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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

    Directory of Open Access Journals (Sweden)

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

    OpenAIRE

    Burdon, Tom J.; Arghya Paul; Nicolas Noiseux; Satya Prakash; Dominique Shum-Tim

    2010-01-01

    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 ...

  3. Enhancement of the Regenerative Potential of Anorganic Bovine Bone Graft Utilizing a Polyglutamate-Modified BMP2 Peptide with Improved Binding to Calcium-Containing Materials.

    Science.gov (United States)

    Bain, Jennifer L; Bonvallet, Paul P; Abou-Arraj, Ramzi V; Schupbach, Peter; Reddy, Michael S; Bellis, Susan L

    2015-09-01

    Autogenous bone is the gold standard material for bone grafting in craniofacial and orthopedic regenerative medicine. However, due to complications associated with harvesting donor bone, clinicians often use commercial graft materials that may lose their osteoinductivity due to processing. This study was aimed to functionalize one of these materials, anorganic bovine bone (ABB), with osteoinductive peptides to enhance regenerative capacity. Two peptides known to induce osteoblastic differentiation of mesenchymal stem cells were evaluated: (1) DGEA, an amino acid motif within collagen I and (2) a biomimetic peptide derived from bone morphogenic protein 2 (BMP2pep). To achieve directed coupling of the peptides to the graft surface, the peptides were engineered with a heptaglutamate domain (E7), which confers specific binding to calcium moieties within bone mineral. Peptides with the E7 domain exhibited greater anchoring to ABB than unmodified peptides, and E7 peptides were retained on ABB for at least 8 weeks in vivo. To assess the osteoinductive potential of the peptide-conjugated ABB, ectopic bone formation was evaluated utilizing a rat subcutaneous pouch model. ABB conjugated with full-length recombinant BMP2 (rBMP2) was also implanted as a model for current clinical treatments utilizing rBMP2 passively adsorbed to carriers. These studies showed that E7BMP2pep/ABB samples induced more new bone formation than all other peptides, and an equivalent amount of new bone as compared with rBMP2/ABB. A mandibular defect model was also used to examine intrabony healing of peptide-conjugated ABB. Bone healing was monitored at varying time points by positron emission tomography imaging with (18)F-NaF, and it was found that the E7BMP2pep/ABB group had greater bone metabolic activity than all other groups, including rBMP2/ABB. Importantly, animals implanted with rBMP2/ABB exhibited complications, including inflammation and formation of cataract-like lesions in the eye, whereas

  4. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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

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

    OpenAIRE

    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...

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  10. 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.

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

    International Nuclear Information System (INIS)

    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 HAMα cells and induced to osteogenic status—their in vivo osteogenesis was subsequently investigated in rats. It was found that HAMα 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 HAMα cells. The expression of osteocalcin mRNA was increased in HAMα cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAMα 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: ► Human amniotic mesenchymal cells include cells (HAMα cells) that have the properties of MSCs. ► HAMα cells have excellent osteogenic differentiation potential. ► Osteogenic differentiation ability of HAMα was amplified by calcium phosphate scaffolds. ► HAMα cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

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

    Science.gov (United States)

    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.

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

    OpenAIRE

    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...

  14. Therapeutic potential of nanoceria in regenerative medicine

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Strategy for regenerative energy sources. Status and development potential

    International Nuclear Information System (INIS)

    Without doubt, in the future, we shall have to cover a growing proportion of our energy requirements by utilizing regenerative energy sources such as the sun, wind, water and biomass. The indisputable advantages of inexhaustibility and environment friendliness are, however, compared with the disadvantages of non-uniform demand as well as partially small potential and high costs. In spite of these facts, there are, in the minds of the public, high expectations and great demands on the electricity supply industry in relation to the further development of regenerative power generation. In the future, RWE Energie AG will strongly intensify its efforts towards improving the economics of regenerative power generation. (orig.)

  16. 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.

  17. 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. PMID:25376489

  18. 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.

  19. Potential of regenerative medicine techniques in canine hepatology.

    Science.gov (United States)

    Schotanus, Baukje A; Penning, Louis C; Spee, Bart

    2013-12-01

    Liver cell turnover is very slow, especially compared to intestines and stomach epithelium and hair cells. Since the liver is the main detoxifying organ in the body, it does not come as a surprise that the liver has an unmatched regenerative capacity. After 70% partial hepatectomy, the liver size returns to normal in about two weeks due to replication of differentiated hepatocytes and cholangiocytes. Despite this, liver diseases are regularly encountered in the veterinary clinic. Dogs primarily present with parenchymal pathologies such as hepatitis. The estimated frequency of canine hepatitis depends on the investigated population and accounts for 1%-2% of our university clinic referral population, and up to 12% in a general population. In chronic and severe acute liver disease, the regenerative and replicative capacity of the hepatocytes and/or cholangiocytes falls short and the liver is not restored. In this situation, proliferation of hepatic stem cells or hepatic progenitor cells (HPCs), on histology called the ductular reaction, comes into play to replace the damaged hepatocytes or cholangiocytes. For unknown reasons the ductular reaction is often too little and too late, or differentiation into fully differentiated hepatocytes or cholangiocytes is hampered. In this way, HPCs fail to fully regenerate the liver. The presence and potential of HPCs does, however, provide great prospectives for their use in regenerative strategies. This review highlights the regulation of, and the interaction between, HPCs and other liver cell types and discusses potential regenerative medicine-oriented strategies in canine hepatitis, making use of (liver) stem cells. PMID:24422896

  20. 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

  1. 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

  2. Regenerative potential of human schneiderian membrane: progenitor cells and epithelial-mesenchymal transition.

    Science.gov (United States)

    Derjac-Aramă, A I; Sarafoleanu, C; Manea, C M; Nicolescu, M I; Vrapciu, A D; Rusu, M C

    2015-12-01

    An innate osteogenic potential of the Schneiderian membrane (SM) is progressively assessed in studies ranging from non-human species to human subjects. It has relevance for endosteal placement and osseointegration. Nestin-expressing osteogenic progenitor cells are allegedly involved in bone formation and remodelling. Nestin phenotype was not assessed previously in human SM. We therefore aimed to fill that particular gap in the literature. Bioptic samples of human adult SM were obtained during surgery from eight adult patients, operated for non-malignant pathologies. Immunohistochemistry on paraffin-embedded tissue samples used primary antibodies against nestin, CD45, CD146, cytokeratin 7 (CK7), and alpha-smooth muscle actin (α-SMA). Nestin expression was consistently found in endothelial cells, and was scarcely encountered in pericytes, putative stromal stem/progenitor cells, as well as in glandular epithelial cells. Moreover, woven bone formation in the periosteal layer of the SM can also be regarded as evidence of the osteogenic potential of this membrane. Nestin and CD45 expression in cells of the primary bone supports the osteogenic potential of SM nestin-expressing cells and a possible involvement of hematopoietic stem cells in maxillary sinus floor remodeling. CD146, a known inducer of epithelial-mesenchymal transition (EMT), was expressed in epithelia, as was CK7. Isolated stromal cells were found expressing CD146, CK7 and α-SMA, suggesting that regenerative processes happening in the SM may also involve processes of EMT which generate stem/progenitor cells. This study provides additional evidence for the regenerative potential of the Schneiderian membrane and identifies potential roles for cells of its stem niche in osteogenesis. PMID:26414809

  3. Research Sees Potential to Make Bone, Muscle from Human Stem Cells

    Science.gov (United States)

    ... Sees Potential to Make Bone, Muscle From Human Stem Cells Could be a major advance for regenerative medicine, scientists say To use the ... the ability to quickly coax human embryonic (pluripotent) stem cells to ... a major advance in regenerative medicine. Pluripotent means the cells can ...

  4. Phenotypic characterization of the bone marrow stem cells used in regenerative cellular therapy

    International Nuclear Information System (INIS)

    Regenerative medicine is a novel therapeutic method with broad potential for the treatment of various illnesses, based on the use of bone marrow (BM) stem cells, whose phenotypic characterization is limited. The paper deals with the expression of different cell membrane markers in mononuclear BM cells from 14 patients who underwent autologous cell therapy, obtained by medullary puncture and mobilization to peripheral blood, with the purpose of characterizing the different types of cells present in that heterogeneous cellular population and identifying the adhesion molecules involved in their adhesion. A greater presence was observed of adherent stem cells from the marrow stroma in mononuclear cells obtained directly from the BM; a larger population of CD90+cells in mononuclear cells from CD34-/CD45-peripheral blood with a high expression of molecules CD44 and CD62L, which suggests a greater presence of mesenchymal stem cells (MSC) in mobilized cells from the marrow stroma. The higher levels of CD34+cells in peripheral blood stem cells with a low expression of molecules CD117-and DR-suggests the presence of hematopoietic stem cells, hemangioblasts and progenitor endothelial cells mobilized to peripheral circulation. It was found that mononuclear cells from both the BM and peripheral blood show a high presence of stem cells with expression of adhesion molecule CD44 (MMC marker), probably involved in their migration, settling and differentiation

  5. 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.

  6. Suction assisted liposuction does not impair the regenerative potential of adipose derived stem cells

    OpenAIRE

    Duscher, Dominik; Luan, Anna; Rennert, Robert C; Atashroo, David; Maan, Zeshaan N; Brett, Elizabeth A.; Whittam, Alexander J.; Ho, Natalie; Lin, Michelle; Hu, Michael S.; Graham G Walmsley; Wenny, Raphael; Schmidt, Manfred; Schilling, Arndt F.; Machens, Hans-Günther

    2016-01-01

    Background Adipose-derived stem cells (ASCs) have been identified as a population of multipotent cells with promising applications in tissue engineering and regenerative medicine. ASCs are abundant in fat tissue, which can be safely harvested through the minimally invasive procedure of liposuction. However, there exist a variety of different harvesting methods, with unclear impact on ASC regenerative potential. The aim of this study was thus to compare the functionality of ASCs derived from t...

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

    International Nuclear Information System (INIS)

    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

  8. 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

  9. 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

  10. 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...

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. MSCs-Derived Exosomes: Cell-Secreted Nanovesicles with Regenerative Potential.

    Science.gov (United States)

    Marote, Ana; Teixeira, Fábio G; Mendes-Pinheiro, Bárbara; Salgado, António J

    2016-01-01

    Exosomes are membrane-enclosed nanovesicles (30-150 nm) that shuttle active cargoes between different cells. These tiny extracellular vesicles have been recently isolated from mesenchymal stem cells (MSCs) conditioned medium, a population of multipotent cells identified in several adult tissues. MSCs paracrine activity has been already shown to be the key mediator of their elicited regenerative effects. On the other hand, the individual contribution of MSCs-derived exosomes for these effects is only now being unraveled. The administration of MSCs-derived exosomes has been demonstrated to restore tissue function in multiple diseases/injury models and to induce beneficial in vitro effects, mainly mediated by exosomal-enclosed miRNAs. Additionally, the source and the culture conditions of MSCs have been shown to influence the regenerative responses induced by exosomes. Therefore, these studies reveal that MSCs-derived exosomes hold a great potential for cell-free therapies that are safer and easier to manipulate than cell-based products. Nevertheless, this is an emerging research field and hence, further studies are required to understand the full dimension of this complex intercellular communication system and how it can be optimized to take full advantage of its therapeutic effects. In this mini-review, we summarize the most significant new advances in the regenerative properties of MSCs-derived exosomes and discuss the molecular mechanisms underlying these effects. PMID:27536241

  16. Regenerative potential and anti-bacterial activity of tetracycline loaded apatitic nanocarriers for the treatment of periodontitis

    International Nuclear Information System (INIS)

    Current treatment of periodontal infections includes mechanical debridement, administration of antibiotics and bone grafting. Oral administration of antibiotics results in undesirable side effects, while current modes of local administration are affected by problems concerning allergic response to the polymeric carrier agents. We have developed an osteoconductive drug delivery system composed of apatitic nanocarriers capable of providing sustained delivery of drugs in the periodontium. Calcium deficient hydroxyapatite (CDHA) nanocarriers of different Ca/P ratios were synthesized and characterized using the x-ray diffraction method, transmission electron microscopy, inductively coupled plasma atomic emission spectroscopy, Fourier transform infrared spectroscopy and the BET gas isotherm method. Loading and release studies performed with tetracycline showed a sustained release of up to 88% in phosphate buffered saline over a period of five days. Antibacterial activity studies showed that the tetracycline loaded CDHA (TC-CDHA) nanocarriers were effective against S. aureus and E. coli bacteria. The biocompatibility of the TC-CDHA nanocarriers was demonstrated using an alamar blue assay and further characterized by cell uptake studies. Interestingly, cell uptake of drug loaded CDHA also increased the cellular proliferation of human periodontal ligament fibroblast cells. Hence, it can be concluded that the CDHA nanocarriers are ideal drug delivery agents and have bone regenerative potential for local periodontal applications. (paper)

  17. 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.

  18. 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.

  19. 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.

  20. 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. PMID:27622532

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

    Science.gov (United States)

    Asuelime, Grace E; Shi, Yanhong

    2012-08-01

    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. PMID:22371436

  2. 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

  3. Subchondral Bone Regenerative Effect of Two Different Biomaterials in the Same Patient

    Directory of Open Access Journals (Sweden)

    Marco Cavallo

    2013-01-01

    Full Text Available This case report aims at highlighting the different effects on subchondral bone regeneration of two different biomaterials in the same patient, in addition to bone marrow derived cell transplantation (BMDCT in ankle. A 15-year-old boy underwent a first BMDCT on a hyaluronate membrane to treat a deep osteochondral lesion (8 mm. The procedure failed: subchondral bone was still present at MRI. Two years after the first operation, the same procedure was performed on a collagen membrane with DBM filling the defect. After one year, AOFAS score was 100 points, and MRI showed a complete filling of the defect. The T2 mapping MRI after one year showed chondral tissue with values in the range of hyaline cartilage. In this case, DBM and the collagen membrane were demonstrated to be good biomaterials to restore subchondral bone: this is a critical step towards the regeneration of a healthy hyaline cartilage.

  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. Human periodontal ligament stem cells cultured onto cortico-cancellous scaffold drive bone regenerative process.

    Science.gov (United States)

    Diomede, F; Zini, N; Gatta, V; Fulle, S; Merciaro, I; D'Aurora, M; La Rovere, R M; Traini, T; Pizzicannella, J; Ballerini, P; Caputi, S; Piattelli, A; Trubiani, O

    2016-01-01

    The purpose of this work was to test, in vitro and in vivo, a new tissue-engineered construct constituted by porcine cortico-cancellous scaffold (Osteobiol Dual Block) (DB) and xeno-free ex vivo culture of human Periodontal Ligament Stem Cells (hPDLSCs). hPDLSCs cultured in xeno-free media formulation preserved the stem cells' morphological features, the expression of stemness and pluripotency markers, and their ability to differentiate into mesenchymal lineage. Transmission electron microscopy analysis suggested that after one week of culture, both noninduced and osteogenic differentiation induced cells joined and grew on DB secreting extracellular matrix (ECM) that in osteogenic induced samples was hierarchically assembled in fibrils. Quantitative RT-PCR (qRT-PCR) showed the upregulation of key genes involved in the bone differentiation pathway in both differentiated and undifferentiated hPDLSCs cultured with DB (hPDLSCs/DB). Functional studies revealed a significant increased response of calcium transients in the presence of DB, both in undifferentiated and differentiated cells stimulated with calcitonin and parathormone, suggesting that the biomaterial could drive the osteogenic differentiation process of hPDLSCs. These data were confirmed by the increase of gene expression of L-type voltage-dependent Ca2+ (VDCCL), subunits α1C and α2D1 in undifferentiated cells in the presence of DB. In vivo implantation of the hPDLSCs/DB living construct in the mouse calvaria evidenced a precocious osteointegration and vascularisation process. Our results suggest consideration of DB as a biocompatible, osteoinductive and osteoconductive biomaterial, making it a promising tool to regulate cell activities in biological environments and for a potential use in the development of new custom-made tissue engineering. PMID:27633707

  6. 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.

  7. Low-level vibrations retain bone marrow's osteogenic potential and augment recovery of trabecular bone during reambulation.

    Directory of Open Access Journals (Sweden)

    Engin Ozcivici

    Full Text Available Mechanical disuse will bias bone marrow stromal cells towards adipogenesis, ultimately compromising the regenerative capacity of the stem cell pool and impeding the rapid and full recovery of bone morphology. Here, it was tested whether brief daily exposure to high-frequency, low-magnitude vibrations can preserve the marrow environment during disuse and enhance the initiation of tissue recovery upon reambulation. Male C57BL/6J mice were subjected to hindlimb unloading (HU, n = 24, HU interrupted by weight-bearing for 15 min/d (HU+SHAM, n = 24, HU interrupted by low-level whole body vibrations (0.2 g, 90 Hz for 15 min/d (HU+VIB, n = 24, or served as age-matched controls (AC, n = 24. Following 3 w of disuse, half of the mice in each group were released for 3 w of reambulation (RA, while the others were sacrificed. RA+VIB mice continued to receive vibrations for 15 min/d while RA+SHAM continued to receive sham loading. After disuse, HU+VIB mice had a 30% greater osteogenic marrow stromal cell population, 30% smaller osteoclast surface, 76% greater osteoblast surface but similar trabecular bone volume fraction compared to HU. After 3 w of reambulation, trabecular bone of RA+VIB mice had a 30% greater bone volume fraction, 51% greater marrow osteoprogenitor population, 83% greater osteoblast surfaces, 59% greater bone formation rates, and a 235% greater ratio of bone lining osteoblasts to marrow adipocytes than RA mice. A subsequent experiment indicated that receiving the mechanical intervention only during disuse, rather than only during reambulation, was more effective in altering trabecular morphology. These data indicate that the osteogenic potential of bone marrow cells is retained by low-magnitude vibrations during disuse, an attribute which may have contributed to an enhanced recovery of bone morphology during reambulation.

  8. Osteogenic Potential of Multipotent Adult Progenitor Cells for Calvaria Bone Regeneration

    Science.gov (United States)

    Lee, Dong Joon; Park, Yonsil; Hu, Wei-Shou; Ko, Ching-Chang

    2016-01-01

    Osteogenic cells derived from rat multipotent adult progenitor cells (rMAPCs) were investigated for their potential use in bone regeneration. rMAPCs are adult stem cells derived from bone marrow that have a high proliferation capacity and the differentiation potential to multiple lineages. They may also offer immunomodulatory properties favorable for applications for regenerative medicine. rMAPCs were cultivated as single cells or as 3D aggregates in osteogenic media for up to 38 days, and their differentiation to bone lineage was then assessed by immunostaining of osteocalcin and collagen type I and by mineralization assays. The capability of rMAPCs in facilitating bone regeneration was evaluated in vivo by the direct implantation of multipotent adult progenitor cell (MAPC) aggregates in rat calvarial defects. Bone regeneration was examined radiographically, histologically, and histomorphometrically. Results showed that rMAPCs successfully differentiated into osteogenic lineage by demonstrating mineralized extracellular matrix formation in vitro and induced new bone formation by the effect of rMAPC aggregates in vivo. These outcomes confirm that rMAPCs have a good osteogenic potential and provide insights into rMAPCs as a novel adult stem cell source for bone regeneration. PMID:27239552

  9. 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

  10. 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.

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

    International Nuclear Information System (INIS)

    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.

  12. 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.

  13. 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

  14. Equine mesenchymal stem cells from bone marrow, adipose tissue and umbilical cord: immunophenotypic characterization and differentiation potential

    OpenAIRE

    Barberini, Danielle Jaqueta; Freitas, Natália Pereira Paiva; Magnoni, Mariana Sartori; Maia, Leandro; Listoni, Amanda Jerônimo; Heckler, Marta Cristina; Sudano, Mateus Jose; Golim, Marjorie Assis; da Cruz Landim-Alvarenga, Fernanda; Amorim, Rogério Martins

    2014-01-01

    Introduction Studies with mesenchymal stem cells (MSCs) are increasing due to their immunomodulatory, anti-inflammatory and tissue regenerative properties. However, there is still no agreement about the best source of equine MSCs for a bank for allogeneic therapy. The aim of this study was to evaluate the cell culture and immunophenotypic characteristics and differentiation potential of equine MSCs from bone marrow (BM-MSCs), adipose tissue (AT-MSCs) and umbilical cord (UC-MSCs) under identic...

  15. 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.

  16. Effects of Loading or Unloading on the Regenerative Potential of Injured Skeletal Muscle in Mice

    Science.gov (United States)

    Goto, Katsumasa; Matsuba, Yusuke; Ohno, Yoshitaka; Sugiura, Takao; Hashimoto, Naohiro; Ohira, Yoshinobu; Yoshioka, Toshitada

    2008-06-01

    The present study was performed to investigate the influence of unloading on the regenerative process of injured skeletal muscle. Male mice (C57BL/6J), aged 8 weeks, were randomly divided into 4 groups; normal cage control (CC), cardiotoxin (CTX)-injected (CX), hindlimb suspended (HS), and HS+CX (SX) groups. HS, as the preconditioning, was performed for 2 weeks in group HS and SX. The animals in group CC and CX were maintained in 1-G environment. And then, CTX was injected into soleus muscles bilaterally in CX and SX groups. HS was continued for additional 6 weeks in group HS and SX. Soleus muscles were dissected after 2, 4, and 6 weeks. Wet weight and protein content of soleus in group CX decreased, but recovered to the level of group CC after 6 weeks. Atrophy, caused by 2-week HS, in group HS and SX was maintained throughout the experimental period. The numbers of satellite cells in HS and SX groups after 2, 4, and 6 weeks were lower than those in group CC. The number of satellite cells in CX group was increased by the CTX-injection compared with group CC. On the other hand, satellite cell number in CTX-injected group SX after 2, 4, and 6 weeks were lower than that in group HS. Percentage of fibers with central nuclei, relative to the total muscle fibers, in HS and SX groups at week 6 was higher than that in group CC. That in group CX was also increased at 2nd and 4th week, but was lowered toward the control level after 6 week. It was suggested that loading plays a key role for the activation of the regenerating potential of injured skeletal muscle.

  17. 蝾螈颌骨再生生物学的研究进展%Newt jaw bone regenerative biology research progress

    Institute of Scientific and Technical Information of China (English)

    王琰; 陈希哲

    2013-01-01

    The regeneration are commonly existing animal life phenomenon. Based on the international academic circles to Newt limb regenerative form histology, cell biology and molecular biology research foundation, Newt jaw bone regenerative biology of literature review on the study of mammals, regeneration ability of research, and even on human reproductive medicine research provides beneficial inspirations.%  再生是动物界普遍存在的生命现象。本文将从蝾螈肢体再生的形态组织学、细胞生物学和分子生物学研究基础等几个方面,对蝾螈颌骨再生生物学研究进展的进行文献回顾,以期对哺乳动物的再生能力研究提供一定的帮助。

  18. Bone Forming Potential of An-Organic Bovine Bone Graft: A Cone Beam CT study

    OpenAIRE

    Uzbek, Usman Haider; Rahman, Shaifulizan Ab; Alam, Mohammad Khursheed; gillani, syed wasif

    2014-01-01

    Purpose: An-organic bovine bone graft is a xenograft with the potential of bone formation. The aim of this study was to evaluate the bone density using cone beam computed tomography scans around functional endosseous implant in the region of both augmented maxillary sinus with the an-organic bovine bone graft and the alveolar bone over which the graft was placed to provide space for the implants.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

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

    DEFF Research Database (Denmark)

    Bjørndal, Lars; Pedersen, Sune Demant Nørgaard; Dabelsteen, Sally

    2014-01-01

    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...... 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....... 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...

  8. Cross-talk between Bone Marrow and Tissue Injury : Novel Regenerative Therapy for Severely Damaged Tissues by Mobilizing Bone Marrow Mesenchymal Stem Cells in Vivo

    OpenAIRE

    Tamai, Katsuto; Kaneda, Yasufumi

    2013-01-01

    group box 1 (HMGB1), which mobilizes a sub-population of non-hematopoietic cells from bone marrow into the circulation to repair skin and restore Col 7 expression. These bone marrow-derived epithelial stem/progenitor cells are derived from a lineage-negative, platelet-derived growth factor alpha-positive mesenchymal stem cell pool in bone marrow, which represents less than 0.3% of the total bone marrow cell population. In addition, systemic administration of HMGB1 to wounded wild-type mice le...

  9. BONE TUMOR ENVIRONMENT AS POTENTIAL THERAPEUTIC TARGET IN EWING SARCOMA

    Directory of Open Access Journals (Sweden)

    Françoise eREDINI

    2015-12-01

    Full Text Available Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, ES is an aggressive, rapidly fatal malignancy that mainly develops in osseous sites (85%, but also in extraskeletal soft tissue. It spreads naturally to the lungs, bones and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption is responsible for the clinical features of bone tumors including pain, vertebral collapse and spinal cord compression. Based on the vicious cycle concept of tumor cells and bone resorbing cells, drugs which target osteoclasts may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable niche for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing Sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates (BPs or drugs blocking the pro-resorbing cytokine Receptor Activator of NF-kappa B Ligand (RANKL. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma.

  10. Regenerative burner

    Energy Technology Data Exchange (ETDEWEB)

    Davies, T.E.; Quinn, D.E.; Watson, J.E.

    1986-08-05

    A regenerative burner is described operable in fire and flue modes comprising: a burner shell having first and second internal chambers, the first chamber being disposed on the flame axis of the burner and the second chamber surrounding the radial perimeter of the first chamber; a gas permeable annular regenerative bed separating the first and second chambers such that gas flow between the first and second chambers must travel through the regenerative bed in a generally radial direction with respect to the flame axis; means for supplying combustion air to the second chamber when the burner is in the fire mode and for exhausting the products of combustion from the second chamber when the burner is in the flue mode; and means for supplying fuel in the vicinity of the flame axis for mixing with combustion air to support combustion when the burner is in the fire mode.

  11. 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

    the osteoinductive stimulus throughout the bone defect. Six sheep underwent a bilateral humerus drill defect. The drill hole was filled with a compound consisting of 100 mg CMC, 100 mg collagen powder, and 1 ccm autologous full blood in one side, and a combination of this filler compound and 20 mg Colloss E...... 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...... was calculated with both QCT and microCT. Bone volume to total volume (BV/TV) was analyzed using microCT and histomorphometry. Although not statistically significant, results showed increased bone BMD after 16 weeks in microCT data and an increased BV/TV after 16 weeks in both microCT and histology. Correlation...

  12. 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.

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

    OpenAIRE

    Abir Oueida El-Sadik

    2010-01-01

    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 sign...

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

    Science.gov (United States)

    Kuwabara, Tomoko; Asashima, Makoto

    2012-06-01

    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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. A Therapeutic Potential for Marine Skeletal Proteins in Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Bruce Milthorpe

    2013-04-01

    Full Text Available A vital ingredient for engineering bone tissue, in the culture dish, is the use of recombinant matrix and growth proteins to help accelerate the growth of cultivated tissues into clinically acceptable quantities. The skeletal organic matrices of calcifying marine invertebrates are an untouched potential source of such growth inducing proteins. They have the advantage of being ready-made and retain the native state of the original protein. Striking evidence shows that skeleton building bone morphogenic protein-2/4 (BMP and transforming growth factor beta (TGF-β exist within various marine invertebrates such as, corals. Best practice mariculture and the latest innovations in long-term marine invertebrate cell cultivation can be implemented to ensure that these proteins are produced sustainably and supplied continuously. This also guarantees that coral reef habitats are not damaged during the collection of specimens. Potential proteins for bone repair, either extracted from the skeleton or derived from cultivated tissues, can be identified, evaluated and retrieved using chromatography, cell assays and proteomic methods. Due to the current evidence for bone matrix protein analogues in marine invertebrates, together with the methods established for their production and retrieval there is a genuine prospect that they can be used to regenerate living bone for potential clinical use.

  20. Regenerative Zahnmedizin

    OpenAIRE

    Steffen, R.; C. Moret; van Waes, H

    2011-01-01

    Bei der Behandlung von unreifen, nekrotischen Zähnen ist es zu einem Paradigmawechsel gekommen. Die regenerative, endodontische Behandlung solcher Zähne stützt sich auf die Erkenntnisse aus der biobasierten, regenerativen Forschung, um solche Zähne weiter reifen lassen zu können. Ergebnisse der Grundlagenforschung lassen vermuten, dass Stamm- und Vorläuferzellen aus Pulparesten, dem Periodont und der apikalen Papille zur Wiederbesiedlung von sterilisierten Pulpahöhlen beitragen können....

  1. 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

  2. Regenerative burner

    Energy Technology Data Exchange (ETDEWEB)

    Gitman, G.M.

    1990-05-08

    This patent describes a method of combusting fuel in a furnace having a pair of regenerative burners, each burner having a combustion chamber. It comprises: supplying fuel and oxygen alternatively to each burner to create alternating firing burners wherein the oxygen is supplied from two sources providing first and second oxidizing gases having different oxygen concentrations and simultaneously alternating the application of negative pressure to the remaining non-firing burner to recover heat from flue gases exhausted by the regenerative bed of the non-firing burner to be used further to preheat at least part of the oxygen being supplied to the firing burner; mixing the fuel with a fraction of the oxygen under substoichiometric combustion condition to create products of incomplete combustion to form a hot, luminous flame core containing partially pyrolized fuel; and mixing the partially pyrolyzed fuel with a remaining fraction of the oxygen to complete combustion of the pyrolized fuel; and controlling the total flow of fuel and oxygen supplied to each burner to provide each burner with a desired flame stoichiometry.

  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. Effects of microstructure and water on the electrical potentials in bone induced by ultrasound irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Tsuneda, H.; Matsukawa, S.; Takayanagi, S.; Matsukawa, M., E-mail: mmatsuka@mail.doshisha.ac.jp [Wave Electronics Research Center, Laboratory of Ultrasonic Electronics, Doshisha University, 1-3, Tatara Miyakodani, Kyotanabe, Kyoto 610-0321 (Japan); Mizuno, K. [Underwater Technology Collaborative Research Center, Institute of Industrial Science, The University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo 153-8505 (Japan); Yanagitani, T. [Graduate School of Engineering, Nagoya Institute of Technology, Gokiso cho, Showa-ku, Nagoya 466-8555 (Japan)

    2015-02-16

    The healing mechanism of bone fractures by low intensity pulse ultrasound is yet to be fully understood. There have been many discussions regarding how the high frequency dynamic stress can stimulate numerous cell types through various pathways. As one possible initial process of this mechanism, we focus on the piezoelectricity of bone and demonstrate that bone can generate electrical potentials by ultrasound irradiation in the MHz range. We have fabricated ultrasonic bone transducers using bovine cortical bone as the piezoelectric device. The ultrasonically induced electrical potentials in the transducers change as a function of time during immersed ultrasonic pulse measurements and become stable when the bone is fully wet. In addition, the magnitude of the induced electrical potentials changes owing to the microstructure in the cortical bone. The potentials of transducers with haversian structure bone are higher than those of plexiform structure bone, which informs about the effects of bone microstructure on the piezoelectricity.

  5. [Use of adipose tissue in regenerative medicine].

    Science.gov (United States)

    Casteilla, L; Planat-Benard, V; Bourin, P; Laharrague, P; Cousin, B

    2011-04-01

    Adipose tissue is abundant and well known for its involvement in obesity and associated metabolic disorders. Its uses in regenerative medicine recently attracted many investigators, as large amounts of this tissue can be easily obtained using liposuction and it contains several populations of immature cells. The largest pool of such cells corresponds to immature stromal cells, called adipose-derived stromal cells (ADSCs). These cells are purified after proteolytic digestion of adipose tissue and selection by an adherent step. ADSCs display many common features with mesenchymal stem cells derived from bone marrow, including paracrine activity, but with some specific features, among which a greater angiogenic potential. This potential is now investigating at clinical level to treat critical ischemic hindlimb by autologous cells. Other potentials are also investigated and the treatment of fistula associated or not with Crohn's disease is reaching now phase III level.

  6. 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.

  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. 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.

  9. Bone marrow cells contribute to tissue regeneration in the intestine and skin.

    OpenAIRE

    Brittan, M

    2005-01-01

    Adult bone marrow contains progenitor cells that can extricate themselves from their bone marrow cavity niche, and engraft within foreign tissues, whereupon they produce specific differentiated adult lineages. Bone marrow engraftment is upregulated with increasing regenerative pressure, which has triggered speculation as to the therapeutic potential of bone marrow cells. In this thesis, I describe for the first time, that transplanted adult bone marrow cells engraft within the intestines of m...

  10. Regenerative partition structures

    OpenAIRE

    Gnedin, Alexander; Pitman, Jim

    2004-01-01

    We consider Kingman's partition structures which are regenerative with respect to a general operation of random deletion of some part. Prototypes of this class are the Ewens partition structures which Kingman characterised by regeneration after deletion of a part chosen by size-biased sampling. We associate each regenerative partition structure with a corresponding regenerative composition structure, which (as we showed in a previous paper) can be associated in turn with a regenerative random...

  11. Glutamate signalling and its potential application to tissue engineering of bone

    Directory of Open Access Journals (Sweden)

    Mason D.

    2004-04-01

    Full Text Available Mechanical loading of the skeleton is important for maintenance of adequate bone mass and defined mechanical stimuli are highly osteogenic. The identification of mechanoresponsive signalling molecules in bone may allow osteogenic signals to be mimicked. This approach would be useful in the treatment of bone pathologies where the skeleton is too weak to withstand osteogenic forces and to tissue engineering of bone where the mechanical environment of bone cells is disrupted. Glutamate has been implicated as a mediator of mechanical signalling in bone. Evidence for glutamate signalling in bone, its role in mechanotransduction and potential applications of this pathway to tissue engineering of bone is considered in this review. Glutamate receptors, transporters and proteins that regulate glutamate release, are all expressed in bone cells. Glutamate receptor activation affects both osteoblast and osteoclast phenotypes revealing a potential for therapeutic manipulation of glutamate signalling to enhance bone formation. Glutamate transporters contribute to this system by regulating extracellular glutamate concentrations and acting as glutamate-gated ion channels. Artificial regulation of glutamate receptors or transporters may be used to increase the bone forming capacity of osteoblasts. This novel approach may potentially enhance bone tissue engineering strategies.

  12. Adipose Tissue-Derived Stem Cells in Regenerative Medicine

    Science.gov (United States)

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

    2016-01-01

    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.

  13. 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

  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. Bone morphogenetic protein-2: a potential regulator in scleral remodeling

    OpenAIRE

    Hu, Jianmin; Cui, Dongmei; Yang, Xiao; Wang, Shaowei; Hu, Shoulong; Li, Chuanxu; Zeng, Junwen

    2008-01-01

    Purpose Bone morphogenetic protein 2 (BMP-2) is a member of the main subgroup of bone morphogenetic proteins within the transforming growth factor-β superfamily. BMP-2 is involved in numerous cellular functions including development, cell proliferation, apoptosis, and extracellular matrix synthesis. We examined BMP-2 expression in human scleral fibroblasts (HSF) and assessed the effects of recombinant human BMP-2 (rhBMP-2) on HSF proliferation, matrix metalloproteinase-2 (MMP-2), and tissue i...

  16. 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. PMID:27408457

  17. 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.

  18. Isolation of Human Adipose-Derived Stromal Cells Using Laser-Assisted Liposuction and Their Therapeutic Potential in Regenerative Medicine

    OpenAIRE

    Chung, Michael T.; Zimmermann, Andrew S.; Paik, Kevin J.; Shane D Morrison; 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

    2013-01-01

    This study examined the impact of laser-assisted liposuction on the quality and differentiation potential of adipose-derived stromal cells (ASCs). It was found that laser-assisted liposuction negatively impacts the biology of ASCs, and therefore cell harvest using suction-assisted liposuction is preferable for tissue-engineering purposes.

  19. [Bone tissue morphological structure in congenital deformations of the jaws].

    Science.gov (United States)

    Shishkanov, A V; Panin, M G; Shipkova, T P; Chumakov, A A; Komnova, Z D

    2001-01-01

    Morphological structure of bone tissue was studied in various types of congenital deformations of the jaws. Morphological changes in the bone with deformations and the severity of these disorders depended not so much on the type on the deformation, but mainly on its severity, which can be explained by a drastic increase of functional exercise because of impaired occlusion and impossibility of proper chewing. Decelerated weak restructuring of bone tissue and imperfect osteogenesis in deformed bone, similar in various types of deformations, were demonstrated on morphological material. These changes can affect the regenerative potential of the bone in operated zones. PMID:11881460

  20. The myocardial regenerative potential of three-dimensional engineered cardiac tissues composed of multiple human iPS cell-derived cardiovascular cell lineages.

    Science.gov (United States)

    Masumoto, Hidetoshi; Nakane, Takeichiro; Tinney, Joseph P; Yuan, Fangping; Ye, Fei; Kowalski, William J; Minakata, Kenji; Sakata, Ryuzo; Yamashita, Jun K; Keller, Bradley B

    2016-01-01

    Human induced pluripotent stem cells (hiPSCs) are a robust source for cardiac regenerative therapy due to their potential to support autologous and allogeneic transplant paradigms. The in vitro generation of three-dimensional myocardial tissue constructs using biomaterials as an implantable hiPSC-derived myocardium provides a path to realize sustainable myocardial regeneration. We generated engineered cardiac tissues (ECTs) from three cellular compositions of cardiomyocytes (CMs), endothelial cells (ECs), and vascular mural cells (MCs) differentiated from hiPSCs. We then determined the impact of cell composition on ECT structural and functional properties. In vitro force measurement showed that CM+EC+MC ECTs possessed preferential electromechanical properties versus ECTs without vascular cells indicating that incorporation of vascular cells augmented tissue maturation and function. The inclusion of MCs facilitated more mature CM sarcomeric structure, preferential alignment, and activated multiple tissue maturation pathways. The CM+EC+MC ECTs implanted onto infarcted, immune tolerant rat hearts engrafted, displayed both host and graft-derived vasculature, and ameliorated myocardial dysfunction. Thus, a composition of CMs and multiple vascular lineages derived from hiPSCs and incorporated into ECTs promotes functional maturation and demonstrates myocardial replacement and perfusion relevant for clinical translation. PMID:27435115

  1. Apple ethanol extract promotes proliferation of human adult stem cells, which involves the regenerative potential of stem cells.

    Science.gov (United States)

    Lee, Jienny; Shin, Moon Sam; Kim, Mi Ok; Jang, Sunghee; Oh, Sae Woong; Kang, Mingyeong; Jung, Kwangseon; Park, Yong Seek; Lee, Jongsung

    2016-09-01

    Tissue regeneration using adult stem cells (ASCs) has significant potential as a novel treatment for many degenerative diseases. Previous studies have established that age negatively affects the proliferation status and differentiation potential of ASCs, suggesting a possible limitation in their potential therapeutic use. Therefore, we hypothesized that apple extract might exert beneficial effects on ASCs. The specific objectives were to investigate the proliferative effect of apple ethanol extract on human adipose tissue-derived mesenchymal stem cells (ADSCs) and human cord blood-derived mesenchymal stem cells (CB-MSCs), and identify the possible molecular mechanisms. Apple extract promoted proliferation of ADSCs and CB-MSCs as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Click-iT 5-ethynyl-2'-deoxyuridine flow cytometry assays. In addition, phosphorylation of p44/42 MAPK (ERK), mammalian target of rapamycin (mTOR), p70 S6 kinase (p70S6K), S6 ribosomal protein (S6RP), eukaryotic initiation factor (eIF) 4B and eIF4E was induced stepwise in ADSCs. Furthermore, apple extract significantly induced the production of vascular endothelial growth factor and interleukin-6 in both ADSCs and CB-MSCs. Similarly, apple extract-induced phosphorylation of the mTOR/p70S6K/S6RP/eIF4B/eIF4E pathway was blocked by pretreatment with PD98059, a specific ERK inhibitor. These results indicate that apple extract-induced proliferation of ADSCs under serum-free conditions is mediated by ERK-dependent cytokine production. Moreover, the beneficial effect of apple extract on proliferation of ASCs may overcome the limitation in therapeutic use of stem cells in tissue regeneration and maintenance of stem cell homeostasis. PMID:27632912

  2. 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

    including bone marrow and umbilical cord blood. The objective of this study was to provide an in vitro comparison of the chondrogenic potential in MSC derived from adult bone marrow (BM-MSC) and umbilical cord blood (CB-MSC). Results: MSC from both sources produced tissue with cartilage-like morphology...

  3. 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...

  4. 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.

  5. 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.

