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Sample records for current stem cell

  1. Limbal stem cell transplantation: current perspectives

    Directory of Open Access Journals (Sweden)

    Atallah MR

    2016-04-01

    Full Text Available Marwan Raymond Atallah, Sotiria Palioura, Victor L Perez, Guillermo Amescua Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Abstract: Regeneration of the corneal surface after an epithelial insult involves division, migration, and maturation of a specialized group of stem cells located in the limbus. Several insults, both intrinsic and extrinsic, can precipitate destruction of the delicate microenvironment of these cells, resulting in limbal stem cell deficiency (LSCD. In such cases, reepithelialization fails and conjunctival epithelium extends across the limbus, leading to vascularization, persistent epithelial defects, and chronic inflammation. In partial LSCD, conjunctival epitheliectomy, coupled with amniotic membrane transplantation, could be sufficient to restore a healthy surface. In more severe cases and in total LSCD, stem cell transplantation is currently the best curative option. Before any attempts are considered to perform a limbal stem cell transplantation procedure, the ocular surface must be optimized by controlling causative factors and comorbid conditions. These factors include adequate eyelid function or exposure, control of the ocular surface inflammatory status, and a well-lubricated ocular surface. In cases of unilateral LSCD, stem cells can be obtained from the contralateral eye. Newer techniques aim at expanding cells in vitro or in vivo in order to decrease the need for large limbal resection that may jeopardize the “healthy” eye. Patients with bilateral disease can be treated using allogeneic tissue in combination with systemic immunosuppressive therapy. Another emerging option for this subset of patients is the use of noncorneal cells such as mucosal grafts. Finally, the use of keratoprosthesis is reserved for patients who are not candidates for any of the aforementioned options, wherein the choice of the type of keratoprosthesis depends on

  2. Current applications of human pluripotent stem cells: possibilities and challenges.

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    Ho, Pai-Jiun; Yen, Men-Luh; Yet, Shaw-Fang; Yen, B Linju

    2012-01-01

    Stem cells are self-renewable cells with the differentiation capacity to develop into somatic cells with biological functions. This ability to sustain a renewable source of multi- and/or pluripotential differentiation has brought new hope to the field of regenerative medicine in terms of cell therapy and tissue engineering. Moreover, stem cells are invaluable tools as in vitro models for studying diverse fields, from basic scientific questions such as developmental processes and lineage commitment, to practical application including drug screening and testing. The stem cells with widest differentiation potential are pluripotent stem cells (PSCs), which are rare cells with the ability to generate somatic cells from all three germ layers. PSCs are considered the most optimal choice for therapeutic potential of stem cells, bringing new impetus to the field of regenerative medicine. In this article, we discuss the therapeutic potential of human PSCs (hPSCs) including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), reviewing the current preclinical and clinical data using these stem cells. We describe the classification of different sources of hPSCs, ongoing research, and currently encountered clinical obstacles of these novel and versatile human stem cells.

  3. Current status of stem cells in cardiac repair.

    Science.gov (United States)

    Henning, Robert J

    2018-03-01

    One out of every two men and one out of every three women greater than the age of 40 will experience an acute myocardial infarction (AMI) at some time during their lifetime. As more patients survive their AMIs, the incidence of congestive heart failure (CHF) is increasing. 6 million people in the USA have ischemic cardiomyopathies and CHF. The search for new and innovative treatments for patients with AMI and CHF has led to investigations and use of human embryonic stem cells, cardiac stem/progenitor cells, bone marrow-derived mononuclear cells and mesenchymal stem cells for treatment of these heart conditions. This paper reviews current investigations with human embryonic, cardiac, bone marrow and mesenchymal stem cells, and also stem cell paracrine factors and exosomes.

  4. Chick stem cells: Current progress and future prospects

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    Intarapat, Sittipon; Stern, Claudio D.

    2013-01-01

    Chick embryonic stem cells (cESCs) can be derived from cells obtained from stage X embryos (blastoderm stage); these have the ability to contribute to all somatic lineages in chimaeras, but not to the germ line. However, lines of stem cells that are able to contribute to the germ line can be established from chick primordial germ cells (cPGCs) and embryonic germ cells (cEGCs). This review provides information on avian stem cells, emphasizing different sources of cells and current methods for derivation and culture of pluripotent cells from chick embryos. We also review technologies for isolation and derivation of chicken germ cells and the production of transgenic birds. PMID:24103496

  5. Neoplastic stem cells: current concepts and clinical perspectives.

    Science.gov (United States)

    Schulenburg, Axel; Brämswig, Kira; Herrmann, Harald; Karlic, Heidrun; Mirkina, Irina; Hubmann, Rainer; Laffer, Sylvia; Marian, Brigitte; Shehata, Medhat; Krepler, Clemens; Pehamberger, Hubert; Grunt, Thomas; Jäger, Ulrich; Zielinski, Christoph C; Valent, Peter

    2010-11-01

    Neoplastic stem cells have initially been characterized in myeloid leukemias where NOD/SCID mouse-repopulating progenitors supposedly reside within a CD34+/Lin- subset of the malignant clone. These progenitors are considered to be self-renewing cells responsible for the in vivo long-term growth of neoplastic cells in leukemic patients. Therefore, these cells represent an attractive target of therapy. In some lymphoid leukemias, NOD/SCID mouse-repopulating cells were also reported to reside within the CD34+/Lin- subfraction of the clone. More recently, several attempts have been made to transfer the cancer stem cell concept to solid tumors and other non-hematopoietic neoplasms. In several of these tumors, the cell surface antigens AC133 (CD133) and CD44 are considered to indicate the potential of a cell to initiate permanent tumor formation in vivo. However, several questions concerning the phenotype, self-renewal capacity, stroma-dependence, and other properties of cancer- or leukemia-initiating cells remain to be solved. The current article provides a summary of our current knowledge on neoplastic (cancer) stem cells, with special emphasis on clinical implications and therapeutic options as well as a discussion about conceptual and technical limitations. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  6. Stem Cells

    Science.gov (United States)

    Stem cells are cells with the potential to develop into many different types of cells in the body. ... the body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  7. Stem Cell Basics

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    ... Tips Info Center Research Topics Federal Policy Glossary Stem Cell Information General Information Clinical Trials Funding Information Current ... Basics » Stem Cell Basics I. Back to top Stem Cell Basics I. Introduction: What are stem cells, and ...

