of scaffolds in combination with stem cells and growth factors provides a valuable tool for guided bone regeneration, especially for complex anatomic defects. Before translation to human medicine, regenerative strategies must be developed in animal models to improve effectiveness and efficiency. The pig presents as a useful model due to similar macro- and microanatomy and favorable logistics of use. This review examines data that provides strong support for the clinical translation of the pig model for bone regeneration.

  20. High power regenerative laser amplifier

    Science.gov (United States)

    Miller, J.L.; Hackel, L.A.; Dane, C.B.; Zapata, L.E.

    1994-02-08

    A regenerative amplifier design capable of operating at high energy per pulse, for instance, from 20-100 Joules, at moderate repetition rates, for instance from 5-20 Hertz is provided. The laser amplifier comprises a gain medium and source of pump energy coupled with the gain medium; a Pockels cell, which rotates an incident beam in response to application of a control signal; an optical relay system defining a first relay plane near the gain medium and a second relay plane near the rotator; and a plurality of reflectors configured to define an optical path through the gain medium, optical relay and Pockels cell, such that each transit of the optical path includes at least one pass through the gain medium and only one pass through the Pockels cell. An input coupler, and an output coupler are provided, implemented by a single polarizer. A control circuit coupled to the Pockels cell generates the control signal in timed relationship with the input pulse so that the input pulse is captured by the input coupler and proceeds through at least one transit of the optical path, and then the control signal is applied to cause rotation of the pulse to a polarization reflected by the polarizer, after which the captured pulse passes through the gain medium at least once more and is reflected out of the optical path by the polarizer before passing through the rotator again to provide an amplified pulse. 7 figures.

  1. Staged regenerative sorption heat pump

    Science.gov (United States)

    Jones, Jack A. (Inventor)

    1995-01-01

    A regenerative adsorbent heat pump process and system for cooling and heating a space. A sorbent is confined in a plurality of compressors of which at least four are first stage and at least four are second stage. The first stage operates over a first pressure region and the second stage over a second pressure region which is higher than the first. Sorbate from the first stage enters the second stage. The sorbate loop includes a condenser, expansion valve, evaporator and the compressors. A single sorbate loop can be employed for single-temperature-control such as air conditioning and heating. Two sorbate loops can be used for two-temperature-control as in a refrigerator and freezer. The evaporator temperatures control the freezer and refrigerator temperatures. Alternatively the refrigerator temperature can be cooled by the freezer with one sorbate loop. A heat transfer fluid is circulated in a closed loop which includes a radiator and the compressors. Low temperature heat is exhausted by the radiator. High temperature heat is added to the heat transfer fluid entering the compressors which are desorbing vapor. Heat is transferred from compressors which are sorbing vapor to the heat transfer fluid, and from the heat transfer fluid to the compressors which are desorbing vapor. Each compressor is subjected to the following phases, heating to its highest temperature, cooling down from its highest temperature, cooling to its lowest temperature, and warming up from its lowest temperature. The phases are repeated to complete a cycle and regenerate heat.

  2. Recent considerations in regenerative endodontic treatment approaches

    Directory of Open Access Journals (Sweden)

    Hacer Aksel

    2014-09-01

    Conclusion: Although the regenerative treatment approaches have good clinical outcomes in the majority of case reports, the outcomes are unpredictable. Since the current clinical protocols for regenerative endodontics do not fully fulfill the triad of tissue engineering ((growth factors, scaffold and stem cells, further translational studies are required to achieve more pulp- and dentin-like tissue in the root canal system to achieve pulp regeneration.

  3. SEE SAW BASED REGENERATIVE POWER SYSTEM

    OpenAIRE

    Tribhuwan Singh; Shahzad Ali

    2016-01-01

    Research related to electrical vehicles is gaining importance due to the energy crisis. Using regenerative braking when braking, improves the efficiency of an electric vehicle as it recovers energy that could go to waste if mechanical brakes were used. A novel regenerative braking system for neighborhood electric vehicles was designed, prototyped and tested. The proposed system utilizes a seesaw system to capture energy whereas the conventional systems regenerate to the batteries. The user ha...

  4. Regenerative Medicine-Opportunities and Challenges

    Institute of Scientific and Technical Information of China (English)

    Zhengguo Wang

    2006-01-01

    In this paper, the definitions and contents of regenerative medicine, including tissue engineering, cell therapy, cytokine therapy and microecologic cure, were presented. And then, the prospects and difficulties for clinical application of these therapies were further mentioned. It indicated that the regenerative medicine came to a new era with full of opportunities and challenges. To face and seize this evanescent opportunity is worthy of detailed discussions.

  5. Biodegradable Thermogel as Culture Matrix of Bone Marrow Mesenchymal Stem Cells for Potential Cartilage Tissue Engineering

    Institute of Scientific and Technical Information of China (English)

    Yan-bo Zhang; Jian-xun Ding; Wei-guo Xu; Jie Wu; Fei Chang; Xiu-li Zhuang; Xue-si Chen

    2014-01-01

    Poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer was synthesized through the ring-opening polymerization of LA and GA with PEG as macroinitiator and stannous octoate as catalyst.The amphiphilic copolymer self-assembled into micelles in aqueous solutions,and formed hydrogels as the increase of temperature at relatively high concentrations (> 15 wt%).The favorable degradability of the hydrogel was confirmed by in vitro and in vivo degradation experiments.The good cellular and tissular compatibilities of the thermogel were demonstrated.The excellent adhesion and proliferation of bone marrow mesenchymal stem cells endowed PLGA-PEG-PLGA thermogelling hydrogel with fascinating prospect for cartilage tissue engineering.

  6. Characteristics of industrial and laboratory meat and bone meal ashes and their potential applications.

    Science.gov (United States)

    Coutand, Marie; Cyr, Martin; Deydier, Eric; Guilet, Richard; Clastres, Pierre

    2008-02-11

    This paper reports the characterization of four meat and bone meal (MBM) ashes obtained from specific incineration (laboratory) and from co-incineration (industrial process). Three out of the four MBM ashes were mainly composed of calcium phosphates (hydroxyapatite and whitlockite). Their compositions (major and trace) were in the range for natural phosphate rocks. Trace element contents, including heavy metals, were below 0.6% and industrial ashes contained much more heavy metals than laboratory ash. The amounts of leached elements were low, especially for laboratory ash. According to the European classification of waste to be landfilled, the laboratory ash can be classified as an inert waste. Two industrial ashes are mostly inert. Only one ash is highly leachable and needs a stabilization treatment to be classified at least in the category of hazardous waste. It seems, from these results, that possibilities other than landfilling could be considered to give economic value to these ashes.

  7. Potential Roles of Bone Morphogenetic Protein (BMP-9 in Human Liver Diseases

    Directory of Open Access Journals (Sweden)

    Blanca Herrera

    2014-03-01

    Full Text Available Bone morphogenetic proteins (BMP-2 to BMP-15 belong to the Transforming Growth Factor (TGF-β superfamily and, besides their well-documented roles during embryogenesis and bone formation, some of them have recently been described to be involved in the pathogenesis of different organs, including the liver. The role of BMPs in liver damage responses including hepatocellular carcinoma (HCC development has only begun to be addressed and strong evidence supports the concept of a pro-tumorigenic role of BMP signaling in HCC cells. BMP-9 (also termed Growth and Differentiation Factor (GDF-2 represents the most recently discovered member of the BMP family. We have previously demonstrated that in HCC patient samples BMP-9 expression was positively associated with the tumor seize (“T stage” and that it enhanced cell migration and induced epithelial to mesenchymal transition (EMT in HCC cells in vitro. In another study we recently found that BMP-9 promotes growth in HCC cells, but not in non-transformed hepatocytes. Published as well as unpublished results obtained with primary hepatocytes support the concept of a dual function of BMP-9 in the liver: while in primary, non-malignant cells BMP-9 stabilizes the epithelial phenotype and inhibits proliferation, in HCC cells it induces cell growth and the acquisition of a migratory phenotype. In this review article we summarize current knowledge about BMPs in liver diseases, with special focus on the role of BMP-9 in HCC development and progression, that may provide new clues for a better understanding of the contribution of BMP-signaling to chronic liver diseases.