  6. A new biphasic osteoinductive calcium composite material with a negative Zeta potential for bone augmentation

    Directory of Open Access Journals (Sweden)

    Maciejewski Oliver

    2009-06-01

    Full Text Available Abstract The aim of the present study was to analyze the osteogenic potential of a biphasic calcium composite material (BCC with a negative surface charge for maxillary sinus floor augmentation. In a 61 year old patient, the BCC material was used in a bilateral sinus floor augmentation procedure. Six months postoperative, a bone sample was taken from the augmented regions before two titanium implants were inserted at each side. We analyzed bone neoformation by histology, bone density by computed tomography, and measured the activity of voltage-activated calcium currents of osteoblasts and surface charge effects. Control orthopantomograms were carried out five months after implant insertion. The BCC was biocompatible and replaced by new mineralized bone after being resorbed completely. The material demonstrated a negative surface charge (negative Zeta potential which was found to be favorable for bone regeneration and osseointegration of dental implants.

  7. Poly (L-lactide-co-e caprolactone) microspheres laden with bioactive glass-ceramic and alendronate sodium as bone regenerative scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Mondal, Titash [Sree Chitra Tirunal Institute of Medical Science and Technology, Biomedical Technology Wing, Thiruvananthpuram-695012 (India); Rubber Technology Centre, Indian Institute of Technology, Kharagpur-721302, West Bengal (India); Sunny, M.C. [Sree Chitra Tirunal Institute of Medical Science and Technology, Biomedical Technology Wing, Thiruvananthpuram-695012 (India); Khastgir, D. [Rubber Technology Centre, Indian Institute of Technology, Kharagpur-721302, West Bengal (India); Varma, H.K. [Sree Chitra Tirunal Institute of Medical Science and Technology, Biomedical Technology Wing, Thiruvananthpuram-695012 (India); Ramesh, P., E-mail: rameshsct@gmail.com [Sree Chitra Tirunal Institute of Medical Science and Technology, Biomedical Technology Wing, Thiruvananthpuram-695012 (India)

    2012-05-01

    Microspheric scaffolds of poly-(lactide-co-caprolactone) loaded with alendronate sodium, a family precursor of bisphosphonate drug and bioactive glass-ceramic (BGS) were prepared for the treatment of osteoporosis like bone defects with the rationale of getting a combined effect/concurrent advantage of osteoclast apoptosis as well as the augmentation of bone regeneration. The porous microspheres were generated by oil in water/solvent evaporation technique. The distribution of bioactive glass-ceramic was evidenced by the microcomputed tomography ({mu}-CT) and scanning electron microscopy analyses. The microspheres were evaluated for their in vitro cytocompatibility using L929 cell line and were found to be noncytotoxic. The osteoinductivity of the scaffold was assessed by its response in simulated body fluid and observed an excellent hydroxy carbonate apatite (HCA) layer formation on the surface which revealed the bone bonding and bone regeneration capability of the scaffold. The cell adhesion studies was performed with L-929 cell line and a marking cell growth on the surface as well as in the pores of the bioactive glass-ceramic as well as bioactive glass-ceramic cum drug incorporated microspheres was evidenced by the Confocal laser scanning microscopy (CLSM) investigation. No cell adhesion was observed onto the surface of the bare microspheres prepared by the copolymer alone where as the bioactive glass-ceramic and drug cum bioactive glass-ceramic loaded microspheres were found to promote the cell adhesion. The viability of the adhered cells on the microspheres was checked by flourescein diacetate (FDA) staining and it was observed that the adhered cells were viable and metabolically active. The release of the drug, alendronate sodium, directly into the problem site makes the presently prepared microsphere superior to the oral variety of drug available which is associated with oral discomfort and low bioavailability. - Highlights: Black

  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. Could we also be regenerative superheroes, like salamanders?

    Science.gov (United States)

    Dall'Agnese, Alessandra; Puri, Pier Lorenzo

    2016-09-01

    Development of methods to reawaken the semi-dormant regenerative potential that lies within adult human tissues would hold promise for the restoration of diseased or damaged organs and tissues. While most of the regeneration potential is suppressed in many vertebrates, including humans, during adult life, urodele amphibians (salamanders) retain their regenerative ability throughout adulthood. Studies in newts and axolotls, two salamander models, have provided significant knowledge about adult limb regeneration. In this review, we present a comparative analysis of salamander and mammalian regeneration and discuss how evolutionarily altered properties of the regenerative environment can be exploited to restore full regenerative potential in the human body. PMID:27338874

  10. 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.

  11. In vitro differentiation of endometrial regenerative cells into smooth muscle cells: Α potential approach for the management of pelvic organ prolapse.

    Science.gov (United States)

    Chen, Xiuhui; Kong, Xianchao; Liu, Dongzhe; Gao, Peng; Zhang, Yanhua; Li, Peiling; Liu, Meimei

    2016-07-01

    Pelvic organ prolapse (POP), is a common condition in parous women. Synthetic mesh was once considered to be the standard of care; however, the use of synthetic mesh is limited by severe complications, thus creating a need for novel approaches. The application of cell-based therapy with stem cells may be an ideal alternative, and specifically for vaginal prolapse. Abnormalities in vaginal smooth muscle (SM) play a role in the pathogenesis of POP, indicating that smooth muscle cells (SMCs) may be a potential therapeutic target. Endometrial regenerative cells (ERCs) are an easily accessible, readily available source of adult stem cells. In the present study, ERCs were obtained from human menstrual blood, and phase contrast microscopy and flow cytometry were performed to characterize the morphology and phenotype of the ERCs. SMC differentiation was induced by a transforming growth factor β1-based medium, and the induction conditions were optimized. We defined the SMC characteristics of the induced cells with regard to morphology and marker expression using transmission electron microscopy, western blot analysis, immunocytofluorescence and RT-PCR. Examining the expression of the components of the Smad pathway and phosphorylated Smad2 and Smad3 by western blot analysis, RT-PCR and quantitative PCR demonstrated that the 'TGFBR2/ALK5/Smad2 and Smad3' pathway is involved, and both Smad2 and Smad3 participated in SMC differentiation. Taken together, these findings indicate that ERCs may be a promising cell source for cellular therapy aimed at modulating SM function in the vagina wall and pelvic floor in order to treat POP. PMID:27221348

  12. In vitro differentiation of endometrial regenerative cells into smooth muscle cells: A potential approach for the management of pelvic organ prolapse

    Science.gov (United States)

    CHEN, XIUHUI; KONG, XIANCHAO; LIU, DONGZHE; GAO, PENG; ZHANG, YANHUA; LI, PEILING; LIU, MEIMEI

    2016-01-01

    Pelvic organ prolapse (POP), is a common condition in parous women. Synthetic mesh was once considered to be the standard of care; however, the use of synthetic mesh is limited by severe complications, thus creating a need for novel approaches. The application of cell-based therapy with stem cells may be an ideal alternative, and specifically for vaginal prolapse. Abnormalities in vaginal smooth muscle (SM) play a role in the pathogenesis of POP, indicating that smooth muscle cells (SMCs) may be a potential therapeutic target. Endometrial regenerative cells (ERCs) are an easily accessible, readily available source of adult stem cells. In the present study, ERCs were obtained from human menstrual blood, and phase contrast microscopy and flow cytometry were performed to characterize the morphology and phenotype of the ERCs. SMC differentiation was induced by a transforming growth factor β1-based medium, and the induction conditions were optimized. We defined the SMC characteristics of the induced cells with regard to morphology and marker expression using transmission electron microscopy, western blot analysis, immunocytofluorescence and RT-PCR. Examining the expression of the components of the Smad pathway and phosphorylated Smad2 and Smad3 by western blot analysis, RT-PCR and quantitative PCR demonstrated that the 'TGFBR2/ALK5/Smad2 and Smad3' pathway is involved, and both Smad2 and Smad3 participated in SMC differentiation. Taken together, these findings indicate that ERCs may be a promising cell source for cellular therapy aimed at modulating SM function in the vagina wall and pelvic floor in order to treat POP. PMID:27221348

  13. 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.

  14. 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.

  15. Late Adherent Human Bone Marrow Stromal Cells Form Bone and Restore the Hematopoietic Microenvironment In Vivo

    OpenAIRE

    Verônica Fernandes Vianna; Danielle Cabral Bonfim; Amanda dos Santos Cavalcanti; Marco Cury Fernandes; Suzana Assad Kahn; Priscila Ladeira Casado; Inayá Correa Lima; Murray, Samuel S.; Elsa J. Brochmann Murray; Maria Eugenia Leite Duarte

    2013-01-01

    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...

  16. Translational Models for Musculoskeletal Tissue Engineering and Regenerative Medicine

    OpenAIRE

    Sah, Robert L.; Ratcliffe, Anthony

    2010-01-01

    The National Institutes of Health–sponsored workshop “Translational Models for Musculoskeletal Tissue Engineering and Regenerative Medicine” was held to describe the utility of various translational models for engineered tissues and regenerative medicine therapies targeting intervertebral disc, cartilage, meniscus, ligament, tendon, muscle, and bone. Participants included leaders in the various topics, as well as National Institutes of Health and Food and Drug Administration. The Food and Dru...

  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. 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. PMID:23911120

  19. Bone

    International Nuclear Information System (INIS)

    Bone scanning provides information on the extent of primary bone tumors, on possible metastatic disease, on the presence of osteomyelitis prior to observation of roentgenographic changes so that earlier therapy is possible, on the presence of collagen diseases, on the presence of fractures not disclosed by x-ray films, and on the evaluation of aseptic necrosis. However, the total effect and contribution of bone scanning to the diagnosis, treatment, and ultimate prognosis of pediatric skeletal diseases is, as yet, unknown. (auth)

  20. Studies on {sup 177}Lu-labeled methylene diphosphonate as potential bone-seeking radiopharmaceutical for bone pain palliation

    Energy Technology Data Exchange (ETDEWEB)

    Abbasi, Imtiaz Ahmed, E-mail: imtiaz_abbasi@yahoo.co

    2011-04-15

    Objective: {sup 99m}Tc-MDP (technetium-99{sup m}-labeled methylene diphosphonate) has been widely used as a radiopharmaceutical for bone scintigraphy in cases of metastatic bone disease. {sup 177}Lu is presently considered as an excellent radionuclide for developing bone pain palliation agents. No study on preparing a complex of {sup 177}Lu with MDP has been reported yet. Based on these facts, it was hypothesized that a bone-seeking {sup 177}Lu-MDP (lutetium-177-labeled MDP) radiopharmaceutical could be developed as an agent for palliative radiotherapy of bone pain due to skeletal metastases. Biodistribution studies after intravenous injection of {sup 177}Lu-MDP complex in rats may yield important information to assess its potential for clinical use as a bone pain palliation agent for the treatment of bone metastases. Methods: {sup 177}Lu was produced by irradiating natural Lu{sub 2}O{sub 3} (10 mg) target at a thermal flux {approx}8.0x10{sup 13} n/cm{sup 2} per second for 12 h in the swimming pool-type reactor.{sup 177}Lu was labeled with MDP by adding nearly 37 MBq (1.0 mCi) of {sup 177}LuCl{sub 3} to a vial containing 10 mg MDP. The radiochemical purity and labeling efficiencies were determined by thin layer chromatography. Labeling of {sup 177}Lu with MDP was optimized, and one sample was subjected to high-performance liquid chromatography (HPLC) analysis. Twelve Sprague-Dawley rats were injected with 18.5 MBq (0.5 mCi). {sup 177}Lu-MDP in a volume of 0.1 ml was injected intravenously and then sacrificed at 2 min, 1 h, 2 h and 22 h (three rats at each time point) after injection. Samples of various organs were separated, weighed and measured for radioactivity and expressed as percent uptake of injected dose per gram. Bioevaluation studies with rats under gamma-camera were also performed to verify the results. Results: The quality control using thin layer chromatography has shown >99% radiochemical purity of {sup 177}Lu-MDP complex. Chromatography with Whatman 3

  1. Bone morphogenetic protein-2: a potential regulator in scleral remodeling

    Science.gov (United States)

    Hu, Jianmin; Cui, Dongmei; Yang, Xiao; Wang, Shaowei; Hu, Shoulong; Li, Chuanxu

    2008-01-01

    Purpose Bone morphogenetic protein 2 (BMP-2) is a member of the main subgroup of bone morphogenetic proteins within the transforming growth factor-β superfamily. BMP-2 is involved in numerous cellular functions including development, cell proliferation, apoptosis, and extracellular matrix synthesis. We examined BMP-2 expression in human scleral fibroblasts (HSF) and assessed the effects of recombinant human BMP-2 (rhBMP-2) on HSF proliferation, matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-2 (TIMP-2). Methods We used confocal fluorescence microscopy (CFM) to study BMP-2 distribution in HSF cells and frozen human scleral sections. The influence of rhBMP-2 on cell proliferation at different concentrations (0 ng/ml, 1 ng/ml, 10 ng/ml, and 100 ng/ml) was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The effects of rhBMP-2 on the cell cycle were investigated with flow cytometric analysis. Reverse transcription polymerase chain reaction (RT–PCR) and enzyme-linked immunosorbent assay (ELISA) were used to examine MMP-2 and TIMP-2 mRNAs and secreted proteins in HSF that were incubated with rhBMP-2. Results BMP-2 protein expression from human sclera was confirmed by CFM. Cell proliferation was significantly increased with 100 ng/ml rhBMP-2 in a time-dependent manner (p<0.05). The HSF cell cycle moved to the S and S+G2M phases after rhBMP-2 stimulation at 100 ng/ml compared to normal cells (p<0.05). TIMP-2 mRNA levels were significantly increased in HSF incubated for 24 h with 100 ng/ml rhBMP-2 (p<0.01). A 48 h incubation with 10 ng/ml or 100 ng/ml rhBMP-2 resulted in significantly increased TIMP-2 mRNA and protein expression and significantly decreased MMP-2 mRNA expression (p<0.01) while MMP-2 protein expression significantly decreased at 100 ng/ml rhBMP-2 (p<0.01). Conclusions Human sclera fibroblasts expressed BMP-2, which promoted cell proliferation, and elicited changes in MMP-2 and TIMP-2

  2. [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.

  3. 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

  4. 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.

  5. Microscale Regenerative Heat Exchanger

    Science.gov (United States)

    Moran, Matthew E.; Stelter, Stephan; Stelter, Manfred

    2006-01-01

    The device described herein is designed primarily for use as a regenerative heat exchanger in a miniature Stirling engine or Stirling-cycle heat pump. A regenerative heat exchanger (sometimes called, simply, a "regenerator" in the Stirling-engine art) is basically a thermal capacitor: Its role in the Stirling cycle is to alternately accept heat from, then deliver heat to, an oscillating flow of a working fluid between compression and expansion volumes, without introducing an excessive pressure drop. These volumes are at different temperatures, and conduction of heat between these volumes is undesirable because it reduces the energy-conversion efficiency of the Stirling cycle.

  6. 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.

  7. Tissue engineering and regenerative medicine in musculoskeletal oncology.

    Science.gov (United States)

    Holzapfel, Boris Michael; Wagner, Ferdinand; Martine, Laure Christine; Reppenhagen, Stephan; Rudert, Maximilian; Schuetz, Michael; Denham, Jim; Schantz, Jan-Thorsten; Hutmacher, Dietmar Werner

    2016-09-01

    Currently used surgical techniques to reconstruct tissue defects after resection of musculoskeletal tumours are associated with high complication rates. This drives a strong demand for innovative therapeutic concepts that are able to improve the clinical outcomes of patients suffering from bone and soft tissue tumours. Tissue engineering and regenerative medicine (TE&RM) provides a technology platform based on biochemical, molecular, cellular and biomaterials modules to selectively direct tissue healing processes for improved defect regeneration. At the same time, precautionary measures have to be taken when these instruments are used in cancer patients to prevent any promotion of tumour growth or metastatic spread. On the other hand, several innovative TE&RM tools are being developed such as multi-functionalized biomaterials, drug-delivering nanomaterials or genetically engineered stem cells that per se have the potential to mediate anti-cancer effects, act synergistically with currently used chemotherapeutics and/or radiotherapy regimens and reduce their side effects. Recently, scientists became conscious that TE&RM strategies may not only be utilized to advance contemporary tissue reconstruction techniques but also to develop personalized diagnostic tools and clinically relevant disease models for cancer patients. Eventually, prospective randomized clinical trials combined with comparative outcome analyses are a conditio sine qua non to shape the benefits of personalized regenerative therapies for the standardized management of patients with musculoskeletal tumours.

  8. Bioprinting in Regenerative Medicine

    OpenAIRE

    Manuela Monti

    2016-01-01

    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. 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.....

  10. 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.

  11. Quo Vadis medycyno regeneracyjna?: Quo Vadis Regenerative Medicine?

    OpenAIRE

    Ratajczak, Mariusz Z.; Suszyńska, Malwina

    2013-01-01

    There are presented the most important sources of pluripotent stem cells for potential application in the regenerative medicine. This review summarizes also advantages and disadvantages for potential application of these cells in clinical medicine.

  12. 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.

  13. Preparation, chemistry and physical properties of bone-derived hydroxyapatite particles having a negative zeta potential

    Energy Technology Data Exchange (ETDEWEB)

    Doostmohammadi, Ali, E-mail: alidm14@ma.iut.ac.ir [Biomaterials Research Center, Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Isfahan University of Medical Sciences, Isfahan 81746-73461 (Iran, Islamic Republic of); Monshi, Ahmad [Biomaterials Research Center, Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Salehi, Rasoul [Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan 81746-73461 (Iran, Islamic Republic of); Fathi, M.H. [Biomaterials Research Center, Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Karbasi, Saeed [Medical Physics and Biomedical Engineering Group, School of Medicine, Isfahan University of Medical Sciences, Isfahan (Iran, Islamic Republic of); Pieles, Uwe [Institute for Chemistry and Bioanalytics, School of Life Sciences, University of Applied Sciences of Northwestern Switzerland, Muttenz (Switzerland); Daniels, A.U. [Laboratory of Biomechanics and Biocalorimetry, Coaltion for Clinical Morphology and Biomedical Engineering, University of Basel Faculty of Medicine, Basel (Switzerland)

    2012-02-15

    Highlights: Black-Right-Pointing-Pointer Natural and relatively pure hydroxyapatite particles can be obtained from bovine bone. Black-Right-Pointing-Pointer A Complete characterization of bone-derived HA particles was carried out. Black-Right-Pointing-Pointer Bone-derived HA particles reveal a negative zeta potential in physiological saline at 37 Degree-Sign C. - Abstract: Animal bone-derived calcium hydroxyapatite (HA) particles were produced and characterized. Adult bovine femoral bone was boiled, washed, cleaned and heated in air at 700 Degree-Sign C for 2 h. The resulting macro-porous solid was ground, crushed and sieved into particles <50 {mu}m. SEM showed the particles were agglomerations of crystals {approx}50-500 nm across. XRD showed highly crystalline HA with nominal MgO and no detectable CaO. FTIR spectroscopy yielded typical HA absorptions, plus absorptions at 1457 and 1412 cm{sup -1} (MgCO{sub 3} or CaCO{sub 3}) and 874 cm{sup -1} (CaHPO{sub 4}). Main elements by EDXRF were Ca and P (molar ratio 1.93 vs. theoretical ratio 1.67). Minor amounts of Si, Mg and Na were detected, plus traces of K, Sr, Zn, Ba, V, Al, Mn, Pb, Cu and Fe. EDX detected Ca, P, Na and Mg. BET gas adsorption surface area was {approx}2.23 m{sup 2} g{sup -1} and theoretical particle size {approx}857 nm. Laser DLS indicated {approx}40% of particles were {approx}952 nm in diameter, plus {approx}50% were {approx}760 nm - in close agreement with BET calculations. By laser Doppler electrophoresis (LDE) the zeta potential of the bone-derived HA particles suspended in 0.154 M NaCl was negative for pH 6-11 and -9.25 {+-} 0.9 mV at pH 7.4. Negative zeta potential is reported to favor attachment and proliferation of bone cells. HA particles produced synthetically are reported to have positive zeta potentials. The source of the negative potential was not determined but may stem from factors peculiar to producing HA particles from bone. The results suggest further investigation for biomedical use.

  14. Potential Effects of Phytoestrogen Genistein in Modulating Acute Methotrexate Chemotherapy-Induced Osteoclastogenesis and Bone Damage in Rats

    Directory of Open Access Journals (Sweden)

    Tristan J. King

    2015-08-01

    Full Text Available Chemotherapy-induced bone damage is a frequent side effect which causes diminished bone mineral density and fracture in childhood cancer sufferers and survivors. The intensified use of anti-metabolite methotrexate (MTX and other cytotoxic drugs has led to the need for a mechanistic understanding of chemotherapy-induced bone loss and for the development of protective treatments. Using a young rat MTX-induced bone loss model, we investigated potential bone protective effects of phytoestrogen genistein. Oral gavages of genistein (20 mg/kg were administered daily, for seven days before, five days during, and three days after five once-daily injections (sc of MTX (0.75 mg/kg. MTX treatment reduced body weight gain and tibial metaphyseal trabecular bone volume (p < 0.001, increased osteoclast density on the trabecular bone surface (p < 0.05, and increased the bone marrow adipocyte number in lower metaphyseal bone (p < 0.001. Genistein supplementation preserved body weight gain (p < 0.05 and inhibited ex vivo osteoclast formation of bone marrow cells from MTX-treated rats (p < 0.001. However, MTX-induced changes in bone volume, trabecular architecture, metaphyseal mRNA expression of pro-osteoclastogenic cytokines, and marrow adiposity were not significantly affected by the co-administration of genistein. This study suggests that genistein may suppress MTX-induced osteoclastogenesis; however, further studies are required to examine its potential in protecting against MTX chemotherapy-induced bone damage.

  15. Regenerative medicine: learning from past examples.

    Science.gov (United States)

    Couto, Daniela S; Perez-Breva, Luis; Cooney, Charles L

    2012-11-01

    Regenerative medicine products have characteristically shown great therapeutic potential, but limited market success. Learning from the past attempts at capturing value is critical for new and emerging regenerative medicine therapies to define and evolve their business models as new therapies emerge and others mature. We propose a framework that analyzes technological developments along with alternative business models and illustrates how to use both strategically to map value capture by companies in regenerative medicine. We analyze how to balance flexibility of the supply chain and clarity in the regulatory pathway for each business model and propose the possible pathways of evolution between business models. We also drive analogies between cell-based therapies and other healthcare products such as biologicals and medical devices and suggest how to strategically evolve from these areas into the cell therapy space. PMID:22697402

  16. Stem Cells Applications in Regenerative Medicine and Disease Therapeutics

    Science.gov (United States)

    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. PMID:27516776

  17. 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.

  18. 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. PMID:24957845

  19. 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.

  20. Potential bone-inducing activity in vitro of recombinant human bone morphogenetic protein-7 from a CHO expression system

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-yan; SHI Wei-wei; WANG Hao; LI Bo-hua; YANG Yang; TAN Min; XUE Jing-ya; GUO Ya-jun

    2005-01-01

    Objective: To express the recombinant human bone morphogenetic protein-7 (rhBMP-7) in Chinese hamster ovary(CHO) cells, and to establish the in vitro biological activity assay of rhBMP-7.Methods: Human BMP-7 cDNA was subcloned into p114 mammalian expression vector and transfected to CHO cells by using the Lipofectamine2000 transfection method. CHO cell supernatants were harvested and analyzed to identify the molecule mass of secreted rhBMP-7 and examine its biological activity in vitro to stimulate the synthesis of alkaline phophatase(ALP), a characteristic of osteoblast phenotypes. Results:rhBMP-7 was produced stably in CHO cells, as a processed mature disulfide-linked homodimer, with an apparent molecular mass of 36 000. Examination of the rhBMP-7 biological activity showed that rhBMP-7 specifically stimulated the production of ALP(4-fold increase at 100 ng of rhBMP-7/ml). Conclusion: The rhBMP-7 from CHO expression system has significant biological activity in induction of osteoblast phenotype, which demonstrates rhBMP-7 has the potential bone regeneration activity.

  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. 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.

  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. 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

    2016-01-01

    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 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. PMID:27240395

  5. 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

  6. 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.

  7. 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

  8. Mechanical properties and osteogenic potential of hydroxyapatite-PLGA-collagen biomaterial for bone regeneration.

    Science.gov (United States)

    Bhuiyan, Didarul B; Middleton, John C; Tannenbaum, Rina; Wick, Timothy M

    2016-08-01

    A bone graft is a complicated structure that provides mechanical support and biological signals that regulate bone growth, reconstruction, and repair. A single-component material is inadequate to provide a suitable combination of structural support and biological stimuli to promote bone regeneration. Multicomponent composite biomaterials lack adequate bonding among the components to prevent phase separation after implantation. We have previously developed a novel multistep polymerization and fabrication process to construct a nano-hydroxyapatite-poly(D,L-lactide-co-glycolide)-collagen biomaterial (abbreviated nHAP-PLGA-collagen) with the components covalently bonded to each other. In the present study, the mechanical properties and osteogenic potential of nHAP-PLGA-collagen are characterized to assess the material's suitability to support bone regeneration. nHAP-PLGA-collagen films exhibit tensile strength very close to that of human cancellous bone. Human mesenchymal stem cells (hMSCs) are viable on 2D nHAP-PLGA-collagen films with a sevenfold increase in cell population after 7 days of culture. Over 5 weeks of culture, hMSCs deposit matrix and mineral consistent with osteogenic differentiation and bone formation. As a result of matrix deposition, nHAP-PLGA-collagen films cultured with hMSCs exhibit 48% higher tensile strength and fivefold higher moduli compared to nHAP-PLGA-collagen films without cells. More interestingly, secretion of matrix and minerals by differentiated hMSCs cultured on the nHAP-PLGA-collagen films for 5 weeks mitigates the loss of mechanical strength that accompanies PLGA hydrolysis. PMID:27120980

  9. 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...

  10. 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.

  11. 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.

  12. Mesenchymal stem cell-based therapies in regenerative medicine: applications in rheumatology.

    Science.gov (United States)

    Maumus, Marie; Guérit, David; Toupet, Karine; Jorgensen, Christian; Noël, Danièle

    2011-01-01

    Growing knowledge on the biology of mesenchymal stem cells (MSCs) has provided new insights into their potential clinical applications, particularly for rheumatologic disorders. Historically, their potential to differentiate into cells of the bone and cartilage lineages has led to a variety of experimental strategies to investigate whether MSCs can be used for tissue engineering approaches. Beyond this potential, MSCs also display immunosuppressive properties, which have prompted research on their capacity to suppress local inflammation and tissue damage in a variety of inflammatory autoimmune diseases and, in particular, in rheumatoid arthritis. Currently, an emerging field of research comes from the possibility that these cells, through their trophic/regenerative potential, may also influence the course of chronic degenerative disorders and prevent cartilage degradation in osteoarthritis. This review focuses on these advances, specifically on the biological properties of MSCs, including their immunoregulatory characteristics, differentiation capacity and trophic potential, as well as the relevance of MSC-based therapies for rheumatic diseases. PMID:21457518

  13. 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.

  14. Emerging regenerative approaches for periodontal reconstruction: a systematic review from the AAP Regeneration Workshop.

    Science.gov (United States)

    Lin, Zhao; Rios, Hector F; Cochran, David L

    2015-02-01

    More than 30 years have passed since the first successful application of regenerative therapy for treatment of periodontal diseases. Despite being feasible, periodontal regeneration still faces numerous challenges, and complete restoration of structure and function of the diseased periodontium is often considered an unpredictable task. This review highlights developing basic science and technologies for potential application to achieve reconstruction of the periodontium. A comprehensive search of the electronic bibliographic database PubMed was conducted to identify different emerging therapeutic approaches reported to influence either biologic pathways and/or tissues involved in periodontal regeneration. Each citation was assessed based on its abstract, and the full text of potentially eligible reports was retrieved. Based on the review of the full papers, their suitability for inclusion in this report was determined. In principle, only reports from scientifically well-designed studies that presented preclinical in vivo (animal studies) or clinical (human studies) evidence for successful periodontal regeneration were included. Hence, in vitro studies, namely those conducted in laboratories without any live animals, were excluded. In case of especially recent and relevant reviews with a narrow focus on specific regenerative approaches, they were identified as such, and thereby the option of referring to them to summarize the status of a specific approach, in addition to or instead of listing each separately, was preserved. Admittedly, the presence of subjectivity in the selection of studies to include in this overview cannot be excluded. However, it is believed that the contemporary approaches described in this review collectively represent the current efforts that have reported preclinical or clinical methods to successfully enhance regeneration of the periodontium. Today's challenges facing periodontal regenerative therapy continue to stimulate important research

  15. A facile fabrication of porous PMMA as a potential bone substitute

    Energy Technology Data Exchange (ETDEWEB)

    Han Jing; Ma Guiping [State Key Laboratory of Chemical Resource Engineering, Key Laboratory of Beijing City on Preparation and Processing of Novel Polymer Materials, Beijing University of Chemical Technology, Beijing 100029 (China); Nie Jun, E-mail: niejun@mail.buct.edu.cn [State Key Laboratory of Chemical Resource Engineering, Key Laboratory of Beijing City on Preparation and Processing of Novel Polymer Materials, Beijing University of Chemical Technology, Beijing 100029 (China); College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072 (China)

    2011-10-10

    This study is aimed to develop porous poly(methyl methacrylate) (PMMA) as a potential bone substitute via a facile fabrication method. Composites consisting of water-soluble chitosan oligosaccharide (CSO) and PMMA were prepared by combining freeze-drying with radical polymerization. Open porous PMMA with controlled porosities were obtained after the CSO was extracted gradually from the composites. The CSO aqueous solutions with different concentrations were frozen and then freeze-dried to obtain interconnected porous framework. Methyl methacrylate with initiators and a crosslink agent was introduced into the porous framework and polymerized, resulting in two-continuous phase composites. The mechanical properties of the initial composites and porous materials after immersion in PBS for 8 weeks were investigated. Dynamic mechanical analysis was conducted to study the mechanical strength of the composite, compared with bulk PMMA. Porosity and morphology of porous PMMA were studied using the liquid displacement method and scanning electron microscopy, respectively. Thermogravimetric analysis indicated that composite exhibited better thermal stability than bulk PMMA. The composites became porous materials after extracting bioactive CSO component. The mechanical properties of porous materials were closer to those of cancellous bone. The generation of pores using CSO seems to be a promising method to prepare porous PMMA as a potential bone substitute. - Research Highlights: {yields} Chitosan oligosaccharide (CSO) /poly(methyl methacrylate) composites was fabricated. {yields} The composites became interconnected porous PMMA after CSO was dissolved. {yields} The introduction of CSO could modulate the properties of PMMA matrix. {yields} The generation of pores using CSO is a facile method to obtain porous PMMA. {yields} The porous PMMA has potential in biomedical field as a bone substitute.

  16. 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.

  17. 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 (p<0.005). Regenerative material NCS showed an average 63.15% bone yield improvement over the control sample, NCS+alg showed 55.55% and NanoGen showed 37.5%. The bone regeneration process 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.

  18. How stem cells manage to escape senescence and ageing - while they can: A recent study reveals that autophagy is responsible for senescence-dependent loss of regenerative potential of muscle stem cells during ageing.

    Science.gov (United States)

    Ricchetti, Miria

    2016-09-01

    Skeletal muscle stem cells or satellite cells are responsible for muscle regeneration in the adult. Although satellite cells are highly resistant to stress, and display greater capacity to repair molecular damage than the committed progeny, their regenerative potential declines with age. During ageing, satellite cells switch to a state of permanent cell cycle arrest or senescence which prevents their activation. A recent study reveals that the senescence of satellite cell relies on defective autophagy, the quality control mechanism that degrades damaged proteins and organelles. Molecular damage is generated by oxidative stress that also promotes epigenetic changes that activate the expression of master genes, in a double-hit mechanism that ensures senescence. Importantly, genetic, and pharmacological correction of defective autophagy reverses satellite cell senescence and restores muscle regeneration in geriatric mice, with perspectives of modulating age-related functional decline of muscle. This study provides new clues to understand stem cell and organismal ageing. PMID:27389857

  19. Clinical significance of interleukin (IL)-6 in cancer metastasis to bone: potential of anti-IL-6 therapies

    International Nuclear Information System (INIS)

    Metastatic events to the bone occur frequently in numerous cancer types such as breast, prostate, lung, and renal carcinomas, melanoma, neuroblastoma, and multiple myeloma. Accumulating evidence suggests that the inflammatory cytokine interleukin (IL)-6 is frequently upregulated and is implicated in the ability of cancer cells to metastasize to bone. IL-6 is able to activate various cell signaling cascades that include the STAT (signal transducer and activator of transcription) pathway, the PI3K (phosphatidylinositol-3 kinase) pathway, and the MAPK (mitogen-activated protein kinase) pathway. Activation of these pathways may explain the ability of IL-6 to mediate various aspects of normal and pathogenic bone remodeling, inflammation, cell survival, proliferation, and pro-tumorigenic effects. This review article will discuss the role of IL-6: 1) in bone metabolism, 2) in cancer metastasis to bone, 3) in cancer prognosis, and 4) as potential therapies for metastatic bone cancer

  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. 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.

  2. 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.

  3. 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).

  4. Potential therapeutic role of cisplatinum in autologous bone marrow transplantation: in vitro eradication of neuroblastoma cells from bone marrow.

    OpenAIRE

    Bettan-Renaud, L.; De Vathaire, F.; Bénard, J.; Morardet, N.; Pauzie, N.; Bayet, S.; Hartmann, O; Parmentier, C.

    1989-01-01

    Cisplatinum may prove to be a valuable agent for the elimination of diseased cells in the bone marrow of patients with neuroblastoma. In this study, we measured the efficacy of cisplatinum on human neuroblastoma cell lines and on normal human bone marrow progenitors, GM-CFC and CFU-F. Data indicate that the therapeutic index of cisplatinum is high. We set up an experimental model consisting of a mixture of human bone marrow and human neuroblastoma cells in order to confirm these preliminary r...

  5. PEM regenerative fuel cells

    Science.gov (United States)

    Swette, Larry L.; Laconti, Anthony B.; McCatty, Stephen A.

    1993-11-01

    This paper will update the progress in developing electrocatalyst systems and electrode structures primarily for the positive electrode of single-unit solid polymer proton exchange membrane (PEM) regenerative fuel cells. The work was done with DuPont Nafion 117 in complete fuel cells (40 sq cm electrodes). The cells were operated alternately in fuel cell mode and electrolysis mode at 80 C. In fuel cell mode, humidified hydrogen and oxygen were supplied at 207 kPa (30 psi); in electrolysis mode, water was pumped over the positive electrode and the gases were evolved at ambient pressure. Cycling data will be presented for Pt-Ir catalysts and limited bifunctional data will be presented for Pt, Ir, Ru, Rh, and Na(x)Pt3O4 catalysts as well as for electrode structure variations.

  6. Application of Regenerative Medicine for Kidney Diseases

    OpenAIRE

    Yokoo, Takashi; Fukui, Akira; Kobayashi, Eiji

    2007-01-01

    Following recent advancements of stem cell research, the potential for organ regeneration using somatic stem cells as an ultimate therapy for organ failure has increased. However, anatomically complicated organs such as the kidney and liver have proven more refractory to stem cell-based regenerative techniques. At present, kidney regeneration is considered to require one of two approaches depending on the type of renal failure, namely acute renal failure (ARF) and chronic renal failure (CRF).

  7. Regenerative Endodontics: A Road Less Travelled

    OpenAIRE

    Bansal, Ramta; Jain, Aditya; 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 pati...

  8. Rethinking Regenerative Medicine: A Macrophage-Centered Approach

    OpenAIRE

    Brown, Bryan N.; Sicari, Brian M.; Badylak, Stephen F.

    2014-01-01

    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 heretof...

  9. Stem Cells Applications in Regenerative Medicine and Disease Therapeutics

    OpenAIRE

    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 regen...

  10. Biomimetic treatment on dental implants for short -term bone regeneration

    OpenAIRE

    Gil Mur, Francisco Javier; Manzanares, Norberto; Badet de Mena, Armando; Aparicio Bádenas, Conrado José; Ginebra Molins, Maria Pau

    2013-01-01

    Objectives The main purpose of this work was to assess the short-term bone regenerative potential of new osteoconductive implants. The novelty of the study lies in the analysis of the effectiveness of a novel two-step treatment which combines shot-blasting with a thermo-chemical treatment, at very short times after implant placement in a minipig model. Materials and methods Three hundred twenty implants with four different surface treatments, namely bioactivated sur...

  11. 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.

  12. 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. PMID:19256773

  13. 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.

  14. 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.

  15. 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. PMID:25218755

  16. 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. PMID:27389708

  17. 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

  18. 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

  19. Regenerative Perspective in Modern Dentistry

    OpenAIRE

    Mihnea Ioan Nicolescu

    2016-01-01

    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...

  20. 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.

  1. 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.

  2. A novel, truncated human bone morphogenetic protein-2:construction, expression ,functions and clinical potential

    Institute of Scientific and Technical Information of China (English)

    XU Fang

    2001-01-01

    @@ Introduction As a member of the bone morphogenetic protein (BMP) family, BMP-2 plays important roles not only in bone regeneration and bone repair but also in cell proliferation, apoptosis, differentiation and morphogenesis. The BMP-2 remarkable ability to stimulate new bone growth results in the development of a novel therapy strategy for bone mass defect due to accidents or diseases. Because the BMP-2 itself, in conjunction with a suitable matrix, is sufficient to stimulate genesis of new bone, the genetically engineered BMP-2 has good applied prospects.

  3. 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.

  4. 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. J Biomed Mater Res Part B: Appl Biomater, 104B: 676-685, 2016. PMID:26699211

  5. Stem cell platforms for regenerative medicine.

    Science.gov (United States)

    Nelson, Timothy J; Behfar, Atta; Yamada, Satsuki; Martinez-Fernandez, Almudena; Terzic, Andre

    2009-06-01

    The pandemic of chronic degenerative diseases associated with aging demographics mandates development of effective approaches for tissue repair. As diverse stem cells directly contribute to innate healing, the capacity for de novo tissue reconstruction harbors a promising role for regenerative medicine. Indeed, a spectrum of natural stem cell sources ranging from embryonic to adult progenitors has been recently identified with unique characteristics for regeneration. The accessibility and applicability of the regenerative armamentarium has been further expanded with stem cells engineered by nuclear reprogramming. Through strategies of replacement to implant functional tissues, regeneration to transplant progenitor cells or rejuvenation to activate endogenous self-repair mechanisms, the overarching goal of regenerative medicine is to translate stem cell platforms into practice and achieve cures for diseases limited to palliative interventions. Harnessing the full potential of each platform will optimize matching stem cell-based biologics with the disease-specific niche environment of individual patients to maximize the quality of long-term management, while minimizing the needs for adjunctive therapy. Emerging discovery science with feedback from clinical translation is therefore poised to transform medicine offering safe and effective stem cell biotherapeutics to enable personalized solutions for incurable diseases. PMID:19779576

  6. The Potential Application of Pulsed Ultrasound on Bone Defect Repair via Developmental Engineering: An In Vitro Study.

    Science.gov (United States)

    Wang, Jue; Tang, Na; Xiao, Qiang; Zhao, Lixing; Li, Yu; Li, Juan; Wang, Jun; Zhao, Zhihe; Tan, Lijun

    2016-05-01

    Repairing bone defect by recapitulation of endochondral bone formation, known as developmental engineering, has been a promising approach in bone tissue engineering. The critical issue in this area is how to effectively construct the hypertrophic cartilaginous template in vitro and enhance in vivo endochondral ossification process after implantation. Pulsed ultrasound stimulation has been widely used in the clinic for accelerating bone healing in fractures and nonunions. The aim of this study was to investigate whether ultrasound (US) could accelerate in vitro chondrogenesis and the hypertrophic process in certain microenvironments. Rat bone marrow mesenchymal stem cells were chondrogenic or hypertrophic differentiated in a three-dimensional pellet culture system with different media, and treated with different intensities of US. US exposure promoted chondrogenic differentiation of stem cells and inhibited their transition into the hypertrophic stage in a chondrogenic-friendly microenvironment. US significantly advanced hypertrophic differentiation of bone marrow stem cell pellets in hypertrophic medium after chondrogenesis. Our data indicated that pulsed US promoted in vitro chondrogenic and hypertrophic differentiation of stem cell pellets in specific culture conditions. The present study proves the potential application of US in the in vitro stage of "developmental engineering" for bone development and repair. PMID:26526417

  7. 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. PMID:27333785

  8. 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.

  9. [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.