  8. Stem cell maintenance by manipulating signaling pathways: past, current and future

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    Chen, Xi; Ye, Shoudong; Ying, Qi-Long

    2015-01-01

    Pluripotent stem cells only exist in a narrow window during early embryonic development, whereas multipotent stem cells are abundant throughout embryonic development and are retainedin various adult tissues and organs. While pluripotent stem cell lines have been established from several species, including mouse, rat, and human, it is still challenging to establish stable multipotent stem cell lines from embryonic or adult tissues. Based on current knowledge, we anticipate that by manipulating extrinsic and intrinsic signaling pathways, most if not all types of stem cells can be maintained in a long-term culture. In this article, we summarize current culture conditions established for the long-term maintenance of authentic pluripotent and multipotent stem cells and the signaling pathways involved. We also discuss the general principles of stem cell maintenance and propose several strategies on the establishment of novel stem cell lines through manipulation of signaling pathways. [BMB Reports 2015; 48(12): 668-676] PMID:26497581

  9. Current perspectives in Set7 mediated stem cell differentiation

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    Nazanin Karimnia

    2016-12-01

    Full Text Available Set7 is a key regulatory enzyme involved in the methylation of lysine residues of histone and non-histone proteins. This lysine methyltransferase is induced during stem cell differentiation and regulates lineage specific gene transcription and cell fate. In this article we discuss recent experimental evidence identifying regulatory targets under the control of Set7 as well as emerging evidence of regulation in stem cell differentiation. Furthermore, we discuss the function of non-coding RNAs regulated by Set7 implicated in cell plasticity.

  10. Stem Cells as New Agents for the Treatment of Infertility: Current and Future Perspectives and Challenges

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    Vladislav Volarevic

    2014-01-01

    Full Text Available Stem cells are undifferentiated cells that are present in the embryonic, fetal, and adult stages of life and give rise to differentiated cells that make up the building blocks of tissue and organs. Due to their unlimited source and high differentiation potential, stem cells are considered as potentially new therapeutic agents for the treatment of infertility. Stem cells could be stimulated in vitro to develop various numbers of specialized cells including male and female gametes suggesting their potential use in reproductive medicine. During past few years a considerable progress in the derivation of male germ cells from pluripotent stem cells has been made. In addition, stem cell-based strategies for ovarian regeneration and oocyte production have been proposed as future clinical therapies for treating infertility in women. In this review, we summarized current knowledge and present future perspectives and challenges regarding the use of stem cells in reproductive medicine.

  11. Biphasic electrical currents stimulation promotes both proliferation and differentiation of fetal neural stem cells.

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    Keun-A Chang

    2011-04-01

    Full Text Available The use of non-chemical methods to differentiate stem cells has attracted researchers from multiple disciplines, including the engineering and the biomedical fields. No doubt, growth factor based methods are still the most dominant of achieving some level of proliferation and differentiation control--however, chemical based methods are still limited by the quality, source, and amount of the utilized reagents. Well-defined non-chemical methods to differentiate stem cells allow stem cell scientists to control stem cell biology by precisely administering the pre-defined parameters, whether they are structural cues, substrate stiffness, or in the form of current flow. We have developed a culture system that allows normal stem cell growth and the option of applying continuous and defined levels of electric current to alter the cell biology of growing cells. This biphasic current stimulator chip employing ITO electrodes generates both positive and negative currents in the same culture chamber without affecting surface chemistry. We found that biphasic electrical currents (BECs significantly increased the proliferation of fetal neural stem cells (NSCs. Furthermore, BECs also promoted the differentiation of fetal NSCs into neuronal cells, as assessed using immunocytochemistry. Our results clearly show that BECs promote both the proliferation and neuronal differentiation of fetal NSCs. It may apply to the development of strategies that employ NSCs in the treatment of various neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases.

  12. Current Stem Cell Biomarkers and Their Functional Mechanisms in Prostate Cancer

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    Kaile Zhang

    2016-07-01

    Full Text Available Currently there is little effective treatment available for castration resistant prostate cancer, which is responsible for the majority of prostate cancer related deaths. Emerging evidence suggested that cancer stem cells might play an important role in resistance to traditional cancer therapies, and the studies of cancer stem cells (including specific isolation and targeting on those cells might benefit the discovery of novel treatment of prostate cancer, especially castration resistant disease. In this review, we summarized major biomarkers for prostate cancer stem cells, as well as their functional mechanisms and potential application in clinical diagnosis and treatment of patients.

  13. Stem cells

    NARCIS (Netherlands)

    Jukes, Jojanneke; Both, Sanne; Post, Janine; van Blitterswijk, Clemens; Karperien, Marcel; de Boer, Jan; van Blitterswijk, Clemens A.