  8. Potential Roles of Bone Morphogenetic Protein (BMP)-9 in Human Liver Diseases

    Science.gov (United States)

    Herrera, Blanca; Dooley, Steven; Breitkopf-Heinlein, Katja

    2014-01-01

    Bone morphogenetic proteins (BMP-2 to BMP-15) belong to the Transforming Growth Factor (TGF)-β superfamily and, besides their well-documented roles during embryogenesis and bone formation, some of them have recently been described to be involved in the pathogenesis of different organs, including the liver. The role of BMPs in liver damage responses including hepatocellular carcinoma (HCC) development has only begun to be addressed and strong evidence supports the concept of a pro-tumorigenic role of BMP signaling in HCC cells. BMP-9 (also termed Growth and Differentiation Factor (GDF)-2) represents the most recently discovered member of the BMP family. We have previously demonstrated that in HCC patient samples BMP-9 expression was positively associated with the tumor seize (“T stage”) and that it enhanced cell migration and induced epithelial to mesenchymal transition (EMT) in HCC cells in vitro. In another study we recently found that BMP-9 promotes growth in HCC cells, but not in non-transformed hepatocytes. Published as well as unpublished results obtained with primary hepatocytes support the concept of a dual function of BMP-9 in the liver: while in primary, non-malignant cells BMP-9 stabilizes the epithelial phenotype and inhibits proliferation, in HCC cells it induces cell growth and the acquisition of a migratory phenotype. In this review article we summarize current knowledge about BMPs in liver diseases, with special focus on the role of BMP-9 in HCC development and progression, that may provide new clues for a better understanding of the contribution of BMP-signaling to chronic liver diseases. PMID:24670474

  9. Current overview on challenges in regenerative endodontics

    Science.gov (United States)

    Bansal, Ramta; Jain, Aditya; Mittal, Sunandan

    2015-01-01

    Introduction: Regenerative endodontics provides hope of converting the non-vital tooth into vital once again. It focuses on substituting traumatized and pathological pulp with functional pulp tissue. Current regenerative procedures successfully produce root development but still fail to re-establish real pulp tissue and give unpredictable results. There are several drawbacks that need to be addressed to improve the quality and efficiency of the treatment. Aim: The aim of this review article is to discuss major priorities that ought to be dealt before applications of regenerative endodontics flourish the clinical practice. Materials and Methods: A web-based research on MEDLINE was done using filter terms Review, published in the last 10 years and Dental journals. Keywords used for research were “regenerative endodontics,” “dental stem cells,” “growth factor regeneration,” “scaffolds,” and “challenges in regeneration.” This review article screened about 150 articles and then the relevant information was compiled. Results: Inspite of the impressive growth in regenerative endodontic field, there are certain loopholes in the existing treatment protocols that might sometimes result in undesired and unpredictable outcomes. Conclusion: Considerable research and development efforts are required to improve and update existing regenerative endodontic strategies to make it an effective, safe, and biological mode to save teeth. PMID:25657518

  10. Current overview on challenges in regenerative endodontics.

    Science.gov (United States)

    Bansal, Ramta; Jain, Aditya; Mittal, Sunandan

    2015-01-01

    Regenerative endodontics provides hope of converting the non-vital tooth into vital once again. It focuses on substituting traumatized and pathological pulp with functional pulp tissue. Current regenerative procedures successfully produce root development but still fail to re-establish real pulp tissue and give unpredictable results. There are several drawbacks that need to be addressed to improve the quality and efficiency of the treatment. The aim of this review article is to discuss major priorities that ought to be dealt before applications of regenerative endodontics flourish the clinical practice. A web-based research on MEDLINE was done using filter terms Review, published in the last 10 years and Dental journals. Keywords used for research were "regenerative endodontics," "dental stem cells," "growth factor regeneration," "scaffolds," and "challenges in regeneration." This review article screened about 150 articles and then the relevant information was compiled. Inspite of the impressive growth in regenerative endodontic field, there are certain loopholes in the existing treatment protocols that might sometimes result in undesired and unpredictable outcomes. Considerable research and development efforts are required to improve and update existing regenerative endodontic strategies to make it an effective, safe, and biological mode to save teeth.

  11. Current overview on challenges in regenerative endodontics

    Directory of Open Access Journals (Sweden)

    Ramta Bansal

    2015-01-01

    Full Text Available Introduction: Regenerative endodontics provides hope of converting the non-vital tooth into vital once again. It focuses on substituting traumatized and pathological pulp with functional pulp tissue. Current regenerative procedures successfully produce root development but still fail to re-establish real pulp tissue and give unpredictable results. There are several drawbacks that need to be addressed to improve the quality and efficiency of the treatment. Aim: The aim of this review article is to discuss major priorities that ought to be dealt before applications of regenerative endodontics flourish the clinical practice. Materials and Methods: A web-based research on MEDLINE was done using filter terms Review, published in the last 10 years and Dental journals. Keywords used for research were "regenerative endodontics," "dental stem cells," "growth factor regeneration," "scaffolds," and "challenges in regeneration." This review article screened about 150 articles and then the relevant information was compiled. Results: Inspite of the impressive growth in regenerative endodontic field, there are certain loopholes in the existing treatment protocols that might sometimes result in undesired and unpredictable outcomes. Conclusion: Considerable research and development efforts are required to improve and update existing regenerative endodontic strategies to make it an effective, safe, and biological mode to save teeth.

  12. Regenerative Medicine Applications in Wound Care.

    Science.gov (United States)

    Ali Nilforoushzadeh, Mohammad; Mollapour Sisakht, Mahsa; Marcus Seifalian, Alexander; Amir Amirkhani, Mohammad; Reza Banafsheh, Hamid; Verdi, Javad; Sharifzad, Farzaneh; Taghiabadi, Ehsan

    2017-09-29

    During the last two decades, a number of studies have been published on different aspects of regenerative medicine in the field of dermatology. The following article aims at integrating all available information about regenerative dermatology, from the past to the present. In addition, we focused on most well-known application of regenerative medicine in dermatology field, wound healing, especially for burns and non-healing wounds based on available skin replacement in market. The present review focuses on providing an overview on available products in market and on-going clinical trials. These are valuable to get the picture of latest trends and also helpful for clinicians. In future, regenerative dermatology may encompass more effective and time-saving therapies for treating skin injuries and diseases. However, more clinical trials are required to establish standardized protocols and ascertain the safety, long-term effects, and efficacy of the novel therapeutic methods in regenerative dermatology. Despite several improvements in this field, extensive research is required for performing successful and precise clinical trials in future. Further improvements would enable the researchers to develop new products in this field. In this review, we have discussed the most recent breakthroughs in the field of regenerative dermatology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Adipose tissue-derived stem cells show considerable promise for regenerative medicine applications.

    Science.gov (United States)

    Harasymiak-Krzyżanowska, Izabela; Niedojadło, Alicja; Karwat, Jolanta; Kotuła, Lidia; Gil-Kulik, Paulina; Sawiuk, Magdalena; Kocki, Janusz

    2013-12-01

    The stromal-vascular cell fraction (SVF) of adipose tissue can be an abundant source of both multipotent and pluripotent stem cells, known as adipose-derived stem cells or adipose tissue-derived stromal cells (ADSCs). The SVF also contains vascular cells, targeted progenitor cells, and preadipocytes. Stromal cells isolated from adipose tissue express common surface antigens, show the ability to adhere to plastic, and produce forms that resemble fibroblasts. They are characterized by a high proliferation potential and the ability to differentiate into cells of meso-, ecto- and endodermal origin. Although stem cells obtained from an adult organism have smaller capabilities for differentiation in comparison to embryonic and induced pluripotent stem cells (iPSs), the cost of obtaining them is significantly lower. The 40 years of research that mainly focused on the potential of bone marrow stem cells (BMSCs) revealed a number of negative factors: the painful sampling procedure, frequent complications, and small cell yield. The number of stem cells in adipose tissue is relatively large, and obtaining them is less invasive. Sampling through simple procedures such as liposuction performed under local anesthesia is less painful, ensuring patient comfort. The isolated cells are easily grown in culture, and they retain their properties over many passages. That is why adipose tissue has recently been treated as an attractive alternative source of stem cells. Essential aspects of ADSC biology and their use in regenerative medicine will be analyzed in this article.

  14. [A regenerative anemia in infants: 2 cases of Pearson´s syndrome].

    Science.gov (United States)

    Martínez de Zabarte Fernández, José M; Rodríguez-Vigil Iturrate, Carmen; Martínez Faci, Cristina; García Jiménez, Inmaculada; Murillo Sanjuan, Laura; Muñoz Mellado, Ascensión

    2017-02-01

    Anemia is very common in infants. Although its causes are usually not severe and treatable, proper etiologic diagnosis should be established. When anemia is non-regenerative, it can be caused by aplastic anemia, myelodysplastic syndrome, bone marrow infiltration or hematopoietic factors deficiencies. Another possible cause is Pearson's syndrome, a rare mitochondrial disease that causes non-regenerative anemia associated with other cytopenias, pancreatic insufficiency, lactic acidosis and great variability in clinical presentation conditioned by heteroplasmy. It is characteristic to find in bone marrow studies variable vacuolization in erythroblastic progenitors and ring sideroblasts. The diagnosis is established by genetic study of mitochondrial deoxyribonucleic acid performed by Southern blot analysis (complete mitochondrial deoxyribonucleic acid amplification by polymerase chain reaction -long), obtaining 70-80% deletion of 4977 bp (NMD 8343-13459). There is no curative therapy and support treatment is the only available nowadays. Death is frequent in early years of life.