  10. [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 < 0.05) and 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. PMID:22476418

  11. Regenerative biomaterials: a review.

    Science.gov (United States)

    Banyard, Derek A; Bourgeois, Jenna Martin; Widgerow, Alan D; Evans, Gregory R D

    2015-06-01

    The authors present a review of biomaterials, substances traditionally derived from human or animal tissue or, more recently, biodegradable synthetics modeled after naturally occurring resources. These constructs differ from purely synthetic materials in that they are degraded or incorporated into a host's tissue. These biomaterials include a diverse array of medical products, such as acellular dermal matrix, bone substitutes, and injectables. In this review, the authors examine various clinical applications, including burn reconstruction and wound healing, breast surgery, complex abdominal wall reconstruction, craniofacial repair, and cosmetic surgery. Biomaterials such as acellular dermal matrix have proven beneficial in difficult-to-treat applications; however, more prospective data are needed to determine their true efficacy and cost-effectiveness. PMID:26017603

  12. 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

  13. 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

  14. Peri-implantitis Treatment with a Regenerative Approach: Clinical Outcomes on Reentry.

    Science.gov (United States)

    Parma-Benfenati, Stefano; Roncati, Marisa; Galletti, Primo; Tinti, Carlo

    2015-01-01

    This case series presents clinical outcomes on reentry using regenerative submerged and nonsubmerged approaches in peri-implant defects; pre- and posttreatment assessments of nine implants in six patients are presented. A mean bone fill value of 91.3% with a 4.88-mm mean bone gain was obtained. Neither approach led to additional bone loss or required additional bone augmentation procedures. Strict methods of implant surface decontamination and detoxification were used on all patients, regardless of implant surface characteristics. The regenerative procedure was effective in the treatment of moderate to advanced peri-implantitis lesions without compromising the previous fixed implant-supported prostheses. These preliminary results are reasonably encouraging in that all cases showed bone gains. Nevertheless, caution must be exercised when determining reosseointegration, because it is not possible to ascertain it in clinical practice.

  15. 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

  16. Tailoring the degradation and biological response of a magnesium-strontium alloy for potential bone substitute application.

    Science.gov (United States)

    Han, Junjie; Wan, Peng; Ge, Ye; Fan, Xinmin; Tan, Lili; Li, Jianjun; Yang, Ke

    2016-01-01

    Bone defects are very challenging in orthopedic practice. There are many practical and clinical shortcomings in the repair of the defect by using autografts, allografts or xenografts, which continue to motivate the search for better alternatives. The ideal bone grafts should provide mechanical support, fill osseous voids and enhance the bone healing. Biodegradable magnesium-strontium (Mg-Sr) alloys demonstrate good biocompatibility and osteoconductive properties, which are promising biomaterials for bone substitutes. The aim of this study was to evaluate and pair the degradation of Mg-Sr alloys for grafting with their clinical demands. The microstructure and performance of Mg-Sr alloys, in vitro degradation and biological properties including in vitro cytocompatibility and in vivo implantation were investigated. The results showed that the as-cast Mg-Sr alloy exhibited a rapid degradation rate compared with the as-extruded alloy due to the intergranular distribution of the second phase and micro-galvanic corrosion. However, the initial degradation could be tailored by the coating protection, which was proved to be cytocompatible and also suitable for bone repair observed by in vivo implantation. The integrated fracture calluses were formed and bridged the fracture gap without gas bubble accumulation, meanwhile the substitutes simultaneously degraded. In conclusion, the as-cast Mg-Sr alloy with coating is potential to be used for bone substitute alternative. PMID:26478374

  17. 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.

  18. 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. PMID:25044885

  19. 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.

  20. Cell interactions in bone tissue engineering

    OpenAIRE

    Pirraco, Rogério; Marques, A. P.; Reis, R. L.

    2010-01-01

    Bone fractures, where the innate regenerative bone response is compromised, represent between 4 and 8 hundred thousands of the total fracture cases, just in the United States. Bone tissue engineering (TE) brought the notion that, in cases such as those, it was preferable to boost the healing process of bone tissue instead of just adding artificial parts that could never properly replace the native tissue. However, despite the hype, bone TE so far could not live up to its promises and...

  1. Cell interactions in bone tissue engineering

    OpenAIRE

    Pirraco, R. P.; Marques, A. P.; Reis, R. L.

    2009-01-01

    Abstract Bone fractures, where the innate regenerative bone response is compromised, represent between 4 and 8 hundred thousands of the total fracture cases, just in the United States. Bone tissue engineering (TE) brought the notion that, in cases such as those, it was preferable to boost the healing process of bone tissue instead of just adding artificial parts that could never properly replace the native tissue. However, despite the hype, bone TE so far could not live up to its promises and...

  2. Osteogenic potential of bone-lining cells in the adult skeleton

    International Nuclear Information System (INIS)

    Radiation-induced osteogenic sarcomas are believed to arise from proliferating osteogenic precursor cells. The identity and location of these cells in the adult skeleton is not well understood. In order to determine reliable cell dose estimates, it is important to determine the osteogenic pathway in the adult skeleton. Bone-lining cells (BLCs) cover inactive endosteal surfaces in the adult skeleton of long-lived animals. BLCs are flat elongated cells which are directly apposed to the bone surface. They have cell processes extending into canaliculi and have gap junctions at some contacts with other bone-lining cells. The morphology of the bone-lining cell and its proximity to the bone surface can only be resolved at the ultrastructural level. These cells are a distinct morphologic phenotype but have been referred to by a variety of names including resting osteoblasts, surface osteocytes, and flattened mesenchymal cells. The BLC, as a distinct phenotype, should not be confused with the more descriptive term cells lining the bone surface of bone lining cells, sometimes used to include any cell near the bone. The purpose of the study was to determine what role, if any, the bone-lining cells have in the osteogenic process. Do these cells proliferate and contribute to the population of osteoblasts?

  3. 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.

  4. Diffusion of Protease into Meat & Bone Meal for Solubility Improvement and Potential Inactivation of the BSE Prion

    Science.gov (United States)

    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 prions. Treatment with protease is generally effective in reducing insoluble, thermally-denatured proteins ...

  5. Osteogenic potential of human calcitonin gene-related peptide alpha gene-modified bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    WANG Yi-sheng; WANG Ya-han; ZHAO Guo-qiang; LI Yue-bai

    2011-01-01

    Background Most of the basic and clinical studies of osteonecrosis of the femoral head (ONFH) are restricted to bone tissues only,whereas various systems are involved in the onset and development of ONFH,including nervous system.Peptidergic nerve participates in the neuronal regulation of bone metabolism and anabolism,and plays key roles in the growth,repair and reconstruction of bone.Calcitonin gene-related peptide (CGRP),which is secreted by peptidergic nerve,is the main mediator of bone metabolism.It dramatically promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).Additionally,it enhances the osteoblast mass and the rate of osteoblast formation,and reduces the bone resorption by acting on osteoblasts and osteoclasts.Hence,we aimed to construct recombinant retrovirus vector pLNCX2-hCGRPα and to investigate the proliferation and osteogenic potential of hCGRPα-producing BMSCs (BMSCs/pLNCX2-hCGRPα) after virus infection.Methods The constructed recombinant retrovirus vector pLNCX2-hCGRPα was transfected into PT67 packaging cells by lipofectamine 2000.Virus was collected for BMSCs infection.The mRNA and protein expression of hCGRPα was examined by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting,respectively.The cell proliferation was determined by methyl thiazoleterazolium (MTT) assay.The osteogenic potential of BMSCs was evaluated by alkaline phosphatase (ALP) activity.Results Both mRNA and protein expression of hCGRPα was detected in BMSCs/pLNCX2-hCGRPα cells.These cells exhibited significantly elevated proliferation and ALP value as compared with control BMSCs (P <0.05).Conclusion BMSCs/pLNCX2-hCGRPα cells could stably express hCGRPα and showed promoted proliferation ability and osteogenic potential as compared with control BMSCs.

  6. 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...... as the surface marker expression profile of OA- versus control BMSCs. BMSCs were isolated from bone marrow aspirates of n=14 patients with advanced-stage idiopathic hip OA (67±6years) and n=15 healthy individuals (61±4years). Proliferation was quantified by total DNA content and colony......-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...

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

    -Dlk1FA1) and its correlation with bone turnover markers. s-Dlk1/FA1 and bone turnover markers (serum cross-linked C-telopeptide [s-CTX] and serum osteocalcin) were measured in two cohorts: a group of pre- and postmenopausal women (n = 100) and a group of postmenopausal women, where half had received...

  12. 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.

  13. Modelling the regenerative niche: a major challenge in biomaterials research.

    Science.gov (United States)

    Kirkpatrick, C James

    2015-12-01

    By definition, biomaterials are developed for clinical application. In the field of regenerative medicine their principal function is to play a significant, and, if possible, an instructive role in tissue healing. In the last analysis the latter involves targeting the 'regenerative niche'. The present paper will address the problem of simulating this niche in the laboratory and adopts a life science approach involving the harnessing of heterotypic cellular communication to achieve this, that is, the ability of cells of different types to mutually influence cellular functions. Thus, co-culture systems using human cells are the methodological focus and will concern four exemplary fields of regeneration, namely, bone, soft tissue, lower respiratory tract and airway regeneration. The working hypothesis underlying this approach is that in vitro models of higher complexity will be more clinically relevant than simple monolayer cultures of transformed cell lines in testing innovative strategies with biomaterials for regeneration. PMID:26816650

  14. Regenerative Medicine: Charting a New Course in Wound Healing

    Science.gov (United States)

    Gurtner, Geoffrey C.; Chapman, Mary Ann

    2016-01-01

    Significance: Chronic wounds are a prevalent and costly problem in the United States. Improved treatments are needed to heal these wounds and prevent serious complications such as infection and amputation. Recent Advances: In wound healing, as in other areas of medicine, technologies that have the potential to regenerate as opposed to repair tissue are gaining ground. These include customizable nanofiber matrices incorporating novel materials; a variety of autologous and allogeneic cell types at various stages of differentiation (e.g., pluripotent, terminally differentiated); peptides; proteins; small molecules; RNA inhibitors; and gene therapies. Critical Issues: Wound healing is a logical target for regenerative medicine due to the accessibility and structure of skin, the regenerative nature of healing, the lack of good limb salvage treatments, and the current use of cell therapies. However, more extensive knowledge of pathophysiologic targets is needed to inform regenerative strategies, and new technologies must demonstrate value in terms of outcomes and related health economic measures to achieve successful market access and penetration. Future Directions: Due to similarities in cell pathways and developmental mechanisms, regenerative technologies developed in one therapeutic area may be applicable to others. Approaches that proceed from human genomic or other big data sources to models are becoming increasingly common and will likely suggest novel therapeutic avenues. To fully capitalize on the advances in regenerative medicine, studies must demonstrate the value of new therapies in identified patient populations, and sponsors must work with regulatory agencies to develop appropriate dossiers supporting timely approval. PMID:27366592

  15. 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.

  16. Bisphosphonate-Related Osteonecrosis of the Jaw Bone: Radiological Pattern and the Potential Role of CBCT in Early Diagnosis

    Directory of Open Access Journals (Sweden)

    James Olutayo

    2010-04-01

    Full Text Available Objectives: To systematize the clinico-radiological symptoms and course of bisphosphonate-related osteonecrosis of jaw bone and to evaluate the diagnostic potential of various radiological techniques to detect mild osteonecrosis in each stage of the disease.Material and Methods: The sample consisted of 22 patients previously diagnosed with extraoral malignant disease. Diagnosis was based on a clinical examination in conjunction to digital panoramic radiography and cone beam computed tomography (CBCT. Two dentomaxillofacial radiologists reviewed all images.Results: Twenty patients showed mandibular involvement clinically, while two others had a maxillary involvement. Four stages of the disease were proposed based on the clinico-radiological findings. Subclinical cortical and lamina dura thickening was detected with only three-dimensional CBCT and periapical images, while ulceration and cortical bone thickening was detected only by three-dimensional CBCT. Mixed sclerotic, lytic bone destruction involving alveolar and basal bone with or without encroachment on the mandibular canal, pathological mandibular fractures were detected by two-dimensional panoramic and three-dimensional CBCT images. Other findings are non healing extraction sockets, periapical radiolucencies, osteolysis, sequestra, oroantral fistula, and periosteal new bone formation.Conclusions: The present study showed that bisphosphonate-related osteonecrosis of jaw bone occurs in four distinct clinico-radiological stages. For mild cases, panoramic image diagnosis was much less obvious, whereas cone beam computed tomography was able to fully characterise the bony lesions and describe their extent and involvement of neighbouring structures in all cases. Thus cone beam computed tomography might better contribute to the prevention of bisphosphonate-related osteonecrosis of jaw bone as well to the disease management.

  17. Canine Bone Marrow Stromal Cells Promote Functional Recovery in Mice with Spinal Cord Injury

    OpenAIRE

    Oda, Yasutaka; Tani, Kenji; ASARI, Yusuke; Quintanilha, Luiz Fernando; HARAGUCHI, Tomoya; MOMOTA, Yutaka; Katayama, Masaaki; Itamoto, Kazuhito; Nakazawa, Hiroshi; TAURA, Yasuho

    2014-01-01

    ABSTRACT Regenerative therapy has begun to be clinically applied in humans and dogs to treat neurological disorders, such as spinal cord injury (SCI). Here, we show the therapeutic potential of transplantation of cultured canine bone marrow stromal cells (BMSCs) into mice with SCI. Canine BMSC transplantation therapy was performed, immediately after the spinal cord was injured. Canine BMSC therapy enhanced functional recovery of the hind limbs in mice with SCI. Nestin-positive cells were obse...

  18. Transcriptomic portrait of human Mesenchymal Stromal/Stem cells isolated from bone marrow and placenta

    OpenAIRE

    Roson-Burgo, Beatriz; Sanchez-Guijo, Fermin; del Cañizo, Consuelo; De Las Rivas, Javier

    2014-01-01

    Background Human Mesenchymal Stromal/Stem Cells (MSCs) are adult multipotent cells that behave in a highly plastic manner, inhabiting the stroma of several tissues. The potential utility of MSCs is nowadays strongly investigated in the field of regenerative medicine and cell therapy, although many questions about their molecular identity remain uncertain. Results MSC primary cultures from human bone marrow (BM) and placenta (PL) were derived and verified by their immunophenotype standard patt...

  19. Playing with bone and fat

    DEFF Research Database (Denmark)

    Gimble, Jeffrey M.; Zvonic, Sanjin; Floyd, Z. Elisabeth;

    2006-01-01

    The relationship between bone and fat formation within the bone marrow microenvironment is complex and remains an area of active investigation. Classical in vitro and in vivo studies strongly support an inverse relationship between the commitment of bone marrow-derived mesenchymal stem cells or s...... or stromal cells to the adipocyte and osteoblast lineage pathways. In this review, we focus on the recent literature exploring the mechanisms underlying these differentiation events and discuss their implications relevant to osteoporosis and regenerative medicine....

  20. 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.

  1. Bone cement/layered double hydroxide nanocomposites as potential biomaterials for joint implant.

    Science.gov (United States)

    Kapusetti, Govinda; Misra, Nira; Singh, Vakil; Kushwaha, R K; Maiti, Pralay

    2012-12-01

    Poly(methyl methacrylate)-based bone cement and layered double hydroxide (LDH) nanocomposites have been used as a grouting material for total joint arthroplasty. Few weight percentage of nanoLDH was uniformly dispersed in the bone cement matrix to have adequate interaction with matrix polymer. Mechanical strength, stiffness, toughness, and fatigue resistance of the nanocomposites are found to be higher than that of pure bone cement. Nanocomposites are thermally stable as compared to pristine bone cement. Direct mixing of the nanoLDH without any organic solvent makes these nanocomposites biocompatible. Biocompatibility was evaluated and compared with that of commercial bone cement by measuring hydrophilic nature, hemolysis assay, thrombosis assay, and deposition of apatite in simulated body fluid immersion. Finally, the viability of human osteoblast cells on the above developed nanocomposites was testified for actual biocompatibility. The experiment showed better cell growth in nanocomposites as compared to pure bone cement. Thus, these nanocomposites are found to be better grouting material than bone cement. PMID:22733710

  2. Potential role of proinflammatory cytokines in nerve damage related bone loss.

    Science.gov (United States)

    Miesse, Andrew M; Willey, Jeffrey S; Bateman, Ted A

    2004-01-01

    An estimated 375,000 people are currently suffering from spinal cord injuries and another 1.5 million are afflicted by peripheral nerve damage in the United States. Wolf's Law states that a bone grows or remodels in response to the stresses that are placed on it. Forces applied to bones that occur due to normal daily activity allow for healthy resorption and formation of bones. Periods of immobilization caused by nerve damage have a profound effect on the integrity of bone, causing an increased risk of bone fracture. The need for investigating ways of combating this secondary effect of nerve damage is imperative to the long-term health of spinal cord injury and peripheral nerve damage patients. Our lab uses two sciatic nerve damage models in mice to mimic the bone loss caused by recoverable, sciatic nerve crush (NC), and non-recoverable, sciatic neurectomy (NX), injuries. We are examining the hypothesis that recoverable damage actually causes an accelerated loss of bone mass compared to the permanently damaged nerve because of the transport of proinflammatory cytokines from the site of the nerve damage to the locally affected bone. This inflammatory response, and the hypothesized differences between the two models, will be examined via ELISA of the quadriceps to investigate the relative degree of proinflammatory cytokines local to the damage site. Understanding the cellular mechanisms that occur at nerve injury sites will allow for improved care and long-term treatment of patients. A preliminary analysis of the bone loss associate with these two nerve injury models indicate approximately a 50% greater decline in femoral mass of the NC femur compared to the NX limb, supporting the proinflammatory hypothesis. PMID:15133969

  3. Evaluation of genetic potential of Bacopa monnieri extract in Mouse bone marrow cells by chromosomal analysis test

    Directory of Open Access Journals (Sweden)

    Shilki Vishnoi

    2013-06-01

    Full Text Available Herbs have always been used as a common source of medicines, the Bacopa monnieri is an important herb used in Aruveda as a traditional medicinal system of India. In the present investigations, the genotoxic potential of Bacopa monnieri Hydromethanolic extract (BMH was evaluated employing Chromosomal analysis assay invivo. BMH was administered to Swiss Albino mice as i.p. dose of 80mg/kg, 160mg/kg, 240mg/kg body wt., 24 hours prior the administration of cyclophosphamide (CP (positive control at the dose of 50 mg/kg body wt. A dose-dependent, significant decrease in chromosome aberration was observed with respect to control. Result suggested that BMHhave a preventive potential against CP induced chromosomal aberration in Swiss albino mouse bone marrow cells at the dose tested. Therefore seems to have a preventive potential against Chromosomal aberrations in Swiss Albinomouse bone marrow cells.

  4. Regulation of Sclerostin Expression in Multiple Myeloma by Dkk-1: A Potential Therapeutic Strategy for Myeloma Bone Disease.

    Science.gov (United States)

    Eda, Homare; Santo, Loredana; Wein, Marc N; Hu, Dorothy Z; Cirstea, Diana D; Nemani, Neeharika; Tai, Yu-Tzu; Raines, Sarah E; Kuhstoss, Stuart Allen; Munshi, Nikhil C; Kronenberg, Henry M; Raje, Noopur S

    2016-06-01

    Sclerostin is a potent inhibitor of osteoblastogenesis. Interestingly, newly diagnosed multiple myeloma (MM) patients have high levels of circulating sclerostin that correlate with disease stage and fractures. However, the source and impact of sclerostin in MM remains to be defined. Our goal was to determine the role of sclerostin in the biology of MM and its bone microenvironment as well as investigate the effect of targeting sclerostin with a neutralizing antibody (scl-Ab) in MM bone disease. Here we confirm increased sclerostin levels in MM compared with precursor disease states like monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM. Furthermore, we found that a humanized MM xenograft mouse model bearing human MM cells (NOD-SCID.CB17 male mice injected intravenously with 2.5 million of MM1.S-Luc-GFP cells) demonstrated significantly higher concentrations of mouse-derived sclerostin, suggesting a microenvironmental source of sclerostin. Associated with the increased sclerostin levels, activated β-catenin expression levels were lower than normal in MM mouse bone marrow. Importantly, a high-affinity grade scl-Ab reversed osteolytic bone disease in this animal model. Because scl-Ab did not demonstrate significant in vitro anti-MM activity, we combined it with the proteasome inhibitor carfilzomib. Our data demonstrated that this combination therapy significantly inhibited tumor burden and improved bone disease in our in vivo MM mouse model. In agreement with our in vivo data, sclerostin expression was noted in marrow stromal cells and osteoblasts of MM patient bone marrow samples. Moreover, MM cells stimulated sclerostin expression in immature osteoblasts while inhibiting osteoblast differentiation in vitro. This was in part regulated by Dkk-1 secreted by MM cells and is a potential mechanism contributing to the osteoblast dysfunction noted in MM. Our data confirm the role of sclerostin as a potential therapeutic target in MM bone disease

  5. Functional imaging for regenerative medicine

    OpenAIRE

    Leahy, Martin; Thompson, Kerry; Zafar, Haroon; Alexandrov, Sergey; Foley, Mark; O’Flatharta, Cathal; Dockery, Peter

    2016-01-01

    In vivo imaging is a platform technology with the power to put function in its natural structural context. With the drive to translate stem cell therapies into pre-clinical and clinical trials, early selection of the right imaging techniques is paramount to success. There are many instances in regenerative medicine where the biological, biochemical, and biomechanical mechanisms behind the proposed function of stem cell therapies can be elucidated by appropriate imaging. Imaging techniques can...

  6. CMD kinetics and regenerative medicine

    OpenAIRE

    Anjamrooz, Seyed Hadi

    2016-01-01

    The author’s theory of the cell memory disc (CMD) offers a radical and holistic picture of the cell from both functional and structural perspectives. Despite all of the attention that has been focused on different regenerative strategies, several serious CMD-based obstacles still remain that make current cell therapies inherently unethical, harmful, and largely ineffective from a clinical viewpoint. Accordingly, unless there is a real breakthrough in finding an alternative or complementary ap...

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

    Science.gov (United States)

    Che, Chun-Tao; Wong, Man Sau; Lam, Christopher Wai Kei

    2016-01-01

    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. PMID:26927052

  8. 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.

  9. Solar Airplanes and Regenerative Fuel Cells

    Science.gov (United States)

    Bents, David J.

    2007-01-01

    A solar electric aircraft with the potential to "fly forever" has captured NASA's interest, and the concept for such an aircraft was pursued under Aeronautics Environmental Research Aircraft and Sensor Technology (ERAST) project. Feasibility of this aircraft happens to depend on the successful development of solar power technologies critical to NASA's Exploration Initiatives; hence, there was widespread interest throughout NASA to bring these technologies to a flight demonstration. The most critical is an energy storage system to sustain mission power during night periods. For the solar airplane, whose flight capability is already limited by the diffuse nature of solar flux and subject to latitude and time of year constraints, the feasibility of long endurance flight depends on a storage density figure of merit better than 400-600 watt-hr per kilogram. This figure of merit is beyond the capability of present day storage technologies (other than nuclear) but may be achievable in the hydrogen-oxygen regenerative fuel cell (RFC). This potential has led NASA to undertake the practical development of a hydrogen-oxygen regenerative fuel cell, initially as solar energy storage for a high altitude UAV science platform but eventually to serve as the primary power source for NASAs lunar base and other planet surface installations. Potentially the highest storage capacity and lowest weight of any non-nuclear device, a flight-weight RFC aboard a solar-electric aircraft that is flown continuously through several successive day-night cycles will provide the most convincing demonstration that this technology's widespread potential has been realized. In 1998 NASA began development of a closed cycle hydrogen oxygen PEM RFC under the Aeronautics Environmental Research Aircraft and Sensor Technology (ERAST) project and continued its development, originally for a solar electric airplane flight, through FY2005 under the Low Emissions Alternative Power (LEAP) project. Construction of

  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. Comparative Analysis of Remyelinating Potential of Focal and Intravenous Administration of Autologous Bone Marrow Cells Into the Rat Demyelinated Spinal Cord

    OpenAIRE

    Inoue, Michio; HONMOU, OSAMU; Oka, Shinichi; Houkin, Kiyohiro; Hashi,Kazuo; Kocsis, Jeffery D.

    2003-01-01

    The remyelinating potential of autologous bone marrow cells was studied after direct injection and following intravenous injection into rats with a demyelinated lesion in the spinal cord. Both focal and intravenous injections of acutely isolated mononuclear bone marrow cell fractions resulted in varying degrees of remyelination. Suspensions of bone marrow cells collected from the same rat were delivered at varied concentrations (102 to 105 for direct injection and 104 to 107 for i.v. injectio...

  12. 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.

  13. 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. PMID:26493491

  14. Bone-sparing and anti-inflammatory potential of the novel selective glucocorticoid receptor modulator, compound A

    OpenAIRE

    Thiele, Sylvia

    2013-01-01

    Rheumatoid arthritis (RA) is a common chronic inflammatory disease that affects about 1% of the Western population. Glucocorticoids (GC) are widely used for the treatment of RA and other immune-mediated diseases, such as asthma, but their use is associated with adverse effects on bone metabolism. Because of that, new selective GC receptor (GR) agonists (SEGRAs) with the potential for an improved risk/benefit profile have been developed. Compound A (CpdA) is a novel SEGRA, which showed an impr...

  15. 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.

  16. 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.

  17. 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.

  18. Fabrication of an integrated cartilage/bone joint prosthesis and its potential application in joint replacement.

    Science.gov (United States)

    Hou, Yi; Chen, Chen; Zhou, Song; Li, Yubao; Wang, Danqing; Zhang, Li

    2016-06-01

    An integrated cartilage/bone joint prosthesis was designed and fabricated using a two-step molding injection method, in which ethylene-vinyl acetate copolymer (EVA) was used as the upper cartilage layer, and hydroxyapatite/polyamide66 (HA/PA66) composites as the underlying bone layer. Holes punched in the underlying layer improved the interfacial bonding strength between the two layers by means of the mechanical interlocking obviously. Then, the physicochemical properties and in vivo behaviors of the integrated joint prosthesis were investigated. The results showed that the upper layer displayed good bio-tribological properties which were suitable for the articular cartilage replacement, while the underlying layer demonstrated good mechanical performance, excellent biocompatibility and high bioactivity, and could accelerate bone regeneration and the early bio-fixation of the prosthesis. Therefore, the prosthesis prepared here will have a wide prospect to be used in joint replacement. PMID:26889776

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

    Science.gov (United States)

    Kagiya, Tadayoshi

    2016-01-01

    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. PMID:27529224

  20. Ceramic application for regenerative burner system

    Energy Technology Data Exchange (ETDEWEB)

    Han, D.B.; Park, B.H.; Kim, Y.W.; Bae, W.S. [RIST, Pohang (Korea)

    1999-05-01

    Recently, regenerative burner system was developed and begins to be gradually used for better energy savings. Compared to conventional burner system, the regenerative one has the several merits such as higher fuel efficiency, light weight of apparatus, low harmful toxic gas and homogeneous heating zone, etc. The regenerative material, a very important component of the new regenerative burner system should possess the properties of low specific density, higher surface area and high specific heat capacity. Ceramics is the best regenerative material because of stable mechanical properties even at high temperature and better thermal properties and excellent chemical stability. In this study, alumina ball, alumina tube, 3-D ceramic foam and honeycomb as regenerative materials were tested and evaluated. The computer simulation was conducted and compared to the result of field test. This paper is aimed to introduce a new application of ceramics at high temperature. 7 refs., 5 figs., 3 tabs.

  1. 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

  2. Researches on regenerative medicine-current state

    OpenAIRE

    WANG Zheng-guo; Xiao, Kai

    2012-01-01

    【Abstract】 Since 1980s, the rapid development of tissue engineering and stem cell research has pushed re-generative medicine to a new fastigium, and regenerative medicine has become a noticeable research field in the international biology and medicine. In China, about 100 million patients need repair and regeneration treatment every year, while the number is much larger in the world. Regenerative medicine could provide effective salvation for these patients. Both Chinese ...

  3. Mesenchymal stem cells in regenerative rehabilitation

    OpenAIRE

    Nurkovic, Jasmin; Dolicanin, Zana; Mustafic, Fahrudin; Mujanovic, Rifat; Memic, Mensur; Grbovic, Vesna; Skevin, Aleksandra Jurisic; Nurkovic, Selmina

    2016-01-01

    [Purpose] Regenerative medicine and rehabilitation contribute in many ways to a specific plan of care based on a patient’s medical status. The intrinsic self-renewing, multipotent, regenerative, and immunosuppressive properties of mesenchymal stem cells offer great promise in the treatment of numerous autoimmune, degenerative, and graft-versus-host diseases, as well as tissue injuries. As such, mesenchymal stem cells represent a therapeutic fortune in regenerative medicine. The aim of this re...

  4. 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.

  5. 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

  6. Heat regenerative external combustion engine

    Science.gov (United States)

    Duva, Anthony W.

    1993-10-01

    A heat regenerative external combustion engine is disclosed. The engine includes fuel inlet means which extends along the exhaust passage and/or combustion chamber in order to preheat the fuel, To provide for preheating by gases in both the combustion chamber and the exhaust passage, the combustion chamber is arranged annularly around the drive shaft and between the cylinders. This configuration also is advantageous in that it reduces the noise of combustion. The engine of the invention is particularly well-suited for use in a torpedo.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Gingiva as a new and the most accessible source of mesenchymal stem cells from the oral cavity to be used in regenerative therapies.

    Science.gov (United States)

    Górski, Bartłomiej

    2016-01-01

    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. PMID:27594561

  15. 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.

  16. TLR Stimulation of Bone Marrow Lymphoid Precursors from Childhood Acute Leukemia Modifies Their Differentiation Potentials

    OpenAIRE

    Elisa Dorantes-Acosta; Eduardo Vadillo; Adriana Contreras-Quiroz; Juan Carlos Balandrán; Lourdes Arriaga-Pizano; Jessica Purizaca; Sara Huerta-Yepez; Elva Jiménez; Wendy Aguilera; Aurora Medina-Sanson; Héctor Mayani; Rosana Pelayo

    2013-01-01

    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 comp...

  17. 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.

  18. 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.

  19. Materials science tools for regenerative medicine

    Science.gov (United States)

    Richardson, Wade Nicholas

    Regenerative therapies originating from recent technological advances in biology could revolutionize medicine in the coming years. In particular, the advent of human pluripotent stem cells (hPSCs), with their ability to become any cell in the adult body, has opened the door to an entirely new way of treating disease. However, currently these medical breakthroughs remain only a promise. To make them a reality, new tools must be developed to surmount the new technical hurdles that have arisen from dramatic departure from convention that this field represents. The collected work presented in this dissertation covers several projects that seek to apply the skills and knowledge of materials science to this tool synthesizing effort. The work is divided into three chapters. The first deals with our work to apply Raman spectroscopy, a tool widely used for materials characterization, to degeneration in cartilage. We have shown that Raman can effectively distinguish the matrix material of healthy and diseased tissue. The second area of work covered is the development of a new confocal image analysis for studying hPSC colonies that are chemical confined to uniform growth regions. This tool has important application in understanding the heterogeneity that may slow the development of hPSC -based treatment, as well as the use of such confinement in the eventually large-scale manufacture of hPSCs for therapeutic use. Third, the use of structural templating in tissue engineering scaffolds is detailed. We have utilized templating to tailor scaffold structures for engineering of constructs mimicking two tissues: cartilage and lung. The work described here represents several important early steps towards large goals in regenerative medicine. These tools show a great deal of potential for accelerating progress in this field that seems on the cusp of helping a great many people with otherwise incurable disease.

  20. ''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.)

  1. 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.

  2. 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...

  3. A regenerative elastocaloric heat pump

    DEFF Research Database (Denmark)

    Engelbrecht, Kurt; Eriksen, Dan; Dallolio, Stefano;

    2016-01-01

    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......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...... based on caloric effects. These results open up the possibility of using the elastocaloric effect in various cooling and heat-pumping applications....

  4. 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.

  5. Unitized regenerative fuel cell system

    Science.gov (United States)

    Burke, Kenneth A. (Inventor)

    2008-01-01

    A Unitized Regenerative Fuel Cell system uses heat pipes to convey waste heat from the fuel cell stack to the reactant storage tanks. The storage tanks act as heat sinks/sources and as passive radiators of the waste heat from the fuel cell stack. During charge up, i.e., the electrolytic process, gases are conveyed to the reactant storage tanks by way of tubes that include dryers. Reactant gases moving through the dryers give up energy to the cold tanks, causing water vapor in with the gases to condense and freeze on the internal surfaces of the dryer. During operation in its fuel cell mode, the heat pipes convey waste heat from the fuel cell stack to the respective reactant storage tanks, thereby heating them such that the reactant gases, as they pass though the respective dryers on their way to the fuel cell stacks retrieve the water previously removed.

  6. Current overview on dental stem cells applications in regenerative dentistry

    OpenAIRE

    Bansal, Ramta; Jain, Aditya

    2015-01-01

    Teeth are the most natural, noninvasive source of stem cells. Dental stem cells, which are easy, convenient, and affordable to collect, hold promise for a range of very potential therapeutic applications. We have reviewed the ever-growing literature on dental stem cells archived in Medline using the following key words: Regenerative dentistry, dental stem cells, dental stem cells banking, and stem cells from human exfoliated deciduous teeth. Relevant articles covering topics related to dental...

  7. Regenerative liver surgeries: the alphabet soup of emerging techniques.

    Science.gov (United States)

    Parekh, Maansi; Kluger, Michael D; Griesemer, Adam; Bentley-Hibbert, Stuart

    2016-01-01

    New surgical procedures taking advantage of the regenerative abilities of the liver are being introduced as potential curative therapies to these patients either to provide auxiliary support while the native liver recovers or undergoes hypertrophy. For patients with hepatocellular carcinoma outside of the Milan criteria or bilobar colorectal metastases liver transplantation is not an option. Fulminant hepatic failure can be treated but requires life-long immunosuppression. These complex surgical procedures require high quality and directed imaging. PMID:26830622

  8. 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.

  9. CXCL12/Stromal-Cell-Derived Factor-1 Effectively Replaces Endothelial Progenitor Cells to Induce Vascularized Ectopic Bone

    NARCIS (Netherlands)

    Eman, Rhandy M; Hoorntje, Edgar T; Oner, F Cumhur; Kruyt, Moyo C; Dhert, Wouter J A; Alblas, Jacqueline

    2014-01-01

    Bone defect healing is highly dependent on the simultaneous stimulation of osteogenesis and vascularization. In bone regenerative strategies, combined seeding of multipotent stromal cells (MSCs) and endothelial progenitor cells (EPCs) proves their mutual stimulatory effects. Here, we investigated wh

  10. 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.

  11. Biomimetic chitosan-calcium phosphate composites with potential applications as bone substitutes: preparation and characterization.

    Science.gov (United States)

    Tanase, Constantin E; Popa, Marcel I; Verestiuc, Liliana

    2012-04-01

    A novel biomimetic technique for obtaining chitosan-calcium phosphates (Cs-CP) scaffolds are presented: calcium phosphates are precipitated from its precursors, CaCl(2) and NaH(2) PO(4) on the Cs matrix, under physiological conditions (human body temperature and body fluid pH; 37°C and pH = 7.2, respectively). Materials composition and structure have been confirmed by various techniques: elemental analysis, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), and scanning electron microscopy (SEM). FTIR and SEM data have shown the arrangement of the calcium phosphates-hydroxyapatite (CP-Hap) onto Cs matrix. In this case the polymer is acting as glue, bonding the calcium phosphates crystals. Behavior in biological simulated fluids (phosphate buffer solution-PBS and PBS-albumin) revealed an important contribution of the chelation between -NH3(+) and Ca(2+) on the scaffold interaction with aqueous mediums; increased quantities of chitosan in composites permit the interaction with human albumin and improve the retention of fluid. The composites are slightly degraded by the lysozyme which facilitates an in vivo degradation control of bone substitutes. Modulus of elasticity is strongly dependent of the ratio chitosan/calcium phosphates and recommends the obtained biomimetic composites as promising materials for a prospective bone application. PMID:22121073

  12. 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.

  13. 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

  14. Characterization of mesenchymal stem cells with in vivo bone forming capacity: "Bone building blocks"

    NARCIS (Netherlands)

    Prins, H.

    2011-01-01

    This thesis describes the investigation of the characteristics of cultured MSC with a special focus on the MSCs with in vivo bone forming capacity. The most relevant contributions of the work described in this thesis to the field of regenerative medicine, and bone tissue engineering research field i

  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. 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

  17. Strontium-89 for prostate cancer with bone metastases. The potential of cancer control and improvement of overall survival

    International Nuclear Information System (INIS)

    Strontium-89 (Sr-89) has been considered to have a tumoricidal effect with minimal adverse events. However, few reports have investigated these effects in detail. In this study, we examined the tumoricidal and pain-relief effects of Sr-89 on prostate cancer with bone metastasis as well as survival. A retrospective study was performed involving 31 prostate cancer patients with bone metastasis treated with Sr-89. Using prostate specific antigen (PSA) as an evaluation criterion of cancer control, patients were divided into PSA responder and non-responder groups, and the survival rates of these groups were compared. In addition, using the total amount of painkillers administered as an evaluation criterion of pain relief, patients were divided into pain responder and non-responder groups, and the survival rates of these groups were also compared. As secondary investigation items, age, PSA (ng/ml), pain site, extent of the disease, the presence or absence of castration-resistant prostatic cancer (CRPC), the presence or absence of a past medical history of treatment with docetaxel in CRPC cases, Gleason Score, hemoglobin (g/dl), platelet (Plt) (/μl), serum carboxyterminal telopeptide of type I collagen (ng/ml), and bone-alkaline phosphatase (BAP) (U/l) were investigated. Longer survival was expected for the PSA responder group than for the PSA non-responder group, and whether the spine was the pain site and the presence or absence of CRPC were useful as predictors of this. Plt was suggested to be a useful indicator. Furthermore, the survival time was significantly longer in the pain responder group than in the pain non-responder group, and whether the pain site was present in the spine was considered to be a predictor; however, no significant difference was noted in any of the items assumed to be biomarkers. Sr-89 has the potential to control PSA and prolong survival. A large-scale prospective study of the therapeutic effect of Sr-89 is expected. (author)

  18. On a Flywheel-Based Regenerative Braking System for Regenerative Energy Recovery

    OpenAIRE

    Hsu, Tai-Ran

    2013-01-01

    This paper presents a unique flywheel-based regenerative energy recovery, storage and release system developed at the author's laboratory. It can recover and store regenerative energy produced by braking a motion generator with intermittent rotary velocity such as the rotor of a wind turbogenerator subject to intermittent intake wind and the axels of electric and hybrid gas-electric vehicles during frequent coasting and braking. Releasing of the stored regenerative energy in the flywheel is c...

  19. 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.

  20. Late Adherent Human Bone Marrow Stromal Cells Form Bone and Restore the Hematopoietic Microenvironment In Vivo

    Science.gov (United States)

    Vianna, Verônica Fernandes; Bonfim, Danielle Cabral; Cavalcanti, Amanda dos Santos; Fernandes, Marco Cury; Kahn, Suzana Assad; Casado, Priscila Ladeira; Lima, Inayá Correa; Murray, Samuel S.; Murray, Elsa J. Brochmann; Duarte, Maria Eugenia Leite

    2013-01-01

    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. PMID:23710460

  1. Low NO[sub x] regenerative burner

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1992-12-01

    A joint development project between British Gas and Hotwork Development has resulted in maintaining the efficiency of a regenerative burner but without the penalty of the higher NO[sub x] emissions normally associated with combustion air preheat. (author)

  2. 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...

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. Regenerative Medicine from Protocol to Patient

    OpenAIRE

    Gustav Steinhoff

    2011-01-01

    The essentials of the upcoming and rapidly changing specialty of regenerative medicine, which has kindled high hopes among the clinical and scientific community as well as the society, are presented concisely in this book. Considering the multivariate sub-specialties within regenerative medicine, starting with cell biology and allied basic sciences through translational research to clinical application in various specialties of medicine, enormous efforts are mandatory to bring a comprehensive...

  8. Regenerative burner use on reheat furnaces

    Energy Technology Data Exchange (ETDEWEB)

    Baggley, G.W. [Bloom Engineering Co. Inc., Pittsburgh, PA (United States)

    1995-06-01

    The environmental advantages of using regenerative burner technology on steel reheat furnaces are explored in this article, in particular improved fuel energy efficiencies and reduced pollution emissions, of nitrogen oxides and carbon monoxide. Experience of the use of regenerative burners in the United States and Japan, where they have achieved significant market penetration is also described, including a case history of a top-fired billet reheat furnace installed in the United States. (UK)

  9. Low NO sub x regenerative burner

    Energy Technology Data Exchange (ETDEWEB)

    Hovis, J.E.; Finke, H.P.