    2008-01-01

    This chapter defines stem cells and their properties. It identifies the major differences between embryonic and adult stem cells. Stem cells can be defined by two properties: the ability to make identical copies of themselves and the ability to form other cell types of the body. These properties are

  14. Stem Cell Information: Glossary

    Science.gov (United States)

    ... Tips Info Center Research Topics Federal Policy Glossary Stem Cell Information General Information Clinical Trials Funding Information Current ... here Home » Glossary Back to top Glossary Adult stem cell Astrocyte Blastocoel Blastocyst Bone marrow stromal cells Bone ...

  15. Types of Stem Cells

    Science.gov (United States)

    ... Stem Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... Learn About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

  16. Current reprogramming systems in regenerative medicine: from somatic cells to induced pluripotent stem cells.

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    Hu, Chenxia; Li, Lanjuan

    2016-01-01

    Induced pluripotent stem cells (iPSCs) paved the way for research fields including cell therapy, drug screening, disease modeling and the mechanism of embryonic development. Although iPSC technology has been improved by various delivery systems, direct transduction and small molecule regulation, low reprogramming efficiency and genomic modification steps still inhibit its clinical use. Improvements in current vectors and the exploration of novel vectors are required to balance efficiency and genomic modification for reprogramming. Herein, we set out a comprehensive analysis of current reprogramming systems for the generation of iPSCs from somatic cells. By clarifying advantages and disadvantages of the current reprogramming systems, we are striding toward an effective route to generate clinical grade iPSCs.

  17. Alternating current electric field effects on neural stem cell viability and differentiation.

    Science.gov (United States)

    Matos, Marvi A; Cicerone, Marcus T

    2010-01-01

    Methods utilizing stem cells hold tremendous promise for tissue engineering applications; however, many issues must be worked out before these therapies can be routinely applied. Utilization of external cues for preimplantation expansion and differentiation offers a potentially viable approach to the use of stem cells in tissue engineering. The studies reported here focus on the response of murine neural stem cells encapsulated in alginate hydrogel beads to alternating current electric fields. Cell viability and differentiation was studied as a function of electric field magnitude and frequency. We applied fields of frequency (0.1-10) Hz, and found a marked peak in neural stem cell viability under oscillatory electric fields with a frequency of 1 Hz. We also found an enhanced propensity for astrocyte differentiation over neuronal differentiation in the 1 Hz cultures, as compared to the other field frequencies we studied. Published 2010 American Institute of Chemical Engineers

  18. Current status of treating neurodegenerative disease with induced pluripotent stem cells.

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    Pen, A E; Jensen, U B

    2017-01-01

    Degenerative diseases of the brain have proven challenging to treat, let alone cure. One of the treatment options is the use of stem cell therapy, which has been under investigation for several years. However, treatment with stem cells comes with a number of drawbacks, for instance the source of these cells. Currently, a number of options are tested to produce stem cells, although the main issues of quantity and ethics remain for most of them. Over recent years, the potential of induced pluripotent stem cells (iPSCs) has been widely investigated and these cells seem promising for production of numerous different tissues both in vitro and in vivo. One of the major advantages of iPSCs is that they can be made autologous and can provide a sufficient quantity of cells by culturing, making the use of other stem cell sources unnecessary. As the first descriptions of iPSC production with the transcription factors Sox2, Klf4, Oct4 and C-Myc, called the Yamanaka factors, a variety of methods has been developed to convert somatic cells from all germ layers to pluripotent stem cells. Improvement of these methods is necessary to increase the efficiency of reprogramming, the quality of pluripotency and the safety of these cells before use in human trials. This review focusses on the current accomplishments and remaining challenges in the production and use of iPSCs for treatment of neurodegenerative diseases of the brain such as Alzheimer's disease and Parkinson's disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. 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.

  20. Milestones of Hematopoietic Stem Cell Transplantation – From First Human Studies to Current Developments

    Science.gov (United States)

    Juric, Mateja Kralj; Ghimire, Sakhila; Ogonek, Justyna; Weissinger, Eva M.; Holler, Ernst; van Rood, Jon J.; Oudshoorn, Machteld; Dickinson, Anne; Greinix, Hildegard T.

    2016-01-01

    Since the early beginnings, in the 1950s, hematopoietic stem cell transplantation (HSCT) has become an established curative treatment for an increasing number of patients with life-threatening hematological, oncological, hereditary, and immunological diseases. This has become possible due to worldwide efforts of preclinical and clinical research focusing on issues of transplant immunology, reduction of transplant-associated morbidity, and mortality and efficient malignant disease eradication. The latter has been accomplished by potent graft-versus-leukemia (GvL) effector cells contained in the stem cell graft. Exciting insights into the genetics of the human leukocyte antigen (HLA) system allowed improved donor selection, including HLA-identical related and unrelated donors. Besides bone marrow, other stem cell sources like granulocyte-colony stimulating-mobilized peripheral blood stem cells and cord blood stem cells have been established in clinical routine. Use of reduced-intensity or non-myeloablative conditioning regimens has been associated with a marked reduction of non-hematological toxicities and eventually, non-relapse mortality allowing older patients and individuals with comorbidities to undergo allogeneic HSCT and to benefit from GvL or antitumor effects. Whereas in the early years, malignant disease eradication by high-dose chemotherapy or radiotherapy was the ultimate goal; nowadays, allogeneic HSCT has been recognized as cellular immunotherapy relying prominently on immune mechanisms and to a lesser extent on non-specific direct cellular toxicity. This chapter will summarize the key milestones of HSCT and introduce current developments. PMID:27881982

  1. Learn About Stem Cells

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    ... Patient Handbook Stem Cell Glossary Search Toggle Nav Stem Cell Basics Stem cells are the foundation from which ... original cell’s DNA, cytoplasm and cell membrane. About stem cells Stem cells are the foundation of development in ...