  15. Osteogenic potential of porous {beta}-tricalcium phosphate ({beta}-TCP) combined with cultured bone. Tissue engineered bone using a biodegradable material as a scaffold

    Energy Technology Data Exchange (ETDEWEB)

    Fu, S.; Yamada, Y.; Honda, M.; Ueda, M. [Nagoya Univ. (Japan). Dept. of Protective Care for Masticatory Disorders; Yoshikawa, T. [Nara Medical Univ. (Japan). First Dept. of Pathology; Hibino, Y.; Hata, K. [Nagoya Univ. (Japan). Dept. of Tissue Engineering; Niimi, A. [Nagoya Univ. (Japan). Dept. of Protective Care for Masticatory Disorders; Chunichi Hospital (Japan). Dept. of Oral and Maxillofacial Surgery; Okazaki, Y. [Nagoya Univ. (Japan). Dept. of Protective Care for Masticatory Disorders; Nagoya Univ. (Japan). Dept. of Tissue Engineering

    2001-07-01

    Recently, the tissue engineering approach has widespread attention for regeneration. The present study was undertaken to evaluate whether biodegradable porous {beta}-tricalcium phosphate ({beta}-TCP) can be used as a scaffold for cultured bone marrow cells or not. Marrow cells were obtained from bone shaft of rat femur and cultured in a standard medium for 10 days, then trypsinized to combine cells with ceramics. An additional subculture was done for cells/ceramics composite in a standard medium with the addition of {beta}-glycerophosphate, ascorbic acid and dexamethason. The 20 day subcultured composites were implanted into subcutaneous sites of syngeneic rats. These implants were harvested at 4 and 8 weeks postimplantation, and prepared for the histological analysis. In the histological analysis of composites at 4 weeks postimplantation, active bone formation could be found in the composites. The bone formation was evidenced by active osteoblast lining on the surfaces of bone. At 8 weeks, more extensive bone formation was observed in the composites. These results suggested that beta-TCP could play a role as scaffold of tissueengineered bone derived from marrow cells. (orig.)

  16. Electric field as a potential directional cue in homing of bone marrow-derived mesenchymal stem cells to cutaneous wounds.

    Science.gov (United States)

    Zimolag, Eliza; Borowczyk-Michalowska, Julia; Kedracka-Krok, Sylwia; Skupien-Rabian, Bozena; Karnas, Elzbieta; Lasota, Slawomir; Sroka, Jolanta; Drukala, Justyna; Madeja, Zbigniew

    2017-02-01

    Bone marrow-derived cells are thought to participate and enhance the healing process contributing to skin cells or releasing regulatory cytokines. Directional cell migration in a weak direct current electric field (DC-EF), known as electrotaxis, may be a way of cell recruitment to the wound site. Here we examined the influence of electric field on bone marrow adherent cells (BMACs) and its potential role as a factor attracting mesenchymal stem cells to cutaneous wounds. We observed that in an external EF, BMAC movement was accelerated and highly directed with distinction of two cell populations migrating toward opposite poles: mesenchymal stem cells migrated toward the cathode, whereas macrophages toward the anode. Analysis of intracellular pathways revealed that macrophage electrotaxis mostly depended on Rho family small GTPases and calcium ions, but interruption of PI3K and Arp2/3 had the most pronounced effect on electrotaxis of MSCs. However, in all cases we observed only a partial decrease in directionality of cell movement after inhibition of certain proteins. Additionally, although we noticed the accumulation of EGFR at the cathodal side of MSCs, it was not involved in electrotaxis. Moreover, the cell reaction to EF was very dynamic with first symptoms occurring within <1min. In conclusion, the physiological DC-EF may act as a factor positioning bone marrow cells within a wound bed and the opposite direction of MSC and macrophage movement did not result either from utilizing different signalling or redistribution of investigated cell surface receptors. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Gene delivery nanocarriers of bioactive glass with unique potential to load BMP2 plasmid DNA and to internalize into mesenchymal stem cells for osteogenesis and bone regeneration

    Science.gov (United States)

    Kim, Tae-Hyun; Singh, Rajendra K.; Kang, Min Sil; Kim, Joong-Hyun; Kim, Hae-Won

    2016-04-01

    The recent development of bioactive glasses with nanoscale morphologies has spurred their specific applications in bone regeneration, for example as drug and gene delivery carriers. Bone engineering with stem cells genetically modified with this unique class of nanocarriers thus holds great promise in this avenue. Here we report the potential of the bioactive glass nanoparticle (BGN) system for the gene delivery of mesenchymal stem cells (MSCs) targeting bone. The composition of 15% Ca-added silica, proven to be bone-bioactive, was formulated into surface aminated mesoporous nanospheres with enlarged pore sizes, to effectively load and deliver bone morphogenetic protein-2 (BMP2) plasmid DNA. The enlarged mesopores were highly effective in loading BMP2-pDNA with an efficiency as high as 3.5 wt% (pDNA w.r.t. BGN), a level more than twice than for small-sized mesopores. The BGN nanocarriers released the genetic molecules in a highly sustained manner (for as long as 2 weeks). The BMP2-pDNA/BGN complexes were effectively internalized to rat MSCs with a cell uptake level of ~73%, and the majority of cells were transfected to express the BMP2 protein. Subsequent osteogenesis of the transfected MSCs was demonstrated by the expression of bone-related genes, including bone sialoprotein, osteopontin, and osteocalcin. The MSCs transfected with BMP2-pDNA/BGN were locally delivered inside a collagen gel to the target calvarium defects. The results showed significantly improved bone regeneration, as evidenced by the micro-computed tomographic, histomorphometric and immunohistochemical analyses. This study supports the excellent capacity of the BGN system as a pDNA-delivery nanocarrier in MSCs, and the engineered system, BMP2-pDNA/BGN with MSCs, may be considered a new promising candidate to advance the therapeutic potential of stem cells through genetic modification, targeting bone defects and diseases.The recent development of bioactive glasses with nanoscale morphologies has

  18. Extracellular Matrix Scaffolds for Tissue Engineering and Regenerative Medicine.

    Science.gov (United States)

    Yi, Sheng; Ding, Fei; Gong, Leiiei; Gu, Xiaosong

    2017-01-01

    The extracellular matrix is produced by the resident cells in tissues and organs, and secreted into the surrounding medium to provide biophysical and biochemical support to the surrounding cells due to its content of diverse bioactive molecules. Recently, the extracellular matrix has been used as a promising approach for tissue engineering. Emerging studies demonstrate that extracellular matrix scaffolds are able to create a favorable regenerative microenvironment, promote tissue-specific remodeling, and act as an inductive template for the repair and functional reconstruction of skin, bone, nerve, heart, lung, liver, kidney, small intestine, and other organs. In the current review, we will provide a critical overview of the structure and function of various types of extracellular matrix, the construction of three-dimensional extracellular matrix scaffolds, and their tissue engineering applications, with a focus on translation of these novel tissue engineered products to the clinic. We will also present an outlook on future perspectives of the extracellular matrix in tissue engineering and regenerative medicine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Endothelial Jagged-1 Is Necessary for Homeostatic and Regenerative Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Michael G. Poulos

    2013-09-01

    Full Text Available The bone marrow (BM microenvironment is composed of multiple niche cells that, by producing paracrine factors, maintain and regenerate the hematopoietic stem cell (HSC pool (Morrison and Spradling, 2008. We have previously demonstrated that endothelial cells support the proper regeneration of the hematopoietic system following myeloablation (Butler et al., 2010; Hooper et al., 2009; Kobayashi et al., 2010. Here, we demonstrate that expression of the angiocrine factor Jagged-1, supplied by the BM vascular niche, regulates homeostatic and regenerative hematopoiesis through a Notch-dependent mechanism. Conditional deletion of Jagged-1 in endothelial cells (Jag1(ECKO mice results in a profound decrease in hematopoiesis and premature exhaustion of the adult HSC pool, whereas quantification and functional assays demonstrate that loss of Jagged-1 does not perturb vascular or mesenchymal compartments. Taken together, these data demonstrate that the instructive function of endothelial-specific Jagged-1 is required to support the self-renewal and regenerative capacity of HSCs in the adult BM vascular niche.