    1991-01-08

    This patent describes improvements in a regenerative burner having a regenerative bed, a burner port and a fuel nozzle. The improvement comprises: a burner baffle having apertures therein for selectively directing combustion air and inducing combustion gas recirculation into a primary combustion zone for suppressing NO{sub x} emissions, the baffle and the fuel nozzle being positioned substantially adjacent the burner port and being substantially coplanar in a plane perpendicular to a burner axis.

  10. 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...

  11. Current overview on challenges in regenerative endodontics

    OpenAIRE

    Ramta Bansal; Aditya Jain; Sunandan Mittal

    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 artic...

  12. Double regenerative amplification of picosecond pulses

    Science.gov (United States)

    Bai, Zhen-ao; Chen, Li-yuan; Bai, Zhen-xu; Chen, Meng; Li, Gang

    2012-04-01

    An double Nd:YAG regenerative amplification picosecond pulse laser is demonstrated under the semiconductor saturable absorption mirror(SESAM) mode-locking technology and regenerative amplification technology, using BBO crystal as PC electro-optic crystal. The laser obtained is 20.71ps pulse width at 10 KHz repetition rate, and the energy power is up to 4W which is much larger than the system without pre-amplification. This result will lay a foundation for the following amplification.

  13. 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.

  14. 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.

  15. Regenerative Therapy as an Adjunct to Periapical Surgery: A Case Report

    OpenAIRE

    Chaturvedy, Vivek; Chaturvedy, Shefali

    2012-01-01

    ABSTRACT Large periapical defects may adversely affect the success rate of endodontic surgery. Use of regenerative therapy may enhance the prognosis of such teeth. A case of traumatized upper anterior teeth with infected radicular cyst and associated sinus tract reported to the dental hospital. A periradicular surgical procedure was performed to remove the nonhealing pathological tissue. To augment the repair a bioactive bone graft material was placed. Six months interim results showed positi...

  16. Regenerative Applications Using Tooth Derived Stem Cells in Other Than Tooth Regeneration: A Literature Review

    OpenAIRE

    Yun-Jong Park; Seunghee Cha; Young-Seok Park

    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...

  17. METHODS TO VALIDATE TOOTH-SUPPORTING REGENERATIVE THERAPIES

    Science.gov (United States)

    Padial-Molina, Miguel; Marchesan, Julie T.; Taut, Andrei D.; Jin, Qiming; Giannobile, William V.; Rios, Hector F.

    2012-01-01

    SUMMARY In humans, microbially-induced inflammatory periodontal diseases are the primary initiators that disrupt the functional and structural integrity of the periodontium (i.e., the alveolar bone, the periodontal ligament, and the cementum). The re-establishment of its original structure, properties and function constitutes a significant challenge in the development of new therapies to regenerate tooth-supporting defects. Preclinical models represent an important in vivo tool to critically evaluate and analyze key aspects of novel regenerative therapies including: 1) Safety, 2) Effectiveness, 3) Practicality, and 4) Functional and structural stability over time. Therefore, these models provide foundational data that supports the clinical validation and the development of novel innovative regenerative periodontal technologies. Steps are provided on the use of the root fenestration animal model for the proper evaluation of periodontal outcome measures using the following parameters: descriptive histology, histomorphometry, immunostaining techniques, three-dimensional imaging, electron microscopy, gene expression analyses and safety assessments. These methods will prepare investigators and assist them in identifying key endpoints that can then be adapted to later stage human clinical trials. PMID:22566053

  18. 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.

  19. Nanocomposites and bone regeneration

    Science.gov (United States)

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

    2011-12-01

    This manuscript focuses on bone repair/regeneration using tissue engineering strategies, and highlights nanobiotechnology developments leading to novel nanocomposite systems. About 6.5 million fractures occur annually in USA, and about 550,000 of these individual cases required the application of a bone graft. Autogenous and allogenous bone have been most widely used for bone graft based therapies; however, there are significant problems such as donor shortage and risk of infection. Alternatives using synthetic and natural biomaterials have been developed, and some are commercially available for clinical applications requiring bone grafts. However, it remains a great challenge to design an ideal synthetic graft that very closely mimics the bone tissue structurally, and can modulate the desired function in osteoblast and progenitor cell populations. Nanobiomaterials, specifically nanocomposites composed of hydroxyapatite (HA) and/or collagen are extremely promising graft substitutes. The biocomposites can be fabricated to mimic the material composition of native bone tissue, and additionally, when using nano-HA (reduced grain size), one mimics the structural arrangement of native bone. A good understanding of bone biology and structure is critical to development of bone mimicking graft substitutes. HA and collagen exhibit excellent osteoconductive properties which can further modulate the regenerative/healing process following fracture injury. Combining with other polymeric biomaterials will reinforce the mechanical properties thus making the novel nano-HA based composites comparable to human bone. We report on recent studies using nanocomposites that have been fabricated as particles and nanofibers for regeneration of segmental bone defects. The research in nanocomposites, highlight a pivotal role in the future development of an ideal orthopaedic implant device, however further significant advancements are necessary to achieve clinical use.

  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 Grøndahl; Frøbert, Ole; Holst-Hansen, Claus;

    2012-01-01

    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......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...

  1. 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.

  2. 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

  3. Growth and Potential Damage of Human Bone-Derived Cells on Fresh and Aged Fullerene C60 Films

    Directory of Open Access Journals (Sweden)

    Jiri Vacik

    2013-04-01

    Full Text Available Fullerenes are nanoparticles composed of carbon atoms arranged in a spherical hollow cage-like structure. Numerous studies have evaluated the therapeutic potential of fullerene derivates against oxidative stress-associated conditions, including the prevention or treatment of arthritis. On the other hand, fullerenes are not only able to quench, but also to generate harmful reactive oxygen species. The reactivity of fullerenes may change in time due to the oxidation and polymerization of fullerenes in an air atmosphere. In this study, we therefore tested the dependence between the age of fullerene films (from one week to one year and the proliferation, viability and metabolic activity of human osteosarcoma cells (lines MG-63 and U-2 OS. We also monitored potential membrane and DNA damage and morphological changes of the cells. After seven days of cultivation, we did not observe any cytotoxic morphological changes, such as enlarged cells or cytosolic vacuole formation. Furthermore, there was no increased level of DNA damage. The increasing age of the fullerene films did not cause enhancement of cytotoxicity. On the contrary, it resulted in an improvement in the properties of these materials, which are more suitable for cell cultivation. Therefore, fullerene films could be considered as a promising material with potential use as a bioactive coating of cell carriers for bone tissue engineering.

  4. 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.

  5. Hepatoregenerative role of bone morphogenetic protein-9

    Science.gov (United States)

    Sosa, Ivan; Cvijanovic, Olga; Celic, Tanja; Cuculic, Drazen; Crncevic-Orlic, Zeljka; Vukelic, Lucian; Cvek, Sanja Zoricic; Dudaric, Luka; Bosnar, Alan; Bobinac, Dragica

    2011-01-01

    Summary Bone morphogenetic protein-9 (BMP-9) is a member of the transforming growth factor beta (TGF-β) superfamily of cytokines, which regulate cell growth and differentiation during embryogenesis. Apart of that, the hypoglycemic potential of BMP-9 is of great interest. It has been confirmed that BMP-9, like insulin, improves glycemia in diabetic mice and regulates directional glucose metabolism in hepatocytes; therefore it is proposed to be a candidate hepatic insulin-sensitizing substance (HISS). In liver fibrosis, due to the portocaval shunt, insulin bypasses the organ and the liver undergoes atrophy. Parenteral administration of insulin reverses atrophy by stimulating mitogenic activity of the hepatocytes. Because BMP-9 has a signaling pathway similar to other BMPs and insulin, it is to be expected that BMP-9 has a certain regenerative role in the liver, supporting the above-mentioned is evidence of BMP-9 expression in Dissè’s spaces and BMP-7’s mitogenic activity in mucosal cells. However, further studies are needed to confirm the possible regenerative role of BMP-9. PMID:22129908

  6. Cell and biomolecule delivery for regenerative medicine

    International Nuclear Information System (INIS)

    Regenerative medicine is an exciting field that aims to create regenerative alternatives to harvest tissues for transplantation. In this approach, the delivery of cells and biological molecules plays a central role. The scaffold (synthetic temporary extracellular matrix) delivers cells to the regenerative site and provides three-dimensional environments for the cells. To fulfil these functions, we design biodegradable polymer scaffolds with structural features on multiple size scales. To enhance positive cell-material interactions, we design nano-sized structural features in the scaffolds to mimic the natural extracellular matrix. We also integrate micro-sized pore networks to facilitate mass transport and neo tissue regeneration. We also design novel polymer devices and self-assembled nanospheres for biomolecule delivery to recapitulate key events in developmental and wound healing processes. Herein, we present recent work in biomedical polymer synthesis, novel processing techniques, surface engineering and biologic delivery. Examples of enhanced cellular/tissue function and regenerative outcomes of these approaches are discussed to demonstrate the excitement of the biomimetic scaffold design and biologic delivery in regenerative medicine. (topical review)

  7. 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.

  8. Functional imaging for regenerative medicine.

    Science.gov (United States)

    Leahy, Martin; Thompson, Kerry; Zafar, Haroon; Alexandrov, Sergey; Foley, Mark; O'Flatharta, Cathal; Dockery, Peter

    2016-01-01

    In vivo imaging is a platform technology with the power to put function in its natural structural context. With the drive to translate stem cell therapies into pre-clinical and clinical trials, early selection of the right imaging techniques is paramount to success. There are many instances in regenerative medicine where the biological, biochemical, and biomechanical mechanisms behind the proposed function of stem cell therapies can be elucidated by appropriate imaging. Imaging techniques can be divided according to whether labels are used and as to whether the imaging can be done in vivo. In vivo human imaging places additional restrictions on the imaging tools that can be used. Microscopies and nanoscopies, especially those requiring fluorescent markers, have made an extraordinary impact on discovery at the molecular and cellular level, but due to their very limited ability to focus in the scattering tissues encountered for in vivo applications they are largely confined to superficial imaging applications in research laboratories. Nanoscopy, which has tremendous benefits in resolution, is limited to the near-field (e.g. near-field scanning optical microscope (NSNOM)) or to very high light intensity (e.g. stimulated emission depletion (STED)) or to slow stochastic events (photo-activated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM)). In all cases, nanoscopy is limited to very superficial applications. Imaging depth may be increased using multiphoton or coherence gating tricks. Scattering dominates the limitation on imaging depth in most tissues and this can be mitigated by the application of optical clearing techniques that can impose mild (e.g. topical application of glycerol) or severe (e.g. CLARITY) changes to the tissue to be imaged. Progression of therapies through to clinical trials requires some thought as to the imaging and sensing modalities that should be used. Smoother progression is facilitated by the use of

  9. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  10. Bone Regeneration from PLGA Micro-Nanoparticles

    Science.gov (United States)

    Ortega-Oller, Inmaculada; Padial-Molina, Miguel; Galindo-Moreno, Pablo; O'Valle, Francisco; Jódar-Reyes, Ana Belén; Peula-García, Jose Manuel

    2015-01-01

    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. PMID:26509156

  11. 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.

  12. 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.

  13. Overcoming immunological barriers in regenerative medicine.

    Science.gov (United States)

    Zakrzewski, Johannes L; van den Brink, Marcel R M; Hubbell, Jeffrey A

    2014-08-01

    Regenerative therapies that use allogeneic cells are likely to encounter immunological barriers similar to those that occur with transplantation of solid organs and allogeneic hematopoietic stem cells (HSCs). Decades of experience in clinical transplantation hold valuable lessons for regenerative medicine, offering approaches for developing tolerance-induction treatments relevant to cell therapies. Outside the field of solid-organ and allogeneic HSC transplantation, new strategies are emerging for controlling the immune response, such as methods based on biomaterials or mimicry of antigen-specific peripheral tolerance. Novel biomaterials can alter the behavior of cells in tissue-engineered constructs and can blunt host immune responses to cells and biomaterial scaffolds. Approaches to suppress autoreactive immune cells may also be useful in regenerative medicine. The most innovative solutions will be developed through closer collaboration among stem cell biologists, transplantation immunologists and materials scientists. PMID:25093888

  14. Regenerative urology clinical trials: an ethical assessment of road blocks and solutions

    NARCIS (Netherlands)

    Oerlemans, A.J.M.; Feitz, W.F.J.; Leeuwen, E. van; Dekkers, W.J.M.

    2013-01-01

    Tissue engineering--part of regenerative medicine--is a promising technology that could potentially offer elegant solutions to urogenital defects, but so far, it has fallen short of its potential. Within experimental studies for bladder and urethra reconstructions, two clinical applications have bee

  15. Improved Regenerative Sorbent-Compressor Refrigerator

    Science.gov (United States)

    Jones, Jack A.

    1992-01-01

    Conceptual regenerative sorbent-compressor refrigerator attains regeneration efficiency and, therefore, overall power efficiency and performance greater than conventional refrigerators. Includes two fluid loops. In one, CH2FCF3 (R134a) ciculates by physical adsorption and desorption in four activated-charcoal sorption compressors. In other, liquid or gas coolant circulated by pump. Wave of regenerative heating and cooling propagates cyclically like peristatic wave among sorption compressors and associated heat exchangers. Powered by electricity, oil, gas, solar heat, or waste heat. Used as air conditioners, refrigerators, and heat pumps in industrial, home, and automotive applications.

  16. Functionalized Nanostructures with Application in Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Milán Bustamante

    2012-03-01

    Full Text Available In the last decade, both regenerative medicine and nanotechnology have been broadly developed leading important advances in biomedical research as well as in clinical practice. The manipulation on the molecular level and the use of several functionalized nanoscaled materials has application in various fields of regenerative medicine including tissue engineering, cell therapy, diagnosis and drug and gene delivery. The themes covered in this review include nanoparticle systems for tracking transplanted stem cells, self-assembling peptides, nanoparticles for gene delivery into stem cells and biomimetic scaffolds useful for 2D and 3D tissue cell cultures, transplantation and clinical application.

  17. 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

  18. Comparative study of the chondrogenic potential of human bone marrow stromal cells, neonatal chondrocytes and adult chondrocytes

    International Nuclear Information System (INIS)

    Research highlights: → This study has characterised three different cell types under conditions similar to those used for autologous chondrocyte implantation (ACI) for applications in cartilage repair/regeneration. → Compared for the first time the chondrogenic potential of neonatal chondrocytes with human bone marrow stromal cells (HBMSCs) and adult chondrocytes. → Demonstrated that adult chondrocytes hold greatest potential for use in ACI based on their higher proliferation rates, lower alkaline phosphatise activity and enhanced expression of chondrogenic genes. → Demonstrated the need for chondroinduction as a necessary pre-requisite to efficient chondrogenesis in vitro and, by extrapolation, for cell based therapy (e.g. ACI or cartilage tissue engineering). -- Abstract: Cartilage tissue engineering is still a major clinical challenge with optimisation of a suitable source of cells for cartilage repair/regeneration not yet fully addressed. The aims of this study were to compare and contrast the differences in chondrogenic behaviour between human bone marrow stromal cells (HBMSCs), human neonatal and adult chondrocytes to further our understanding of chondroinduction relative to cell maturity and to identify factors that promote chondrogenesis and maintain functional homoeostasis. Cells were cultured in monolayer in either chondrogenic or basal medium, recapitulating procedures used in existing clinical procedures for cell-based therapies. Cell doubling time, morphology and alkaline phosphatase specific activity (ALPSA) were determined at different time points. Expression of chondrogenic markers (SOX9, ACAN and COL2A1) was compared via real time polymerase chain reaction. Amongst the three cell types studied, HBMSCs had the highest ALPSA in basal culture and lowest ALPSA in chondrogenic media. Neonatal chondrocytes were the most proliferative and adult chondrocytes had the lowest ALPSA in basal media. Gene expression analysis revealed a difference in the

  19. In vitro and in vivo investigations on bone regeneration potential of laminated hydroxyapatite/gelatin nanocomposite scaffold along with DBM

    International Nuclear Information System (INIS)

    Bone regeneration ability of a scaffold strongly depends on its structure and the size of its components. In this study, a nanostructured scaffold was designed for bone repair using nano hydroxyapatite (nHA) (8–16 nm × 50–80 nm) and gelatin (GEL) as main components. In vitro investigations of calcium matrix deposition and gene expression of the seeded cells for this scaffold, demineralized bone matrix (DBM), scaffold plus DBM, and the control group were carried out. Bone regeneration in rat calvarium with critical defect size after 1, 4, and 8 weeks post implantation was investigated. The calcium matrix depositions by the osteoblast and RUNX2, ALP, osteonectin, and osteocalcin gene expression in scaffold were more significant than in other groups. Histomorphometry analysis confirmed in vitro results. In vitro and in vivo bone regeneration were least in scaffold plus DBM group. Enhanced effects in scaffold could be attributed to the shape and size of nHA particles and good architecture of the scaffold. Reduction of bone regeneration might be due to tight bonding of BMPs and nHA particles in the third group. Results obtained from this study confirmed that nano-scale size of the main components and the scaffold architecture (pore diameter, interconnectivity pores, etc.) have significant effects on bone regeneration ability of the scaffold and are important parameters in designing a temporary bone substitute.

  20. 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...

  1. Growth-Factor Nanocapsules That Enable Tunable Controlled Release for Bone Regeneration.

    Science.gov (United States)

    Tian, Haijun; Du, Juanjuan; Wen, Jing; Liu, Yang; Montgomery, Scott R; Scott, Trevor P; Aghdasi, Bayan; Xiong, Chengjie; Suzuki, Akinobu; Hayashi, Tetsuo; Ruangchainikom, Monchai; Phan, Kevin; Weintraub, Gil; Raed, Alobaidaan; Murray, Samuel S; Daubs, Michael D; Yang, Xianjin; Yuan, Xu-Bo; Wang, Jeffrey C; Lu, Yunfeng

    2016-08-23

    Growth factors are of great potential in regenerative medicine. However, their clinical applications are largely limited by the short in vivo half-lives and the narrow therapeutic window. Thus, a robust controlled release system remains an unmet medical need for growth-factor-based therapies. In this research, a nanoscale controlled release system (degradable protein nanocapsule) is established via in situ polymerization on growth factor. The release rate can be finely tuned by engineering the surface polymer composition. Improved therapeutic outcomes can be achieved with growth factor nanocapsules, as illustrated in spinal cord fusion mediated by bone morphogenetic protein-2 nanocapsules. PMID:27227573

  2. 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.

  3. 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...

  4. Comparisons of Differentiation Potential in Human Mesenchymal Stem Cells from Wharton’s Jelly, Bone Marrow, and Pancreatic Tissues

    Directory of Open Access Journals (Sweden)

    Shih-Yi Kao

    2015-01-01

    Full Text Available Background. Type 1 diabetes mellitus results from autoimmune destruction of β-cells. Insulin-producing cells (IPCs differentiated from mesenchymal stem cells (MSCs in human tissues decrease blood glucose levels and improve survival in diabetic rats. We compared the differential ability and the curative effect of IPCs from three types of human tissue to determine the ideal source of cell therapy for diabetes. Methods. We induced MSCs from Wharton’s jelly (WJ, bone marrow (BM, and surgically resected pancreatic tissue to differentiate into IPCs. The in vitro differential function of these IPCs was compared by insulin-to-DNA ratios and C-peptide levels after glucose challenge. In vivo curative effects of IPCs transplanted into diabetic rats were monitored by weekly blood glucose measurement. Results. WJ-MSCs showed better proliferation and differentiation potential than pancreatic MSCs and BM-MSCs. In vivo, WJ-IPCs significantly reduced blood glucose levels at first week after transplantation and maintained significant decrease till week 8. BM-IPCs reduced blood glucose levels at first week but gradually increased since week 3. In resected pancreas-IPCs group, blood glucose levels were significantly reduced till two weeks after transplantation and gradually increased since week 4. Conclusion. WJ-MSCs are the most promising stem cell source for β-cell regeneration in diabetes treatment.

  5. Technical solutions to improve cardiac regenerative therapy

    NARCIS (Netherlands)

    van Slochteren, F.J.

    2014-01-01

    The therapeutic options for patients suffering from ischemic heart disease (IHD) are limited, and worldwide 23 million patients suffer from heart failure (HF). Therefore there is a strong need for alternative therapies for IHD. Since cardiac regenerative therapies have shown promising results in bas

  6. Characterization of a new fish-derived bioactive neuropeptide involved in bone remodelling. Its physiological function and therapeutic potential.

    Directory of Open Access Journals (Sweden)

    Paula Suarez-Bregua

    2014-04-01

    Full Text Available A complex network of autocrine and paracrine signals, hormones and neuronal factors preserve the structural integrity of the skeleton and regulate mineral metabolism in vertebrates. We have characterized a new neuropeptide belonging to parathyroid hormone (PTH family. PTH family members are known to play a key role in maintaining mineral homeostasis, bone remodeling and in regulating embryonic development of skeleton and other tissues. This new neuropeptide is synthesized by two clusters of neurons located in lateral hypothalamus as showed in whole mount in situ hybridization. The functional characterization of the gene using a stable transgenic line revealed its key role in the regulation of bone mineral density. Moreover, phylogenetic analyses and comparative genomics results of conserved synteny reveal that this new neuropeptide is a new ohnolog of the PTH family present in teleosts and some tetrapods like chicken, but absent in mammals . Our findings suggest a new brain to bone pathway, where neuronal factors from hypothalamus signal to receptors on bone cells promoting bone remodeling. Further investigations about this new neuropeptide system would be relevant for developing therapies for bone mineral disorders in humans, since this neuropeptide has a conserved domain similar to other PTH-related peptides which have anabolic effects on bone.

  7. 45S5 Bioactive Glass-Based Composite Scaffolds with Polymer Coatings for Bone Tissue Engineering Therapeutics

    OpenAIRE

    Li, Wei

    2015-01-01

    Bone tissue engineering is a rapidly developing interdisciplinary field. An effective approach to bone tissue engineering aims to restore the function of damaged bone tissue or to regenerate bone tissue with the aid of scaffolds made from engineered biomaterials. The scaffolds should act as temporary matrices for cell attachment, proliferation, migration, differentiation and extracellular matrix deposition, with consequent bone ingrowth until the new bone tissue is totally restored or regener...

  8. Bone Biopsy

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Bone Biopsy Bone biopsy uses a needle and imaging guidance ... limitations of Bone Biopsy? What is a Bone Biopsy? A bone biopsy is an image-guided procedure ...

  9. Bone Diseases

    Science.gov (United States)

    ... avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. Different kinds ... break Osteogenesis imperfecta makes your bones brittle Paget's disease of bone makes them weak Bones can also ...

  10. Surgical Non-Regenerative Treatments for Peri-Implantitis: a Systematic Review

    Directory of Open Access Journals (Sweden)

    Ausra Ramanauskaite

    2016-09-01

    Full Text Available Objectives: The purposes of the present study were 1 to systematically review the literature on the surgical non-regenerative treatments of peri-implantitis and 2 to determine a predictable therapeutic option for the clinical management of peri-implantitis lesions. Material and Methods: The study search was performed on primary database MEDLINE and EMBASE from 2005 until 2016. Sequential screenings at the title, abstract, and full-text levels were performed. Clinical human studies in the English language that had reported changes in probing depth (PD and/or bleeding on probing (BOP and/or radiologic marginal bone level changes after peri-implantitis surgical non-regenerative treatment at 6-month follow-up or longer were included accordingly PRISMA guidelines. Results: The first electronic and hand search resulted in 765 citations. From 16 full-text articles reviewed, 6 were included in this systematic review. Surgical non-regenerative methods were found to be efficient in reducing clinical parameters. BOP and PD values were significantly decreased following implantoplasty and systematic administration of antibacterials, but not after local application of chemical compounds or diode laser. Similarly, significant improvement in clinical and radiographic parameters was found only after implantoplasty compared with resective surgery alone. We found significant heterogeneity in study designs and treatments provided among the pooled studies. All of the studies revealed an unclear or high risk of bias. Conclusions: Surgical non-regenerative treatment of peri-implantitis was found to be effective to reduce the soft tissue inflammation and decrease probing depth. More randomized controlled clinical trials are needed to assess the efficacy of surgical non-regenerative therapy of peri-implantitis.

  11. Regenerative material for aneurysm embolization A 3-dimensional culture system of fibroblasts and calcium alginate gel

    Institute of Scientific and Technical Information of China (English)

    Jingdong Zhang; Kan Xu; Jinlu Yu; Jun Wang; Qi Luo

    2011-01-01

    Calcium alginate gel (CAG) has been shown to successfully model aneurysm embolization within a short period of time. However, gradually degrading CAG potentially results in aneurysm recanalization.In the present study, a regenerative embolic material was designed by seeding rat fibroblasts in a CAG. The study investigated the feasibility of constructing a 3-dimensional culture system. The fibroblasts grew well and firmly attached to the CAG. CAG was conducive for fibroblast growth, and resulted in a 3-dimensional culture system. Results show that CAG can be used theoretically as a vascular, regenerative, embolic material.

  12. Design, clinical translation and immunological response of biomaterials in regenerative medicine

    Science.gov (United States)

    Sadtler, Kaitlyn; Singh, Anirudha; Wolf, Matthew T.; Wang, Xiaokun; Pardoll, Drew M.; Elisseeff, Jennifer H.

    2016-07-01

    The field of regenerative medicine aims to replace tissues lost as a consequence of disease, trauma or congenital abnormalities. Biomaterials serve as scaffolds for regenerative medicine to deliver cells, provide biological signals and physical support, and mobilize endogenous cells to repair tissues. Sophisticated chemistries are used to synthesize materials that mimic and modulate native tissue microenvironments, to replace form and to elucidate structure-function relationships of cell-material interactions. The therapeutic relevance of these biomaterial properties can only be studied after clinical translation, whereby key parameters for efficacy can be defined and then used for future design. In this Review, we present the development and translation of biomaterials for two tissue engineering targets, cartilage and cornea, both of which lack the ability to self-repair. Finally, looking to the future, we discuss the role of the immune system in regeneration and the potential for biomaterial scaffolds to modulate immune signalling to create a pro-regenerative environment.

  13. Design, clinical translation and immunological response of biomaterials in regenerative medicine

    Science.gov (United States)

    Sadtler, Kaitlyn; Singh, Anirudha; Wolf, Matthew T.; Wang, Xiaokun; Pardoll, Drew M.; Elisseeff, Jennifer H.

    2016-07-01

    The field of regenerative medicine aims to replace tissues lost as a consequence of disease, trauma or congenital abnormalities. Biomaterials serve as scaffolds for regenerative medicine to deliver cells, provide biological signals and physical support, and mobilize endogenous cells to repair tissues. Sophisticated chemistries are used to synthesize materials that mimic and modulate native tissue microenvironments, to replace form and to elucidate structure–function relationships of cell–material interactions. The therapeutic relevance of these biomaterial properties can only be studied after clinical translation, whereby key parameters for efficacy can be defined and then used for future design. In this Review, we present the development and translation of biomaterials for two tissue engineering targets, cartilage and cornea, both of which lack the ability to self-repair. Finally, looking to the future, we discuss the role of the immune system in regeneration and the potential for biomaterial scaffolds to modulate immune signalling to create a pro-regenerative environment.

  14. Evaluation of the performance of a motion capture system for small displacement recording and a discussion for its application potential in bone deformation in vivo measurements

    OpenAIRE

    Yang, Pengfei; Sanno, Maximilian; Brüggemann, Gert-Peter; Rittweger, Jörn

    2012-01-01

    The aim of this study is to evaluate the performance of a motion capture system and discuss the application potential of the proposed system in in vivo bone-segment deformation measurements. In this study, the effects of the calibration procedure, camera distance and marker size on the accuracy and precision of the motion capture system have been investigated by comparing the captured movement of the markers with reference movement. The results indicated that the system resolution...

  15. Regenerative endodontics: A state of the art

    Directory of Open Access Journals (Sweden)

    Rashmi Bansal

    2011-01-01

    Full Text Available Scientific advances in the creation of restorative biomaterials, in vitro cell culture technology, tissue grafting, tissue engineering, molecular biology and the human genome project provide the basis for the introduction of new technologies into dentistry. Non-vital infected teeth have long been treated with root canal therapy (for mature root apex and apexification (for immature root apex, or doomed to extraction. Although successful, current treatments fail to re-establish healthy pulp tissue in these teeth. But, what if the non-vital tooth could be made vital once again? That is the hope offered by regenerative endodontics, an emerging field focused on replacing traumatized and diseased pulp with functional pulp tissue. Restoration of vitality of non-vital tooth is based on tissue engineering and revascularization procedures. The purpose of this article is to review these biological procedures and the hurdles that must be overcome to develop regenerative endodontic procedures.

  16. First lasing of the regenerative amplifier FEL

    International Nuclear Information System (INIS)

    The regenerative amplifier free-electron laser (RAFEL) is a high-gain RF-linac FEL capable of producing high optical power from a compact design. The combination of a high-gain and small optical feedback enables the FEL to reach saturation and produce a high optical power and high extraction efficiency without the risk of optical damage to the mirrors. This paper summarizes the first lasing of the regenerative amplifier FEL and describes recent experimental results. The highest optical energy achieved thus far at 16.3 μm is 1.7 J over a train of 900 micropulses. We infer pulse energy of 1.9 mJ in each 16 ps micropulse, corresponding to a peak power of 120 MW

  17. Micro-Scale Regenerative Heat Exchanger

    Science.gov (United States)

    Moran, Matthew E.; Stelter, Stephan; Stelter, Manfred

    2004-01-01

    A micro-scale regenerative heat exchanger has been designed, optimized and fabricated for use in a micro-Stirling device. Novel design and fabrication techniques enabled the minimization of axial heat conduction losses and pressure drop, while maximizing thermal regenerative performance. The fabricated prototype is comprised of ten separate assembled layers of alternating metal-dielectric composite. Each layer is offset to minimize conduction losses and maximize heat transfer by boundary layer disruption. A grating pattern of 100 micron square non-contiguous flow passages were formed with a nominal 20 micron wall thickness, and an overall assembled ten-layer thickness of 900 microns. Application of the micro heat exchanger is envisioned in the areas of micro-refrigerators/coolers, micropower devices, and micro-fluidic devices.

  18. Regenerative Medicine from Protocol to Patient

    Directory of Open Access Journals (Sweden)

    Gustav Steinhoff

    2011-01-01

    Full Text Available The essentials of the upcoming and rapidly changing specialty of regenerative medicine, which has kindled high hopes among the clinical and scientific community as well as the society, are presented concisely in this book. Considering the multivariate sub-specialties within regenerative medicine, starting with cell biology and allied basic sciences through translational research to clinical application in various specialties of medicine, enormous efforts are mandatory to bring a comprehensive text book of this nature. The authors deserve kudos for this. This book comprehensively describes and reviews the current progress in stem cell research and regenerative medicine, in five main parts: (I Biology of Tissue Regeneration; (II Stem Cell Science and Technology; (III Tissue Engineering, Biomaterials and Nanotechnology; (IV Regenerative Therapies; and (V Regulation and Ethics. It fully covers all the major components in the field. Each chapter, written by the experts in the respective areas of work, throws light on the intricacies in detail, making this book immensely useful for students, clinicians and scientists interested in regenerative medicine. However, there is still scope for further refinement of some chapters. In Part II Stem Cell Science and Technology, three important stem cell types- muscle stem cells (satellite cells, stem cells from the skin and hair follicles, and stem cells from the gut epithelium-may be added as three individual chapters which probably the authors could consider for the next edition, as these cell types represent unique stem cells that have distinct properties and replenish specifically muscle, skin, hair, and gut epithelium respectively. In the chapter on cardiac stem cells, a table summarizing the properties of the four different types of cardiac stem cells described in the text may give readers more clear comparison of the pros and cons on these cells and know their properties better. The future direction

  19. Evaluation of Osteoconductive and Osteogenic Potential of a Dentin-Based Bone Substitute Using a Calvarial Defect Model

    Directory of Open Access Journals (Sweden)

    Ibrahim Hussain

    2012-01-01

    Full Text Available The aim of this study was to assess the osteoconductive and osteogenic properties of processed bovine dentin using a robust rabbit calvarial defect model. In total, 16 New Zealand White rabbits were operated to create three circular defects in the calvaria. One defect was left unfilled, one filled with collected autogenous bone, and the third defect was filled with the dentin-based bone substitute. Following surgery and after a healing period of either 1 or 6 weeks, a CT scan was obtained. Following sacrificing, the tissues were processed for histological examination. The CT data showed the density in the area grafted with the dentin-based material was higher than the surrounding bone and the areas grafted with autologous bone after 1 week and 6 weeks of healing. The area left unfilled remained an empty defect after 1 week and 6 weeks. Histological examination of the defects filled with the dentin product after 6 weeks showed soft tissue encapsulation around the dentin particles. It can be concluded that the rabbit calvarial model used in this study is a robust model for the assessment of bone materials. Bovine dentin is a biostable material; however, it may not be suitable for repairing large 4-wall defects.

  20. Average Regression-Adjusted Controlled Regenerative Estimates

    OpenAIRE

    Lewis, Peter A.W.; Ressler, Richard

    1991-01-01

    Proceedings of the 1991 Winter Simulation Conference Barry L. Nelson, W. David Kelton, Gordon M. Clark (eds.) One often uses computer simulations of queueing systems to generate estimates of system characteristics along with estimates of their precision. Obtaining precise estimates, espescially for high traffic intensities, can require large amounts of computer time. Average regression-adjusted controlled regenerative estimates result from combining the two techniques ...

  1. Regenerative ceramic burner has highest efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Gettings, M.

    1986-01-01

    Regenerative ceramic burners consisting of a double gas/air burner and utilising waste heat which is stored via regenerators are described. The system is capable of operating at 1400/sup 0/C, it removes about 85-90% of energy from hot waste gases and exhibits energy savings of 40-60% over cold nozzle mix burners and 20-25% over recuperative burners. (UK).

  2. Nanotechnology in regenerative medicine: the materials side

    OpenAIRE

    Engel López, Elisabeth; Michiardi, A; Navarro, M.; Lacroix, Damien Jerome; Planell Estany, Josep Anton

    2008-01-01

    Regenerative medicine is an emerging multidisciplinary field that aims to restore, maintain or enhance tissues and hence organ functions. Regeneration of tissues can be achieved by the combination of living cells, which will provide biological functionality, and materials, which act as scaffolds to support cell proliferation. Mammalian cells behave in vivo in response to the biological signals they receive from the surrounding environment, which is structured by nanometre-scaled components. T...

  3. Fluorescent Cell Imaging in Regenerative Medicine

    OpenAIRE

    Etai Sapoznik; Guoguang Niu; Yu Zhou; Murphy, Sean V.; Shay Soker

    2016-01-01

    Fluorescent protein imaging, a promising tool in biological research, incorporates numerous applications that can be of specific use in the field of regenerative medicine. To enhance tissue regeneration efforts, scientists have been developing new ways to monitor tissue development and maturation in vitro and in vivo. To that end, new imaging tools and novel fluorescent proteins have been developed for the purpose of performing deep-tissue high-resolution imaging. These new methods, such as i...

  4. Upconversion Nanoparticles for Bioimaging and Regenerative Medicine

    OpenAIRE

    González-Béjar, María; Francés-Soriano, Laura; Pérez-Prieto, Julia

    2016-01-01

    Nanomaterials are proving useful for regenerative medicine in combination with stem cell therapy. Nanoparticles (NPs) can be administrated and targeted to desired tissues or organs and subsequently be used in non-invasive real-time visualization and tracking of cells by means of different imaging techniques, can act as therapeutic agent nanocarriers, and can also serve as scaffolds to guide the growth of new tissue. NPs can be of different chemical nature, such as gold, iron oxide, cadmium se...

  5. New nanostructured biomaterials for regenerative medicine

    OpenAIRE

    A. Sgambato

    2016-01-01

    Innovative approaches in tissue engineering and regenerative medicine based on decellularized extracellular matrix (ECM) scaffolds and tissues are quickly growing. ECM proteins are particularly adequate toward tissue regeneration applications, since they are natural biomaterials that can be bio-activated with signalling molecules able to influence cell fate, driving cell responses and tissue regeneration. Indeed, it is well recognized that cells perceive and respond to their microenvironment;...

  6. Regenerative repair of damaged meniscus with autologous adipose tissue-derived stem cells.

    Science.gov (United States)

    Pak, Jaewoo; Lee, Jung Hun; Lee, Sang Hee

    2014-01-01

    Mesenchymal stem cells (MSCs) are defined as pluripotent cells found in numerous human tissues, including bone marrow and adipose tissue. Such MSCs, isolated from bone marrow and adipose tissue, have been shown to differentiate into bone and cartilage, along with other types of tissues. Therefore, MSCs represent a promising new therapy in regenerative medicine. The initial treatment of meniscus tear of the knee is managed conservatively with nonsteroidal anti-inflammatory drugs and physical therapy. When such conservative treatment fails, an arthroscopic resection of the meniscus is necessary. However, the major drawback of the meniscectomy is an early onset of osteoarthritis. Therefore, an effective and noninvasive treatment for patients with continuous knee pain due to damaged meniscus has been sought. Here, we present a review, highlighting the possible regenerative mechanisms of damaged meniscus with MSCs (especially adipose tissue-derived stem cells (ASCs)), along with a case of successful repair of torn meniscus with significant reduction of knee pain by percutaneous injection of autologous ASCs into an adult human knee.

  7. Mesenchymal stem cells in regenerative rehabilitation

    Science.gov (United States)

    Nurkovic, Jasmin; Dolicanin, Zana; Mustafic, Fahrudin; Mujanovic, Rifat; Memic, Mensur; Grbovic, Vesna; Skevin, Aleksandra Jurisic; Nurkovic, Selmina

    2016-01-01

    [Purpose] Regenerative medicine and rehabilitation contribute in many ways to a specific plan of care based on a patient’s medical status. The intrinsic self-renewing, multipotent, regenerative, and immunosuppressive properties of mesenchymal stem cells offer great promise in the treatment of numerous autoimmune, degenerative, and graft-versus-host diseases, as well as tissue injuries. As such, mesenchymal stem cells represent a therapeutic fortune in regenerative medicine. The aim of this review is to discuss possibilities, limitations, and future clinical applications of mesenchymal stem cells. [Subjects and Methods] The authors have identified and discussed clinically and scientifically relevant articles from PubMed that have met the inclusion criteria. [Results] Direct treatment of muscle injuries, stroke, damaged peripheral nerves, and cartilage with mesenchymal stem cells has been demonstrated to be effective, with synergies seen between cellular and physical therapies. Over the past few years, several researchers, including us, have shown that there are certain limitations in the use of mesenchymal stem cells. Aging and spontaneous malignant transformation of mesenchymal stem cells significantly affect the functionality of these cells. [Conclusion] Definitive conclusions cannot be made by these studies because limited numbers of patients were included. Studies clarifying these results are expected in the near future. PMID:27390452

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

    OpenAIRE

    EL Smith; JM Kanczler; ROC Oreffo

    2013-01-01

    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 b...