  2. Spermatogonial stem cell transplantation and male infertility: Current status and future directions

    Directory of Open Access Journals (Sweden)

    Connor M. Forbes

    2018-03-01

    Full Text Available Objective: To summarise the current state of research into spermatogonial stem cell (SSC therapies with a focus on future directions, as SSCs show promise as a source for preserving or initiating fertility in otherwise infertile men. Materials and methods: We performed a search for publications addressing spermatogonial stem cell transplantation in the treatment of male infertility. The search engines PubMed and Google Scholar were used from 1990 to 2017. Search terms were relevant for spermatogonial stem cell therapies. Titles of publications were screened for relevance; abstracts were read, if related and full papers were reviewed for directly pertinent original research. Results: In all, 58 papers were found to be relevant to this review, and were included in appropriate subheadings. This review discusses the various techniques that SSCs are being investigated to treat forms of male infertility. Conclusions: Evidence does not yet support clinical application of SSCs in humans. However, significant progress in the in vitro and in vivo development of SSCs, including differentiation into functional germ cells, gives reason for cautious optimism for future research. Keywords: Non-obstructive azoospermia, Fertility preservation, Onco-fertility, Male infertility, Stem cell therapy, Allograft

  3. Plant stem cell niches.

    Science.gov (United States)

    Aichinger, Ernst; Kornet, Noortje; Friedrich, Thomas; Laux, Thomas

    2012-01-01

    Multicellular organisms possess pluripotent stem cells to form new organs, replenish the daily loss of cells, or regenerate organs after injury. Stem cells are maintained in specific environments, the stem cell niches, that provide signals to block differentiation. In plants, stem cell niches are situated in the shoot, root, and vascular meristems-self-perpetuating units of organ formation. Plants' lifelong activity-which, as in the case of trees, can extend over more than a thousand years-requires that a robust regulatory network keep the balance between pluripotent stem cells and differentiating descendants. In this review, we focus on current models in plant stem cell research elaborated during the past two decades, mainly in the model plant Arabidopsis thaliana. We address the roles of mobile signals on transcriptional modules involved in balancing cell fates. In addition, we discuss shared features of and differences between the distinct stem cell niches of Arabidopsis.

  4. Use of Adult Stem Cells for Cartilage Tissue Engineering: Current Status and Future Developments

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    Catherine Baugé

    2015-01-01

    Full Text Available Due to their low self-repair ability, cartilage defects that result from joint injury, aging, or osteoarthritis, are the most often irreversible and are a major cause of joint pain and chronic disability. So, in recent years, researchers and surgeons have been working hard to elaborate cartilage repair interventions for patients who suffer from cartilage damage. However, current methods do not perfectly restore hyaline cartilage and may lead to the apparition of fibro- or hypertrophic cartilage. In the next years, the development of new strategies using adult stem cells, in scaffolds, with supplementation of culture medium and/or culture in low oxygen tension should improve the quality of neoformed cartilage. Through these solutions, some of the latest technologies start to bring very promising results in repairing cartilage from traumatic injury or chondropathies. This review discusses the current knowledge about the use of adult stem cells in the context of cartilage tissue engineering and presents clinical trials in progress, as well as in the future, especially in the field of bioprinting stem cells.

  5. Concise review: current status of stem cells and regenerative medicine in lung biology and diseases.

    Science.gov (United States)

    Weiss, Daniel J

    2014-01-01

    Lung diseases remain a significant and devastating cause of morbidity and mortality worldwide. In contrast to many other major diseases, lung diseases notably chronic obstructive pulmonary diseases (COPDs), including both asthma and emphysema, are increasing in prevalence and COPD is expected to become the third leading cause of disease mortality worldwide by 2020. New therapeutic options are desperately needed. A rapidly growing number of investigations of stem cells and cell therapies in lung biology and diseases as well as in ex vivo lung bioengineering have offered exciting new avenues for advancing knowledge of lung biology as well as providing novel potential therapeutic approaches for lung diseases. These initial observations have led to a growing exploration of endothelial progenitor cells and mesenchymal stem (stromal) cells in clinical trials of pulmonary hypertension and COPD with other clinical investigations planned. Ex vivo bioengineering of the trachea, larynx, diaphragm, and the lung itself with both biosynthetic constructs as well as decellularized tissues have been used to explore engineering both airway and vascular systems of the lung. Lung is thus a ripe organ for a variety of cell therapy and regenerative medicine approaches. Current state-of-the-art progress for each of the above areas will be presented as will discussion of current considerations for cell therapy-based clinical trials in lung diseases. © AlphaMed Press.

  6. Spermatogonial stem cell transplantation and male infertility: Current status and future directions.

    Science.gov (United States)

    Forbes, Connor M; Flannigan, Ryan; Schlegel, Peter N

    2018-03-01

    To summarise the current state of research into spermatogonial stem cell (SSC) therapies with a focus on future directions, as SSCs show promise as a source for preserving or initiating fertility in otherwise infertile men. We performed a search for publications addressing spermatogonial stem cell transplantation in the treatment of male infertility. The search engines PubMed and Google Scholar were used from 1990 to 2017. Search terms were relevant for spermatogonial stem cell therapies. Titles of publications were screened for relevance; abstracts were read, if related and full papers were reviewed for directly pertinent original research. In all, 58 papers were found to be relevant to this review, and were included in appropriate subheadings. This review discusses the various techniques that SSCs are being investigated to treat forms of male infertility. Evidence does not yet support clinical application of SSCs in humans. However, significant progress in the in vitro and in vivo development of SSCs, including differentiation into functional germ cells, gives reason for cautious optimism for future research.