  20. Bone Formation with Deproteinized Bovine Bone Mineral or Biphasic Calcium Phosphate in the Presence of Autologous Platelet Lysate: Comparative Investigation in Rabbit

    Directory of Open Access Journals (Sweden)

    Carole Chakar

    2014-01-01

    Full Text Available Bone substitutes alone or supplemented with platelet-derived concentrates are widely used to promote bone regeneration but their potency remains controversial. The aim of this study was, therefore, to compare the regenerative potential of preparations containing autologous platelet lysate (APL and particles of either deproteinized bovine bone mineral (DBBM or biphasic calcium phosphate (BCP, two bone substitutes with different resorption patterns. Rabbit APL was prepared by freeze-thawing a platelet suspension. Critical-size defects in rabbit femoral condyle were filled with DBBM or DBBM+APL and BCP or BCP+APL. Rabbits were sacrificed after six weeks and newly formed bone and residual implanted material were evaluated using nondemineralized histology and histomorphometry. New bone was observed around particles of all fillers tested. In the defects filled with BCP, the newly formed bone area was greater (70%; P<0.001 while the residual material area was lower (60%; P<0.001 than that observed in those filled with DBBM. New bone and residual material area of defects filled with either APL+DBBM or APL+BCP were similar to those observed in those filled with the material alone. In summary, osteoconductivity and resorption of BCP were greater than those of DBBM, while APL associated with either DBBM or BCP did not have an additional benefit.

  1. Translating Regenerative Biomaterials Into Clinical Practice.

    Science.gov (United States)

    Stace, Edward T; Dakin, Stephanie G; Mouthuy, Pierre-Alexis; Carr, Andrew J

    2016-01-01

    Globally health care spending is increasing unsustainably. This is especially true of the treatment of musculoskeletal (MSK) disease where in the United States the MSK disease burden has doubled over the last 15 years. With an aging and increasingly obese population, the surge in MSK related spending is only set to worsen. Despite increased funding, research and attention to this pressing health need, little progress has been made toward novel therapies. Tissue engineering and regenerative medicine (TERM) strategies could provide the solutions required to mitigate this mounting burden. Biomaterial-based treatments in particular present a promising field of potentially cost-effective therapies. However, the translation of a scientific development to a successful treatment is fraught with difficulties. These barriers have so far limited translation of TERM science into clinical treatments. It is crucial for primary researchers to be aware of the barriers currently restricting the progression of science to treatments. Researchers need to act prospectively to ensure the clinical, financial, and regulatory hurdles which seem so far removed from laboratory science do not stall or prevent the subsequent translation of their idea into a treatment. The aim of this review is to explore the development and translation of new treatments. Increasing the understanding of these complexities and barriers among primary researchers could enhance the efficiency of biomaterial translation. © 2015 Wiley Periodicals, Inc.

  2. Natural products for treatment of bone erosive diseases: The effects and mechanisms on inhibiting osteoclastogenesis and bone resorption.

    Science.gov (United States)

    An, Jing; Hao, Dingjun; Zhang, Qian; Chen, Bo; Zhang, Rui; Wang, Yi; Yang, Hao

    2016-07-01

    Excessive bone resorption plays a central role on the development of bone erosive diseases, including osteoporosis, rheumatoid arthritis, and periodontitis. Osteoclasts, bone-resorbing multinucleated cells, are differentiated from hemopoietic progenitors of the monocyte/macrophage lineage. Regulation of osteoclast differentiation is considered an effective therapeutic target to the treatment of pathological bone loss. Natural plant-derived products, with potential therapeutic and preventive activities against bone-lytic diseases, have received increasing attention in recent years because of their whole regulative effects and specific pharmacological activities, which are more suitable for long-term use than chemically synthesized medicines. In this review, we summarized the detailed research progress on the active compounds derived from medical plants with potential anti-resorptive effects and their molecular mechanisms on inhibiting osteoclast formation and function. The active ingredients derived from natural plants that are efficacious in suppressing osteoclastogenesis and bone resorption include flavonoids, terpenoids (sesquiterpenoids, diterpenoids, triterpenoids), glycosides, lignans, coumarins, alkaloids, polyphenols, limonoids, quinones and others (steroid, oxoxishhone, fatty acid). Studies have shown that above natural products exert the inhibitory effects via regulating many factors involved in the process of osteoclast differentiation and bone resorption, including the essential cytokines (RANKL, M-CSF), transcription factors (NFATc1, c-Fos), signaling pathways (NF-κB, MAPKs, Src/PI3K/Akt, the calcium ion signaling), osteoclast-specific genes (TRAP, CTSK, MMP-9, integrin β3, OSCAR, DC-STAMP, Atp6v0d2) and local factors (ROS, LPS, NO). The development of osteoclast-targeting natural products is of great value for the prevention or treatment of bone diseases and for bone regenerative medicine.

  3. Human dental pulp stem cells: Applications in future regenerative medicine.

    Science.gov (United States)

    Potdar, Pravin D; Jethmalani, Yogita D

    2015-06-26

    Stem cells are pluripotent cells, having a property of differentiating into various types of cells of human body. Several studies have developed mesenchymal stem cells (MSCs) from various human tissues, peripheral blood and body fluids. These cells are then characterized by cellular and molecular markers to understand their specific phenotypes. Dental pulp stem cells (DPSCs) are having a MSCs phenotype and they are differentiated into neuron, cardiomyocytes, chondrocytes, osteoblasts, liver cells and β cells of islet of pancreas. Thus, DPSCs have shown great potentiality to use in regenerative medicine for treatment of various human diseases including dental related problems. These cells can also be developed into induced pluripotent stem cells by incorporation of pluripotency markers and use for regenerative therapies of various diseases. The DPSCs are derived from various dental tissues such as human exfoliated deciduous teeth, apical papilla, periodontal ligament and dental follicle tissue. This review will overview the information about isolation, cellular and molecular characterization and differentiation of DPSCs into various types of human cells and thus these cells have important applications in regenerative therapies for various diseases. This review will be most useful for postgraduate dental students as well as scientists working in the field of oral pathology and oral medicine.

  4. Arrayed cellular environments for stem cells and regenerative medicine.

    Science.gov (United States)

    Titmarsh, Drew M; Chen, Huaying; Wolvetang, Ernst J; Cooper-White, Justin J

    2013-02-01

    The behavior and composition of both multipotent and pluripotent stem cell populations are exquisitely controlled by a complex, spatiotemporally variable interplay of physico-chemical, extracellular matrix, cell-cell interaction, and soluble factor cues that collectively define the stem cell niche. The push for stem cell-based regenerative medicine models and therapies has fuelled demands for increasingly accurate cellular environmental control and enhanced experimental throughput, driving an evolution of cell culture platforms away from conventional culture formats toward integrated systems. Arrayed cellular environments typically provide a set of discrete experimental elements with variation of one or several classes of stimuli across elements of the array. These are based on high-content/high-throughput detection, small sample volumes, and multiplexing of environments to increase experimental parameter space, and can be used to address a range of biological processes at the cell population, single-cell, or subcellular level. Arrayed cellular environments have the capability to provide an unprecedented understanding of the molecular and cellular events that underlie expansion and specification of stem cell and therapeutic cell populations, and thus generate successful regenerative medicine outcomes. This review focuses on recent key developments of arrayed cellular environments and their contribution and potential in stem cells and regenerative medicine.

  5. Regenerative Applications Using Tooth Derived Stem Cells in Other Than Tooth Regeneration: A Literature Review

    OpenAIRE

    2016-01-01

    Tooth derived stem cells or dental stem cells are categorized according to the location from which they are isolated and represent a promising source of cells for regenerative medicine. Originally, as one kind of mesenchymal stem cells, they are considered an alternative of bone marrow stromal cells. They share many commonalties but maintain differences. Considering their original function in development and the homeostasis of tooth structures, many applications of these cells in dentistry ha...

  6. Therapeutic modulation of growth factors and cytokines in regenerative medicine.

    Science.gov (United States)

    Ioannidou, Effie

    2006-01-01

    , regenerative medicine through stem cell application combined with specific growth factors and cytokines will have great potential in curing a variety of human diseases.

  7. Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis

    Science.gov (United States)

    2015-11-01

    the presence of X-gal (LacZ re- porter gene transcription) and in the absence of leucine (LEU2 reporter gene transcription), histidine (selection for...and can function as a paracrine survival factor for humanmyeloma cells. Cancer Res 2003;63:912–6. 46. Labrinidis A, Diamond P,Martin S, Hay S, Liapis

  8. Facile synthesis, characterization, and antimicrobial activity of cellulose-chitosan-hydroxyapatite composite material: a potential material for bone tissue engineering.