  9. Regenerative Effects of Three Types of Allografts on Rabbit Calvarium: An Animal Study

    Science.gov (United States)

    Rokn, Amir Reza; Shakeri, Abbas Seyed; Etemad-Moghadam, Shahroo; Alaeddini, Mojgan; Shamshiri, Ahmad Reza; Manasheof, Rebecca; Barikani, Hamidreza

    2015-01-01

    Objectives: The aim of this study was to histologically compare the regenerative properties of two allografts manufactured by two Iranian companies. Materials and Methods: In this study, four 8-mm defects were produced in the calvaria of 12 rabbits. In three defects, three types of allografts namely ITB, CenoBone and Grafton were placed and one defect served as control. Samples were prepared and histomorphometric evaluations were carried out after healing periods of four weeks (interval 1) and eight weeks (interval 2). Qualitative and quantities variables were compared and analyzed with SPSS software. Results: Mild inflammation was observed in 45% and 12.5% of the samples in the first and second intervals, respectively. Foreign body reaction was observed in only 5% of the samples. The quality of regenerated bone was immature, mixed and lamellar in 54.5%, 15.9% and 4.5% of the samples, respectively. The rate of allograft resorption was the highest and lowest in the CenoBone and Grafton samples, respectively. The mean amount of regenerated bone was higher in areas containing Grafton; however, the differences were not statistically significant. Conclusion: Despite the differences in the numerical values of bone regeneration, there were no statistically significant differences in bone generation among the material groups, and allografts manufactured in Iran can be suitable alternatives to Grafton with the same good properties. Further studies are necessary to clarify the efficacy of these allografts. PMID:27507993

  10. Stem and progenitor cells: advancing bone tissue engineering.

    Science.gov (United States)

    Tevlin, R; Walmsley, G G; Marecic, O; Hu, Michael S; Wan, D C; Longaker, M T

    2016-04-01

    Unlike many other postnatal tissues, bone can regenerate and repair itself; nevertheless, this capacity can be overcome. Traditionally, surgical reconstructive strategies have implemented autologous, allogeneic, and prosthetic materials. Autologous bone--the best option--is limited in supply and also mandates an additional surgical procedure. In regenerative tissue engineering, there are myriad issues to consider in the creation of a functional, implantable replacement tissue. Importantly, there must exist an easily accessible, abundant cell source with the capacity to express the phenotype of the desired tissue, and a biocompatible scaffold to deliver the cells to the damaged region. A literature review was performed using PubMed; peer-reviewed publications were screened for relevance in order to identify key advances in stem and progenitor cell contribution to the field of bone tissue engineering. In this review, we briefly introduce various adult stem cells implemented in bone tissue engineering such as mesenchymal stem cells (including bone marrow- and adipose-derived stem cells), endothelial progenitor cells, and induced pluripotent stem cells. We then discuss numerous advances associated with their application and subsequently focus on technological advances in the field, before addressing key regenerative strategies currently used in clinical practice. Stem and progenitor cell implementation in bone tissue engineering strategies have the ability to make a major impact on regenerative medicine and reduce patient morbidity. As the field of regenerative medicine endeavors to harness the body's own cells for treatment, scientific innovation has led to great advances in stem cell-based therapies in the past decade.

  11. A potential kidney-bone axis involved in the rapid minute-to-minute regulation of plasma Ca2+

    DEFF Research Database (Denmark)

    Nordholm, Anders; Mace, Maria L; Gravesen, Eva;

    2015-01-01

    BACKGROUND: Understanding the regulation of mineral homeostasis and function of the skeleton as buffer for Calcium and Phosphate has regained new interest with introduction of the syndrome "Chronic Kidney Disease-Mineral and Bone Disorder"(CKD-MBD). The very rapid minute-to-minute regulation...

  12. Artemisinin-derived sesquiterpene lactones as potential antitumour compounds : Cytotoxic action against bone marrow and tumour cells

    NARCIS (Netherlands)

    Beekman, AC; Wierenga, PK; Woerdenbag, HJ; Van Uden, W; Pras, N; Konings, AWT; El-Feraly, FS; Galal, AM; Wikstrom, HV

    1998-01-01

    We determined the in vitro cytotoxic activity of the sesquiterpene lactone endoperoxide artemisinin (1) and some chemically prepared derivatives, which have been found to display cytotoxicity to cloned murine Ehrlich ascites tumour (EAT) cells and human HeLa cells and against murine bone marrow usin

  13. Evaluating of bone healing around porous coated titanium implant and potential systematic bias on the traditional sampling method

    DEFF Research Database (Denmark)

    Babiker, Hassan; Ding, Ming; Overgaard, Søren

    2013-01-01

    could be affected by the various quality and quantity of bone in the local environment. Thus, implant fixation in one part might differ from the other part of the implant. This study aimed to investigate the influence of the sampling method on data evaluation. Material and methods: Titanium alloy implants...

  14. Resistance Training in Type II Diabetes Mellitus: Impact on Areas of Metabolic Dysfunction in Skeletal Muscle and Potential Impact on Bone

    Directory of Open Access Journals (Sweden)

    Richard J. Wood

    2012-01-01

    Full Text Available The prevalence of Type II Diabetes mellitus (T2DM is increasing rapidly and will continue to be a major healthcare expenditure burden. As such, identification of effective lifestyle treatments is paramount. Skeletal muscle and bone display metabolic and functional disruption in T2DM. Skeletal muscle in T2DM is characterized by insulin resistance, impaired glycogen synthesis, impairments in mitochondria, and lipid accumulation. Bone quality in T2DM is decreased, potentially due to the effects of advanced glycation endproducts on collagen, impaired osteoblast activity, and lipid accumulation. Although exercise is widely recognized as an important component of treatment for T2DM, the focus has largely been on aerobic exercise. Emerging research suggests that resistance training (strength training may impose potent and unique benefits in T2DM. The purpose of this review is to examine the role of resistance training in treating the dysfunction in skeletal muscle and the potential role for resistance training in treating the associated dysfunction in bone.

  15. Bone Grafts

    Science.gov (United States)

    ... repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some types of fractures or cancers. Once your body accepts the bone ...

  16. Extracellular Vesicles Derived from Osteogenically Induced Human Bone Marrow Mesenchymal Stem Cells Can Modulate Lineage Commitment

    Directory of Open Access Journals (Sweden)

    Margarida Martins

    2016-03-01

    Full Text Available The effective osteogenic commitment of human bone marrow mesenchymal stem cells (hBMSCs is critical for bone regenerative therapies. Extracellular vesicles (EVs derived from hBMSCs have a regenerative potential that has been increasingly recognized. Herein, the osteoinductive potential of osteogenically induced hBMSC-EVs was examined. hBMSCs secreted negatively charged nanosized vesicles (∼35 nm with EV-related surface markers. The yield of EVs over 7 days was dependent on an osteogenic stimulus (standard chemical cocktail or RUNX2 cationic-lipid transfection. These EVs were used to sequentially stimulate homotypic uncommitted cells during 7 days, matching the seeding density of EV parent cells, culture time, and stimuli. Osteogenically committed hBMSC-EVs induced an osteogenic phenotype characterized by marked early induction of BMP2, SP7, SPP1, BGLAP/IBSP, and alkaline phosphatase. Both EV groups outperformed the currently used osteoinductive strategies. These data show that naturally secreted EVs can guide the osteogenic commitment of hBMSCs in the absence of other chemical or genetic osteoinductors.

  17. Stem Cell Banking for Regenerative and Personalized Medicine

    Directory of Open Access Journals (Sweden)

    David T. Harris

    2014-02-01

    Full Text Available 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.

  18. Genetic Engineering of Mesenchymal Stem Cells for Regenerative Medicine.

    Science.gov (United States)

    Nowakowski, Adam; Walczak, Piotr; Janowski, Miroslaw; Lukomska, Barbara

    2015-10-01

    Mesenchymal stem cells (MSCs), which can be obtained from various organs and easily propagated in vitro, are one of the most extensively used types of stem cells and have been shown to be efficacious in a broad set of diseases. The unique and highly desirable properties of MSCs include high migratory capacities toward injured areas, immunomodulatory features, and the natural ability to differentiate into connective tissue phenotypes. These phenotypes include bone and cartilage, and these properties predispose MSCs to be therapeutically useful. In addition, MSCs elicit their therapeutic effects by paracrine actions, in which the metabolism of target tissues is modulated. Genetic engineering methods can greatly amplify these properties and broaden the therapeutic capabilities of MSCs, including transdifferentiation toward diverse cell lineages. However, cell engineering can also affect safety and increase the cost of therapy based on MSCs; thus, the advantages and disadvantages of these procedures should be discussed. In this review, the latest applications of genetic engineering methods for MSCs with regenerative medicine purposes are presented.

  19. [Regenerative medicine: orthopaedical applications and medico legal questions].

    Science.gov (United States)

    Ricci, S; Ricci, O; Tucci, C E; Massoni, F; Sarra, M V; Ricci, S

    2012-01-01

    Over the last decades, the increase in the global population's mean age has implied a corresponding increase in degenerative disease affecting various anatomical areas and tissues, including bones and cartilages, thus provoking a rising number of disabilities and a wider usage of drugs, mostly anti-inflammatory and cortisone. New developments in technologic and biomedical fields gave birth to new subjects, such as tissue engineering, cell therapy, gene therapy that, by and large, create a knowledge network falling under the concept of Regenerative Medicine. This science is essentially based on the usage of stem cells that can replicate and renovate themselves originating, if adequately stimulated, a number of cell types. Inter alia, in orthopaedic field a particular type of adult stem cells is used, the mesenchymal stem cells (MSCs). If combined with synthetic material produced in laboratories, the usage of these cells has provided inspiration for new study interests; today, it can be applied in various degenerative and post-traumatic pathologies, with great therapeutic benefits for the patient. Actually, many studies write about an improvement in patients' life quality. In this sense appear significant reflections on legal medicine, both in accidents and insurance, of this innovative therapeutic alternative and is hopefully an equally valid process of improvement of regulatory and case law.

  20. Genetic Engineering of Mesenchymal Stem Cells for Regenerative Medicine.

    Science.gov (United States)

    Nowakowski, Adam; Walczak, Piotr; Janowski, Miroslaw; Lukomska, Barbara

    2015-10-01

    Mesenchymal stem cells (MSCs), which can be obtained from various organs and easily propagated in vitro, are one of the most extensively used types of stem cells and have been shown to be efficacious in a broad set of diseases. The unique and highly desirable properties of MSCs include high migratory capacities toward injured areas, immunomodulatory features, and the natural ability to differentiate into connective tissue phenotypes. These phenotypes include bone and cartilage, and these properties predispose MSCs to be therapeutically useful. In addition, MSCs elicit their therapeutic effects by paracrine actions, in which the metabolism of target tissues is modulated. Genetic engineering methods can greatly amplify these properties and broaden the therapeutic capabilities of MSCs, including transdifferentiation toward diverse cell lineages. However, cell engineering can also affect safety and increase the cost of therapy based on MSCs; thus, the advantages and disadvantages of these procedures should be discussed. In this review, the latest applications of genetic engineering methods for MSCs with regenerative medicine purposes are presented. PMID:26140302

  1. The Regenerative Role of the Fetal and Adult Stem Cell Secretome

    Directory of Open Access Journals (Sweden)

    Sveva Bollini

    2013-12-01

    Full Text Available For a long time, the stem cell regenerative paradigm has been based on the assumption that progenitor cells play a critical role in tissue repair by means of their plasticity and differentiation potential. However, recent works suggest that the mechanism underlying the benefits of stem cell transplantation might relate to a paracrine modulatory effect rather than the replacement of affected cells at the site of injury. Therefore, mounting evidence that stem cells may act as a reservoir of trophic signals released to modulate the surrounding tissue has led to a paradigm shift in regenerative medicine. Attention has been shifted from analysis of the stem cell genome to understanding the stem cell “secretome”, which is represented by the growth factors, cytokines and chemokines produced through paracrine secretion. Insights into paracrine-mediated repair support a new approach in regenerative medicine and the isolation and administration of specific stem cell-derived paracrine factors may represent an extremely promising strategy, introducing paracrine-based therapy as a novel and feasible clinical application. In this review, we will discuss the regenerative potential of fetal and adult stem cells, with particular attention to their secretome.

  2. New Therapeutic Window of Regenerative Opportunity in Diabetic Retinopathy by VESGEN Analysis

    Science.gov (United States)

    Parsons-Wingert, Patricia A.

    2012-01-01

    Vascular pattern may serve as a useful new biomarker principle of complex, multi-scale signaling in pathological, physiological angiogenesis and microvascular remodeling. Each angiogenesis stimulator or inhibitor we have analyzed, including VEGF, bFGF, TGF-beta1, angiostatin and triamcinolone acetonide, has induced a novel "fingerprint" or "signature" biomarker vascular pattern that is spatio-temporally unique. Remodeling vasculature thereby provides an informative read-out of dominant molecular signaling, when analyzed by innovative, fractal-based VESsel GENeration (VESGEN) Analysis software. Using VESGEN to analyze ophthalmic clinical vascular images, we recently introduced a potential paradigm shift to the understanding of early-stage progression that suggests new regenerative opportunities for human diabetic retinopathy (DR), the major blinding disease for working-aged adults. In a pilot study, we discovered that angiogenesis oscillates as a surprising, homeostatic-like regeneration of retinal vessels during early progression of DR (IOVS 51(1):498). Results suggest that the term non-proliferative DR may be a misnomer. In new studies, normalization of the vasculature will be determined from the response of vascular pattern to therapeutic monitoring and treatment. We have mapped and quantified in vivo experimental models of angiogenesis, lymphangiogenesis and intravital blood flow from cellular/molecular to higher systems levels that include a murine model of infant retinopathy of prematurity (ROP); developing and pathological coronary and placental-like vessel models; progressive intestinal inflammation, growing murine tumors, and other pathological, physiological and therapeutically treated tissues of transgenic mice and avian embryos. Vascular Alterations, Visual Impairments (VIIP) & Increased Intracranial Pressure (ICP), Immunosuppression & Bone Loss: NASA-defined risk categories for human space exploration and ISS Utilization

  3. REIMBURSEMENT OF CELL-BASED REGENERATIVE THERAPY IN THE UK AND FRANCE.

    Science.gov (United States)

    Mahalatchimy, Aurélie

    2016-01-01

    Cell-based regenerative therapies are presented as being able to cure the diseases of the twenty-first century, especially those coming from the degeneration of the aging human body. But their specific nature based on biological materials raises particular challenging issues on how regulation should frame biomedical innovation for society's benefit regarding public health. The European Union (EU) supports the development of cell-based regenerative therapies that are medicinal products with a specific regulation providing their wide access to the European market for European patients. However, once these medicinal products have obtained a European marketing authorisation, they are still far away from being fully accessible to European patients in all EU Member States. Whereas there is much written on the EU regulatory system for new biotechnologies, there is no systematic legal study comparing the insurance provisions in two EU countries. Focussing on the situation in the UK and France that are based on two different healthcare systems, this paper is based on a comparative methodological approach. It raises the question of regulatory reimbursement mechanisms that determine access to innovative treatments and their consequences for social protection systems in the general context of public health. After having compared the French and English regulations of cell-based regenerative therapy regarding pricing and reimbursement, this papers analyses how England and France are addressing two main challenges of cell-based regenerative therapy, to take into account their long-term benefit through their potential curative nature and their high upfront cost, towards their adoption within the English and French healthcare systems. It concludes that England and France have different general legal frameworks that are not specific to the reimbursement of cell-based regenerative therapy, although their two current and respective trends would bring more convergence between the two

  4. REIMBURSEMENT OF CELL-BASED REGENERATIVE THERAPY IN THE UK AND FRANCE.

    Science.gov (United States)

    Mahalatchimy, Aurélie

    2016-01-01

    Cell-based regenerative therapies are presented as being able to cure the diseases of the twenty-first century, especially those coming from the degeneration of the aging human body. But their specific nature based on biological materials raises particular challenging issues on how regulation should frame biomedical innovation for society's benefit regarding public health. The European Union (EU) supports the development of cell-based regenerative therapies that are medicinal products with a specific regulation providing their wide access to the European market for European patients. However, once these medicinal products have obtained a European marketing authorisation, they are still far away from being fully accessible to European patients in all EU Member States. Whereas there is much written on the EU regulatory system for new biotechnologies, there is no systematic legal study comparing the insurance provisions in two EU countries. Focussing on the situation in the UK and France that are based on two different healthcare systems, this paper is based on a comparative methodological approach. It raises the question of regulatory reimbursement mechanisms that determine access to innovative treatments and their consequences for social protection systems in the general context of public health. After having compared the French and English regulations of cell-based regenerative therapy regarding pricing and reimbursement, this papers analyses how England and France are addressing two main challenges of cell-based regenerative therapy, to take into account their long-term benefit through their potential curative nature and their high upfront cost, towards their adoption within the English and French healthcare systems. It concludes that England and France have different general legal frameworks that are not specific to the reimbursement of cell-based regenerative therapy, although their two current and respective trends would bring more convergence between the two

  5. Bone within a bone

    Energy Technology Data Exchange (ETDEWEB)

    Williams, H.J.; Davies, A.M. E-mail: wendy.turner@roh.nhs.uk; Chapman, S

    2004-02-01

    The 'bone within a bone' appearance is a well-recognized radiological term with a variety of causes. It is important to recognize this appearance and also to be aware of the differential diagnosis. A number of common conditions infrequently cause this appearance. Other causes are rare and some remain primarily of historical interest, as they are no longer encountered in clinical practice. In this review we illustrate some of the conditions that can give the bone within a bone appearance and discuss the physiological and pathological aetiology of each where known.

  6. An Intelligent Regenerative Braking Strategy for Electric Vehicles

    OpenAIRE

    Zhibin Song; Weimin Li; Guoqing Xu; Kun Xu

    2011-01-01

    Regenerative braking is an effective approach for electric vehicles (EVs) to extend their driving range. A fuzzy-logic-based regenerative braking strategy (RBS) integrated with series regenerative braking is developed in this paper to advance the level of energy-savings. From the viewpoint of securing car stability in braking operations, the braking force distribution between the front and rear wheels so as to accord with the ideal distribution curve are considered to prevent vehicles from ex...

  7. An Intelligent Regenerative Braking Strategy for Electric Vehicles

    OpenAIRE

    Guoqing Xu; Weimin Li; Kun Xu; Zhibin Song

    2011-01-01

    Regenerative braking is an effective approach for electric vehicles (EVs) to extend their driving range. A fuzzy-logic-based regenerative braking strategy (RBS) integrated with series regenerative braking is developed in this paper to advance the level of energy-savings. From the viewpoint of securing car stability in braking operations, the braking force distribution between the front and rear wheels so as to accord with the ideal distribution curve are considered to prevent vehicles from ex...

  8. Regenerative Endodontics: Barriers and Strategies for Clinical Translation

    OpenAIRE

    Kim, Sahng G.; Zhou, Jian; Ye, Ling; Cho, Shoko; Suzuki, Takahiro; Fu, Susan Y; Yang, Rujing; Zhou, Xuedong; Mao, Jeremy J.

    2012-01-01

    Despite a great deal of enthusiasm and effort, regenerative endodontics has encountered substantial challenges towards clinical translation. Recent adoption by the American Dental Association (ADA) of evoked pulp bleeding in immature permanent teeth is an important step for regenerative endodontics. However, there is no regenerative therapy for the majority of endodontic diseases. Simple recapitulation of cell therapy and tissue engineering strategies that are under development for other orga...

  9. Bone cysts: unicameral and aneurysmal bone cyst.

    Science.gov (United States)

    Mascard, E; Gomez-Brouchet, A; Lambot, K

    2015-02-01

    Simple and aneurysmal bone cysts are benign lytic bone lesions, usually encountered in children and adolescents. Simple bone cyst is a cystic, fluid-filled lesion, which may be unicameral (UBC) or partially separated. UBC can involve all bones, but usually the long bone metaphysis and otherwise primarily the proximal humerus and proximal femur. The classic aneurysmal bone cyst (ABC) is an expansive and hemorrhagic tumor, usually showing characteristic translocation. About 30% of ABCs are secondary, without translocation; they occur in reaction to another, usually benign, bone lesion. ABCs are metaphyseal, excentric, bulging, fluid-filled and multicameral, and may develop in all bones of the skeleton. On MRI, the fluid level is evocative. It is mandatory to distinguish ABC from UBC, as prognosis and treatment are different. UBCs resolve spontaneously between adolescence and adulthood; the main concern is the risk of pathologic fracture. Treatment in non-threatening forms consists in intracystic injection of methylprednisolone. When there is a risk of fracture, especially of the femoral neck, surgery with curettage, filling with bone substitute or graft and osteosynthesis may be required. ABCs are potentially more aggressive, with a risk of bone destruction. Diagnosis must systematically be confirmed by biopsy, identifying soft-tissue parts, as telangiectatic sarcoma can mimic ABC. Intra-lesional sclerotherapy with alcohol is an effective treatment. In spinal ABC and in aggressive lesions with a risk of fracture, surgical treatment should be preferred, possibly after preoperative embolization. The risk of malignant transformation is very low, except in case of radiation therapy.

  10. Nanotechnology-based approaches for regenerative medicine and biosensing

    Science.gov (United States)

    Solanki, Aniruddh P.

    The recent emergence of nanotechnology has set high expectations in many fields of science, especially in biology and medicine. Nanotechnology-based approaches are expected to solve key questions in the emerging field of regenerative medicine. Regenerative medicine essentially deals with regeneration of cells, ultimately leading to the formation of tissues and organs. For this purpose, stem cells, embryonic stem cells or adult stem cells, are thought to be ideal resources. However, many challenges need to be addressed before the full therapeutic potential of stem cells can be harnessed. Controlling the differentiation of stem cells into cells of a specific lineage is extremely vital and challenging. Addressing this challenge, in this work, novel nanotechnology-based approaches for controlling the differentiation of neural stem cells (NSCs) into neurons has been presented. Regeneration of damaged neurons, due to traumatic injuries or degenerative diseases, is extremely challenging. For this purpose, NSCs can be used as resources that can differentiate into neurons, thus having great potential in solving needs of many patients suffering from such conditions. For controlling the differentiation of stem cells, soluble cues (comprising of small molecules and biomolecules) and insoluble cues (cell-cell interactions and cell-microenvironment interactions) play a very important role. The delivery of soluble cues, such as genetic material, into stem cells is extremely challenging. The initial part of this work presents the use of nanomaterials for efficiently delivering soluble cues such as small molecules and small interfering RNA (siRNA) into NSCs for controlling their differentiation into neurons. However, for regenerative purposes, it is preferred that least amounts of the delivery vehicle be used. Thus, the following part of the thesis presents the development and applications of nanotechnology-based approaches for enhancing the differentiation of NSCs into neurons

  11. Compressorless Gas Storage and Regenerative Hydrogen Purification Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Microwave regenerative sorption media gas storage/delivery techniques are proposed to address both compressed gas management and hydrogen purification requirements...

  12. Cell fusion of bone marrow cells and somatic cell reprogramming by embryonic stem cells

    OpenAIRE

    Bonde, Sabrina; Pedram, Mehrdad; Stultz, Ryan; Zavazava, Nicholas

    2010-01-01

    Bone marrow transplantation is a curative treatment for many diseases, including leukemia, autoimmune diseases, and a number of immunodeficiencies. Recently, it was claimed that bone marrow cells transdifferentiate, a much desired property as bone marrow cells are abundant and therefore could be used in regenerative medicine to treat incurable chronic diseases. Using a Cre/loxP system, we studied cell fusion after bone marrow transplantation. Fused cells were chiefly Gr-1+, a myeloid cell mar...

  13. The possibilities of stem cell application in regenerative medicine

    Directory of Open Access Journals (Sweden)

    Galiniak Sabina

    2016-03-01

    Full Text Available Stem cells are characterized by their ability to self-renew and differentiate into various cell types. They offer great potential for a wide range of applications, however, medical studies on the use of embryonal stem cells are largely limited to bioethical issues searching for alternative sources of stem cells, which include isolating cells from adult organisms or inducing pluripotentiality of somatic cells by administration of transcription factors. Nowadays, stem cells are used to study the mechanisms of cell differentiation and treat diseases that are commonly considered to be incurable, such as diabetes and neurodegenerative diseases, as well as enable regeneration of skin damage and myocardium. This review introduces the subject of stem cells, their sources and application in regenerative medicine.

  14. Current overview on dental stem cells applications in regenerative dentistry

    Science.gov (United States)

    Bansal, Ramta; Jain, Aditya

    2015-01-01

    Teeth are the most natural, noninvasive source of stem cells. Dental stem cells, which are easy, convenient, and affordable to collect, hold promise for a range of very potential therapeutic applications. We have reviewed the ever-growing literature on dental stem cells archived in Medline using the following key words: Regenerative dentistry, dental stem cells, dental stem cells banking, and stem cells from human exfoliated deciduous teeth. Relevant articles covering topics related to dental stem cells were shortlisted and the facts are compiled. The objective of this review article is to discuss the history of stem cells, different stem cells relevant for dentistry, their isolation approaches, collection, and preservation of dental stem cells along with the current status of dental and medical applications. PMID:25810631

  15. Human Stromal (Mesenchymal) Stem Cells from Bone Marrow, Adipose Tissue and Skin Exhibit Differences in Molecular Phenotype and Differentiation Potential

    DEFF Research Database (Denmark)

    Al-Nbaheen, May; Vishnubalaji, Radhakrishnan; Ali, Dalia;

    2013-01-01

    Human stromal (mesenchymal) stem cells (hMSCs) are multipotent stem cells with ability to differentiate into mesoderm-type cells e.g. osteoblasts and adipocytes and thus they are being introduced into clinical trials for tissue regeneration. Traditionally, hMSCs have been isolated from bone marrow......, but the number of cells obtained is limited. Here, we compared the MSC-like cell populations, obtained from alternative sources for MSC: adipose tissue and skin, with the standard phenotype of human bone marrow MSC (BM-MSCs). MSC from human adipose tissue (human adipose stromal cells (hATSCs)) and human skin......, MSC populations obtained from different tissues exhibit significant differences in their proliferation, differentiation and molecular phenotype, which should be taken into consideration when planning their use in clinical protocols....

  16. Phosphorous-containing polymers for regenerative medicine

    International Nuclear Information System (INIS)

    Disease and injury have resulted in a large, unmet need for functional tissue replacements. Polymeric scaffolds can be used to deliver cells and bioactive signals to address this need for regenerating damaged tissue. Phosphorous-containing polymers have been implemented to improve and accelerate the formation of native tissue both by mimicking the native role of phosphorous groups in the body and by attachment of other bioactive molecules. This manuscript reviews the synthesis, properties, and performance of phosphorous-containing polymers that can be useful in regenerative medicine applications. (paper)

  17. In vitro evaluation of biomimetic chitosan-calcium phosphate scaffolds with potential application in bone tissue engineering.

    Science.gov (United States)

    Tanase, C E; Sartoris, A; Popa, M I; Verestiuc, L; Unger, R E; Kirkpatrick, C J

    2013-04-01

    This work reports on the physicochemical properties and in vitro cytotoxicity assessment of chitosan-calcium phosphate (Cs-CP) scaffolds for bone tissue engineering, which were synthesized by a novel biomimetic co-precipitation method. X-ray diffraction (XRD) along with scanning electron microscopy (SEM) analysis confirmed the porous morphology of the scaffolds and the amorphous nature of the inorganic phase with different crystallite sizes and the formation of various forms of calcium phosphate. Compressive mechanical testing revealed that the Young's modulus of the biomaterials is in the range of human trabecular bone. In vitro tests were performed on the biomaterials for up to 14 days to study the behavior of the osteoblast-like human cell line (MG63), primary human osteoblasts (HOS) and human dermal microvascular endothelial cells (HDMEC). The cytotoxicity was evaluated by the MTS assay for cell metabolism and the detection of membrane integrity (lactate dehydrogenase-LDH release). An expression of the vascular endothelial growth factor (VEGF) in the cell supernatants was quantified by ELISA. Cell viability gave values close to untreated controls for MG63 and HOS, while in the case of HDMEC the viability after 2 weeks in the cell culture was between 80-90%. The cytotoxicity induced by the Cs-CP scaffolds on MG63, HOS and HDMEC in vitro was evaluated by the amount of LDH released, which is a sensitive and accurate marker for cellular toxicity. The increased levels of VEGF obtained in the osteoblast culture highlights its important role in the regulation of vascularization and bone remodeling. The biological responses of the Cs-CP scaffolds demonstrate a similar proliferation and differentiation characteristics of the cells comparable to the controls. These results reveal that biomimetic Cs-CP composite scaffolds are promising biomaterials for bone tissue engineering; their in vivo response remains to be tested. PMID:23343569

  18. In vitro evaluation of biomimetic chitosan–calcium phosphate scaffolds with potential application in bone tissue engineering

    International Nuclear Information System (INIS)

    This work reports on the physicochemical properties and in vitro cytotoxicity assessment of chitosan–calcium phosphate (Cs–CP) scaffolds for bone tissue engineering, which were synthesized by a novel biomimetic co-precipitation method. X-ray diffraction (XRD) along with scanning electron microscopy (SEM) analysis confirmed the porous morphology of the scaffolds and the amorphous nature of the inorganic phase with different crystallite sizes and the formation of various forms of calcium phosphate. Compressive mechanical testing revealed that the Young's modulus of the biomaterials is in the range of human trabecular bone. In vitro tests were performed on the biomaterials for up to 14 days to study the behavior of the osteoblast-like human cell line (MG63), primary human osteoblasts (HOS) and human dermal microvascular endothelial cells (HDMEC). The cytotoxicity was evaluated by the MTS assay for cell metabolism and the detection of membrane integrity (lactate dehydrogenase-LDH release). An expression of the vascular endothelial growth factor (VEGF) in the cell supernatants was quantified by ELISA. Cell viability gave values close to untreated controls for MG63 and HOS, while in the case of HDMEC the viability after 2 weeks in the cell culture was between 80–90%. The cytotoxicity induced by the Cs–CP scaffolds on MG63, HOS and HDMEC in vitro was evaluated by the amount of LDH released, which is a sensitive and accurate marker for cellular toxicity. The increased levels of VEGF obtained in the osteoblast culture highlights its important role in the regulation of vascularization and bone remodeling. The biological responses of the Cs–CP scaffolds demonstrate a similar proliferation and differentiation characteristics of the cells comparable to the controls. These results reveal that biomimetic Cs–CP composite scaffolds are promising biomaterials for bone tissue engineering; their in vivo response remains to be tested. (paper)

  19. Prostaglandin E2: from clinical applications to its potential role in bone- muscle crosstalk and myogenic differentiation.

    Science.gov (United States)

    Mo, Chenglin; Romero-Suarez, Sandra; Bonewald, Lynda; Johnson, Mark; Brotto, Marco

    2012-12-01

    Prostaglandin E(2) (PGE(2)), a prostanoid synthesized from arachidonic acid via the cyclooxygenase pathway, is a modulator of physiological responses including inflammation, fever, and muscle regeneration. Several patents have been filed that are related to PGE(2), one of them being directly related to skeletal muscles. In this report, we first summarize the key patents describing inventions for the utilization of PGE(2) for either diagnostic or therapeutic purposes, including skeletal muscle. In the second part of our work we present new and exciting data that demonstrates that PGE(2) accelerates skeletal muscle myogenic differentiation. Our discovery resulted from our recent and novel concept of bone-muscle crosstalk. Bone and muscle are anatomically intimate endocrine organs and we aimed to determine whether this anatomical intimacy also translates into a biochemical communication from bone cells to muscle cells at the in vitro level. The effects of MLOY4 osteocyte-like cell conditioned medium (CM) and three osteocyte-secreted factors, PGE(2), sclerostin and monocyte chemotactic protein (MCP-3), on C2C12 myogenic differentiation were evaluated using morphological analyses, a customized 96-gene PCR array, and measurements of intracellular calcium levels. MLO-Y4 CM and PGE(2), but not sclerostin and MCP-3, induced acceleration of myogenesis of C2C12 myoblasts that was linked with significant modifications in intracellular calcium homeostasis. This finding should further stimulate the pursuit of new patents to explore the use of PGE(2) and the new concept of bone-muscle crosstalk for the development and application of inventions designed to treat muscle diseases characterized by enhanced muscle wasting, such as sarcopenia. PMID:23092433

  20. Encapsulation of bone morphogenic protein-2 with Cbfa1-overexpressing osteogenic cells derived from human embryonic stem cells in hydrogel accelerates bone tissue regeneration.

    Science.gov (United States)

    Kim, Min Jung; Park, Ji Sun; Kim, Sinae; Moon, Sung-Hwan; Yang, Han Na; Park, Keun-Hong; Chung, Hyung-Min

    2011-08-01

    Bone tissue defects caused by trauma and disease are significant problems in orthopedic surgery. Human embryonic stem cells (hESCs) hold great promise for the treatment of bone tissue disease in regenerative medicine. In this study, we have established an effective method for the differentiation of osteogenic cells derived from hESCs using a lentiviral vector containing the transcription factor Cbfa1. Differentiation was initiated in embryoid body formation of Cbfa1-expressing hESCs, resulting in a highly purified population of osteogenic cells based on flow cytometric analysis. These cells also showed characteristics of osteogenic cells in vitro, as determined by reverse-transcription (RT)-polymerase chain reaction and immunocytochemistry using osteoblast-specific markers. We also evaluated the regenerative potential of Cbfa1-expressing cells derived from hESCs (hESC-CECs) compared with hESCs and the osteogenic effects of bone morphogenic protein-2 (BMP2) encapsulated in thermoreversible hydrogel in vivo. hESC-CECs were embedded in hydrogel constructs enriched with BMP2 to promote bone regeneration. We observed prominent mineralization and the formation of nodule-like structures using von Kossa and alizarin red S staining. In addition, the expression patterns of osteoblast-specific genes were verified by RT-polymerase chain reaction, and immunohistochemical analysis revealed that collagen type 1 and Cbfa1 were highly expressed in hESC-CECs compared with other cell types. Taken together, our results suggest that encapsulation of hESC-CECs with BMP2 in hydrogel constructs appears to be a promising method to enhance the in vitro osteoblastic differentiation and in vivo osteogenic activity of hESC-CECs.

  1. Reengineered graft copolymers as a potential alternative for the bone tissue engineering application by inducing osteogenic markers expression and biocompatibility.

    Science.gov (United States)

    Thangavelu, Muthukumar; R Narasimha, Raghavan; Adithan, Aravinthan; A, Chandrasekaran; Jong-Hoon, Kim; Thotapalli Parvathaleswara, Sastry

    2016-07-01

    Composite scaffolds of nano-hydroxyapatite with demineralized bone matrix were prepared and they were graft copolymerized for better bone regeneration and drug delivery applications. The graft copolymers were characterized for their physiochemical properties using conventional methods like FTIR, TGA, XRD and SEM. The scaffolds were seeded with 3T3 and MG63 cells for studying their biocompatibility and their temporal expression of ALP activity, the rate of calcium deposition and their gene expression of collagen type I (Coll-1), osteopontin (OP), osteonectin (ON), and osteocalcin (OC) were studied. In vivo studies were conducted using sub-cutaneous implantation models in male Wister rats for 6 months. Periodic radiography and post-autopsy histopathology was analysed at 15days, 1, 2, 3, 4, 5, and 6 months. The obtained in vitro results clearly confirm that the bone scaffolds prepared in this study are biocompatible, superior osteoinductivity, capable of supporting growth, maturation of MG 63 osteoblast like cells; the gene expression profile revealed that the material is capable of supporting the in vitro growth and maturation of osteoblast-like cells and maturation. The in vivo results stand a testimony to the in vitro results in proving the biocompatibility and osteoinductivity of the materials.

  2. Differentiation potential of bone marrow mesenchymal stem cells into retina in normal and laser-injured rat eye

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jie; SHAN Qing; MA Ping; JIANG Yanming; CHEN Peng; WEN Jingxia; ZHOU You; QIAN Huanwen; PEI Xuetao

    2004-01-01

    Bone marrow mesenchymal stem cells (MSCs) can develop into hematopoietic and mesenchymal lineages but have not been known to participate in the production of retina. Here we report that bone marrow mesenchymal stem cells, after being subretinally transplanted into normal or Nd: YAG laser-injured rat eye, can integrate into RPE layer, photoreceptor layer, bipolar cell layer and ganglion layer. DAPI-labeling detection was used to trace the origin of the repopulating cells. DAPI fluorescence was used to identify retina cells of bone marrow origin 10, 20, 35 and 50 days after transplantation. No formation of rosettes was found but some random cells were found at the end of the observation. MSCs-originated cells spread more widely in the injured retinas than in the normal ones. Immunohistochemical detection showed that though the cells could express neuronal nuclei (NeuN), neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP) and cytokeratin (CK), the proteins expression in the injured transplantation group was abnormal in some region compared with that in the normal transplantation group. Electroretinogram (ERG) showed that ERG-b wave of the injured transplantation group is significantly higher than that of the two laser-injured control groups. These results suggest that a proportion of MSCs can differentiate into retina-like structure in vivo and the differentiation differs in normal and laser-injured retinas.

  3. Reengineered graft copolymers as a potential alternative for the bone tissue engineering application by inducing osteogenic markers expression and biocompatibility.

    Science.gov (United States)

    Thangavelu, Muthukumar; R Narasimha, Raghavan; Adithan, Aravinthan; A, Chandrasekaran; Jong-Hoon, Kim; Thotapalli Parvathaleswara, Sastry

    2016-07-01

    Composite scaffolds of nano-hydroxyapatite with demineralized bone matrix were prepared and they were graft copolymerized for better bone regeneration and drug delivery applications. The graft copolymers were characterized for their physiochemical properties using conventional methods like FTIR, TGA, XRD and SEM. The scaffolds were seeded with 3T3 and MG63 cells for studying their biocompatibility and their temporal expression of ALP activity, the rate of calcium deposition and their gene expression of collagen type I (Coll-1), osteopontin (OP), osteonectin (ON), and osteocalcin (OC) were studied. In vivo studies were conducted using sub-cutaneous implantation models in male Wister rats for 6 months. Periodic radiography and post-autopsy histopathology was analysed at 15days, 1, 2, 3, 4, 5, and 6 months. The obtained in vitro results clearly confirm that the bone scaffolds prepared in this study are biocompatible, superior osteoinductivity, capable of supporting growth, maturation of MG 63 osteoblast like cells; the gene expression profile revealed that the material is capable of supporting the in vitro growth and maturation of osteoblast-like cells and maturation. The in vivo results stand a testimony to the in vitro results in proving the biocompatibility and osteoinductivity of the materials. PMID:26998863

  4. The application of bone morphogenetic proteins to periodontal and peri-implant tissue regeneration: A literature review

    OpenAIRE

    Sasikumar, Karuppanan P.; Sugumari Elavarasu; Jayaprakash S Gadagi

    2012-01-01

    Progress in understanding the role of bone morphogenetic proteins (BMPs) in craniofacial and tooth development and the demonstration of stem cells in periodontal ligament have set the stage for periodontal regenerative therapy and tissue engineering. Furthermore, recent approval by the Food and Drug Administration of recombinant human BMPs for accelerating bone fusion in slow-healing fractures indicates that this protein family may prove useful in designing regenerative treatments in periodon...

  5. Transient Receptor Potential Channel and Interleukin-17A Involvement in LTTL Gel Inhibition of Bone Cancer Pain in a Rat Model.

    Science.gov (United States)

    Wang, Juyong; Zhang, Ruixin; Dong, Changsheng; Jiao, Lijing; Xu, Ling; Liu, Jiyong; Wang, Zhengtao; Lao, Lixing

    2015-07-01

    Cancer pain management is a challenge for which Chinese herbal medicine might be useful. To study the spinal mechanisms of the Chinese medicated gel Long-Teng-Tong-Luo (LTTL), a 7-herb compound, on bone cancer pain, a bone cancer pain model was made by inoculating the tibias of female rats with Walker 256 cells. LTTL gel or inert gel, 0.5 g/cm(2)/d, was applied to the skin of tumor-bearing tibias for 21 days beginning a day after the inoculation. Mechanical threshold and paw withdrawal latency to thermal stimulation was measured. Transient receptor potential (TRP) cation channels in lumbar dorsal root ganglia (DRG) were immunostained and counted, and lumbar spinal cord interleukin-17A (IL-17A) was measured with real-time polymerase chain reaction and enzyme-linked immunosorbent assay. TRP antagonists and interleukin (IL)-17A antibodies were intrathecally administered to determine their effects on bone cancer pain. The gel significantly (P cancer-induced mechanical allodynia and thermal hyperalgesia and inhibited cancer-enhanced expression of IL-17A in spinal astrocytes and the TRP subfamily members V1, A1, and V4 in lumbar DRG. Intrathecal TRP antagonists at 10 µg significantly (P cancer pain. IL-17A antibodies inhibited cancer pain, suggesting that IL-17A promotes such pain. The data show that LTTL gel inhibits cancer pain, and this might be accounted for by the decrease in expression of DRG TRP channels and spinal astrocyte IL-17A. PMID:26100378

  6. Histological evaluation of alternative film for regenerative techniques: experimentalstudy in rat mandibles

    Directory of Open Access Journals (Sweden)

    Ranulfo Duarte de AZEVEDO NETO

    2009-09-01

    Full Text Available Introduction:Today, Teflon is used for many biological applications in medicine and dentistry. In dentistry,it is used especially as a barrier,in the guided tissue regeneration (GTR and guided bone regeneration(GBRtechniques, presenting different levels of success. Objective:The objective of the present study was to evaluate through histological analysis the use of a Teflon film placed over intra-oral bone defectssurgically created in rats. Material and methods:16 adult male rats(WISTAR were divided in two groups:group T (test and C(control.Two experimental monitoring periods were analyzed: one and threeweeks. Bone defects were surgically created in the right mandible, withthe use of a carbide bur (3 mm diameter,anterior to the mentonianregion.In T group, bone defect was covered with a film of Teflon(expanded polytetrafluoroethylene, e-PTFE.In C group, defect wasfilled only with blood clot.After monitoring periods went through,animals were euthanized. Results: Due to the high malleability Teflonfilm filled the experimental defects, which caused a local tissue response characterized by the presence of a chronicle and acute inflammatoryinfiltrate,either at 1 or 3 weeks T groups.In 3-week T group, it waspossible to observe the development of bone tissue with initial matrix mineralization only from the edges of the defect. Bone developmentfrom the edges also happened in C group,with absence of intenseinflammatory processes.However,maintenance of tissue volume was poor.Conclusion: In the presented experimental model it was possibleto conclude that filling bone defect with Teflon film was prejudicial tolocal bone repair.To use Teflon film for regenerative techniques it isnecessary to improve physical properties,diminishing its malleability.