  7. Spermatogonial stem cells: Current biotechnological advances in reproduction and regenerative medicine.

    Science.gov (United States)

    Aponte, Pedro Manuel

    2015-05-26

    Spermatogonial stem cells (SSCs) are the germ stem cells of the seminiferous epithelium in the testis. Through the process of spermatogenesis, they produce sperm while concomitantly keeping their cellular pool constant through self-renewal. SSC biology offers important applications for animal reproduction and overcoming human disease through regenerative therapies. To this end, several techniques involving SSCs have been developed and will be covered in this article. SSCs convey genetic information to the next generation, a property that can be exploited for gene targeting. Additionally, SSCs can be induced to become embryonic stem cell-like pluripotent cells in vitro. Updates on SSC transplantation techniques with related applications, such as fertility restoration and preservation of endangered species, are also covered on this article. SSC suspensions can be transplanted to the testis of an animal and this has given the basis for SSC functional assays. This procedure has proven technically demanding in large animals and men. In parallel, testis tissue xenografting, another transplantation technique, was developed and resulted in sperm production in testis explants grafted into ectopical locations in foreign species. Since SSC culture holds a pivotal role in SSC biotechnologies, current advances are overviewed. Finally, spermatogenesis in vitro, already demonstrated in mice, offers great promises to cope with reproductive issues in the farm animal industry and human clinical applications.

  8. Stem Cells and Aging.

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    Koliakos, George

    2017-02-01

    The article is a presentation at the 4th Conference of ESAAM, which took place on October 30-31, 2015, in Athens, Greece. Its purpose was not to cover all aspects of cellular aging but to share with the audience of the Conference, in a 15-minute presentation, current knowledge about the rejuvenating and repairing somatic stem cells that are distinct from other stem cell types (such as embryonic or induced pluripotent stem cells), emphasize that our body in old age cannot take advantage of these rejuvenating cells, and provide some examples of novel experimental stem cell applications in the field of rejuvenation and antiaging biomedical research.

  9. Moderate hypoxia influences potassium outward currents in adipose-derived stem cells.

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    Mayuri Prasad

    Full Text Available Moderate hypoxic preconditioning of adipose-derived stem cells (ASCs enhances properties such as proliferation and secretion of growth factors, representing a valuable strategy to increase the efficiency of cell-based therapies. In a wide variety of cells potassium (K+ channels are key elements involved in the cellular responses to hypoxia, suggesting that ASCs cultured under low oxygen conditions may display altered electrophysiological properties. Here, the effects of moderate hypoxic culture on proliferation, whole-cell currents, and ion channel expression were investigated using human ASCs cultured at 5% and 20% oxygen. Although cell proliferation was greatly enhanced, the dose-dependent growth inhibition by the K+ channel blocker tetraethylammonium (TEA was not significantly affected by hypoxia. Under both normoxic and hypoxic conditions, ASCs displayed outward K+ currents composed by Ca2+-activated, delayed rectifier, and transient components. Hypoxic culture reduced the slope of the current-voltage curves and caused a negative shift in the voltage activation threshold of the whole-cell currents. However, the TEA-mediated shift of voltage activation threshold was not affected by hypoxia. Semiquantitative real-time RT-PCR revealed that expression of genes encoding for various ion channels subunits related to oxygen sensing and proliferation remained unchanged after hypoxic culture. In conclusion, outward currents are influenced by moderate hypoxia in ASCs through a mechanism that is not likely the result of modulation of TEA-sensitive K+ channels.

  10. Stem cell treatment for avascular necrosis of the femoral head: current perspectives

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    Houdek MT

    2014-04-01

    Full Text Available Matthew T Houdek,1 Cody C Wyles,2 John R Martin,1 Rafael J Sierra11Department of Orthopedic Surgery, 2School of Medicine, Mayo Clinic, Rochester, MN, USAAbstract: Avascular necrosis (AVN of the femoral head is a progressive disease that predominantly affects younger patients. Although the exact pathophysiology of AVN has yet to be elucidated, the disease is characterized by a vascular insult to the blood supply of the femoral head, which can lead to collapse of the femoral head and subsequent degenerative changes. If AVN is diagnosed in the early stages of the disease, it may be possible to attempt surgical procedures which preserve the hip joint, including decompression of the femoral head augmented with concentrated bone marrow. The use of autologous stem cells has shown promise in halting the progression of AVN of the femoral head, and subsequently preventing young patients from undergoing total hip arthroplasty. The purpose of this study was to review the current use of stem cells for the treatment of AVN of the femoral head.Keywords: avascular necrosis, femoral head, osteonecrosis, stem cells, concentrated bone marrow

  11. Stem Cells

    DEFF Research Database (Denmark)

    Sommerlund, Julie

    2004-01-01

    In his influential essay on markets, An essay on framing and overflowing (1998), Michel Callon writes that `the growing complexity of industrialized societies [is] due in large part to the movements of the technosciences, which are causing connections and interdependencies to proliferate'. This p...... and tantalizing than stem cells, in research, in medicine, or as products.......'. This paper is about tech-noscience, and about the proliferation of connections and interdependencies created by it.More specifically, the paper is about stem cells. Biotechnology in general has the power to capture the imagination. Within the field of biotechnology nothing seems more provocative...

  12. Induced pluripotent stem cells and personalized medicine: current progress and future perspectives

    OpenAIRE

    Chun, Yong Soon; Byun, Kyunghee; Lee, Bonghee

    2011-01-01

    Generation of induced pluripotent stem cells (iPSCs) has revolutionized the field of regenerative medicine by providing researchers with a unique tool to derive disease-specific stem cells for study. iPSCs can self-renew and can differentiate into many cell types, offering a potentially unlimited source of cells for targeted differentiation into somatic effector cells. Hence, iPSCs are likely to be invaluable for therapeutic applications and disease-related research. In this review, we summar...