    Science.gov (United States)

    Mututuvari, Tamutsiwa M; Harkins, April L; Tran, Chieu D

    2013-11-01

    Hydroxyapatite (HAp) is often used as a bone-implant material because it is biocompatible and osteoconductive. However, HAp possesses poor rheological properties and it is inactive against disease-causing microbes. To improve these properties, we developed a green method to synthesize multifunctional composites containing: (1) cellulose (CEL) to impart mechanical strength; (2) chitosan (CS) to induce antibacterial activity thereby maintaining a microbe-free wound site; and (3) HAp. In this method, CS and CEL were co-dissolved in an ionic liquid (IL) and then regenerated from water. HAp was subsequently formed in situ by alternately soaking [CEL+CS] composites in aqueous solutions of CaCl2 and Na2 HPO4 . At least 88% of IL used was recovered for reuse by distilling the aqueous washings of [CEL+CS]. The composites were characterized using FTIR, XRD, and SEM. These composites retained the desirable properties of their constituents. For example, the tensile strength of the composites was enhanced 1.9 times by increasing CEL loading from 20% to 80%. Incorporating CS in the composites resulted in composites which inhibited the growth of both Gram positive (MRSA, S. aureus and VRE) and Gram negative (E. coli and P. aeruginosa) bacteria. These findings highlight the potential use of [CEL+CS+HAp] composites as scaffolds in bone tissue engineering.

  9. Late Adherent Human Bone Marrow Stromal Cells Form Bone and Restore the Hematopoietic Microenvironment In Vivo

    Directory of Open Access Journals (Sweden)

    Verônica Fernandes Vianna

    2013-01-01

    Full Text Available Bone marrow stromal cells (BMSCs are a valuable resource for skeletal regenerative medicine because of their osteogenic potential. In spite of the very general term “stem cell,” this population of cells is far from homogeneous, and different BMSCs clones have greatly different phenotypic properties and, therefore, potentially different therapeutic potential. Adherence to a culture flask surface is a primary defining characteristic of BMSCs. We hypothesized that based on the adherence time we could obtain an enriched population of cells with a greater therapeutic potential. We characterized two populations of bone marrow-derived cells, those that adhered by three days (R-cells and those that did not adhere by three days but did by six days (L-cells. Clones derived from L-cells could be induced into adipogenic, chondrogenic, and osteogenic differentiation in vitro. L-cells appeared to have greater proliferative capacity, as manifested by larger colony diameter and clones with higher CD146 expression. Only clones from L-cells developed bone marrow stroma in vivo. We conclude that the use of late adherence of BMSCs is one parameter that can be used to enrich for cells that will constitute a superior final product for cell therapy in orthopedics.

  10. Development of Novel Biocomposite Scaffold of Chitosan-Gelatin/Nanohydroxyapatite for Potential Bone Tissue Engineering Applications

    Science.gov (United States)

    Dan, Yang; Liu, Ouyang; Liu, Yong; Zhang, Yuan-Yuan; Li, Shuai; Feng, Xiao-bo; Shao, Zeng-wu; Yang, Cao; Yang, Shu-Hua; Hong, Ji-bo

    2016-11-01

    In this study, a three-dimensional chitosan-gelatin/nanohydroxyapatite (ChG/nHaP) scaffold was successfully fabricated and characterized in terms of swelling, degradation, cell proliferation, cell attachment, and mineralization characterizations. The ChG/nHaP scaffold was fabricated with a mean pore size of 100-180 μm. Our results showed that the physicochemical and biological properties of the scaffolds were affected by the presence of HaP. The swelling and degradation characteristics of the ChG scaffold were remarkably decreased by the addition of HaP. On the other hand, the presence of HaP remarkably improved the MC3T3-E1 cell attachment and cell growth in the scaffold membrane. The biocompatible nature of the ChG/nHaP scaffold leads to the development of finely scaled mineral deposits on the scaffold membrane. Thus, HaP played an important role in improving the biological performance of the scaffold. Therefore, the ChG/nHaP scaffold could be applied as a suitable material for bone tissue engineering applications.

  11. Stem Cell Banking for Regenerative and Personalized Medicine.

    Science.gov (United States)

    Harris, David T

    2014-02-26

    Regenerative medicine, tissue engineering and gene therapy offer the opportunity to treat and cure many of today's intractable afflictions. These approaches to personalized medicine often utilize stem cells to accomplish these goals. However, stem cells can be negatively affected by donor variables such as age and health status at the time of collection, compromising their efficacy. Stem cell banking offers the opportunity to cryogenically preserve stem cells at their most potent state for later use in these applications. Practical stem cell sources include bone marrow, umbilical cord blood and tissue, and adipose tissue. Each of these sources contains stem cells that can be obtained from most individuals, without too much difficulty and in an economical fashion. This review will discuss the advantages and disadvantages of each stem cell source, factors to be considered when contemplating banking each stem cell source, the methodology required to bank each stem cell source, and finally, current and future clinical uses of each stem cell source.

  12. Multiscale Inorganic Hierarchically Materials: Towards an Improved Orthopaedic Regenerative Medicine.

    Science.gov (United States)

    Ruso, Juan M; Sartuqui, Javier; Messina, Paula V

    2015-01-01

    Bone is a biologically and structurally sophisticated multifunctional tissue. It dynamically responds to biochemical, mechanical and electrical clues by remodelling itself and accordingly the maximum strength and toughness are along the lines of the greatest applied stress. The challenge is to develop an orthopaedic biomaterial that imitates the micro- and nano-structural elements and compositions of bone to locally match the properties of the host tissue resulting in a biologically fixed implant. Looking for the ideal implant, the convergence of life and materials sciences occurs. Researchers in many different fields apply their expertise to improve implantable devices and regenerative medicine. Materials of all kinds, but especially hierarchical nano-materials, are being exploited. The application of nano-materials with hierarchical design to calcified tissue reconstructive medicine involve intricate systems including scaffolds with multifaceted shapes that provides temporary mechanical function; materials with nano-topography modifications that guarantee their integration to tissues and that possesses functionalized surfaces to transport biologic factors to stimulate tissue growth in a controlled, safe, and rapid manner. Furthermore materials that should degrade on a timeline coordinated to the time that takes the tissues regrow, are prepared. These implantable devices are multifunctional and for its construction they involve the use of precise strategically techniques together with specific material manufacturing processes that can be integrated to achieve in the design, the required multifunctionality. For such reasons, even though the idea of displacement from synthetic implants and tissue grafts to regenerative-medicine-based tissue reconstruction has been guaranteed for well over a decade, the reality has yet to emerge. In this paper, we examine the recent approaches to create enhanced bioactive materials. Their design and manufacturing procedures as well

  13. Molecular imaging of potential bone metastasis from differentiated thyroid cancer: a case report

    Directory of Open Access Journals (Sweden)

    Arasho Belachew

    2011-10-01

    Full Text Available Abstract Introduction Molecular imaging of the spine is a rarely used diagnostic method for which only a few case reports exist in the literature. Here, to the best of our knowledge we present the first case of a combination of molecular imaging by single photon emission computer tomography and positron emission tomography used in post-operative spinal diagnostic assessment. Case presentation We present the case of a 50-year-old Caucasian woman experiencing progressive spinal cord compression caused by a vertebral metastasis of a less well differentiated thyroid cancer. Following tumor resection and vertebral stabilization, total thyroidectomy was performed revealing follicular thyroid carcinoma pT2 pNxM1 (lung, bone. During follow-up our patient underwent five radioiodine therapy procedures (5.3 to 5.7 GBq each over a two-year period. Post-therapeutic I-131 scans showed decreasing uptake in multiple Pulmonary metastases. However, following an initial decrease, stimulated thyroglobulin remained at pathologically increased levels, indicating further neoplastic activity. F18 Fludeoxyglucose positron emission tomography, which was performed in parallel, showed remaining hypermetabolism in the lungs but no hypermetabolism of the spinal lesions correlating with the stable neurological examinations. While on single photon emission computer tomography images Pulmonary hyperfixation of I-131 disappeared (most likely indicating dedifferentiation, there was persistent spinal hyperfixation at the operated level and even higher fixation at the spinal process of L3. Based on the negative results of the spinal F18 fludeoxyglucose positron emission tomography, a decision was made not to operate again on the spine since our patient was completely asymptomatic and the neurological risk seemed to be too high. During further follow-up our patient remained neurologically stable. Conclusions Molecular imaging by F18 fludeoxyglucose positron emission tomography helps

  14. Hypoxia-Inducible Factor-1α: A Potential Factor for the Enhancement of Osseointegration between Dental Implants and Tissue-Engineered Bone

    Directory of Open Access Journals (Sweden)

    Duohong Zou

    2011-07-01

    Full Text Available Introduction: Tissue-engineered bones are widely utilized to protect healthy tissue, reduce pain, and increase the success rate of dental implants. one of the most challenging obstacles lies in obtaining effective os-seointegration between dental implants and tissue-engineered structures. Deficiencies in vascularization, osteogenic factors, oxygen, and other nutrients inside the tissue-engineered bone during the early stages following implantation all inhibit effective osseointe-gration. Oxygen is required for aerobic metabolism in bone and blood vessel tissues, but oxygen levels inside tissue-engineered bone are not suf-ficient for cell proliferation. HIF-1α is a pivotal regulator of hypoxic and ischemic vascular responses, driving transcriptional activation of hundreds of genes involved in vascular reactivity, angiogenesis, arteriogenesis, and osteogenesis.The hypothesis: Hypoxia-Inducible Factor-1α seems a potential factor for the enhancement of osseointegration between dental implants and tissue-engineered bone.Evaluation of the hypothesis: Enhancement of HIF-1α protein expression is recognized as the most promising approach for angiogenesis, because it can induce multiple angiogenic targets in a coordinated manner. Therefore, it will be a novel potential therapeutic methods targeting HIF-1α expression to enhance osseointegration be-tween dental implants and tissue-engineered bone.