  7. New bio-ceramization processes applied to vegetable hierarchical structures for bone regeneration: an experimental model in sheep.

    Science.gov (United States)

    Filardo, Giuseppe; Kon, Elizaveta; Tampieri, Anna; Cabezas-Rodríguez, Rafael; Di Martino, Alessandro; Fini, Milena; Giavaresi, Gianluca; Lelli, Marco; Martínez-Fernández, Julian; Martini, Lucia; Ramírez-Rico, Joaquin; Salamanna, Francesca; Sandri, Monica; Sprio, Simone; Marcacci, Maurilio

    2014-02-01

    Bone loss is still a major problem in orthopedics. The purpose of this experimental study is to evaluate the safety and regenerative potential of a new scaffold based on a bio-ceramization process for bone regeneration in long diaphyseal defects in a sheep model. The scaffold was obtained by transformation of wood pieces into porous biomorphic silicon carbide (BioSiC®). The process enabled the maintenance of the original wood microstructure, thus exhibiting hierarchically organized porosity and high mechanical strength. To improve cell adhesion and osseointegration, the external surface of the hollow cylinder was made more bioactive by electrodeposition of a uniform layer of collagen fibers that were mineralized with biomimetic hydroxyapatite, whereas the internal part was filled with a bio-hybrid HA/collagen composite. The final scaffold was then implanted in the metatarsus of 15 crossbred (Merinos-Sarda) adult sheep, divided into 3 groups: scaffold alone, scaffold with platelet-rich plasma (PRP) augmentation, and scaffold with bone marrow stromal cells (BMSCs) added during implantation. Radiological analysis was performed at 4, 8, 12 weeks, and 4 months, when animals were sacrificed for the final radiological, histological, and histomorphometric evaluation. In all tested treatments, these analyses highlighted the presence of newly formed bone at the bone scaffolds' interface. Although a lack of substantial effect of PRP was demonstrated, the scaffold+BMSC augmentation showed the highest value of bone-to-implant contact and new bone growth inside the scaffold. The findings of this study suggest the potential of bio-ceramization processes applied to vegetable hierarchical structures for the production of wood-derived bone scaffolds, and document a suitable augmentation procedure in enhancing bone regeneration, particularly when combined with BMSCs.

  8. 3D printed PLA-based scaffolds: a versatile tool in regenerative medicine.

    Science.gov (United States)

    Serra, Tiziano; Mateos-Timoneda, Miguel A; Planell, Josep A; Navarro, Melba

    2013-10-01

    Rapid prototyping (RP), also known as additive manufacturing (AM), has been well received and adopted in the biomedical field. The capacity of this family of techniques to fabricate customized 3D structures with complex geometries and excellent reproducibility has revolutionized implantology and regenerative medicine. In particular, nozzle-based systems allow the fabrication of high-resolution polylactic acid (PLA) structures that are of interest in regenerative medicine. These 3D structures find interesting applications in the regenerative medicine field where promising applications including biodegradable templates for tissue regeneration purposes, 3D in vitro platforms for studying cell response to different scaffolds conditions and for drug screening are considered among others. Scaffolds functionality depends not only on the fabrication technique, but also on the material used to build the 3D structure, the geometry and inner architecture of the structure, and the final surface properties. All being crucial parameters affecting scaffolds success. This Commentary emphasizes the importance of these parameters in scaffolds' fabrication and also draws the attention toward the versatility of these PLA scaffolds as a potential tool in regenerative medicine and other medical fields.

  9. Preparation and characterization of polylactide/poly(ε-caprolactone-poly(ethylene glycol-poly(ε-caprolactone hybrid fibers for potential application in bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Wang YL

    2014-04-01

    Full Text Available YueLong Wang,1,2,* Gang Guo,1,* HaiFeng Chen,2 Xiang Gao,1 RangRang Fan,1 DongMei Zhang,1 LiangXue Zhou2 1State Key Laboratory of Biotherapy and Cancer Center, 2Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China *These authors contributed equally to this paper Abstract: The aim of this study was to develop a kind of osteogenic biodegradable composite graft consisting of human placenta-derived mesenchymal stem cell (hPMSC material for site-specific repair of bone defects and attenuation of clinical symptoms. The novel nano- to micro-structured biodegradable hybrid fibers were prepared by electrospinning. The characteristics of the hybrid membranes were investigated by a range of methods, including Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. Morphological study with scanning electron microscopy showed that the average fiber diameter and the number of nanoscale pores on each individual fiber surface decreased with increasing concentration of poly(ε-caprolactone-poly(ethylene glycol-poly(ε-caprolactone (PCEC. The prepared polylactide (PLA/PCEC fibrous membranes favored hPMSC attachment and proliferation by providing an interconnected, porous, three-dimensional mimicked extracellular environment. What is more, hPMSCs cultured on the electrospun hybrid PLA/PCEC fibrous scaffolds could be effectively differentiated into bone-associated cells by positive alizarin red staining. Given the good cellular response and excellent osteogenic potential in vitro, the electrospun PLA/PCEC fibrous scaffolds could be one of the most promising candidates for bone tissue engineering. Keywords: electrospinning, PLA, PCEC, hPMSCs, bone tissue engineering

  10. Allogeneic compact bone-derived mesenchymal stem cell transplantation increases survival of mice exposed to lethal total body irradiation: a potential immunological mechanism

    Institute of Scientific and Technical Information of China (English)

    Qiao Shukai; Ren Hanyun; Shi Yongjin; Liu Wei

    2014-01-01

    Background Radiation-induced injury after accidental or therapeutic total body exposure to ionizing radiation has serious pathophysiological consequences,and currently no effective therapy exists.This study was designed to investigate whether transplantation of allogeneic murine compact bone derived-mesenchymal stem cells (CB-MSCs) could improve the survival of mice exposed to lethal dosage total body irradiation (TBI),and to explore the potential immunoprotective role of MSCs.Methods BALB/c mice were treated with 8 Gy TBI,and then some were administered CB-MSCs isolated from C57BL/6 mice.Survival rates and body weight were analyzed for 14 days post-irradiation.At three days post-irradiation,we evaluated IFN-Y and IL-4 concentrations; CD4+CD25+Foxp3+ regulatory T cell (Treg) percentage; CXCR3,CCR5,and CCR7 expressions on CD3+T cells; and splenocyte T-bet and GATA-3 mRNA levels.CB-MSC effects on bone marrow hemopoiesis were assessed via colony-forming unit granulocyte/macrophage (CFU-GM) assay.Results After lethal TBI,compared to non-transplanted mice,CB-MSC-transplanted mice exhibited significantly increased survival,body weight,and CFU-GM counts of bone marrow cells (P<0.05),as well as higher Treg percentages,reduced IFN-Y,CXCR3 and CCR5 down-regulation,and CCR7 up-regulation.CB-MSC transplantation suppressed Th1 immunity.Irradiated splenocytes directly suppressed CFU-GM formation from bone marrow cells,and CB-MSC co-culture reversed this inhibition.Conclusion Allogeneic CB-MSC transplantation attenuated radiation-induced hematopoietic toxicity,and provided immunoprotection by alleviating lymphocyte-mediated CFU-GM inhibition,expanding Tregs,regulating T cell chemokine receptor expressions,and skewing the Th1/Th2 balance toward anti-inflammatory Th2 polarization.

  11. Multiple excitation regenerative amplifier inertial confinement system

    International Nuclear Information System (INIS)

    The invention relates to apparatus and methods for producing high intensity laser radiation generation which is achieved through an optical amplifier-storage ring design. One or two synchronized, counterpropagating laser pulses are injected into a regenerative amplifier cavity and amplified by gain media which are pumped repetitively by electrical or optical means. The gain media excitation pulses are tailored to efficiently amplify the laser pulses during each transit. After the laser pulses have been amplified to the desired intensity level, they are either switched out of the cavity by some switch means, as for example an electro-optical device, for any well known laser end uses, or a target means may be injected into the regenerative amplifier cavity in such a way as to intercept simultaneously the counterpropagating laser pulses. One such well known end uses to which this invention is intended is for production of high density and temperature plasmas suitable for generating neutrons, ions and x-rays and for studying matter heated by high intensity laser radiation

  12. PRMT7 Preserves Satellite Cell Regenerative Capacity

    Directory of Open Access Journals (Sweden)

    Roméo Sébastien Blanc

    2016-02-01

    Full Text Available Regeneration of skeletal muscle requires the continued presence of quiescent muscle stem cells (satellite cells, which become activated in response to injury. Here, we report that whole-body protein arginine methyltransferase PRMT7−/− adult mice and mice conditionally lacking PRMT7 in satellite cells using Pax7-CreERT2 both display a significant reduction in satellite cell function, leading to defects in regenerative capacity upon muscle injury. We show that PRMT7 is preferentially expressed in activated satellite cells and, interestingly, PRMT7-deficient satellite cells undergo cell-cycle arrest and premature cellular senescence. These defects underlie poor satellite cell stem cell capacity to regenerate muscle and self-renew after injury. PRMT7-deficient satellite cells express elevated levels of the CDK inhibitor p21CIP1 and low levels of its repressor, DNMT3b. Restoration of DNMT3b in PRMT7-deficient cells rescues PRMT7-mediated senescence. Our findings define PRMT7 as a regulator of the DNMT3b/p21 axis required to maintain muscle stem cell regenerative capacity.

  13. Regenerative fuel cell systems R and D

    Energy Technology Data Exchange (ETDEWEB)

    Mitlitsky, F.; Myers, B.; Weisberg, A.H. [Lawrence Livermore National Lab., Livermore, CA (United States)

    1998-08-01

    Regenerative fuel cell (RFC) systems produce power and electrolytically regenerate their reactants using stacks of electrochemical cells. Energy storage systems with extremely high specific energy (> 400 Wh/kg) have been designed that use lightweight pressure vessels to contain the gases generated by reversible (unitized) regenerative fuel cells (URFCs). Progress is reported on the development, integration, and operation of rechargeable energy storage systems with such high specific energy. Lightweight pressure vessels that enable high specific energies have been designed with performance factors (burst pressure/internal volume/tank weight) > 50 km (2.0 million inches), and a vessel with performance factor of 40 km (1.6 million inches) was fabricated. New generations of both advanced and industry-supplied hydrogen tankage are under development. A primary fuel cell test rig with a single cell (46 cm{sup 2} active area) has been modified and operated reversibly as a URFC (for up to 2010 cycles on a single cell). This URFC uses bifunctional electrodes (oxidation and reduction electrodes reverse roles when switching from charge to discharge, as with a rechargeable battery) and cathode feed electrolysis (water is fed from the hydrogen side of the cell). Recent modifications also enable anode feed electrolysis (water is fed from the oxygen side of the cell). Hydrogen/halogen URFCs, capable of higher round-trip efficiency than hydrogen/oxygen URFCs, have been considered, and will be significantly heavier. Progress is reported on higher performance hydrogen/oxygen URFC operation with reduced catalyst loading.

  14. ``HYTEC''—A thermally regenerative fuel cell

    Science.gov (United States)

    Roy, Prodyot; Salamah, Samir A.; Maldonado, Jerry; Narkiewicz, Regina S.

    1993-01-01

    HYTEC (Hydrogen Thermo-Electrochemical Converter) is a thermally regenerative fuel cell for direct conversion of heat into electricity. The principles of basic cell operation involve ionic transport of hydrogen through a hydride-ion (H-) conducting, molten electrolyte, and reaction with alkali metals, oxygen, or air. In order to operate HYTEC in a thermally regenerative mode, pure Li and Na, or a mixture of Li/Na alloy, is used for reaction with hydrogen, to form metal hydride which is subsequently decomposed to metal and hydrogen at higher temperatures. The reactants are then separated and redirected to the electrochemical cell. In the cell the molten, H--conducting electrolyte is immobilized between two thin hydrogen-permeable, solid, metallic electrodes which also act as current collectors. The H2 gas first diffuses through the cathode electrode and forms a hydride ion (H+e→H-) at the cathode-electrolyte interface. The H- ion subsequently migrated through the electrolyte under a chemical potential gradient created by the presence of the alkali metal in the anode chamber. The H- ion releases the electron to form hydrogen atoms (H-→H+e) at the anode-electrolyte interface. The hydrogen atom diffuses through the anode electrode and reacts with the alkali metal to form metal hydride. The electron released passes through the load circuit to complete the cycle. In the regeneration scheme, the fuel cell is operated at temperature T1. The metal hydride formed at the anode is pumped to the decomposition chamber through a recuperator. The metal hydride is decomposed at a higher temperature, T2, by an external heat source. The H2 gas is separated from the alkali metal by a H2-permeable, solid, metallic membrane and fed into the anode chamber of the cell. The hydrogen-depleted alkali metal is directed to the cathode chamber of the cell, via the recuperator, to complete the cycle. To date, electrochemical feasibility of the concept has been experimentally demonstrated. A

  15. Hyaluronan scaffold supports osteogenic differentiation of bone marrow concentrate cells.

    Science.gov (United States)

    Cavallo, C; Desando, G; Ferrari, A; Zini, N; Mariani, E; Grigolo, B

    2016-01-01

    Osteochondral lesions are considered a challenge for orthopedic surgeons. Currently, the treatments available are often unsatisfactory and unable to stimulate tissue regeneration. Tissue engineering offers a new therapeutic strategy, taking into account the role exerted by cells, biomaterial and growth factors in restoring tissue damage. In this light, Mesenchymal Stem Cells (MSCs) have been indicated as a fascinating tool for regenerative medicine thanks to their ability to differentiate into bone, cartilage and adipose tissue. However, in vitro-cultivation of MSCs could be associated with some risks such as de-differentiation/reprogramming, infection and contaminations of the cells. To overcome these shortcomings, a new approach is represented by the use of Bone Marrow Concentrate (BMC), that could allow the delivery of cells surrounded by their microenvironment in injured tissue. For this purpose, cells require a tridimensional scaffold that can support their adhesion, proliferation and differentiation. This study is focused on the potentiality of BMC seeded onto a hyaluronan-based scaffold (Hyaff-11) to differentiate into osteogenic lineage. This process depends on the specific interaction between cells derived from bone marrow (surrounded by their niche) and scaffold, that create an environment able to support the regeneration of damaged tissue. The data obtained from the present study demonstrate that BMC grown onto Hyaff-11 are able to differentiate toward osteogenic sense, producing specific osteogenic genes and matrix proteins.

  16. Regenerative approach to bilateral rostral mandibular reconstruction in a case series of dogs

    Directory of Open Access Journals (Sweden)

    Boaz eArzi

    2015-03-01

    Full Text Available Extensive rostral mandibulectomy in dogs typically results in instability of the mandibles that may lead to malocclusion, difficulty in eating and drinking, food prehension, and pain of the temporomandibular joint. Large rostral mandibular defects are challenging to reconstruct due to the complex geometry of this region. In order to restore mandibular continuity and stability following extensive rostral mandibulectomy, we developed a surgical technique using a combination of intraoral and extraoral approaches, a locking titanium plate and a compression resistant matrix (CRM infused with rhBMP-2. Furthermore, surgical planning that consisted of computed tomographic (CT scanning and 3D model printing were utilized. We describe a regenerative surgical technique for immediate or delayed reconstruction of critical-size rostral mandibular defects in 5 dogs. Three dogs had healed with intact gingival covering over the mandibular defect and had immediate return to normal function and occlusion. Two dogs had the complication of focal plate exposure and dehiscence, which was corrected with mucosal flaps and suturing; these dogs have since healed with intact gingival covering over the mandibular defect. Mineralized tissue formation was palpated clinically within 2 weeks and solid bone formation within 3 months. Computed tomography findings at 6 months postoperatively demonstrated that the newly regenerated mandibular bone had increased in mineral volume with evidence of integration between the native bone, new bone and CRM compared to the immediate postoperative CT. We conclude that rostral mandibular reconstruction using a regenerative approach provides an excellent solution for restoring mandibular continuity and preventing mandibular instability in dogs.

  17. TISSUE REGENERATION. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration.

    Science.gov (United States)

    Zhang, Yongyou; Desai, Amar; Yang, Sung Yeun; Bae, Ki Beom; Antczak, Monika I; Fink, Stephen P; Tiwari, Shruti; Willis, Joseph E; Williams, Noelle S; Dawson, Dawn M; Wald, David; Chen, Wei-Dong; Wang, Zhenghe; Kasturi, Lakshmi; Larusch, Gretchen A; He, Lucy; Cominelli, Fabio; Di Martino, Luca; Djuric, Zora; Milne, Ginger L; Chance, Mark; Sanabria, Juan; Dealwis, Chris; Mikkola, Debra; Naidoo, Jacinth; Wei, Shuguang; Tai, Hsin-Hsiung; Gerson, Stanton L; Ready, Joseph M; Posner, Bruce; Willson, James K V; Markowitz, Sanford D

    2015-06-12

    Agents that promote tissue regeneration could be beneficial in a variety of clinical settings, such as stimulating recovery of the hematopoietic system after bone marrow transplantation. Prostaglandin PGE2, a lipid signaling molecule that supports expansion of several types of tissue stem cells, is a candidate therapeutic target for promoting tissue regeneration in vivo. Here, we show that inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. In a chemical screen, we identify a small-molecule inhibitor of 15-PGDH (SW033291) that increases prostaglandin PGE2 levels in bone marrow and other tissues. SW033291 accelerates hematopoietic recovery in mice receiving a bone marrow transplant. The same compound also promotes tissue regeneration in mouse models of colon and liver injury. Tissues from 15-PGDH knockout mice demonstrate similar increased regenerative capacity. Thus, 15-PGDH inhibition may be a valuable therapeutic strategy for tissue regeneration in diverse clinical contexts.

  18. Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease

    Directory of Open Access Journals (Sweden)

    Harrison MR

    2013-01-01

    Full Text Available Michael R Harrison, Terence Z Wong, Andrew J Armstrong, Daniel J GeorgeDuke Cancer Institute, Durham, NC, USABackground: Radium-223 chloride (223Ra; Alpharadin is an alpha-emitting radioisotope that targets areas of osteoblastic metastasis and is excreted by the small intestine. When compared with beta-emitters (eg, strontium-89, samarium-153, 223Ra delivers a high quantity of energy per track length with short tissue penetration.Objective: This review describes the mechanism, radiobiology, and preclinical development of 223Ra and discusses the clinical data currently available regarding its safety and efficacy profile.Methods: Data from clinical trials including abstracts were collected and reviewed using the PubMed Database, as well as the American Society of Clinical Oncology abstract database.Conclusion: Current bone-targeted therapies fall into two main categories: antiresorptive agents (eg, zoledronic acid, denosumab, which have been shown to delay skeletal-related events, and radiopharmaceuticals (eg, samarium-153, which may have a role in pain palliation. Historically, neither antiresorptive agents nor radiopharmaceuticals have shown definitive evidence of improved overall survival or other antitumor effects in metastatic castrate-resistant prostate cancer (mCRPC. Radiopharmaceuticals are limited by myelosuppresion, thrombocytopenia, and renal excretion. In a recently reported randomized Phase III trial in men with symptomatic bone-metastatic CRPC who had received or were ineligible for docetaxel chemotherapy, 223Ra treatment resulted in improved overall survival and delayed skeletal-related events. Toxicity consisted of minor gastrointestinal side effects and mild neutropenia and thrombocytopenia that were rarely severe. Pending regulatory approval, 223Ra may represent a unique and distinct option for an important subgroup of patients with mCRPC; future trials should address its use in combination or in sequence with existing and novel

  19. Potential regenerative treatment strategies for intervertebral disc degeneration in dogs

    NARCIS (Netherlands)

    Bach, Frances C; Willems, Nicole; Penning, Louis C; Ito, Keita; Meij, Björn P; Tryfonidou, Marianna A

    2014-01-01

    Pain due to spontaneous intervertebral disc (IVD) disease is common in dogs. In chondrodystrophic (CD) dogs, IVD disease typically develops in the cervical or thoracolumbar spine at about 3-7 years of age, whereas in non-chondrodystrophic (NCD) dogs, it usually develops in the caudal cervical or lum

  20. Potential of salivary gland stem cells in regenerative medicine

    NARCIS (Netherlands)

    Maimets, Martti

    2016-01-01

    Weefselspecifieke volwassen stamcellen hebben de aandacht getrokken van de biomedische gemeenschap doordat ze in staat zijn om alle celtypes van een orgaan te vormen waardoor ze bruikbaar zouden kunnen zijn voor stamceltherapie. De hoop is dat deze cellen beschadigd weefsel kunnen herstellen en well

  1. Thermal Characteristics of Heating-furnace with Regenerative Burner

    OpenAIRE

    HUA, Jianshe; Li, Xiaoming; Kawabata, Nobuyoshi

    2005-01-01

    Thermal characteristics between the heating-furnace with regenerative burner and the classical triple-fired continuous furnace by heat balance testing for two billet steel heating-furnace at the same billet steel heating have been analyzed. In addition, the operating principle, the thermal characteristics and the effect of energy saving for heating-furnace with regenerative burner are introduced.

  2. Numerical Modelling of Regenerative Liquid Propellant Guns with Annular Piston

    OpenAIRE

    K. J. Daniel; D. K. Kharat; K.R. Rao; Shah, S.T.; S. C. Mitra

    1997-01-01

    The development of regenerative liquid propellant guns (RLPGs) needs due consideration of numerous interdependent parameters that affect its performance. To help in this task, computer simulation was undertaken to predict internal ballistics of a conceptual liquid propellant gun. The expected pressure and other important parameters are documented which serve as an aid to the hardware, design of the regenerative liquid propellant guns.

  3. Regenerative medicine. Opportunities and challenges: a brief overview

    OpenAIRE

    Polak, Dame Julia

    2010-01-01

    Regenerative medicine is a new multi-disciplinary field aiming at the repair or replacement of disease body parts. The field is progressing at an unprecedented pace and although the opportunities are immense, many hurdles lie ahead. This brief review analyses the opportunities and challenges faced by regenerative medicine.

  4. Stem Cells: Intellectual Property Issues in Regenerative Medicine

    OpenAIRE

    Zachariades, Nicholas A.

    2013-01-01

    The topic of stem cells for use in regenerative medicine, especially embryonic stem cells, inspires much debate, discussion, and outrage as it slices through the very core moral values of society. These social and moral issues have, in turn, resulted in government policies that have influenced the study of stem cells in regenerative medicine.

  5. Nodular regenerative hyperplasia mimicking cirrhosis of the liver.

    OpenAIRE

    McDonald, J A; Painter, D M; Gallagher, N. D.; McCaughan, G W

    1990-01-01

    Nodular regenerative hyperplasia of the liver usually presents with signs of portal hypertension with little evidence of obvious liver disease. We report a 47 year old man who presented with clinical signs of decompensated cirrhosis, recurrent encephalopathy, and tense ascites but at liver transplant was found to have nodular regenerative hyperplasia associated with a portal vein thrombosis.

  6. In vitro assessment of biomaterial-induced remodeling of subchondral and cancellous bone for the early intervention of joint degeneration with focus on the spinal disc

    Science.gov (United States)

    McCanless, Jonathan D.

    Osteoarthritis-associated pain of the spinal disc, knee, and hip derives from degeneration of cartilagenous tissues in these joints. Traditional therapies have focused on these cartilage (and disc specific nucleus pulposus) changes as a means of treatment through tissue grafting, regenerative synthetic implants, non-regenerative space filling implants, arthroplasty, and arthrodesis. Although such approaches may seem apparent upon initial consideration of joint degeneration, tissue pathology has shown changes in the underlying bone and vascular bed precede the onset of cartilaginous changes. It is hypothesized that these changes precedent joint degeneration and as such may provide a route for early prevention. The current work proposes an injectable biomaterial-based therapy within these subchondral and cancellous bone regions as a means of preventing or reversing osteoarthritis. Two human concentrated platelet releasate-containing alginate hydrogel/beta-tricalcium phosphate composites have been developed for this potential biomaterial application. The undertaking of assessing these materials through bench-, in vitro, and ex vivo work is described herein. These studies showed the capability of the biomaterials to initiate a wound healing response in monocytes, angiogenic and differentiation behavior in immature endothelial cells, and early osteochondral differentiation in mesenchymal stem cells. These cellular activities are associated with fracture healing and endochondral bone formation, demonstrating the potential of the biomaterials to induce osseous and vascular tissue remodeling underlying osteoarthritic joints as a novel therapy for a disease with rapidly growing healthcare costs.

  7. Quantitative evaluation of regularized phase retrieval algorithms on bone scaffolds seeded with bone cells.

    Science.gov (United States)

    Weber, L; Langer, M; Tavella, S; Ruggiu, A; Peyrin, F

    2016-05-01

    In the field of regenerative medicine, there has been a growing interest in studying the combination of bone scaffolds and cells that can maximize newly formed bone. In-line phase-contrast x-ray tomography was used to image porous bone scaffolds (Skelite(©)), seeded with bone forming cells. This technique allows the quantification of both mineralized and soft tissue, unlike with classical x-ray micro-computed tomography. Phase contrast images were acquired at four distances. The reconstruction is typically performed in two successive steps: phase retrieval and tomographic reconstruction. In this work, different regularization methods were applied to the phase retrieval process. The application of a priori terms for heterogeneous objects enables quantitative 3D imaging of not only bone morphology, mineralization, and soft tissue formation, but also cells trapped in the pre-bone matrix. A statistical study was performed to derive statistically significant information on the different culture conditions. PMID:27054380

  8. Quantitative evaluation of regularized phase retrieval algorithms on bone scaffolds seeded with bone cells

    Science.gov (United States)

    Weber, L.; Langer, M.; Tavella, S.; Ruggiu, A.; Peyrin, F.

    2016-05-01

    In the field of regenerative medicine, there has been a growing interest in studying the combination of bone scaffolds and cells that can maximize newly formed bone. In-line phase-contrast x-ray tomography was used to image porous bone scaffolds (Skelite©), seeded with bone forming cells. This technique allows the quantification of both mineralized and soft tissue, unlike with classical x-ray micro-computed tomography. Phase contrast images were acquired at four distances. The reconstruction is typically performed in two successive steps: phase retrieval and tomographic reconstruction. In this work, different regularization methods were applied to the phase retrieval process. The application of a priori terms for heterogeneous objects enables quantitative 3D imaging of not only bone morphology, mineralization, and soft tissue formation, but also cells trapped in the pre-bone matrix. A statistical study was performed to derive statistically significant information on the different culture conditions.

  9. Distribution Atlas of Proliferating Bone Marrow in Non-Small Cell Lung Cancer Patients Measured by FLT-PET/CT Imaging, With Potential Applicability in Radiation Therapy Planning

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, Belinda A., E-mail: Belinda.Campbell@petermac.org [Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Callahan, Jason [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Bressel, Mathias [Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, East Melbourne (Australia); Simoens, Nathalie [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Everitt, Sarah [Radiotherapy Services, Peter MacCallum Cancer Centre, East Melbourne (Australia); Hofman, Michael S.; Hicks, Rodney J. [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Burbury, Kate [Department of Haematology, Peter MacCallum Cancer Centre, East Melbourne (Australia); MacManus, Michael [Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia)

    2015-08-01

    Purpose: Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)–positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility. Methods and Materials: The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status. Results: Fifty-one patients were studied: 67% male; median age 68 (range, 31-87) years; 8% never smokers; 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age. Conclusions: This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interindividual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow; in such cases, individual FLT-PET scans may be required.

  10. Distribution Atlas of Proliferating Bone Marrow in Non-Small Cell Lung Cancer Patients Measured by FLT-PET/CT Imaging, With Potential Applicability in Radiation Therapy Planning

    International Nuclear Information System (INIS)

    Purpose: Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)–positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility. Methods and Materials: The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status. Results: Fifty-one patients were studied: 67% male; median age 68 (range, 31-87) years; 8% never smokers; 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age. Conclusions: This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interindividual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow; in such cases, individual FLT-PET scans may be required

  11. Potential antitumor effects of nitrogen-containing bisphosphonate in hormone receptor negative breast cancer patients with bone metastases

    International Nuclear Information System (INIS)

    This retrospective study evaluated, according to hormone receptor status, the antitumor effects of bisphosphonate especially on survival and disease progression in breast cancer patients with metastatic bone disease. Of 317 patients with initial bone metastasis and known breast cancer subtypes, 230 patients (72.6%) had hormone receptor (HR) positive tumors, and 87 patients (27.4%) had HR negative tumors. We assessed the primary outcome of overall survival (OS), after adjusting for other factors, comparing a group that received bisphosphonates (BPs) with a group that did not receive it. 87.8% of HR positive and 69.0% of HR negative patients received BPs with a median number of 17.7 cycles. Although BPs treatment made no survival benefit in HR positive group, HR negative patients showed a significant prolonged survival when they received BPs treatment (hazard ratio = 0.56 [95% CI 0.34 to 0.91], P = 0.019). In multivariate analysis, disease free interval > 2 years (P = 0.036), a sum of metastatic sites < 3 (P = 0.034), and BP treatments (P = 0.007) were significant factors for survival in HR negative patients. Bisphosphonate treatment can result in a survival benefit in metastatic breast cancer patients with HR negative tumors

  12. Can Bone Tissue Engineering Contribute to Therapy Concepts after Resection of Musculoskeletal Sarcoma?

    Directory of Open Access Journals (Sweden)

    Boris Michael Holzapfel

    2013-01-01

    Full Text Available Resection of musculoskeletal sarcoma can result in large bone defects where regeneration is needed in a quantity far beyond the normal potential of self-healing. In many cases, these defects exhibit a limited intrinsic regenerative potential due to an adjuvant therapeutic regimen, seroma, or infection. Therefore, reconstruction of these defects is still one of the most demanding procedures in orthopaedic surgery. The constraints of common treatment strategies have triggered a need for new therapeutic concepts to design and engineer unparalleled structural and functioning bone grafts. To satisfy the need for long-term repair and good clinical outcome, a paradigm shift is needed from methods to replace tissues with inert medical devices to more biological approaches that focus on the repair and reconstruction of tissue structure and function. It is within this context that the field of bone tissue engineering can offer solutions to be implemented into surgical therapy concepts after resection of bone and soft tissue sarcoma. In this paper we will discuss the implementation of tissue engineering concepts into the clinical field of orthopaedic oncology.

  13. Transient three-dimensional startup side load analysis of a regeneratively cooled nozzle

    Science.gov (United States)

    Wang, Ten-See

    2009-07-01

    The objective of this effort is to develop a computational methodology to capture the side load physics and to anchor the computed aerodynamic side loads with the available data by simulating the startup transient of a regeneratively cooled, high-aspect-ratio nozzle, hot-fired at sea level. The computational methodology is based on an unstructured-grid, pressure-based, reacting flow computational fluid dynamics and heat transfer formulation, and a transient inlet history based on an engine system simulation. Emphases were put on the effects of regenerative cooling on shock formation inside the nozzle, and ramp rate on side load reduction. The results show that three types of asymmetric shock physics incur strong side loads: the generation of combustion wave, shock transitions, and shock pulsations across the nozzle lip, albeit the combustion wave can be avoided with sparklers during hot-firing. Results from both regenerative cooled and adiabatic wall boundary conditions capture the early shock transitions with corresponding side loads matching the measured secondary side load. It is theorized that the first transition from free-shock separation to restricted-shock separation is caused by the Coanda effect. After which the regeneratively cooled wall enhances the Coanda effect such that the supersonic jet stays attached, while the hot adiabatic wall fights off the Coanda effect, and the supersonic jet becomes detached most of the time. As a result, the computed peak side load and dominant frequency due to shock pulsation across the nozzle lip associated with the regeneratively cooled wall boundary condition match those of the test, while those associated with the adiabatic wall boundary condition are much too low. Moreover, shorter ramp time results show that higher ramp rate has the potential in reducing the nozzle side loads.

  14. Development and characterization of an injectable dextrin-based hydrogel for bone regeneration

    OpenAIRE

    Dina M. Silva; Daniella L. Morgado; Delair, T; David, L; Rouif, S.; López-Lacomba, J. L.; A C Maurício; Santos, J. D.; Gama, F. M.

    2014-01-01

    Bone is a dynamic, highly vascularized tissue that remodels itself continuously over an individual ́s lifetime. It plays several important roles in maintaining homeostasis of the body systems [ 1 , 2 ] . However, this regenerative capac ity is limited and, as in the case of large bone defects, where the template for an orchestrated regeneration is absent, surgical proce dures are needed [ 2...

  15. Researches on regenerative medicine——current state and prospect

    Institute of Scientific and Technical Information of China (English)

    WANG Zheng-guo; XIAO Kai

    2012-01-01

    Since 1980s,the rapid development of tissue engineering and stem cell research has pushed regenerative medicine to a new fastigium,and regenerative medicine has become a noticeable research field in the international biology and medicine.In China,about 100 million patients need repair and regeneration treatment every year,while the number is much larger in the world.Regenerative medicine could provide effective salvation for these patients.Both Chinese Academy of Sciences and Chinese Academy of Engineering have made roadmaps of 2010-2050 and 2011-2030 for regenerative medicine.The final goal of the two roadmaps is to make China go up to leading position in most research aspects of regenerative medicine.In accord with this strategy,the government and some enterprises have invested 3-5 billion RMB (0.5-0.8 billion USD)for the research on regenerative medicine.In order to push the translation of regenerative medicine forward - from bench to bedside,a strategic alliance has been established.and it includes 27 top-level research institutes,medical institutes,colleges,universities and enterprises in the field of stem cell and regeneration medicine.Recently the journal,Science,has published a special issue-Regenerative Medicine in China,consisting of 35 papers dealing with stem cell and regeneration,tissue engineering and regeneration,trauma and regeneration and bases for tissue repair and regenerative medicine.It is predicated that a greater breakthrough in theory and practice of regenerative medicine will be achieved in the near future (20 to 30 years).

  16. Evidence for the utricular origin of the vestibular short-latency-evoked potential (VsEP) to bone-conducted vibration in guinea pig.

    Science.gov (United States)

    Chihara, Yasuhiro; Wang, Vivian; Brown, Daniel J

    2013-08-01

    Previous studies have shown that the vestibular short-latency-evoked potential (VsEP) in response to the brief head acceleration stimulus is a compound action potential of neurons innervating the otolith organs. However, due to the lack of direct evidence, it is currently unclear whether the VsEP is primarily generated by the activity of utricular or saccular afferent neurons, or some mixture of the two. Here, we investigated the origin of the VsEP evoked by brief bone-conducted vibration pulses in guinea pigs, using selective destruction of the cochlea, semicircular canals (SCCs), saccule, or utricle, along with neural blockade with tetrodotoxin (TTX) application, and mechanical displacements of the surgically exposed utricular macula. To access each end organ, either a dorsal or a ventral surgical approach was used. TTX application abolished the VsEP, supporting the neurogenic origin of the response. Selective cochlear, SCCs, or saccular destruction had no significant effect on VsEP amplitude, whereas utricular destruction abolished the VsEP completely. Displacement of the utricular membrane changed the VsEP amplitude in a non-monotonic fashion. These results suggest that the VsEP evoked by BCV in guinea pigs represents almost entirely a utricular response. Furthermore, it suggests that displacements of the utricular macula may alter its response to bone-conduction stimuli.

  17. Regenerative decline of stem cells in sarcopenia.

    Science.gov (United States)

    Sousa-Victor, Pedro; Muñoz-Cánoves, Pura

    2016-08-01

    Skeletal muscle mass and function decline with aging, a process known as sarcopenia, which restrains posture maintenance, mobility and quality of life in the elderly. Sarcopenia is also linked to a progressive reduction in the regenerative capacity of the skeletal muscle stem cells (satellite cells), which are critical for myofiber formation in early life stages and for sustaining repair in response to muscle damage or trauma. Here we will review the most recent findings on the causes underlying satellite cell functional decline with aging, and will discuss the prevalent view whereby age-associated extrinsic factor alterations impact negatively on satellite cell-intrinsic mechanisms, resulting in deficient muscle regeneration with aging. Further understanding of the interplay between satellite cell extrinsic and intrinsic factors in sarcopenia will facilitate therapies aimed at improving muscle repair in the increasing aging population. PMID:26921790

  18. Proton-exchange membrane regenerative fuel cells

    Science.gov (United States)

    Swette, Larry L.; LaConti, Anthony B.; McCatty, Stephen A.

    This paper will update the progress in developing electrocatalyst systems and electrode structures primarily for the positive electrode of single-unit solid polymer proton-exchange membrane (PEM) regenerative fuel cells. The work was done with DuPont Nafion 117 in complete fuel cells (40 cm 2 electrodes). The cells were operated alternately in fuel cell mode and electrolysis mode at 80°C. In fuel cell mode, humidified hydrogen and oxygen were supplied at 207 kPa (30 psi); in electrolysis mode, water was pumped over the positive electrode and the gases were evolved at ambient pressure. Cycling data will be presented for Pt-Ir catalysts and limited bifunctional data will be presented for Pt. Ir, Ru. Rh and Na xPt 3O 4 catalysts as well as for electrode structure variations.

  19. Eco-inventory for energy systems: Example regenerative energy systems; Oekoinventare fuer Energiesysteme: Beispiel regenerative Energiesysteme

    Energy Technology Data Exchange (ETDEWEB)

    Doka, G. [Inst. fuer Energietechnik, ETH, Zurich (Switzerland); Frischknecht, R. [Inst. fuer Energietechnik, ETH, Zurich (Switzerland); Hofstetter, P. [Inst. fuer Energietechnik, ETH, Zurich (Switzerland); Knoepfel, I. [Inst. fuer Energietechnik, ETH, Zurich (Switzerland); Suter, P. [Inst. fuer Energietechnik, ETH, Zurich (Switzerland); Walder, E. [Inst. fuer Energietechnik, ETH, Zurich (Switzerland); Dones, R. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1995-10-01

    The article describes the relevant process chains for the final energy supply from regenerative energy sources and the occurring environmental effects, such as emissions of noxious matter and consumption of resources. There is considered the electricity generation in photo-voltaic small-scale plants and water power plants. (orig.) [Deutsch] Der Beitrag beschreibt zur Endenergiebereitstellung aus regenerativen Energiequellen massgeblichen Prozessketten und die dabei auftretenden Umwelteinwirkungen, wie Schadstoffemissionen und Ressourcenverbraeuche. Betrachtet wird die Elektrizitaetserzeugung in photovoltaischen Kleinanlagen und Wasserkraftanlagen. (orig.)

  20. Heat cascading regenerative sorption heat pump

    Science.gov (United States)

    Jones, Jack A. (Inventor)

    1995-01-01

    A simple heat cascading regenerative sorption heat pump process with rejected or waste heat from a higher temperature chemisorption circuit (HTCC) powering a lower temperature physisorption circuit (LTPC) which provides a 30% total improvement over simple regenerative physisorption compression heat pumps when ammonia is both the chemisorbate and physisorbate, and a total improvement of 50% or more for LTPC having two pressure stages. The HTCC contains ammonia and a chemisorbent therefor contained in a plurality of canisters, a condenser-evaporator-radiator system, and a heater, operatively connected together. The LTPC contains ammonia and a physisorbent therefor contained in a plurality of compressors, a condenser-evaporator-radiator system, operatively connected together. A closed heat transfer circuit (CHTC) is provided which contains a flowing heat transfer liquid (FHTL) in thermal communication with each canister and each compressor for cascading heat from the HTCC to the LTPC. Heat is regenerated within the LTPC by transferring heat from one compressor to another. In one embodiment the regeneration is performed by another CHTC containing another FHTL in thermal communication with each compressor. In another embodiment the HTCC powers a lower temperature ammonia water absorption circuit (LTAWAC) which contains a generator-absorber system containing the absorbent, and a condenser-evaporator-radiator system, operatively connected together. The absorbent is water or an absorbent aqueous solution. A CHTC is provided which contains a FHTL in thermal communication with the generator for cascading heat from the HTCC to the LTAWAC. Heat is regenerated within the LTAWAC by transferring heat from the generator to the absorber. The chemical composition of the chemisorbent is different than the chemical composition of the physisorbent, and the absorbent. The chemical composition of the FHTL is different than the chemisorbent, the physisorbent, the absorbent, and ammonia.