  13. Globalization of Stem Cell Science: An Examination of Current and Past Collaborative Research Networks

    Science.gov (United States)

    Luo, Jingyuan; Matthews, Kirstin R. W.

    2013-01-01

    Science and engineering research has becoming an increasingly international phenomenon. Traditional bibliometric studies have not captured the evolution of collaborative partnerships between countries, particularly in emerging technologies such as stem cell science, in which an immense amount of investment has been made in the past decade. Analyzing over 2,800 articles from the top journals that include stem cell research in their publications, this study demonstrates the globalization of stem cell science. From 2000 to 2010, international collaborations increased from 20.9% to 36% of all stem cell publications analyzed. The United States remains the most prolific and the most dominant country in the field in terms of publications in high impact journals. But Asian countries, particularly China are steadily gaining ground. Exhibiting the largest relative growth, the percent of Chinese-authored stem cell papers grew more than ten-fold, while the percent of Chinese-authored international papers increased over seven times from 2000 to 2010. And while the percent of total stem cell publications exhibited modest growth for European countries, the percent of international publications increased more substantially, particularly in the United Kingdom. Overall, the data indicated that traditional networks of collaboration extant in 2000 still predominate in stem cell science. Although more nations are becoming involved in international collaborations and undertaking stem cell research, many of these efforts, with the exception of those in certain Asian countries, have yet to translate into publications in high impact journals. PMID:24069210

  14. Pharmacoeconomics of Hematopoietic Stem Cell Mobilization : An Overview of Current Evidence and Gaps in the Literature

    NARCIS (Netherlands)

    Shaughnessy, Paul; Chao, Nelson; Shapiro, Jamie; Walters, Kent; McCarty, John; Abhyankar, Sunil; Shayani, Sepideh; Helmons, Pieter; Leather, Helen; Pazzalia, Amy; Pickard, Simon

    Adequate hematopoietic stem cell (HSC) mobilization and collection is required prior to proceeding with high dose chemotherapy and autologous hematopoietic stem cell transplant. Cytokines such as G-CSF, GM-CSF, and peg-filgrastim, alone or in combination with plerixafor, and after chemotherapy have

  15. Current Status on Stem Cells and Cancers of the Gastric Epithelium

    Directory of Open Access Journals (Sweden)

    Werner Hoffmann

    2015-08-01

    Full Text Available Gastric cancer is still a leading cause of cancer-related mortality worldwide in spite of declining incidence. Gastric cancers are, essentially, adenocarcinomas and one of the strongest risk factors is still infection with Helicobacter pylori. Within the last years, it became clear that gastric self-renewal and carcinogenesis are intimately linked, particularly during chronic inflammatory conditions. Generally, gastric cancer is now regarded as a disease resulting from dysregulated differentiation of stem and progenitor cells, mainly due to an inflammatory environment. However, the situation in the stomach is rather complex, consisting of two types of gastric units which show bidirectional self-renewal from an unexpectedly large variety of progenitor/stem cell populations. As in many other tumors, cancer stem cells have also been characterized for gastric cancer. This review focuses on the various gastric epithelial stem cells, how they contribute to self-renewal and which routes are known to gastric adenocarcinomas, including their stem cells.

  16. In vitro effect of direct current electrical stimulation on rat mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Sahba Mobini

    2017-01-01

    Full Text Available Background Electrical stimulation (ES has been successfully used to treat bone defects clinically. Recently, both cellular and molecular approaches have demonstrated that ES can change cell behavior such as migration, proliferation and differentiation. Methods In the present study we exposed rat bone marrow- (BM- and adipose tissue- (AT- derived mesenchymal stem cells (MSCs to direct current electrical stimulation (DC ES and assessed temporal changes in osteogenic differentiation. We applied 100 mV/mm of DC ES for 1 h per day for three, seven and 14 days to cells cultivated in osteogenic differentiation medium and assessed viability and calcium deposition at the different time points. In addition, expression of osteogenic genes, Runx2, Osteopontin, and Col1A2 was assessed in BM- and AT-derived MSCs at the different time points. Results Results showed that ES changed osteogenic gene expression patterns in both BM- and AT-MSCs, and these changes differed between the two groups. In BM-MSCs, ES caused a significant increase in mRNA levels of Runx2, Osteopontin and Col1A2 at day 7, while in AT-MSCs, the increase in Runx2 and Osteopontin expression were observed after 14 days of ES. Discussion This study shows that rat bone marrow- and adipose tissue-derived stem cells react differently to electrical stimuli, an observation that could be important for application of electrical stimulation in tissue engineering.

  17. Advancing Stem Cell Biology toward Stem Cell Therapeutics

    OpenAIRE

    Scadden, David; Srivastava, Alok

    2012-01-01

    Here, the International Society for Stem Cell Research (ISSCR) Clinical Translation Committee introduces a series of articles outlining the current status, opportunities, and challenges surrounding the clinical translation of stem cell therapeutics for specific medical conditions.

  18. Current Technologies Based on the Knowledge of the Stem Cells Microenvironments.

    Science.gov (United States)

    Mawad, Damia; Figtree, Gemma; Gentile, Carmine

    2017-01-01

    The stem cell microenvironment or niche plays a critical role in the regulation of survival, differentiation and behavior of stem cells and their progenies. Recapitulating each aspect of the stem cell niche is therefore essential for their optimal use in in vitro studies and in vivo as future therapeutics in humans. Engineering of optimal conditions for three-dimensional stem cell culture includes multiple transient and dynamic physiological stimuli, such as blood flow and tissue stiffness. Bioprinting and microfluidics technologies, including organs-on-a-chip, are among the most recent approaches utilized to replicate the three-dimensional stem cell niche for human tissue fabrication that allow the integration of multiple levels of tissue complexity, including blood flow. This chapter focuses on the physico-chemical and genetic cues utilized to engineer the stem cell niche and provides an overview on how both bioprinting and microfluidics technologies are improving our knowledge in this field for both disease modeling and tissue regeneration, including drug discovery and toxicity high-throughput assays and stem cell-based therapies in humans.