  15. Regenerative Medicine and Stem Cells in Dermatology.

    Science.gov (United States)

    Moioli, Eduardo K; Bolotin, Diana; Alam, Murad

    2017-05-01

    Clinically relevant regenerative medicine is still in its early stages of development. Difficulties in regenerating large-scale and complex structures, the lack of safety data, and the paucity of clinical trials have slowed the process of technological advance. To familiarize the clinician with techniques available in the laboratory and experimental approaches being tested clinically. In addition, a layout is discussed for how dermatologists can lead the way in bringing regenerative medicine to clinical reality. This article reviews the relevant literature on regenerative medicine for dermatological applications and discusses findings and techniques in a clinically relevant context. Multiple cell-free and cell-based approaches for regenerating dermatologic tissues have been reported in the basic science and clinical literature. These are reviewed in the order of complexity. Incremental steps are needed to apply the principles of regenerative medicine to simple medical problems first. Such a stepwise approach would commence, for example, with creation of single-function tissues that could fill soft-tissue defects and proceed to the development of fully functional skin grafts. Likewise, cell-free approaches can build the foundation for the more technically demanding cell-based strategies that are likely necessary for achieving the ultimate goal of regenerative dermatology.

  16. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  17. Intrinsic Sex-Linked Variations in Osteogenic and Adipogenic Differentiation Potential of Bone Marrow Multipotent Stromal Cells

    OpenAIRE

    2015-01-01

    Bone formation and aging are sexually dimorphic. Yet, definition of the intrinsic molecular differences between male and female multipotent mesenchymal stromal cells (MSC) in bone is lacking. This study assessed sex-linked differences in MSC differentiation in 3-, 6-, and 9-month-old C57BL/6J mice. Analysis of tibiae showed that female mice had lower bone volume fraction and higher adipocyte content in the bone marrow compared to age-matched males. While both males and females lost bone mass ...

  18. A Novel Surgical Procedure for Er:YAG Laser-Assisted Periodontal Regenerative Therapy: Case Series.

    Science.gov (United States)

    Taniguchi, Yoichi; Aoki, Akira; Sakai, Kazuto; Mizutani, Koji; Meinzer, Walter; Izumi, Yuichi

    2016-01-01

    The objective of this study was to evaluate an Er:YAG laser (ErL) application for periodontal regenerative surgery in angular bone defects at nine sites in six patients. Debridement was thoroughly performed using a combination of curettage with a Gracey-type curette and ErL irradiation at a panel setting of 70 mJ/pulse and 20 Hz with sterile saline spray. After applying an enamel matrix derivative and autogenous bone grafting, ErL was used to form a blood clot coagulation on the grafted bone surface at 50 mJ/pulse and 20 Hz without water spray for approximately 30 seconds. Twelve months after surgery the mean probing depth had improved from 6.2 mm to 2.0 mm, the mean clinical attachment level had reduced from 7.5 mm to 3.4 mm, and bleeding on probing had improved from (+) to (-). Mean intrabony defect depth decreased from 6.0 mm before surgery to 1.0 mm 12 months after surgery. A novel procedure for periodontal regenerative surgery applying ErL irradiation for thorough decontamination during debridement as well as blood coagulation following autogenous bone grafting seems to have achieved favorable and stable healing of periodontal pockets with significant clinical improvement and desirable regeneration of angular bone defects, including one-wall defects.

  19. Microtomographic and morphometric characterization of a bioceramic bone substitute in dental implantology

    Directory of Open Access Journals (Sweden)

    Deborah Meleo

    2012-01-01

    Full Text Available In recent years, bone tissue regeneration studies have led to a deeper knowledge of chemical and structural features of the best biomaterials to be used as replacements for lost bone structures, with the autologus bone still today the only graft material able to ostegenerate, osteinduct and/or osteoconduct. The difficulties of the small available amount of autologus bone, together with morbidity of a second surgical operation on the same patient, have been overcome using both synthetic and biologic substitute bones. The possibility of investigating morphometric characteristics of substitute bones makes it possible to evaluate the predictability of regenerative processes and, so far, a range of different methods have been used for the purpose. X-ray microtomography (micro-CT is a miniaturized form of conventional tomography, able to analyze the internal structure of small objects, performing three-dimensional images with high spatial resolution (<10 micron pixel size. For a correct analysis, samples need not be altered or treated in any way, as micro-CT is a non-invasive and non-destructive technique. It shows promising results in biomaterial studies and tissue engineering. This work shows the potential applications of this microtomographic technique by means of an in vitro analysis system, in characterizing morphometric features of human bone tissue, and contributes to the use of this technique in studies concerning biomaterials and bioscaffolds inserted in bone tissue.

  20. Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe; Frøbert, Ole; Holst-Hansen, Claus

    2014-01-01

    Background: Treatment of myocardial infarction with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal...... myocardial infarction models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of myocardial infarction, using a fully...... grown non-immunecompromised rat model. Methods: Mesenchymal stem cells were isolated from adipose tissue and bone marrow and compared with respect to surface markers and proliferative capability. To compare the regenerative potential of the two stem cell populations, male Sprague-Dawley rats were...

  1. Endochondral Priming: A Developmental Engineering Strategy for Bone Tissue Regeneration.

    Science.gov (United States)

    Freeman, Fiona E; McNamara, Laoise M

    2017-04-01

    Tissue engineering and regenerative medicine have significant potential to treat bone pathologies by exploiting the capacity for bone progenitors to grow and produce tissue constituents under specific biochemical and physical conditions. However, conventional tissue engineering approaches, which combine stem cells with biomaterial scaffolds, are limited as the constructs often degrade, due to a lack of vascularization, and lack the mechanical integrity to fulfill load bearing functions, and as such are not yet widely used for clinical treatment of large bone defects. Recent studies have proposed that in vitro tissue engineering approaches should strive to simulate in vivo bone developmental processes and, thereby, imitate natural factors governing cell differentiation and matrix production, following the paradigm recently defined as "developmental engineering." Although developmental engineering strategies have been recently developed that mimic specific aspects of the endochondral ossification bone formation process, these findings are not widely understood. Moreover, a critical comparison of these approaches to standard biomaterial-based bone tissue engineering has not yet been undertaken. For that reason, this article presents noteworthy experimental findings from researchers focusing on developing an endochondral-based developmental engineering strategy for bone tissue regeneration. These studies have established that in vitro approaches, which mimic certain aspects of the endochondral ossification process, namely the formation of the cartilage template and the vascularization of the cartilage template, can promote mineralization and vascularization to a certain extent both in vitro and in vivo. Finally, this article outlines specific experimental challenges that must be overcome to further exploit the biology of endochondral ossification and provide a tissue engineering construct for clinical treatment of large bone/nonunion defects and obviate the need for

  2. Bone Tissue Engineering Challenges in Oral & Maxillofacial Surgery.

    Science.gov (United States)

    Smith, Brandon T; Shum, Jonathan; Wong, Mark; Mikos, Antonios G; Young, Simon

    2015-01-01

    Over the past decades, there has been a substantial amount of innovation and research into tissue engineering and regenerative approaches for the craniofacial region. This highly complex area presents many unique challenges for tissue engineers. Recent research indicates that various forms of implantable biodegradable scaffolds may play a beneficial role in the clinical treatment of craniofacial pathological conditions. Additionally, the direct delivery of bioactive molecules may further increase de novo bone formation. While these strategies offer an exciting glimpse into potential future treatments, there are several challenges that still must be overcome. In this chapter, we will highlight both current surgical approaches for craniofacial reconstruction and recent advances within the field of bone tissue engineering. The clinical challenges and limitations of these strategies will help contextualize and inform future craniofacial tissue engineering strategies.