  1. Regenerative therapy for neuronal diseases with transplantation of somatic stem cells

    OpenAIRE

    Kanno, Hiroshi

    2013-01-01

    Pluripotent stem cells, which are capable of differentiating in various species of cells, are hoped to be donor cells in transplantation in regenerative medicine. Embryonic stem (ES) cells and induced pluripotent stem cells have the potential to differentiate in approximately all species of cells. However, the proliferating ability of these cells is high and the cancer formation ability is also recognized. In addition, ethical problems exist in using ES cells. Somatic stem cells with the abil...

  2. The role of tissue engineering and biomaterials in cardiac regenerative medicine

    OpenAIRE

    Zhao, Yimu; Feric, Nicole T.; Thavandiran, Nimalan; Nunes, Sara S.; Radisic, Milica

    2014-01-01

    In recent years, the development of three-dimensional engineered heart tissue (EHT) has made large strides forward due to advances in stem cell biology, materials science, pre-vascularization strategies and nanotechnology. As a result, the role of tissue engineering in cardiac regenerative medicine has become multi-faceted as new applications become feasible. Cardiac tissue engineering has long been established to have the potential to partially or fully restore cardiac function following car...

  3. Major HGF-mediated regenerative pathways are similarly affected in human and canine cirrhosis

    OpenAIRE

    Spee, Bart; Arends, Brigitte; van den Ingh, Ted SGAM; Roskams, Tania; Rothuizen, Jan; Penning, Louis C

    2007-01-01

    Background The availability of non-rodent animal models for human cirrhosis is limited. We investigated whether privately-owned dogs (Canis familiaris) are potential model animals for liver disease focusing on regenerative pathways. Several forms of canine hepatitis were examined: Acute Hepatitis (AH), Chronic Hepatitis (CH), Lobular Dissecting Hepatitis (LDH, a specific form of micronodulair cirrhosis), and Cirrhosis (CIRR). Canine cirrhotic samples were compared to human liver samples from ...

  4. Emerging Applications of Stem Cell and Regenerative Medicine to Sports Injuries

    OpenAIRE

    Ajibade, David A.; Vance, Danica D; Hare, Joshua M.; Kaplan, Lee D.; Lesniak, Bryson P.

    2014-01-01

    Background: The treatment of sports-related musculoskeletal injuries with stem cells has become more publicized because of recent reports of high-profile athletes undergoing stem cell procedures. There has been increased interest in defining the parameters of safety and efficacy and the indications for potential use of stem cells in clinical practice. Purpose: To review the role of regenerative medicine in the treatment of sports-related injuries. Study Design: Review. Method: Relevant studie...

  5. Acellular approaches for regenerative medicine: on the verge of clinical trials with extracellular membrane vesicles?

    OpenAIRE

    Fuster-Matanzo, Almudena; Gessler, Florian; Leonardi, Tommaso; Iraci, Nunzio; Pluchino, Stefano

    2015-01-01

    Extracellular vesicles (EVs) are a heterogeneous population of naturally occurring secreted small vesicles, with distinct biophysical properties and different functions both in physiology and under pathological conditions. In recent years, a number of studies have demonstrated that EVs might hold remarkable potential in regenerative medicine by acting as therapeutically promising nanodrugs. Understanding their final impact on the biology of specific target cells as well as clarification of th...

  6. The social management of biomedical novelty:Facilitating translation in regenerative medicine

    OpenAIRE

    Gardner, John Grant; Webster, Andrew Joseph

    2016-01-01

    Regenerative medicine (RM) is championed as a potential source of curative treatments for a variety of illnesses, and as a generator of economic wealth and prosperity. Alongside this optimism, however, is a sense of concern that the translation of basic science into useful RM therapies will be laboriously slow due to a range of challenges relating to live tissue handling and manufacturing, regulation, reimbursement and commissioning, and clinical adoption. This paper explores the attempts of ...

  7. Elevated interferon-gamma in CNS inflammatory disease: a potential complication for bone marrow reconstitution in MS

    DEFF Research Database (Denmark)

    Hassan-Zahraee, M; Tran, E H; Bourbonnière, L;

    2000-01-01

    Bone marrow transplantation (BMT) is increasingly used to treat Multiple Sclerosis (MS) a CNS inflammatory disease with elevated CNS and systemic IFNgamma levels. We wished to determine the effect of IFNgamma on BM graft survival in a transgenic mouse model for chronic MS. BM transplantation...... into transgenic mice which express elevated levels of IFNgamma in the CNS was unsuccessful. By contrast, there was 100% survival of even fully allogeneic, T-depleted transplants to transgenics that over express TNFalpha in the CNS, using the same MBP promoter. IFNgamma was detectable in spleen of irradiated mice...... but levels were higher in IFNgamma transgenics. BM transplantation into IFNgamma-deficient recipients also had a high failure rate. Transplants of BM from mice lacking expression of IFNgamma-receptor failed, whereas IFNgamma-deficient grafts survived, suggesting that IFNgamma response status of the graft can...

  8. Preparation and biological evaluation of 166Ho-BPAMD as a potential therapeutic bone-seeking agent

    International Nuclear Information System (INIS)

    In this work 166Ho-(4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis (carboxymethyl)-1,4,7,10-(tetraazacyclododec-1-yl) acetic acid (166Ho-BPAMD) complex was prepared successfully with sufficient radiochemical purity of >94 % and specific activity of 244 GBq/mmol at the optimized conditions. The complex demonstrated significant stability at room temperature and in human serum at least for 24 h. Hydroxyapatite (HA) binding assay demonstrated that even at the small amount of HA, >10 mg, above 98 % of the complex is bound to HA. At the pH 7.4, LogP0/w was -1.73 ± 0.02. Both planar imaging and biodistribution studies showed major accumulation of the labelled compound in the bone tissue. (author)

  9. Cryopreserved dental pulp tissues of exfoliated deciduous teeth is a feasible stem cell resource for regenerative medicine.

    Directory of Open Access Journals (Sweden)

    Lan Ma

    Full Text Available Human exfoliated deciduous teeth have been considered to be a promising source for regenerative therapy because they contain unique postnatal stem cells from human exfoliated deciduous teeth (SHED with self-renewal capacity, multipotency and immunomodulatory function. However preservation technique of deciduous teeth has not been developed. This study aimed to evaluate that cryopreserved dental pulp tissues of human exfoliated deciduous teeth is a retrievable and practical SHED source for cell-based therapy. SHED isolated from the cryopreserved deciduous pulp tissues for over 2 years (25-30 months (SHED-Cryo owned similar stem cell properties including clonogenicity, self-renew, stem cell marker expression, multipotency, in vivo tissue regenerative capacity and in vitro immunomodulatory function to SHED isolated from the fresh tissues (SHED-Fresh. To examine the therapeutic efficacy of SHED-Cryo on immune diseases, SHED-Cryo were intravenously transplanted into systemic lupus erythematosus (SLE model MRL/lpr mice. Systemic SHED-Cryo-transplantation improved SLE-like disorders including short lifespan, elevated autoantibody levels and nephritis-like renal dysfunction. SHED-Cryo amended increased interleukin 17-secreting helper T cells in MRL/lpr mice systemically and locally. SHED-Cryo-transplantation was also able to recover osteoporosis bone reduction in long bones of MRL/lpr mice. Furthermore, SHED-Cryo-mediated tissue engineering induced bone regeneration in critical calvarial bone-defect sites of immunocompromised mice. The therapeutic efficacy of SHED-Cryo transplantation on immune and skeletal disorders was similar to that of SHED-Fresh. These data suggest that cryopreservation of dental pulp tissues of deciduous teeth provide a suitable and desirable approach for stem cell-based immune therapy and tissue engineering in regenerative medicine.

  10. Influence of Interleukin-1 Beta on Platelet-Poor Plasma Clot Formation: A Potential Impact on Early Bone Healing.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    Full Text Available Hematoma quality (especially the fibrin matrix plays an important role in the bone healing process. Here, we investigated the effect of interleukin-1 beta (IL-1β on fibrin clot formation from platelet-poor plasma (PPP.Five-milliliter of rat whole-blood samples were collected from the hepatic portal vein. All blood samples were firstly standardized via a thrombelastograph (TEG, blood cell count, and the measurement of fibrinogen concentration. PPP was prepared by collecting the top two-fifths of the plasma after centrifugation under 400 × g for 10 min at 20°C. The effects of IL-1β cytokines on artificial fibrin clot formation from PPP solutions were determined by scanning electronic microscopy (SEM, confocal microscopy (CM, turbidity, and clot lysis assays.The lag time for protofibril formation was markedly shortened in the IL-1β treatment groups (243.8 ± 76.85 in the 50 pg/mL of IL-1β and 97.5 ± 19.36 in the 500 pg/mL of IL-1β compared to the control group without IL-1β (543.8 ± 205.8. Maximal turbidity was observed in the control group. IL-1β (500 pg/mL treatment significantly decreased fiber diameters resulting in smaller pore sizes and increased density of the fibrin clot structure formed from PPP (P < 0.05. The clot lysis assay revealed that 500 pg/mL IL-1β induced a lower susceptibility to dissolution due to the formation of thinner and denser fibers.IL-1β can significantly influence PPP fibrin clot structure, which may affect the early bone healing process.

  11. Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease

    International Nuclear Information System (INIS)

    Radium-223 chloride (223Ra; Alpharadin) is an alpha-emitting radioisotope that targets areas of osteoblastic metastasis and is excreted by the small intestine. When compared with beta-emitters (eg, strontium-89, samarium-153), 223Ra delivers a high quantity of energy per track length with short tissue penetration. This review describes the mechanism, radiobiology, and preclinical development of 223Ra and discusses the clinical data currently available regarding its safety and efficacy profile. Data from clinical trials including abstracts were collected and reviewed using the PubMed Database, as well as the American Society of Clinical Oncology abstract database. Current bone-targeted therapies fall into two main categories: antiresorptive agents (eg, zoledronic acid, denosumab), which have been shown to delay skeletal-related events, and radiopharmaceuticals (eg, samarium-153), which may have a role in pain palliation. Historically, neither antiresorptive agents nor radiopharmaceuticals have shown definitive evidence of improved overall survival or other antitumor effects in metastatic castrate-resistant prostate cancer (mCRPC). Radiopharmaceuticals are limited by myelosuppresion, thrombocytopenia, and renal excretion. In a recently reported randomized Phase III trial in men with symptomatic bone-metastatic CRPC who had received or were ineligible for docetaxel chemotherapy, 223Ra treatment resulted in improved overall survival and delayed skeletal-related events. Toxicity consisted of minor gastrointestinal side effects and mild neutropenia and thrombocytopenia that were rarely severe. Pending regulatory approval, 223Ra may represent a unique and distinct option for an important subgroup of patients with mCRPC; future trials should address its use in combination or in sequence with existing and novel agents

  12. Biphasic Polyurethane/Polylactide Sponges Doped with Nano-Hydroxyapatite (nHAp Combined with Human Adipose-Derived Mesenchymal Stromal Stem Cells for Regenerative Medicine Applications

    Directory of Open Access Journals (Sweden)

    Krzysztof Marycz

    2016-10-01

    Full Text Available Cartilage and bone tissue injuries are common targets in regenerative medicine. The degeneration of cartilage tissue results in tissue loss with a limited ability to regenerate. However, the application of mesenchymal stem cells in the course of such condition makes it possible to manage this disorder by improving the structure of the remaining tissue and even stimulating its regeneration. Nevertheless, in the case of significant tissue loss, standard local injection of cell suspensions is insufficient, due to the low engraftment of transplanted cells. Introduction of mesenchymal stem cells on the surface of a compatible biomaterial can be a promising tool for inducing the regeneration by both retaining the cells at the desired site and filling the tissue gap. In order to obtain such a cell-biomaterial hybrid, we developed complex, biphasic polymer blend biomaterials composed of various polyurethane (PU-to-polylactide (PLA ratios, and doped with different concentrations of nano-hydroxyapatite (nHAp. We have determined the optimal blend composition and nano-hydroxyapatite concentration for adipose mesenchymal stem cells cultured on the biomaterial. We applied biological in vitro techniques, including cell viability assay, determination of oxidative stress factors level, osteogenic and chondrogenic differentiation potentials as well as cell proteomic analysis. We have shown that the optimal composition of biphasic scaffold was 20:80 of PU:PLA with 20% of nHAp for osteogenic differentiation, and 80:20 of PU:PLA with 10% of nHAp for chondrogenic differentiation, which suggest the optimal composition of final biphasic implant for regenerative medicine applications.

  13. Modeling of gene therapy for regenerative cells using intelligent agents.

    Science.gov (United States)

    Adly, Aya Sedky; Aboutabl, Amal Elsayed; Ibrahim, M Shaarawy

    2011-01-01

    Gene therapy is an exciting field that has attracted much interest since the first submission of clinical trials. Preliminary results were very encouraging and prompted many investigators and researchers. However, the ability of stem cells to differentiate into specific cell types holds immense potential for therapeutic use in gene therapy. Realization of this potential depends on efficient and optimized protocols for genetic manipulation of stem cells. It is widely recognized that gain/loss of function approaches using gene therapy are essential for understanding specific genes functions, and such approaches would be particularly valuable in studies involving stem cells. A significant complexity is that the development stage of vectors and their variety are still not sufficient to be efficiently applied in stem cell therapy. The development of scalable computer systems constitutes one step toward understanding dynamics of its potential. Therefore, the primary goal of this work is to develop a computer model that will support investigations of virus' behavior and organization on regenerative tissues including genetically modified stem cells. Different simulation scenarios were implemented, and their results were encouraging compared to ex vivo experiments, where the error rate lies in the range of acceptable values in this domain of application.

  14. Epigenetic modulation of dental pulp stem cells: implications for regenerative endodontics.

    Science.gov (United States)

    Duncan, H F; Smith, A J; Fleming, G J P; Cooper, P R

    2016-05-01

    Dental pulp stem cells (DPSCs) offer significant potential for use in regenerative endodontics, and therefore, identifying cellular regulators that control stem cell fate is critical to devising novel treatment strategies. Stem cell lineage commitment and differentiation are regulated by an intricate range of host and environmental factors of which epigenetic influence is considered vital. Epigenetic modification of DNA and DNA-associated histone proteins has been demonstrated to control cell phenotype and regulate the renewal and pluripotency of stem cell populations. The activities of the nuclear enzymes, histone deacetylases, are increasingly being recognized as potential targets for pharmacologically inducing stem cell differentiation and dedifferentiation. Depending on cell maturity and niche in vitro, low concentration histone deacetylase inhibitor (HDACi) application can promote dedifferentiation of several post-natal and mouse embryonic stem cell populations and conversely increase differentiation and accelerate mineralization in DPSC populations, whilst animal studies have shown an HDACi-induced increase in stem cell marker expression during organ regeneration. Notably, both HDAC and DNA methyltransferase inhibitors have also been demonstrated to dramatically increase the reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) for use in regenerative therapeutic procedures. As the regulation of cell fate will likely remain the subject of intense future research activity, this review aims to describe the current knowledge relating to stem cell epigenetic modification, focusing on the role of HDACi on alteration of DPSC phenotype, whilst presenting the potential for therapeutic application as part of regenerative endodontic regimens. PMID:26011759

  15. Comparative study of osteogenic potential of a composite scaffold incorporating either endogenous bone morphogenetic protein-2 or exogenous phytomolecule icaritin: an in vitro efficacy study.

    Science.gov (United States)

    Chen, S-H; Wang, X-L; Xie, X-H; Zheng, L-Z; Yao, D; Wang, D-P; Leng, Y; Zhang, G; Qin, L

    2012-08-01

    A local delivery system with sustained and efficient release of therapeutic agents from an appropriate carrier is desirable for orthopedic applications. Novel composite scaffolds made of poly (lactic-co-glycolic acid) with tricalcium phosphate (PLGA/TCP) were fabricated by an advanced low-temperature rapid prototyping technique, which incorporated either endogenous bone morphogenetic protein-2 (BMP-2) (PLGA/TCP/BMP-2) or phytomolecule icaritin (ICT) (PLGA/TCP/ICT) at low, middle and high doses. PLGA/TCP served as control. In vitro degradation, osteogenesis and release tests showed statistical differences among PLGA/TCP/ICT, PLGA/TCP and PLGA/TCP/BMP-2 groups, where PLGA/TCP/ICT had the desired slow release of bioactive icaritin in a dose-dependent manner, whereas there was almost no BMP-2 release from the PLGA/TCP/BMP-2 scaffolds. PLGA/TCP/ICT significantly increased more ALP activity, upregulated mRNA expression of osteogenic genes and enhanced calcium deposition and mineralization in rabbit bone marrow stem cells cultured on scaffolds compared with the other two groups. These results indicate the desired degradation rate, osteogenic capability and release property in PLGA/TCP/ICT composite scaffold, as icaritin preserved its bioactivity and structure after incorporation, while PLGA/TCP/BMP-2 did not show an initially expected osteogenic potential, owing to loss of the original bioactivity of BMP-2 during its incorporation and fabrication procedure. The results suggest that PLGA/TCP composite scaffolds incorporating osteogenic ICT might be a promising approach for bone tissue bioengineering and regeneration. PMID:22543006

  16. Recombinant human bone morphogenetic protein induces bone formation

    International Nuclear Information System (INIS)

    The authors have purified and characterized active recombinant human bone morphogenetic protein (BMP) 2A. Implantation of the recombinant protein in rats showed that a single BMP can induce bone formation in vivo. A dose-response and time-course study using the rat ectopic bone formation assay revealed that implantation of 0.5-115 μg of partially purified recombinant human BMP-2A resulted in cartilage by day 7 and bone formation by day 14. The time at which bone formation occurred was dependent on the amount of BMP-2A implanted; at high doses bone formation could be observed at 5 days. The cartilage- and bone-inductive activity of the recombinant BMP-2A is histologically indistinguishable from that of bone extracts. Thus, recombinant BMP-2A has therapeutic potential to promote de novo bone formation in humans

  17. Surgical Regenerative Treatments for Peri-Implantitis: Meta-analysis of Recent Findings in a Systematic Literature Review

    Directory of Open Access Journals (Sweden)

    Povilas Daugela

    2016-09-01

    Full Text Available Objectives: The purpose of the present study was to systematically review the literature on the surgical regenerative treatment of the peri-implantitis and to determine an effective therapeutic predictable option for their clinical management. Material and Methods: The study searched MEDLINE and EMBASE databases from 2006 to 2016. Clinical human studies that had reported changes in probing depth (PD and/or bleeding on probing (BOP and/or radiologic marginal bone level (RBL changes after peri-implantitis surgical treatment at 12-month follow-up or longer were included accordingly to PRISMA guidelines. Results: The initial search obtained 883 citations. After screening and determination of eligibility, 18 articles were included in the review. The meta-analysis of selected studies revealed that the weighted mean RBL fill was 1.97 mm (95% confidence interval [CI] = 1.58 to 2.35 mm, PD reduction was 2.78 mm (95% CI = 2.31 to 3.25 mm, and BOP reduced by 52.5% (95% CI = 41.6 to 63.1%. Defect fill in studies using and not using barrier membranes for graft coverage was 1.86 mm (95% CI = 1.36 to 2.36 mm and 2.12 mm (95% CI = 1.46 to 2.78 mm correspondingly. High heterogeneity among the studies regarding defects morphology, surgical protocols, and selection of biomaterials were found. Conclusions: All included studies underlined an improvement of clinical conditions after the surgical regenerative treatment of peri-implantitis, however, there is a lack of scientific evidence in the literature regarding the superiority of the regenerative versus non-regenerative surgical treatment. The presence of a barrier membrane or submergence in the regenerative procedure does not seem to be fundamental in order to obtain clinical success of the surgery.

  18. 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...... effect on blastema cell viability in vitro. MRI revealed that labelled tissue was clearly visibly in vivo 49 days after amputation and a significant decline in signal intensity of labelled limbs versus sham-operated limbs was evident throughout the complete regeneration period of 84 days. SPIO labelling...

  19. Evaluation of the inflammatory potential of implant materials in a mouse model by bioluminescent imaging of intravenously injected bone marrow cells.

    Science.gov (United States)

    Rais, Bushra; Köster, Mario; Rahim, Muhammad Imran; Pils, Marina; Seitz, Jan-Marten; Hauser, Hansjörg; Wirth, Dagmar; Mueller, Peter P

    2016-09-01

    To evaluate the inflammatory potential of implants a bioluminescent imaging assay was developed using luciferase-expressing bone marrow cells that were injected into the blood circulation of wild-type mice. After subcutaneous implantation of titanium discs as an example for a clinically established biocompatible material, the luminosity was modest. Similarly, low luminosity signals were generated by pure magnesium implants that were used to represent metallic alloys that are presently under investigation as novel degradable implant materials. Increased luminosity was observed in response to degradable polymeric PLGA implants. Surgical wounds induced a basic luminescent response even in the absence of an implant. However, the material-independent response to injury could be minimized using injectable microparticle suspensions. In parallel with the resorption of biodegradable microparticles, the signal induced by PLGA declined faster when compared to non-degradable polystyrene suspensions. By using an interferon type I inducible Mx2 promoter construct to drive luciferase gene expression, the highest luminosity was observed in response to bacteria, indicating that the system could also be employed to monitor implant infections. Overall, labeled bone marrow cells yielded specific, well-defined localized signals that correlated with the inflammatory responses to implants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2149-2158, 2016. PMID:27102724

  20. Postoperative bone marrow alterations: Potential pitfalls in the diagnosis of osteomyelitis with In-111-labeled leukocyte scintigraphy

    International Nuclear Information System (INIS)

    Scintigraphy was used after injection of technetium-99m methylene diphosphonate (MDP) and indium-111-labeled white blood cells (WBCs) to assess for the presence of osteomyelitis in 97 patients who had undergone prior surgical procedures. Thirty-four patients with abnormal In-111-labeled WBC patterns underwent restudy with Tc-99m albumin colloid (AC). Scintigraphic findings were considered positive for osteomyelitis whenever localization of In-111-labeled WBCs exceeded Tc-99m AC activity in extent or focal intensity (discordant pattern). Ten of 12 patients with culture-proved osteomyelitis had discordant patterns; two had false-negative (concordant) patterns. The cases of 20 of 22 patients without infection who were considered to have osteomyelitis on the basis of patterns of In-111-labeled WBCs and Tc-99m MDP were reclassified correctly on the basis of concordant patterns of In-111-labeled WBCs and Tc-99m AC. Radiocolloid images improved the overall scintigraphic specificity for osteomyelitis from 59% without bone marrow imaging to 92%; sensitivity decreased from 94% to 88%

  1. Ospemifene for the treatment of dyspareunia associated with vulvar and vaginal atrophy: potential benefits in bone and breast

    Directory of Open Access Journals (Sweden)

    Soe LH

    2013-09-01

    Full Text Available Lin H Soe, Gregory T Wurz, Chiao-Jung Kao, Michael W DeGregorio Department of Internal Medicine, Division of Hematology and Oncology, School of Medicine, University of California, Davis, Sacramento, CA, USA Abstract: Ospemifene is a selective estrogen receptor modulator (SERM, or estrogen receptor agonist/antagonist, that was recently approved by the US Food and Drug Administration for the treatment of dyspareunia associated with vulvar and vaginal atrophy, a chronic condition that affects up to 60% of postmenopausal women. Ospemifene is the first and only nonestrogen compound approved for this indication. Compared with other approved SERMs, such as tamoxifen, toremifene, bazedoxifene, and raloxifene, the estrogen-like effects of ospemifene in the vaginal epithelium are unique. This review first discusses the rationale for developing ospemifene, including its mechanism of action, and then focuses on the clinical development of ospemifene for the treatment of dyspareunia associated with vulvar and vaginal atrophy. Included are discussions of the effects of ospemifene on the endometrium, serum lipids, coagulation markers, bone, and breast cancer. In conclusion, ospemifene is a SERM with a unique estrogen agonist/antagonist tissue profile that was recently approved in the US for the treatment of dyspareunia associated with vulvar and vaginal atrophy in postmenopausal women. Ospemifene warrants further clinical investigation for the treatment and prevention of osteoporosis and breast cancer. Keywords: ospemifene, dyspareunia, vulvar and vaginal atrophy, osteoporosis, breast cancer

  2. On the "plasticity" of adult stem cells and its application in regenerative medicine

    Institute of Scientific and Technical Information of China (English)

    WANG Yunfang; PEI Xuetao

    2003-01-01

    In recent years, with the increasingly further studies on embryonic stem cells and the recognition of the biologic characteristics of adult stem cells, it has been discovered that adult stem cells have another phenomenon of "plasticity" in addition to the characteristics of strong poten-tial for self-renewal, proliferation and multi-differentiation, which brings us the hope for regenerative medicine --renewing new organ or tissue cells to replace those damagedby injury or diseases. Although the mechanism of "plastic-ity" and its application in the regenerative medicine are still in doubt, thorough exploration in these subjects would open up broad prospects for the use in cell and tissue engineering in the near future.

  3. Bone cysts: unicameral and aneurysmal bone cyst.

    Science.gov (United States)

    Mascard, E; Gomez-Brouchet, A; Lambot, K

    2015-02-01

    Simple and aneurysmal bone cysts are benign lytic bone lesions, usually encountered in children and adolescents. Simple bone cyst is a cystic, fluid-filled lesion, which may be unicameral (UBC) or partially separated. UBC can involve all bones, but usually the long bone metaphysis and otherwise primarily the proximal humerus and proximal femur. The classic aneurysmal bone cyst (ABC) is an expansive and hemorrhagic tumor, usually showing characteristic translocation. About 30% of ABCs are secondary, without translocation; they occur in reaction to another, usually benign, bone lesion. ABCs are metaphyseal, excentric, bulging, fluid-filled and multicameral, and may develop in all bones of the skeleton. On MRI, the fluid level is evocative. It is mandatory to distinguish ABC from UBC, as prognosis and treatment are different. UBCs resolve spontaneously between adolescence and adulthood; the main concern is the risk of pathologic fracture. Treatment in non-threatening forms consists in intracystic injection of methylprednisolone. When there is a risk of fracture, especially of the femoral neck, surgery with curettage, filling with bone substitute or graft and osteosynthesis may be required. ABCs are potentially more aggressive, with a risk of bone destruction. Diagnosis must systematically be confirmed by biopsy, identifying soft-tissue parts, as telangiectatic sarcoma can mimic ABC. Intra-lesional sclerotherapy with alcohol is an effective treatment. In spinal ABC and in aggressive lesions with a risk of fracture, surgical treatment should be preferred, possibly after preoperative embolization. The risk of malignant transformation is very low, except in case of radiation therapy. PMID:25579825

  4. A new biocompatible delivery scaffold containing heparin and bone morphogenetic protein 2.

    Science.gov (United States)

    Thanyaphoo, Suphannee; Kaewsrichan, Jasadee

    2016-09-01

    Silicon-substituted calcium phosphate (Si-CaP) was developed in our laboratory as a biomaterial for delivery in bone tissue engineering. It was fabricated as a 3D-construct of scaffolds using chitosan-trisodium polyphosphate (TPP) cross-linked networks. In this study, heparin was covalently bonded to the residual -NH2 groups of chitosan on the scaffold applying carbodiimide chemistry. Bonded heparin was not leached away from scaffold surfaces upon vigorous washing or extended storage. Recombinant human bone morphogenetic protein 2 (rhBMP-2) was bound to conjugated scaffolds by ionic interactions between the negatively charged SO42- clusters of heparin and positively charged amino acids of rhBMP-2. The resulting scaffolds were inspected for bone regenerative capacity by subcutaneous implanting in rats. Histological observation and mineralization assay were performed after 4 weeks of implantation. Results from both in vitro and in vivo experiments suggest the potential of the developed scaffolds for bone tissue engineering applications in the future. PMID:27383886

  5. A new biocompatible delivery scaffold containing heparin and bone morphogenetic protein 2

    Directory of Open Access Journals (Sweden)

    Thanyaphoo Suphannee

    2016-09-01

    Full Text Available Silicon-substituted calcium phosphate (Si-CaP was developed in our laboratory as a biomaterial for delivery in bone tissue engineering. It was fabricated as a 3D-construct of scaffolds using chitosan-trisodium polyphosphate (TPP cross-linked networks. In this study, heparin was covalently bonded to the residual -NH2 groups of chitosan on the scaffold applying carbodiimide chemistry. Bonded heparin was not leached away from scaffold surfaces upon vigorous washing or extended storage. Recombinant human bone morphogenetic protein 2 (rhBMP-2 was bound to conjugated scaffolds by ionic interactions between the negatively charged SO42- clusters of heparin and positively charged amino acids of rhBMP-2. The resulting scaffolds were inspected for bone regenerative capacity by subcutaneous implanting in rats. Histological observation and mineralization assay were performed after 4 weeks of implantation. Results from both in vitro and in vivo experiments suggest the potential of the developed scaffolds for bone tissue engineering applications in the future.

  6. The application of induced pluripotent stem cells for bone regeneration: current progress and prospects.

    Science.gov (United States)

    Teng, Songsong; Liu, Chaoxu; Krettek, Christian; Jagodzinski, Michael

    2014-08-01

    Loss of healthy bone tissue and dysosteogenesis are still common and significant problems in clinics. Cell-based therapy using mesenchymal stem cells (MSCs) has been performed in patients for quite some time, but the inherent drawbacks of these cells, such as the reductions in proliferation rate and osteogenic differentiation potential that occur with aging, greatly limit their further application. Moreover, embryonic stem cells (ESCs) have brought new hope to osteoregenerative medicine because of their full pluripotent differentiation potential and excellent performance in bone regeneration. However, the ethical issues involved in destroying human embryos and the immune reactions that occur after transplantation are two major stumbling blocks impeding the clinical application of ESCs. Instead, induced pluripotent stem cells (iPSCs), which are ESC-like pluripotent cells that are reprogrammed from adult somatic cells using defined transcription factors, are considered a more promising source of cells for regenerative medicine because they present no ethical or immunological issues. Here, we summarize the primary technologies for generating iPSCs and the biological properties of these cells, review the current advances in iPSC-based bone regeneration and, finally, discuss the remaining challenges associated with these cells, particularly safety issues and their potential application for osteoregenerative medicine.

  7. Strategies for bioengineered scaffolds that support adipose stem cells in regenerative therapies.

    Science.gov (United States)

    Clevenger, Tracy N; Luna, Gabriel; Fisher, Steven K; Clegg, Dennis O

    2016-09-01

    Regenerative medicine possesses the potential to ameliorate damage to tissue that results from a vast range of conditions, including traumatic injury, tumor resection and inherited tissue defects. Adult stem cells, while more limited in their potential than pluripotent stem cells, are still capable of differentiating into numerous lineages and provide feasible allogeneic and autologous treatment options for many conditions. Adipose stem cells are one of the most abundant types of stem cell in the adult human. Here, we review recent advances in the development of synthetic scaffolding systems used in concert with adipose stem cells and assess their potential use for clinical applications.

  8. Bone regeneration: current concepts and future directions

    Directory of Open Access Journals (Sweden)

    McGonagle Dennis

    2011-05-01

    Full Text Available Abstract Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity, such as for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or 'insufficient' bone-regeneration process, including the 'gold standard' autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved 'local' strategies in terms of tissue engineering and gene therapy, or even 'systemic' enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis.

  9. Proximal Tibial Bone Graft

    Science.gov (United States)

    ... Complications Potential problems after a PTBG include infection, fracture of the proximal tibia and pain related to the procedure. Frequently Asked Questions If proximal tibial bone graft is taken from my knee, will this prevent me from being able to ...

  10. Myogenic potential of whole bone marrow mesenchymal stem cells in vitro and in vivo for usage in urinary incontinence.

    Directory of Open Access Journals (Sweden)

    Monica Gunetti

    Full Text Available Urinary incontinence, defined as the complaint of any involuntary loss of urine, is a pathological condition, which affects 30% females and 15% males over 60, often following a progressive decrease of rhabdosphincter cells due to increasing age or secondary to damage to the pelvic floor musculature, connective tissue and/or nerves. Recently, stem cell therapy has been proposed as a source for cell replacement and for trophic support to the sphincter. To develop new therapeutic strategies for urinary incontinence, we studied the interaction between mesenchymal stem cells (MSCs and muscle cells in vitro; thereafter, aiming at a clinical usage, we analyzed the supporting role of MSCs for muscle cells in vitro and in in vivo xenotransplantation. MSCs can express markers of the myogenic cell lineages and give rise, under specific cell culture conditions, to myotube-like structures. Nevertheless, we failed to obtain mixed myotubes both in vitro and in vivo. For in vivo transplantation, we tested a new protocol to collect human MSCs from whole bone marrow, to get larger numbers of cells. MSCs, when transplanted into the pelvic muscles close to the external urethral sphincter, survived for a long time in absence of immunosuppression, and migrated into the muscle among fibers, and towards neuromuscular endplates. Moreover, they showed low levels of cycling cells, and did not infiltrate blood vessels. We never observed formation of cell masses suggestive of tumorigenesis. Those which remained close to the injection site showed an immature phenotype, whereas those in the muscle had more elongated morphologies. Therefore, MSCs are safe and can be easily transplanted without risk of side effects in the pelvic muscles. Further studies are needed to elucidate their integration into muscle fibers, and to promote their muscular transdifferentiation either before or after transplantation.

  11. Novel Regenerative Carbon Analyzer for Water Quality Monitoring Project

    Data.gov (United States)

    National Aeronautics and Space Administration — One of the highest priorities of a regenerative life support system for manned space missions (to the Moon, Mars, and other remote locations) is to recover and...

  12. Ultralightweight, Regeneratively Cooled Combustion Chamber for Mars Ascent Vehicles Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose a high-pressure, regeneratively-cooled combustion chamber that uses novel material selection for extreme reductions in mass. These materials are...

  13. LOX/Methane Regeneratively-Cooled Rocket Engine Development Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Design, build, and test a 5,000 lbf thrust regeneratively cooled combustion chamber at JSC for a low pressure liquid oxygen/methane engine. The engine demonstrates...

  14. Electrolyzer for NASA Lunar Regenerative Fuel Cells Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Water electrolyzer stacks are a key component of regenerative fuel cells, designed to replace batteries as a means of storing electric energy on the lunar surface....

  15. Advanced Space Power Systems (ASPS): Regenerative Fuel Cells (RFC) Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The objective of the regenerative fuel cell project element is to develop power and energy storage technologies that enable new capabilities for future human space...

  16. The economic value of investing in regenerative medicine.

    Science.gov (United States)

    Hussain, Aftab; Rivers, Patrick A

    2009-01-01

    This article discusses the science of regenerative medicine and presents evidence that investments towards the development of this technology will reduce total health care output. Use of regenerative medicine will also be an important factor in eliminating chronic diseases such as diabetes, heart disease, and Parkinson's disease. Investment in regenerative medicine is a sound strategy for several reasons: human suffering will be reduced, if not eliminated; and the economy will be stimulated by creating employment opportunities, generating additional income and tax revenues, increasing worker productivity, creating new conglomerates, and reducing insurance costs. This article discusses some of the latest advances in regenerative medicine as well as the progress that has been made in the development of new stem cell therapies. PMID:20499720

  17. Iron serves as diffusion barrier in thermally regenerative galvanic cell

    Science.gov (United States)

    Crouthamel, C. E.

    1967-01-01

    Pure iron or iron-coated diaphragm provides a hydrogen diffusion electrode for a thermally regenerative galvanic cell. It allows the gas to diffuse through its interatomic spaces and resists the corrosive action of the cell environment.

  18. Use of regenerative energy sources and hydrogen technology 2006. Proceedings

    International Nuclear Information System (INIS)

    This volume contains 25 contributions, which were held on the 13th symposium ''Use of regenerative energy sources and hydrogen technology'' in Stralsund (Germany). Separate documentation items analysing 16 of the contributions have been prepared for the ENERGY database

  19. Targeting Bone Marrow to Potentiate the Anti-Tumor Effect of Tyrosine Kinase Inhibitor in Preclinical Rat Model of Human Glioblastoma

    Science.gov (United States)

    Shaaban, S.; Alsulami, M.; Arbab, S.A.; Ara, R.; Shankar, A.; Iskander, A.; Angara, K.; Jain, M.; Bagher-Ebadian, H.; Achyut, B.R.; Arbab, A.S.

    2016-01-01

    Antiangiogenic agents caused paradoxical increase in pro-growth and pro-angiogenic factors and caused tumor growth in glioblastoma (GBM). It is hypothesized that paradoxical increase in pro-angiogenic factors would mobilize Bone Marrow Derived Cells (BMDCs) to the treated tumor and cause refractory tumor growth. The purposes of the studies were to determine whether whole body irradiation (WBIR) or a CXCR4 antagonist (AMD3100) will potentiate the effect of vatalanib (a VEGFR2 tyrosine kinase inhibitor) and prevent the refractory growth of GBM. Human GBM were grown orthotopically in three groups of rats (control, pretreated with WBIR and AMD3100) and randomly selected for vehicle or vatalanib treatments for 2 weeks. Then all animals underwent Magnetic Resonance Imaging (MRI) followed by euthanasia and histochemical analysis. Tumor volume and different vascular parameters (plasma volume (vp), forward transfer constant (Ktrans), back flow constant (kep), extravascular extracellular space volume (ve) were determined from MRI. In control group, vatalanib treatment increased the tumor growth significantly compared to that of vehicle treatment but by preventing the mobilization of BMDCs and interaction of CXCR4-SDF-1 using WBIR and ADM3100, respectively, paradoxical growth of tumor was controlled. Pretreatment with WBIR or AMD3100 also decreased tumor cell migration, despite the fact that ADM3100 increased the accumulation of M1 and M2 macrophages in the tumors. Vatalanib also increased Ktrans and ve in control animals but both of the vascular parameters were decreased when the animals were pretreated with WBIR and AMD3100. In conclusion, depleting bone marrow cells or CXCR4 interaction can potentiate the effect of vatalanib.

  20. High power, high beam quality regenerative amplifier

    Science.gov (United States)

    Hackel, L.A.; Dane, C.B.

    1993-08-24

    A regenerative laser amplifier system generates high peak power and high energy per pulse output beams enabling generation of X-rays used in X-ray lithography for manufacturing integrated circuits. The laser amplifier includes a ring shaped optical path with a limited number of components including a polarizer, a passive 90 degree phase rotator, a plurality of mirrors, a relay telescope, and a gain medium, the components being placed close to the image plane of the relay telescope to reduce diffraction or phase perturbations in order to limit high peak intensity spiking. In the ring, the beam makes two passes through the gain medium for each transit of the optical path to increase the amplifier gain to loss ratio. A beam input into the ring makes two passes around the ring, is diverted into an SBS phase conjugator and proceeds out of the SBS phase conjugator back through the ring in an equal but opposite direction for two passes, further reducing phase perturbations. A master oscillator inputs the beam through an isolation cell (Faraday or Pockels) which transmits the beam into the ring without polarization rotation. The isolation cell rotates polarization only in beams proceeding out of the ring to direct the beams out of the amplifier. The diffraction limited quality of the input beam is preserved in the amplifier so that a high power output beam having nearly the same diffraction limited quality is produced.

  1. Recent advancements in regenerative dentistry: A review.

    Science.gov (United States)

    Amrollahi, Pouya; Shah, Brinda; Seifi, Amir; Tayebi, Lobat

    2016-12-01

    Although human mouth benefits from remarkable mechanical properties, it is very susceptible to traumatic damages, exposure to microbial attacks, and congenital maladies. Since the human dentition plays a crucial role in mastication, phonation and esthetics, finding promising and more efficient strategies to reestablish its functionality in the event of disruption has been important. Dating back to antiquity, conventional dentistry has been offering evacuation, restoration, and replacement of the diseased dental tissue. However, due to the limited ability and short lifespan of traditional restorative solutions, scientists have taken advantage of current advancements in medicine to create better solutions for the oral health field and have coined it "regenerative dentistry." This new field takes advantage of the recent innovations in stem cell research, cellular and molecular biology, tissue engineering, and materials science etc. In this review, the recently known resources and approaches used for regeneration of dental and oral tissues were evaluated using the databases of Scopus and Web of Science. Scientists have used a wide range of biomaterials and scaffolds (artificial and natural), genes (with viral and non-viral vectors), stem cells (isolated from deciduous teeth, dental pulp, periodontal ligament, adipose tissue, salivary glands, and dental follicle) and growth factors (used for stimulating cell differentiation) in order to apply tissue engineering approaches to dentistry. Although they have been successful in preclinical and clinical partial regeneration of dental tissues, whole-tooth engineering still seems to be far-fetched, unless certain shortcomings are addressed. PMID:27612840

  2. Regenerative burner in the metals industry

    Energy Technology Data Exchange (ETDEWEB)

    Gettings, M.