  19. Current and future regenerative medicine - principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Berg, Lise Charlotte; Betts, Dean H.

    2009-01-01

    This paper provides a bird's-eye perspective of the general principles of stem-cell therapy and tissue engineering; it relates comparative knowledge in this area to the current and future status of equine regenerative medicine.The understanding of equine stem cell biology, biofactors, and scaffolds...... mesenchymal stromal cells, unless there is proof that they exhibit the fundamental in vivo characteristics of pluripotency and the ability to self-renew. That said, these cells from various tissues hold great promise for therapeutic use in horses. The 3 components of tissue engineering - cells, biological...... factors, and biomaterials - are increasingly being applied in equine medicine, fuelled by better scaffolds and increased understanding of individual biofactors and cell sources.The effectiveness of stem cell-based therapies and most tissue engineering concepts has not been demonstrated sufficiently...

  20. Changing paradigms in cranio-facial regeneration: current and new strategies for the activation of endogenous stem cells

    Directory of Open Access Journals (Sweden)

    Luigi eMele

    2016-02-01

    Full Text Available Craniofacial area represent a unique district of human body characterized by a very high complexity of tissues, innervation and vascularization, and being deputed to many fundamental function such as eating, speech, expression of emotions, delivery of sensations such as taste, sight and earing. For this reasons, tissue loss in this area following trauma or for example oncologic resection, have a tremendous impact on patients’ quality of life. In the last 20 years regenerative medicine has emerged as one of the most promising approach to solve problem related to trauma, tissue loss, organ failure etc. One of the most powerful tools to be used for tissue regeneration is represented by stem cells, which have been successfully implanted in different tissue/organs with exciting results. Nevertheless both autologous and allogeneic stem cell transplantation raise many practical and ethical concerns that make this approach very difficult to apply in clinical practice. For this reason different cell free approaches have been developed aiming to the mobilization, recruitment and activation of endogenous stem cells into the injury site avoiding exogenous cells implant but instead stimulating patients’ own stem cells to repair the lesion. To this aim many strategies have been used including functionalized bioscaffold, controlled release of stem cell chemoattractants, growth factors, BMPs, Platelet–Rich-Plasma and other new strategies such as ultrasound wave and laser are just being proposed. Here we review all the current and new strategies used for activation and mobilization of endogenous stem cells in the regeneration of craniofacial tissue.

  1. The Role of Stem Cell Therapeutics in Wound Healing: Current Understanding and Future Directions.

    Science.gov (United States)

    Sorice, Sarah; Rustad, Kristine C; Li, Alexander Y; Gurtner, Geoffrey C

    2016-09-01

    Chronic wounds present unique challenges for healthcare providers as they place patients at increased risk for various morbidities and mortality. Advances in wound care technology have expanded the treatment options available for wound management, but few products fully address the underlying core deficiencies responsible for the development of poorly healing wounds. In the future, addressing these derangements will undoubtedly play a key role in the treatment of these patients. Broad enthusiasm has surrounded the field of stem cell biology, which has shown great promise in repairing damaged tissues across numerous disease phenotypes. In this review, we provide a comprehensive review of the literature and evaluate the present landscape of wound therapeutics while discussing the rationales and allure behind stem cell-based products. We further propose 2 challenges that remain as new stem cell-based therapies are being developed and as this technology moves toward clinical translation. Given the relatively young age of this newer technology in wound healing, numerous challenges continue to surround its effective use including identifying the ideal population of stem cells to use and determining the optimal cell delivery method. However, significant forward progress has been made, with several clinical trials beginning to demonstrate reliable clinical benefit. The upward trajectory of stem cell technologies provides an exciting opportunity to positively impact patient outcomes through the controlled application of regenerative cell-based therapy.

  2. Information on Stem Cell Research

    Science.gov (United States)

    ... Home » Current Research » Focus on Research Focus on Stem Cell Research Stem cells possess the unique ability to differentiate into ... virus infection. To search the complete list of stem cell research projects funded by NIH please go to NIH ...

  3. Stem cell biobanks.

    Science.gov (United States)

    Bardelli, Silvana

    2010-04-01

    Stem cells contribute to innate healing and harbor a promising role for regenerative medicine. Stem cell banking through long-term storage of different stem cell platforms represents a fundamental source to preserve original features of stem cells for patient-specific clinical applications. Stem cell research and clinical translation constitute fundamental and indivisible modules catalyzed through biobanking activity, generating a return of investment.

  4. Human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Abdallah, Basem; Kassem, Moustapha

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being...... introduced into clinical medicine in variety of applications and through different ways of administration. Here, we discuss approaches for isolation, characterization and directing differentiation of human mesenchymal stem cells (hMSC). An update of the current clinical use of the cells is also provided....