  3. Novel modeling of combinatorial miRNA targeting identifies SNP with potential role in bone density.

    Directory of Open Access Journals (Sweden)

    Claudia Coronnello

    Full Text Available MicroRNAs (miRNAs are post-transcriptional regulators that bind to their target mRNAs through base complementarity. Predicting miRNA targets is a challenging task and various studies showed that existing algorithms suffer from high number of false predictions and low to moderate overlap in their predictions. Until recently, very few algorithms considered the dynamic nature of the interactions, including the effect of less specific interactions, the miRNA expression level, and the effect of combinatorial miRNA binding. Addressing these issues can result in a more accurate miRNA:mRNA modeling with many applications, including efficient miRNA-related SNP evaluation. We present a novel thermodynamic model based on the Fermi-Dirac equation that incorporates miRNA expression in the prediction of target occupancy and we show that it improves the performance of two popular single miRNA target finders. Modeling combinatorial miRNA targeting is a natural extension of this model. Two other algorithms show improved prediction efficiency when combinatorial binding models were considered. ComiR (Combinatorial miRNA targeting, a novel algorithm we developed, incorporates the improved predictions of the four target finders into a single probabilistic score using ensemble learning. Combining target scores of multiple miRNAs using ComiR improves predictions over the naïve method for target combination. ComiR scoring scheme can be used for identification of SNPs affecting miRNA binding. As proof of principle, ComiR identified rs17737058 as disruptive to the miR-488-5p:NCOA1 interaction, which we confirmed in vitro. We also found rs17737058 to be significantly associated with decreased bone mineral density (BMD in two independent cohorts indicating that the miR-488-5p/NCOA1 regulatory axis is likely critical in maintaining BMD in women. With increasing availability of comprehensive high-throughput datasets from patients ComiR is expected to become an essential

  4. Chondrogenic potential of mesenchymal stromal cells derived from equine bone marrow and umbilical cord blood

    DEFF Research Database (Denmark)

    Berg, Lise Charlotte; Koch, Thomas Gadegaard; Heerkens, T.

    2009-01-01

    Objective: Orthopaedic injury is the most common cause of lost training days or premature retirement in the equine athlete. Cell-based therapies are a potential new treatment option in musculo-skeletal diseases. Mesenthymal stromal cells (MSC) have been derived from multiple sources in the horse...

  5. In vivo osteoinductive effect and in vitro isolation and cultivation bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Redzić, Amira; Smajilagić, Amer; Aljicević, Mufida; Berberović, Ljubomir

    2010-12-01

    for conventional medicine and autologue bone transplantation. That new horizons have potential to minimize surgery and patient donor morbidity, with more success treatment in bone regenerative and metabolism diseases.

  6. Possible mechanisms of retinal function recovery with the use of cell therapy with bone marrow-derived stem cells

    Directory of Open Access Journals (Sweden)

    Rubens Camargo Siqueira

    2010-10-01

    Full Text Available Bone marrow has been proposed as a potential source of stem cells for regenerative medicine. In the eye, degeneration of neural cells in the retina is a hallmark of such widespread ocular diseases as age-related macular degeneration (AMD and retinitis pigmentosa. Bone marrow is an ideal tissue for studying stem cells mainly because of its accessibility. Furthermore, there are a number of well-defined mouse models and cell surface markers that allow effective study of hematopoiesis in healthy and injured mice. Because of these characteristics and the experience of bone marrow transplantation in the treatment of hematological disease such as leukemia, bone marrow-derived stem cells have also become a major tool in regenerative medicine. Those cells may be able to restore the retina function through different mechanisms: A cellular differentiation, B paracrine effect, and C retinal pigment epithelium repair. In this review, we described these possible mechanisms of recovery of retinal function with the use of cell therapy with bone marrow-derived stem cells.

  7. Platelet-rich plasma in regenerative medicine

    Directory of Open Access Journals (Sweden)

    Guhta Ra Hara and Thaha Basu

    2014-01-01

    Full Text Available Platelet-rich plasma (PRP contains at least seven growth factors including epidermal, plateletderived, transforming, vascular endothelial, fibroblast, insulin-like and keratinocyte growth factor. The therapeutic effect of PRP occurs because of the high concentration of these growth factors compared with those found in normal plasma. In recent years, PRP is widely used across many clinical fields, especially in regenerative medicine. This review aimed at presenting an overview of the applications of PRP in regenerative medicine. The mechanisms of PRP effects on healing are also stated in this review. [Biomed Res Ther 2014; 1(1.000: 25-31

  8. Rebuilding a broken heart: lessons from developmental and regenerative biology.

    Science.gov (United States)

    Kuyumcu-Martinez, Muge N; Bressan, Michael C

    2016-11-01

    In May 2016, the annual Weinstein Cardiovascular Development and Regeneration Conference was held in Durham, North Carolina, USA. The meeting assembled leading investigators, junior scientists and trainees from around the world to discuss developmental and regenerative biological approaches to understanding the etiology of congenital heart defects and the repair of diseased cardiac tissue. In this Meeting Review, we present several of the major themes that were discussed throughout the meeting and highlight the depth and range of research currently being performed to uncover the causes of human cardiac diseases and develop potential therapies. © 2016. Published by The Company of Biologists Ltd.

  9. Umbilical cord blood: a trustworthy source of multipotent stem cells for regenerative medicine.

    Science.gov (United States)

    Jaing, Tang-Her

    2014-01-01

    It is conservatively estimated that one in three individuals in the US might benefit from regenerative medicine therapy. However, the relation of embryonic stem cells (ESCs) to human blastocysts always stirs ethical, political, moral, and emotional debate over their use in research. Thus, for the reasonably foreseeable future, the march of regenerative medicine to the clinic will depend upon the development of non-ESC therapies. Current sources of non-ESCs easily available in large numbers can be found in the bone marrow, adipose tissue, and umbilical cord blood (UCB). UCB provides an immune-compatible source of stem cells for regenerative medicine. Owing to inconsistent results, it is certainly an important and clinically relevant question whether UCB will prove to be therapeutically effective. This review will show that UCB contains multiple populations of multipotent stem cells, capable of giving rise to hematopoietic, epithelial, endothelial, and neural tissues both in vitro and in vivo. Here we raise the possibility that due to unique immunological properties of both the stem cell and non-stem cell components of cord blood, it may be possible to utilize allogeneic cells for regenerative applications without needing to influence or compromise the recipient immune system.

  10. Bone ingrowth potential of electron beam and selective laser melting produced trabecular-like implant surfaces with and without a biomimetic coating.

    Science.gov (United States)

    Biemond, J E; Hannink, G; Verdonschot, N; Buma, P

    2013-03-01

    The bone ingrowth potential of trabecular-like implant surfaces produced by either selective laser melting (SLM) or electron beam melting (EBM), with or without a biomimetic calciumphosphate coating, was examined in goats. For histological analysis and histomorphometry of bone ingrowth depth and bone implant contact specimens were implanted in the femoral condyle of goats. For mechanical push out tests to analyse mechanical implant fixation specimens were implanted in the iliac crest. The follow up periods were 4 (7 goats) and 15 weeks (7 goats). Both the SLM and EBM produced trabecular-like structures showed a variable bone ingrowth after 4 weeks. After 15 weeks good bone ingrowth was found in both implant types. Irrespective to the follow up period, and the presence of a coating, no histological differences in tissue reaction around SLM and EBM produced specimens was found. Histological no coating was detected at 4 and 15 weeks follow up. At both follow up periods the mechanical push out strength at the bone implant interface was significantly lower for the coated SLM specimens compared to the uncoated SLM specimens. The expected better ingrowth characteristics and mechanical fixation strength induced by the coating were not found. The lower mechanical strength of the coated specimens produced by SLM is a remarkable result, which might be influenced by the gross morphology of the specimens or the coating characteristics, indicating that further research is necessary.