    1986-07-01

    The Regenerative Ceramic Burner, RCB is becoming widely accepted in the UK as the successor of the world famous recuperative burner. This paper describes the RCB and its modes of operation and compares it with the recuperative burner. This comparison uses the example of a reheating furnace employed to heat a 10 tonne billet to 1250/sup 0/C. The superior technical performance of the RCB is mirrored in its economic attractiveness. For most medium and large furnace applications the device can pay for itself in less than two years with 40 to 50% fuel savings. Examples of the use of the device are presented from both the steel and aluminium industries. In all cases, operation and worthwhile energy savings have been achieved. In its role on an aluminum melter, the burner has demonstrated its ability to handle contaminated gases with minimum maintenance requirement. The paper concludes with ideas for future developments of the technology which will extend its use into other industry sectors.

  3. Bone Densitometry (Bone Density Scan)

    Science.gov (United States)

    ... of DXA Bone Densitometry? What is a Bone Density Scan (DXA)? Bone density scanning, also called dual-energy x-ray absorptiometry ( ... is today's established standard for measuring bone mineral density (BMD). An x-ray (radiograph) is a noninvasive ...

  4. Study of regenerative medicine in China: demands and clinical translation

    OpenAIRE

    Fu, Xiao-Bing

    2012-01-01

    The repair and regeneration of tissue is a well-discussed topic. Over the past 20 years, with the development of genetics, auxology, stem cell biology, and tissue engineering, tissue repair and regeneration have rapidly developed as emerging "Regenerative Medicine". Regenerative medicine has significant market demand in China. Based on national statistics, injury and poisoning patients rank third in afflictions in city hospitals (accounting for 9.13%) and rank second in afflictions in county ...

  5. Use of genes and cells in regenerative medicine

    OpenAIRE

    Simonson, Oscar

    2015-01-01

    Regenerative medicine is a discipline that aims to achieve regeneration of cells, tissue or organs in order to restore or establish normal functions. There are several strategies that can be used to achieve this goal. Many of the strategies are based on use of genes or cells to regenerate organ functions. The present thesis aim to investigate different gene and cell based methods for the use in regenerative medicine. In paper I a novel peptide conjugate is described for the...

  6. Musculoskeletal Regenerative Engineering: Biomaterials, Structures, and Small Molecules

    OpenAIRE

    Roshan James; Laurencin, Cato T.

    2014-01-01

    Musculoskeletal tissues are critical to the normal functioning of an individual and following damage or degeneration they show extremely limited endogenous regenerative capacity. The future of regenerative medicine is the combination of advanced biomaterials, structures, and cues to re-engineer/guide stem cells to yield the desired organ cells and tissues. Tissue engineering strategies were ideally suited to repair damaged tissues; however, the substitution and regeneration of large tissue vo...

  7. On the Development of an Efficient Regenerative Compressor

    OpenAIRE

    Griffini, D.; Salvadori, S.; Carnevale, M.; A. Cappelletti; Ottanelli, L.; Martelli, F.

    2015-01-01

    Regenerative compressors are attractive machines used in several industrial processes. Their main characteristic is the highly three-dimensional development of the flow. Consequently, usual approach for axial or centrifugal compressors design are not an affordable strategy. The analysis of the rotor/stator coupling is the main issue in the design of regenerative compressors because of the vane-less nature of the stator and the characteristic trajectory of the flow. This paper describes the de...

  8. Bone regeneration with cultured human bone grafts

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, T.; Nakajima, H. [Nara Medical Univ., Kashihara City (Japan). Dept. of Pathology; Nara Medical Univ., Kashihara City (Japan). Dept. of Orthopedic Surgery; Ohgushi, H.; Ueda, Y.; Takakura, Y. [Nara Medical Univ., Kashihara City (Japan). Dept. of Orthopedic Surgery; Uemura, T.; Tateishi, T. [National Inst. for Advanced Interdisciplinary Research (NAIR), Ibaraki (Japan). Tsukuba Research Center; Enomoto, Y.; Ichijima, K. [Nara Medical Univ., Kashihara City (Japan). Dept. of Pathology

    2001-07-01

    From 73 year old female patient, 3 ml of bone marrow was collected from the ilium. The marrow was cultured to concentrate and expand the marrow mesenchymal cells on a culture dish. The cultured cells were then subculturedeither on another culture dish or in porous areas of hydroxyapatite ceramics in the presence of dexamethasone and beta-glycerophosphate (osteo genic medium). The subculturedtissues on the dishes were analyzed by scanning electron microscopy (SEM), and subculturedtissues in the ceramics were implanted intraperitoneally into athymic nude mice. Vigorous growth of spindle-shaped cells and a marked formation of bone matrix beneath the cell layers was observed on the subculture dishes by SEM. The intraperitoneally implanted ceramics with cultured tissues revealed thick layer of lamellar bone together with active osteoblasts lining in many pore areas of the ceramics after 8 weeks. The in vitro bone formations on the culture dishes and in vivo bone formation in porous ceramics were detected. These results indicate that we can assemble an in vitro bone/ceramic construct, and due to the porous framework of the ceramic, the construct has osteogenic potential similar to that of autologous cancellous bone. A significant benefit of this method is that the construct can be made with only a small amount of aspirated marrow cells from aged patients with little host morbidity. (orig.)

  9. Study of regenerative medicine in China: demands and clinical translation

    Directory of Open Access Journals (Sweden)

    Xiao-bing FU

    2012-03-01

    Full Text Available The repair and regeneration of tissue is a well-discussed topic. Over the past 20 years, with the development of genetics, auxology, stem cell biology, and tissue engineering, tissue repair and regeneration have rapidly developed as emerging "Regenerative Medicine". Regenerative medicine has significant market demand in China. Based on national statistics, injury and poisoning patients rank third in afflictions in city hospitals (accounting for 9.13% and rank second in afflictions in county hospitals (accounting for 14.07%. Totally, approximately one hundred million patients suffered from traumatic, genetic and metabolic diseases in China and demand reparative and regenerative medical treatment each year. The Chinese government and its related departments have always attached great importance and support to the development of regenerative medicine, and the Chinese academic circle is involved in a very wide range of diseases and injuries including regenerative medical theory and technology. Stem cell biology, organ engineering and duplication, tissue engineering research and production have developed rapidly, and great portion of these studies have started to appear in applications, which have aroused extensive concerns in international professional circle. In the next 10 years, the Chinese regenerative medical system will be further improved, in both statute and rules, clinical translation will be further accelerated. Breakthroughs are expected in induced differentiation of stem cells and synchronous repair and regeneration of multiple organs, construction of major organs by tissue engineering, large-scale applications of tissue engineering products, and other aspects.

  10. Regenerative Medicine for the Kidney: Renotropic Factors, Renal Stem/Progenitor Cells, and Stem Cell Therapy

    Directory of Open Access Journals (Sweden)

    Akito Maeshima

    2014-01-01

    Full Text Available The kidney has the capacity for regeneration and repair after a variety of insults. Over the past few decades, factors that promote repair of the injured kidney have been extensively investigated. By using kidney injury animal models, the role of intrinsic and extrinsic growth factors, transcription factors, and extracellular matrix in this process has been examined. The identification of renal stem cells in the adult kidney as well as in the embryonic kidney is an active area of research. Cell populations expressing putative stem cell markers or possessing stem cell properties have been found in the tubules, interstitium, and glomeruli of the normal kidney. Cell therapies with bone marrow-derived hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells, and amniotic fluid-derived stem cells have been highly effective for the treatment of acute or chronic renal failure in animals. Embryonic stem cells and induced pluripotent stem cells are also utilized for the construction of artificial kidneys or renal components. In this review, we highlight the advances in regenerative medicine for the kidney from the perspective of renotropic factors, renal stem/progenitor cells, and stem cell therapies and discuss the issues to be solved to realize regenerative therapy for kidney diseases in humans.

  11. Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells

    DEFF Research Database (Denmark)

    Simonsen, Janne Lytoft; Rosada, Cecilia; Serakinci, Nedime;

    2002-01-01

    . The transduced cells have now undergone more than 260 population doublings (PD) and continue to proliferate, whereas control cells underwent senescence-associated proliferation arrest after 26 PD. The cells maintained production of osteoblastic markers and differentiation potential during continuous subculturing...

  12. Regenerative Periodontal Therapy: History and Prospects

    OpenAIRE

    Arasay Calzada Bandomo; Amaray Calzada Bandomo; Clotilde de la Caridad Mora Pérez

    2013-01-01

    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 scientif...

  13. Soy Protein Scaffold Biomaterials for Tissue Engineering and Regenerative Medicine

    Science.gov (United States)

    Chien, Karen B.

    Developing functional biomaterials using highly processable materials with tailorable physical and bioactive properties is an ongoing challenge in tissue engineering. Soy protein is an abundant, natural resource with potential use for regenerative medicine applications. Preliminary studies show that soy protein can be physically modified and fabricated into various biocompatible constructs. However, optimized soy protein structures for tissue regeneration (i.e. 3D porous scaffolds) have not yet been designed. Furthermore, little work has established the in vivo biocompatibility of implanted soy protein and the benefit of using soy over other proteins including FDA-approved bovine collagen. In this work, freeze-drying and 3D printing fabrication processes were developed using commercially available soy protein to create porous scaffolds that improve cell growth and infiltration compared to other soy biomaterials previously reported. Characterization of scaffold structure, porosity, and mechanical/degradation properties was performed. In addition, the behavior of human mesenchymal stem cells seeded on various designed soy scaffolds was analyzed. Biological characterization of the cell-seeded scaffolds was performed to assess feasibility for use in liver tissue regeneration. The acute and humoral response of soy scaffolds implanted in an in vivo mouse subcutaneous model was also investigated. All fabricated soy scaffolds were modified using thermal, chemical, and enzymatic crosslinking to change properties and cell growth behavior. 3D printing allowed for control of scaffold pore size and geometry. Scaffold structure, porosity, and degradation rate significantly altered the in vivo response. Freeze-dried soy scaffolds had similar biocompatibility as freeze-dried collagen scaffolds of the same protein content. However, the soy scaffolds degraded at a much faster rate, minimizing immunogenicity. Interestingly, subcutaneously implanted soy scaffolds affected blood

  14. Feeding and healing the world: through regenerative agriculture and permaculture.

    Science.gov (United States)

    Rhodes, Christopher J

    2012-01-01

    inevitable and imminent, meaning a loss of globalised civilisation and a mandatory return to living in smaller localised communities. Permaculture and regenerative agriculture offer potentially the means to provide food and materials on the small scale, and address the wider issues of carbon emissions, and resource shortages. Since over half the World's population lives in cities, it seems likely that strengthening the resilience of these environments, using urban permaculture, may be a crucial strategy in achieving a measured descent in our use of energy and other resources, rather than an abrupt collapse of civilization. PMID:23469709

  15. Feeding and healing the world: through regenerative agriculture and permaculture.

    Science.gov (United States)

    Rhodes, Christopher J

    2012-01-01

    inevitable and imminent, meaning a loss of globalised civilisation and a mandatory return to living in smaller localised communities. Permaculture and regenerative agriculture offer potentially the means to provide food and materials on the small scale, and address the wider issues of carbon emissions, and resource shortages. Since over half the World's population lives in cities, it seems likely that strengthening the resilience of these environments, using urban permaculture, may be a crucial strategy in achieving a measured descent in our use of energy and other resources, rather than an abrupt collapse of civilization.

  16. Low Bone Density

    Science.gov (United States)

    ... Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your bone density ... people with normal bone density. Detecting Low Bone Density A bone density test will determine whether you ...

  17. Use of bone morphogenetic proteins in mesenchymal stem cell stimulation of cartilage and bone repair

    OpenAIRE

    Scarfì, Sonia

    2016-01-01

    The extracellular matrix-associated bone morphogenetic proteins (BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed i...

  18. Induced Pluripotent Stem Cell Technology in Regenerative Medicine and Biology

    Science.gov (United States)

    Pei, Duanqing; Xu, Jianyong; Zhuang, Qiang; Tse, Hung-Fat; Esteban, Miguel A.

    The potential of human embryonic stem cells (ESCs) for regenerative medicine is unquestionable, but practical and ethical considerations have hampered clinical application and research. In an attempt to overcome these issues, the conversion of somatic cells into pluripotent stem cells similar to ESCs, commonly termed nuclear reprogramming, has been a top objective of contemporary biology. More than 40 years ago, King, Briggs, and Gurdon pioneered somatic cell nuclear reprogramming in frogs, and in 1981 Evans successfully isolated mouse ESCs. In 1997 Wilmut and collaborators produced the first cloned mammal using nuclear transfer, and then Thomson obtained human ESCs from in vitro fertilized blastocysts in 1998. Over the last 2 decades we have also seen remarkable findings regarding how ESC behavior is controlled, the importance of which should not be underestimated. This knowledge allowed the laboratory of Shinya Yamanaka to overcome brilliantly conceptual and technical barriers in 2006 and generate induced pluripotent stem cells (iPSCs) from mouse fibroblasts by overexpressing defined combinations of ESC-enriched transcription factors. Here, we discuss some important implications of human iPSCs for biology and medicine and also point to possible future directions.

  19. Dedifferentiated fat cells: A cell source for regenerative medicine

    Institute of Scientific and Technical Information of China (English)

    Medet; Jumabay; Kristina; I; Bostr?m

    2015-01-01

    The identification of an ideal cell source for tissue regeneration remains a challenge in the stem cell field. The ability of progeny cells to differentiate into other cell types is important for the processes of tissue reconstruction and tissue engineering and has clinical, biochemical or molecular implications. The adaptation of stem cells from adipose tissue for use in regenerative medicine has created a new role for adipocytes. Mature adipocytes can easily be isolated from adipose cell suspensions and allowed to dedifferentiate into lipidfree multipotent cells, referred to as dedifferentiated fat(DFAT) cells. Compared to other adult stem cells, the DFAT cells have unique advantages in their abundance, ease of isolation and homogeneity. Under proper condition in vitro and in vivo, the DFAT cells have exhibited adipogenic, osteogenic, chondrogenic, cardiomyogenc, angiogenic, myogenic, and neurogenic potentials. In this review, we first discuss the phenomena of dedifferentiation and transdifferentiation of cells, and then dedifferentiation of adipocytes in particular. Understanding the dedifferentiation process itself may contribute to our knowledge of normal growth processes, as well as mechanisms of disease. Second, we highlight new developments in DFAT cell culture and summarize the current understanding of DFAT cell properties. The unique features of DFAT cells are promising for clinical applications such as tissue regeneration.

  20. Regenerative fuel cell study for satellites in GEO orbit

    Science.gov (United States)

    Levy, Alexander; Vandine, Leslie L.; Stedman, James K.

    1987-07-01

    Summarized are the results of a 12-month study to identify high performance regenerative hydrogen-oxygen fuel cell concepts for geosynchronous satellite application. Emphasis was placed on concepts with the potential for high energy density (W-hr/lb) and passive means for water and heat management to maximize system reliability. Both polymer membrane and alkaline electrolyte fuel cells were considered, with emphasis on the alkaline cell because of its high performance, advanced state of development, and proven ability to operate in a launch and space environment. Three alkaline system concepts were studied. The first, the integrated design, utilized a configuration in which the fuel cell and electrolysis cells are alternately stacked inside a pressure vessel. Product water is transferred by diffusion during electrolysis and waste heat is conducted through the pressure wall, thus using completely passive means for transfer and control. The second alkaline system, the dedicated design, uses a separate fuel cell and electrolysis stack so that each unit can be optimized in size and weight based on its orbital operating period. The third design was a dual function stack configuration, in which each cell can operate in both fuel cell and electrolysis mode, thus eliminating the need for two separate stacks and associated equipment. Results indicate that using near term technology energy densities between 46 and 52 W-hr/lb can be achieved at efficiencies of 55 percent. System densities of 115 W-hr/lb are contemplated.

  1. The Roles of Epithelial-to-Mesenchymal Transition (EMT and Mesenchymal-to-Epithelial Transition (MET in Breast Cancer Bone Metastasis: Potential Targets for Prevention and Treatment

    Directory of Open Access Journals (Sweden)

    Binnaz Demirkan

    2013-11-01

    Full Text Available Many studies have revealed molecular connections between breast and bone. Genes, important in the control of bone remodeling, such as receptor activator of nuclear kappa (RANK, receptor activator of nuclear kappa ligand (RANKL, vitamin D, bone sialoprotein (BSP, osteopontin (OPN, and calcitonin, are expressed in breast cancer and lactating breast. Epithelial-mesenchymal transition (EMT and mesenchymal-epithelial transition (MET effectors play critical roles during embryonic development, postnatal growth, and epithelial homeostasis, but also are involved in a number of pathological conditions, including wound repair, fibrosis, inflammation, as well as cancer progression and bone metastasis. Transforming growth factor β (TGFβ, insulin-like growth factor I & II (IGF I & II, platelet-derived growth factor (PDGF, parathyroid hormone-related protein (PTH(rP, vascular endothelial growth factor (VEGF, epithelial growth factors II/I (ErbB/EGF, interleukin 6 (IL-6, IL-8, IL-11, IL-1, integrin αvβ3, matrix metalloproteinases (MMPs, catepsin K, hypoxia, notch, Wnt, bone morphogenetic proteins (BMP, and hedgehog signaling pathways are important EMT and MET effectors identified in the bone microenviroment facilitating bone metastasis formation. Recently, Runx2, an essential transcription factor in the regulation of mesenchymal cell differentiation into the osteoblast lineage and proper bone development, is also well-recognized for its expression in breast cancer cells promoting osteolytic bone metastasis. Understanding the precise mechanisms of EMT and MET in the pathogenesis of breast cancer bone metastasis can inform the direction of therapeutic intervention and possibly prevention.

  2. Distinguishing clinical and imaging features of nodular regenerative hyperplasia and large regenerative nodules of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Ames, J.T. [Departments of Radiology, University of Pittsburgh Medical Center Pittsburgh, Pennsylvania (United States); Federle, M.P., E-mail: federle@stanford.ed [Departments of Radiology, University of Pittsburgh Medical Center Pittsburgh, Pennsylvania (United States); Chopra, K. [Departments of Gastroenterology, University of Pittsburgh Medical Center Pittsburgh, Pennsylvania (United States)

    2009-12-15

    Aim: Nodular regenerative hyperplasia (NRH) and large regenerative nodules (LRN) are distinct types of hepatocellular nodules that have been confused in the radiology literature. However, distinction is critical because their clinical significance is quite different. Our purpose was to review the clinical and imaging findings in a series of patients with NRH and LRN in order to identify distinguishing clinical and imaging features. Materials and methods: This was a retrospective case series. The clinical and imaging features were compared in 36 patients with pathological proof of NRH and 23 patients with pathological evidence of LRN. Results: NRH and LRN have different predisposing factors and imaging findings. NRH is often associated with organ transplantation, myeloproliferative disease, or autoimmune processes. Livers with NRH typically do not have enhancing nodules; none of the present patients with NRH had enhancing liver masses. In contrast, LRN are often associated with Budd-Chiari syndrome. Enhancing liver masses were noted in 19 (83%) of the 23 patients with LRN. The p values for the comparisons were less than 0.001 for both enhancing liver masses and hepatic vein thrombosis. Conclusion: NRH and LRN can have distinct clinical presentations and imaging appearances. LRN often result in enhancing liver nodules, whereas NRH usually does not. Clinical and imaging information enables the distinction of LRN and NRH in many cases.

  3. Distinguishing clinical and imaging features of nodular regenerative hyperplasia and large regenerative nodules of the liver

    International Nuclear Information System (INIS)

    Aim: Nodular regenerative hyperplasia (NRH) and large regenerative nodules (LRN) are distinct types of hepatocellular nodules that have been confused in the radiology literature. However, distinction is critical because their clinical significance is quite different. Our purpose was to review the clinical and imaging findings in a series of patients with NRH and LRN in order to identify distinguishing clinical and imaging features. Materials and methods: This was a retrospective case series. The clinical and imaging features were compared in 36 patients with pathological proof of NRH and 23 patients with pathological evidence of LRN. Results: NRH and LRN have different predisposing factors and imaging findings. NRH is often associated with organ transplantation, myeloproliferative disease, or autoimmune processes. Livers with NRH typically do not have enhancing nodules; none of the present patients with NRH had enhancing liver masses. In contrast, LRN are often associated with Budd-Chiari syndrome. Enhancing liver masses were noted in 19 (83%) of the 23 patients with LRN. The p values for the comparisons were less than 0.001 for both enhancing liver masses and hepatic vein thrombosis. Conclusion: NRH and LRN can have distinct clinical presentations and imaging appearances. LRN often result in enhancing liver nodules, whereas NRH usually does not. Clinical and imaging information enables the distinction of LRN and NRH in many cases.

  4. Concise review: bridging the gap: bone regeneration using skeletal stem cell-based strategies-where are we now?

    DEFF Research Database (Denmark)

    Dawson, Jonathan I; Kanczler, Janos; Kassem, Moustapha;

    2014-01-01

    Skeletal stem cells confer to bone its innate capacity for regeneration and repair. Bone regeneration strategies seek to harness and enhance this regenerative capacity for the replacement of tissue damaged or lost through congenital defects, trauma, functional/esthetic problems, and a broad range...... for musculoskeletal regeneration. Stem Cells 2014;32:35-44...

  5. Renewable regenerative energy systems: Practical integration challenges. Paper no. IGEC-1-093

    International Nuclear Information System (INIS)

    Interest in renewable energy systems that employ regenerative components to enable intermittent energy sources to service time varying loads is growing. The overall performance of these systems is intimately linked to the choice of the energy storage media and the efficiency of the energy conversion devices. Recent advances in electrolyser and fuel cell technologies may make small-scale hydrogen buffered renewable energy systems a practical reality in the near term. A research team at the University of Victoria - Institute for Integrated Energy Systems (IESVic) is developing a flexible distributed, laboratory-scale energy system called IRENE (Integrated Renewable Energy Experiment). The initial goal of this research is to explore the potential for constructing a regenerative energy system using early commercial and precommercial hydrogen storage and fuel cell energy conversion devices. Once implemented, research efforts will focus on the dynamic interactions between system elements that arise while servicing short-term transient supply/demand transfer functions. Although simple in concept, numerous integration issues have been encountered while developing IRENE. The fundamental integration issues must be addressed if small-scale renewable regenerative systems are to displace conventional fossil fuel based solutions in the future. The motivation for, the components used, and the practical lessons learned though the development of IRENE will be discussed. (author)

  6. Degradation pattern of porous CaCO3 and hydroxyapatite microspheres in vitro and in vivo for potential application in bone tissue engineering.

    Science.gov (United States)

    Zhong, Qiwei; Li, Wenhua; Su, Xiuping; Li, Geng; Zhou, Ying; Kundu, Subhas C; Yao, Juming; Cai, Yurong

    2016-07-01

    Despite superior clinical handling, excellent biocompatibility, biodegradation property of calcium phosphate needs to be improved to coincide with the rate of new bone formation. In this study, spherical CaCO3 are fabricated in the presence of the silk sericin and then transformed into porous hydroxyapatite (HAP) microspheres via hydrothermal method. The degradation behavior of obtained CaCO3, HAP and their mixture is first investigated in vitro. The result demonstrates that the weight loss of HAP microspheres are almost 24.3% after immersing in pH 7.40 Tris-HCl buffer solution for 12 weeks, which is far slower than that of spherical CaCO3 (97.5%). The degradation speed of the mixtures depends on the proportion of CaCO3 and HAP. The mixture with higher content of CaCO3 possesses a quicker degradation speed. The obtained CaCO3 and HAP microspheres are injected into subcutaneous tissue of ICR mice with the assistance of sodium alginate. The result in vivo also shows an obvious difference of degradation speed between the obtained CaCO3 and HAP microspheres, implying it is feasible to modulate the degradation property of the mixture through changing the proportion of CaCO3 and HAP The good cytocompatibility of the two kinds of microspheres is proved and a mild inflammation response is observed only at early stage of implantation. The job offers a simple method to modify the degradation properties of biomaterial for potential use in bone tissue engineering. PMID:26998866

  7. Age-related molecular genetic changes of murine bone marrow mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Webster Keith A

    2010-04-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSC are pluripotent cells, present in the bone marrow and other tissues that can differentiate into cells of all germ layers and may be involved in tissue maintenance and repair in adult organisms. Because of their plasticity and accessibility these cells are also prime candidates for regenerative medicine. The contribution of stem cell aging to organismal aging is under debate and one theory is that reparative processes deteriorate as a consequence of stem cell aging and/or decrease in number. Age has been linked with changes in osteogenic and adipogenic potential of MSCs. Results Here we report on changes in global gene expression of cultured MSCs isolated from the bone marrow of mice at ages 2, 8, and 26-months. Microarray analyses revealed significant changes in the expression of more than 8000 genes with stage-specific changes of multiple differentiation, cell cycle and growth factor genes. Key markers of adipogenesis including lipoprotein lipase, FABP4, and Itm2a displayed age-dependent declines. Expression of the master cell cycle regulators p53 and p21 and growth factors HGF and VEGF also declined significantly at 26 months. These changes were evident despite multiple cell divisions in vitro after bone marrow isolation. Conclusions The results suggest that MSCs are subject to molecular genetic changes during aging that are conserved during passage in culture. These changes may affect the physiological functions and the potential of autologous MSCs for stem cell therapy.

  8. Metformin Decreases Reactive Oxygen Species, Enhances Osteogenic Properties of Adipose-Derived Multipotent Mesenchymal Stem Cells In Vitro, and Increases Bone Density In Vivo

    Directory of Open Access Journals (Sweden)

    Krzysztof Marycz

    2016-01-01

    Full Text Available Due to its pleiotropic effects, the commonly used drug metformin has gained renewed interest among medical researchers. While metformin is mainly used for the treatment of diabetes, recent studies suggest that it may have further application in anticancer and antiaging therapies. In this study, we investigated the proliferative potential, accumulation of oxidative stress factors, and osteogenic and adipogenic differentiation potential of mouse adipose-derived stem cells (MuASCs isolated from mice treated with metformin for 8 weeks. Moreover, we investigated the influence of metformin supplementation on mice bone density and bone element composition. The ASCs isolated from mice who were treated with metformin for 8 weeks showed highest proliferative potential, generated a robust net of cytoskeletal projections, had reduced expression of markers associated with cellular senescence, and decreased amount of reactive oxygen species in comparison to control group. Furthermore, we demonstrated that these cells possessed greatest osteogenic differentiation potential, while their adipogenic differentiation ability was reduced. We also demonstrated that metformin supplementation increases bone density in vivo. Our result stands as a valuable source of data regarding the in vivo influence of metformin on ASCs and bone density and supports a role for metformin in regenerative medicine.

  9. Metformin Decreases Reactive Oxygen Species, Enhances Osteogenic Properties of Adipose-Derived Multipotent Mesenchymal Stem Cells In Vitro, and Increases Bone Density In Vivo.

    Science.gov (United States)

    Marycz, Krzysztof; Tomaszewski, Krzysztof A; Kornicka, Katarzyna; Henry, Brandon Michael; Wroński, Sebastian; Tarasiuk, Jacek; Maredziak, Monika

    2016-01-01

    Due to its pleiotropic effects, the commonly used drug metformin has gained renewed interest among medical researchers. While metformin is mainly used for the treatment of diabetes, recent studies suggest that it may have further application in anticancer and antiaging therapies. In this study, we investigated the proliferative potential, accumulation of oxidative stress factors, and osteogenic and adipogenic differentiation potential of mouse adipose-derived stem cells (MuASCs) isolated from mice treated with metformin for 8 weeks. Moreover, we investigated the influence of metformin supplementation on mice bone density and bone element composition. The ASCs isolated from mice who were treated with metformin for 8 weeks showed highest proliferative potential, generated a robust net of cytoskeletal projections, had reduced expression of markers associated with cellular senescence, and decreased amount of reactive oxygen species in comparison to control group. Furthermore, we demonstrated that these cells possessed greatest osteogenic differentiation potential, while their adipogenic differentiation ability was reduced. We also demonstrated that metformin supplementation increases bone density in vivo. Our result stands as a valuable source of data regarding the in vivo influence of metformin on ASCs and bone density and supports a role for metformin in regenerative medicine. PMID:27195075

  10. Islet neogenesis potential of human adult stem cells and its applications in cell replacement therapy for diabetes

    Directory of Open Access Journals (Sweden)

    Bhonde RR

    2008-11-01

    Full Text Available In recent years regenerative biology has reached to greater heights due to its therapeutic potential in treating degenerative diseases; as they are not curable by modern medicine. With the advent of research in stem cells and developmental biology the regenerative potential of adult resident stem cells is becoming clearer. The long term objective of regenerative medicine or cell therapy is to treat patients with their own stem cells. These stem cells could be derived from the diseased organs such as skin, liver, pancreas etc. or from reservoirs of multipotent stem cells such as bone marrow or cord blood.Manipulating the ability of tissue resident stem cells as well as from multipotent reservoirs such as bone marrow, umbilical cord and cord blood to give rise to endocrine cells may open new avenues in the treatment of diabetes. A better understanding of stem cell biology would almost certainly allow for the establishment of efficient and reliable cell transplantation experimental programs in the clinic. We show here that multipotent mesenchymal stem cells can be isolated from various sources such as the bone marrow, placenta, umbilical cord. Upon stimulation with specific growth factors they differentiate into islet like clusters (ILCs. When ILCs obtained from the above mentioned sources were transplanted in experimental diabetic mice, restoration of normoglycemia was observed within three weeks of transplantation with concomitant increase in the body weight. These euglycemic mice exhibited normal glucose tolerance test indicating normal utilization of glucose. Allthough the MSCs isolated from all the sources had the same characteristics; they showed significant differences in their islet differentiation potential. ILCs isolated for the human bone marrow did not show any pancreatic hormones in vitro, but upon transplantation they matured into insulin and somatostatin producing hormones. Placental MSCs as well as ILCs showed insulin trascripts

  11. Graphene nanomaterials as biocompatible and conductive scaffolds for stem cells: impact for tissue engineering and regenerative medicine.

    Science.gov (United States)

    Menaa, Farid; Abdelghani, Adnane; Menaa, Bouzid

    2015-12-01

    The discovery of the interesting intrinsic properties of graphene, a two-dimensional nanomaterial, has boosted further research and development for various types of applications from electronics to biomedicine. During the last decade, graphene and several graphene-derived materials, such as graphene oxide, carbon nanotubes, activated charcoal composite, fluorinated graphenes and three-dimensional graphene foams, have been extensively explored as components of biosensors or theranostics, or to remotely control cell-substrate interfaces, because of their remarkable electro-conductivity. To date, despite the intensive progress in human stem cell research, only a few attempts to use carbon nanotechnology in the stem cell field have been reported. Interestingly, most of the recent in vitro studies indicate that graphene-based nanomaterials (i.e. mainly graphene, graphene oxide and carbon nanotubes) promote stem cell adhesion, growth, expansion and differentiation. Although cell viability in vitro is not affected, their potential nanocytoxicity (i.e. nanocompatibility and consequences of uncontrolled nanobiodegradability) in a clinical setting using humans remains unknown. Therefore, rigorous internationally standardized clinical studies in humans that would aim to assess their nanotoxicology are requested. In this paper we report and discuss the recent and pertinent findings about graphene and derivatives as valuable nanomaterials for stem cell research (i.e. culture, maintenance and differentiation) and tissue engineering, as well as for regenerative, translational and personalized medicine (e.g. bone reconstruction, neural regeneration). Also, from scarce nanotoxicological data, we also highlight the importance of functionalizing graphene-based nanomaterials to minimize the cytotoxic effects, as well as other critical safety parameters that remain important to take into consideration when developing nanobionanomaterials.

  12. The influence of bone surface availability in bone remodelling - A mathematical model including coupled geometrical and biomechanical regulations of bone cells

    OpenAIRE

    Pivonka, Peter; Buenzli, Pascal R.; Scheiner, Stefan; Hellmich, Christian; Dunstan, Colin R.

    2012-01-01

    Bone is a biomaterial undergoing continuous renewal. The renewal process is known as bone remodelling and is operated by bone-resorbing cells (osteoclasts) and bone-forming cells (osteoblasts). Both biochemical and biomechanical regulatory mechanisms have been identified in the interaction between osteoclasts and osteoblasts. Here we focus on an additional and poorly understood potential regulatory mechanism of bone cells, that involves the morphology of the microstructure of bone. Bone cells...

  13. Therapeutic inhibition of cathepsin K—reducing bone resorption while maintaining bone formation

    OpenAIRE

    Duong, Le T.

    2012-01-01

    Osteoporosis is a disease of high bone remodeling with an imbalance of bone resorption over bone formation, resulting in decreased bone mineral density and deterioration of bone microarchitecture. From the emerging understandings of the molecular and cellular regulators of bone remodeling, potential new targets for therapeutic intervention for this disease have been identified. Cathepsin K (CatK), a cysteine protease produced by osteoclasts, is the primary enzyme mediating the degradation of ...

  14. Osteogenic potential of murine periosteum for critical-size cranial defects.

    Science.gov (United States)

    Ruvalcaba-Paredes, E K; Hidalgo-Bastida, L A; Sesman-Bernal, A L; Garciadiego-Cazares, D; Pérez-Dosal, M R; Martínez-López, V; Vargas-Sandoval, B; Pichardo-Bahena, R; Ibarra, C; Velasquillo, C

    2016-09-01

    Tissue engineering of bone has combined bespoke scaffolds and osteoinductive factors to maintain functional osteoprogenitor cells, and the periosteum has been confirmed as a satisfactory source of osteoblasts. Suitable matrices have been identified that support cell proliferation and differentiation, including demineralised bone matrix (both compatible and osteoinductive) and acellular human dermis. We have evaluated the osteogenic potential of an osteogenic unit, developed by combining periosteum, demineralised bone matrix, and acellular human dermis, in rodents with critical-size cranial defects. Briefly, remnants from the superior maxillary periosteum were used to harvest cells, which were characterised by flow cytometry and reverse retrotranscriptase-polymerase chain reaction (RT-PCR). Cells were cultured into the osteogenic unit and assessed for viability before being implanted into 3 rodents, These were compared with the control group (n=3) after three months. Histological analyses were made after staining with haematoxylin and eosin and Von Kossa, and immunostaining, and confirmed viable cells that stained for CD90, CD73, CD166, runt-related transcription factor, osteopontin, and collagen type I in the experimental group, while in the control group there was only connective tissue on the edges of the bone in the injury zone. We conclude that osteogenic unit constructs have the osteogenic and regenerative potential for use in engineering bone tissue. PMID:27282080

  15. Potential role of 20S proteasome in maintaining stem cell integrity of human bone marrow stromal cells in prolonged culture expansion

    International Nuclear Information System (INIS)

    Highlights: ► Prolonged culture expansion retards proliferation and induces senescence of hBMSCs. ► Reduced 20S proteasomal activity and expression potentially contribute to cell aging. ► MG132-mediated 20S proteasomal inhibition induces senescence-like phenotype. ► 18α-GA stimulates proteasomal activity and restores replicative senescence. ► 18α-GA retains differentiation without affecting stem cell characterizations. -- Abstract: Human bone marrow stromal cells (hBMSCs) could be used in clinics as precursors of multiple cell lineages following proper induction. Such application is impeded by their characteristically short lifespan, together with the increasing loss of proliferation capability and progressive reduction of differentiation potential after the prolonged culture expansion. In the current study, we addressed the possible role of 20S proteasomes in this process. Consistent with prior reports, long-term in vitro expansion of hBMSCs decreased cell proliferation and increased replicative senescence, accompanied by reduced activity and expression of the catalytic subunits PSMB5 and PSMB1, and the 20S proteasome overall. Application of the proteasome inhibitor MG132 produced a senescence-like phenotype in early passages, whereas treating late-passage cells with 18α-glycyrrhetinic acid (18α-GA), an agonist of 20S proteasomes, delayed the senescence progress, enhancing the proliferation and recovering the capability of differentiation. The data demonstrate that activation of 20S proteasomes assists in counteracting replicative senescence of hBMSCs expanded in vitro.

  16. Bone Cancer

    Science.gov (United States)

    ... cancer. Surgery is often the main treatment for bone cancer. Other treatments may include amputation, chemotherapy, and radiation therapy. Because bone cancer can come back after treatment, regular follow-up visits are important. NIH: National ...

  17. Osteoblasts and their applications in bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Rupani A

    2012-05-01

    Full Text Available Asha Rupani1, Richard Balint2, Sarah H Cartmell1,21Institute of Science and Technology in Medicine, Keele University, Hartshill, Stoke-on-Trent, UK; 2Materials Science Centre, The University of Manchester, Manchester, UKAbstract: Tissue engineering is an emerging therapy that offers a new solution to patients suffering from bone loss. It utilizes cells derived from such sources as a patient's own bone or bone marrow, which are laboratory-isolated, grown (so they multiply in number, and placed onto a degradable material, or scaffold, that has mechanical/chemical properties appropriate to the bone section that it is replacing. The cells plus the scaffold are then grown in a container, or bioreactor, which is necessary as it provides the correct environment required for the cells to proliferate, differentiate, and to produce extracellular matrix. The following review focuses on the use of osteoblasts for bone tissue engineering.Keywords: osteoblast, bone, tissue engineering, regenerative medicine, orthopaedic

  18. Osteograft, plastic material for regenerative medicine

    Science.gov (United States)

    Zaidman, A. M.; Korel, A. V.; Shevchenko, A. I.; Shchelkunova, E. I.; Sherman, K. M.; Predein, Yu. A.; Kosareva, O. S.

    2016-08-01

    Creating tissue-engineering constructs based on the mechanism of cartilage-bone evolution is promising for traumatology and orthopedics. Such a graft was obtained from a chondrograft by transdifferentiation. The hondrograft placed in osteogenic medium is undergoing osteogenic differentiation for 14-30 days. Tissue specificity of the osteograft was studied by morphology, immunohistochemistry, electron microscopy, and the expression of the corresponding genes was estimated. The expression of osteonectin, fibronectin, collagen of type I, izolektin and CD 44 is determined. Alkaline phosphatase and matrix vesicles are determined in osteoblasts. Calcificates are observed in the matrix. Chondrogenic proteins expression is absent. These findings evidence the tissue specificity of the developed osteograft.

  19. Inhibition of calcitonin gene-related peptide and insulin-like growth factor: a potential new therapeutic strategy to reduce bone pain in bone metastases of breast cancer%抑制降钙基因相关肽和胰岛素样生长因子:一种减轻乳腺癌骨转移患者骨痛的新策略

    Institute of Scientific and Technical Information of China (English)

    梁燕

    2010-01-01

    @@ 2009年圣·安东尼奥会议上,Teruhisa Sakurai等作了题名为"Inhibition of calcitonin gene-related peptide and insulin-like growth factor:a potential new therapeutic strategy to reduce bone pain in bone metastases of breastcancer"的报告.

  20. Multifunctional materials for bone cancer treatment

    Directory of Open Access Journals (Sweden)

    Marques C

    2014-05-01

    Full Text Available Catarina Marques,1 José MF Ferreira,1 Ecaterina Andronescu,2 Denisa Ficai,2 Maria Sonmez,3 Anton Ficai21Department of Materials and Ceramics Engineering, Centre for Research in Ceramics and Composite Materials, University of Aveiro, Aveiro, Portugal; 2Faculty of Applied Chemistry and Material Science, University Politehnica of Bucharest, Bucharest, Romania; 3National Research and Development Institute for Textiles and Leather, Bucharest, RomaniaAbstract: The purpose of this review is to present the most recent findings in bone tissue engineering. Special attention is given to multifunctional materials based on collagen and collagen–hydroxyapatite composites used for skin and bone cancer treatments. The multifunctionality of these materials was obtained by adding to the base regenerative grafts proper components, such as ferrites (magnetite being the most important representative, cytostatics (cisplatin, carboplatin, vincristine, methotrexate, paclitaxel, doxorubicin, silver nanoparticles, antibiotics (anthracyclines, geldanamycin, and/or analgesics (ibuprofen, fentanyl. The suitability of complex systems for the intended applications was systematically analyzed. The developmental possibilities of multifunctional materials with regenerative and curative roles (antitumoral as well as pain management in the field of skin and bone cancer treatment are discussed. It is worth mentioning that better materials are likely to be developed by combining conventional and unconventional experimental strategies.Keywords: bone graft, cancer, collagen, magnetite, cytostatics, silver