  11. Graphene and its nanostructure derivatives for use in bone tissue engineering: Recent advances.

    Science.gov (United States)

    Shadjou, Nasrin; Hasanzadeh, Mohammad

    2016-05-01

    Tissue engineering and regenerative medicine represent areas of increasing interest because of the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Tissue-engineered bone constructs have the potential to alleviate the demand arising from the shortage of suitable autograft and allograft materials for augmenting bone healing. Graphene and its derivatives have attracted much interest for applications in bone tissue engineering. For this purpose, this review focuses on more recent advances in tissue engineering based on graphene-biomaterials from 2013 to May 2015. The purpose of this article was to give a general description of studies of nanostructured graphene derivatives for bone tissue engineering. In this review, we highlight how graphene family nanomaterials are being exploited for bone tissue engineering. Firstly, the main requirements for bone tissue engineering were discussed. Then, the mechanism by which graphene based materials promote new bone formation was explained, following which the current research status of main types of nanostructured scaffolds for bone tissue engineering was reviewed and discussed. In addition, graphene-based bioactive glass, as a potential drug/growth factor carrier, was reviewed which includes the composition-structure-drug delivery relationship and the functional effect on the tissue-stimulation properties. Also, the effect of structural and textural properties of graphene based materials on development of new biomaterials for production of bone implants and bone cements were discussed. Finally, the present review intends to provide the reader an overview of the current state of the graphene based biomaterials in bone tissue engineering, its limitations and hopes as well as the future research trends for this exciting field of science.

  12. Nutrient retention capabilities of Nile tilapia ( Oreochromis niloticus) fed bio-regenerative life support system (BLSS) waste residues

    Science.gov (United States)

    Gonzales, John M.; Brown, Paul B.

    Nile tilapia were evaluated as a bio-regenerative sub-process for reducing solid waste potentially encountered in bio-regenerative life support systems. Ten juvenile Nile tilapia (mean weight = 2.05 g) were stocked into triplicate aquaria and fed one of seven experimental diets consisting of vegetable, bacterial, or food waste for a period of seven weeks. Weight gain (g), specific growth rate (mg/d), and daily consumption (g) was significantly higher ( p tilapia's ability to utilize these residues as a food source in bio-regenerative support systems.

  13. A theoretical and experimental analysis of polymerization shrinkage of bone cement: A potential major source of porosity.

    Science.gov (United States)

    Gilbert, J L; Hasenwinkel, J M; Wixson, R L; Lautenschlager, E P

    2000-10-01

    A theoretical basis for understanding polymerization shrinkage of bone cement is presented based on density changes in converting monomer to polymer. Also, an experimental method, based on dilatometry and the Archimedes' principle is presented for highly precise and accurate measurement of unconstrained volumetric shrinkage of bone cement. Furthermore, a theoretical and experimental analysis of polymerization shrinkage in a constrained deformational state is presented to demonstrate that porosity can develop due to shrinkage. Six bone-cement conditions (Simplex-Ptrade mark vacuum and hand mixed, Endurancetrade mark vacuum mixed, and three two-solution experimental bone cements with higher initial monomer levels) were tested for volumetric shrinkage. It was found that shrinkage varied statistically (ptheory that they are the result of shrinkage. The results of this study show that shrinkage of bone cement under certain constrained conditions may result in the development of porosity at the implant-bone cement interface and elsewhere in the polymerizing cement mantle.

  14. Osteogenic Potential of Cultured Bone Marrow Stromal CellsTransfected with Transforming Growth Factor β1 Gene in vitro

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To study the osteogenic potential of cultured bone marrow stromal cells (BMSCs) transfected with transforming growth factor β1 (TGF-β1) gene in vitro, cultured BMSCs were transfected with the complexes of pcDNA3-TGF-β1 and Lipofectamine Reagent in vitro. The cell proliferation was detected by MTT method and the morphological features of transfected BMSCs was observed. ALP stains and PNP method were used to measure ALP activity. In addition, the collagen type Ⅰ propeptides and mineralized matrixes were examined by immunohistochemical staining and tetracycline fluorescence labeling respectively. The morphological and biological characters of the transfected BMSCs were similar to those of osteoblasts and the cell proliferation was promoted. The cell layer displayed strong positive reaction for ALP stains and immunohistochemical staining. ALP activity and collagen type Ⅰ expression increased remarkably after transfection. Mineralized matrixes formed earlier and more in transfected BMSCs as compared with control group. It is concluded that transfecting with TGF-β1 gene could promote the osteogenic potential of cultured BMSCs.

  15. Active Gas Regenerative Liquefier Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We offer a novel liquefier that has the potential to simultaneously increase thermodynamic efficiency and significantly reduce complexity. The ?active gas...

  16. Advances in understanding tissue regenerative capacity and mechanisms in animals

    OpenAIRE

    Poss, Kenneth D.

    2010-01-01

    Questions about how and why tissue regeneration occurs capture the attention of countless biologists, biomedical engineers, and clinicians. Regenerative capacity differs greatly across organs and organisms, and a spectrum of model systems with different technical advantages and regenerative strategies are studied. Several key issues common to natural regenerative events are receiving new attention from improving models and approaches, including: the determination of regenerative capacity; the...

  17. Bone Regeneration from PLGA Micro-Nanoparticles

    Directory of Open Access Journals (Sweden)

    Inmaculada Ortega-Oller

    2015-01-01

    Full Text Available Poly-lactic-co-glycolic acid (PLGA is one of the most widely used synthetic polymers for development of delivery systems for drugs and therapeutic biomolecules and as component of tissue engineering applications. Its properties and versatility allow it to be a reference polymer in manufacturing of nano- and microparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules. It additionally facilitates and extends its use to encapsulate biomolecules such as proteins or nucleic acids that can be released in a controlled way. This review focuses on the use of nano/microparticles of PLGA as a delivery system of one of the most commonly used growth factors in bone tissue engineering, the bone morphogenetic protein 2 (BMP2. Thus, all the needed requirements to reach a controlled delivery of BMP2 using PLGA particles as a main component have been examined. The problems and solutions for the adequate development of this system with a great potential in cell differentiation and proliferation processes under a bone regenerative point of view are discussed.

  18. Nanoengineered implant as a new platform for regenerative nanomedicine using 3D well-organized human cell spheroids

    Science.gov (United States)

    Keller, Laetitia; Idoux-Gillet, Ysia; Wagner, Quentin; Eap, Sandy; Brasse, David; Schwinté, Pascale; Arruebo, Manuel; Benkirane-Jessel, Nadia

    2017-01-01

    In tissue engineering, it is still rare today to see clinically transferable strategies for tissue-engineered graft production that conclusively offer better tissue regeneration than the already existing technologies, decreased recovery times, and less risk of complications. Here a novel tissue-engineering concept is presented for the production of living bone implants combining 1) a nanofibrous and microporous implant as cell colonization matrix and 2) 3D bone cell spheroids. This combination, double 3D implants, shows clinical relevant thicknesses for the treatment of an early stage of bone lesions before the need of bone substitutes. The strategy presented here shows a complete closure of a defect in nude mice calvaria after only 31 days. As a novel strategy for bone regenerative nanomedicine, it holds great promises to enhance the therapeutic efficacy of living bone implants. PMID:28138241

  19. Adult stem cells applied to tissue engineering and regenerative medicine.

    Science.gov (United States)

    Cuenca-López, M D; Zamora-Navas, P; García-Herrera, J M; Godino, M; López-Puertas, J M; Guerado, E; Becerra, J; Andrades, J A

    2008-01-01

    Regeneration takes place in the body at a moment or another throughout life. Bone, cartilage, and tendons (the key components of the structure and articulation in the body) have a limited capacity for self-repair and, after traumatic injury or disease, the regenerative power of adult tissue is often insufficient. When organs or tissues are irreparably damaged, they may be replaced by an artificial device or by a donor organ. However, the number of available donor organs is considerably limited. Generation of tissue-engineered replacement organs by extracting stem cells from the patient, growing them and modifying them in clinical conditions after re-introduction in the body represents an ideal source for corrective treatment. Mesenchymal stem cells (MSCs) are the multipotential progenitors that give rise to skeletal cells, vascular smooth muscle cells, muscle (skeletal and cardiac muscle), adipocytes (fat tissue) and hematopoietic (blood)-supportive stromal cells. MSCs are found in multiple connective tissues, in adult bone marrow, skeletal muscles and fat pads. The wide representation in adult tissues may be related to the existence of a circulating blood pool or that MSCs are associated to the vascular system.

  20. Regenerative Burner System for Thermoelectric Power Sources.

    Science.gov (United States)

    1979-07-01

    wy aid id.nt lfy by block nsaib.r) • k’ all and (or • Thermoelectric ~t special Regenerative Burner Power Sources - 20. AS TRACT (Contlnu. on r...ELECTRIC POWER SOURCES C. Cuazgo~t , J. Angello, & A. Rerchshow.ki Power Source. Division US Army Electronic. Technology and Devices Laboratory

  1. Regenerative medicine: does Erythropoietin have a role?

    Science.gov (United States)

    Buemi, Michele; Lacquaniti, Antonio; Maricchiolo, Giulia; Bolignano, Davide; Campo, Susanna; Cernaro, Valeria; Sturiale, Ale