  5. Osteoporosis: the current status of mesenchymal stem cell-based therapy.

    Science.gov (United States)

    Phetfong, Jitrada; Sanvoranart, Tanwarat; Nartprayut, Kuneerat; Nimsanor, Natakarn; Seenprachawong, Kanokwan; Prachayasittikul, Virapong; Supokawej, Aungkura

    2016-01-01

    Osteoporosis, or bone loss, is a progressive, systemic skeletal disease that affects millions of people worldwide. Osteoporosis is generally age related, and it is underdiagnosed because it remains asymptomatic for several years until the development of fractures that confine daily life activities, particularly in elderly people. Most patients with osteoporotic fractures become bedridden and are in a life-threatening state. The consequences of fracture can be devastating, leading to substantial morbidity and mortality of the patients. The normal physiologic process of bone remodeling involves a balance between bone resorption and bone formation during early adulthood. In osteoporosis, this process becomes imbalanced, resulting in gradual losses of bone mass and density due to enhanced bone resorption and/or inadequate bone formation. Several growth factors underlying age-related osteoporosis and their signaling pathways have been identified, such as osteoprotegerin (OPG)/receptor activator of nuclear factor B (RANK)/RANK ligand (RANKL), bone morphogenetic protein (BMP), wingless-type MMTV integration site family (Wnt) proteins and signaling through parathyroid hormone receptors. In addition, the pathogenesis of osteoporosis has been connected to genetics. The current treatment of osteoporosis predominantly consists of antiresorptive and anabolic agents; however, the serious adverse effects of using these drugs are of concern. Cell-based replacement therapy via the use of mesenchymal stem cells (MSCs) may become one of the strategies for osteoporosis treatment in the future.

  6. Potency of Stem Cells

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Potency of Stem Cells. Totipotent Stem Cells (Zygote + first 2 divisions). -Can form placenta, embryo, and any cell of the body. Pluripotent (Embryonic Stem Cells). -Can form any cell of the body but can not form placenta, hence no embryo. Multipotent (Adult stem cells).

  7. In utero hematopoietic stem cell transfer: current status and future strategies.

    Science.gov (United States)

    Surbek, D V; Gratwohl, A; Holzgreve, W

    1999-07-01

    Successful prenatal treatment of severe immunodeficiencies by allogeneic hematopoietic stem cell transplantation in utero has been reported. Though other diseases like hemoglobinopathies or storage diseases are potentially amenable to this novel therapeutic approach, no success has yet been achieved in recipients without severe immunodeficiency. Graft rejection by the developing fetus and/or lack of selective, competitive advantage of donor versus host stem cells preventing stable engraftment seem to be the major obstacles. Several strategies to overcome these hurdles are being explored in preclinical settings, including timing and repeated dosing of stem cell administration to the fetus, ex vivo modification of the transplant, using different fetal compartments as targets for early stem cell transfer, or inducing microchimerism for postnatal transplantation from the same donor. In addition, the exact definition of the basic concept of early fetal immunologic naivete and the understanding of the molecular basics of migration and homing in fetal hematopoiesis system seem mandatory for a successful approach. Gene therapy using ex vivo transduced autologous cord blood cells or direct gene targeting in utero are other potential means to correct hematopoietic and immunologic single gene disorders in utero, though this approach is still away from the stage of clinical trials.

  8. Mesenchymal stem cell treatment for hemophilia: a review of current knowledge.

    Science.gov (United States)

    Sokal, E M; Lombard, C; Mazza, G

    2015-06-01

    Hemophilia remains a non-curative disease, and patients are constrained to undergo repeated injections of clotting factors. In contrast, the sustained production of endogenous factors VIII (FVIII) or IX (FIX) by the patient's own cells could represent a curative treatment. Gene therapy has thus provided new hope for these patients. However, the issues surrounding the durability of expression and immune responses against gene transfer vectors remain. Cell therapy, involving stem cells expanded in vitro, can provide de novo protein synthesis and, if implanted successfully, could induce a steady-state production of low quantities of factors, which may keep the patient above the level required to prevent spontaneous bleeding. Liver-derived stem cells are already being assessed in clinical trials for inborn errors of metabolism and, in view of their capacity to produce FVIII and FIX in cell culture, they are now also being considered for clinical application in hemophilia patients. © 2015 International Society on Thrombosis and Haemostasis.

  9. Human Embryonic Stem Cell Responses to Ionizing Radiation Exposures: Current State of Knowledge and Future Challenges

    Directory of Open Access Journals (Sweden)

    Mykyta V. Sokolov

    2012-01-01

    Full Text Available Human embryonic stem cells, which are derived from the inner cell mass of the blastocyst, have become an object of intense study over the last decade. They possess two unique properties that distinguish them from many other cell types: (i the ability to self-renew indefinitely in culture under permissive conditions, and (ii the pluripotency, defined as the capability of giving rise to all cell types of embryonic lineage under the guidance of the appropriate developmental cues. The focus of many recent efforts has been on the elucidating the signaling pathways and molecular networks operating in human embryonic stem cells. These cells hold great promise in cell-based regenerative therapies, disease modeling, drug screening and testing, assessing genotoxic and mutagenic risks associated with exposures to a variety of environmental factors, and so forth. Ionizing radiation is ubiquitous in nature, and it is widely used in diagnostic and therapeutic procedures in medicine. In this paper, our goal is to summarize the recent progress in understanding how human embryonic stem cells respond to ionizing radiation exposures, using novel methodologies based on “omics” approaches, and to provide a critical discussion of what remains unknown; thus proposing a roadmap for the future research in this area.

  10. Gene regulation in adult neural stem cells : Current challenges and possible applications

    NARCIS (Netherlands)

    Encinas, J.M.; Fitzsimons, C.P.

    2017-01-01

    Adult neural stem and progenitor cells (NSPCs) offer a unique opportunity for neural regeneration and niche modification in physiopathological conditions, harnessing the capability to modify from neuronal circuits to glial scar. Findings exposing the vast plasticity and potential of NSPCs have

  11. Cloning, Stem Cells, and the Current National Debate: Incorporating Ethics into a Large Introductory Biology Course

    Science.gov (United States)

    Fink, Rachel D.

    2002-01-01

    Discussing the ethical issues involved in topics such as cloning and stem cell research in a large introductory biology course is often difficult. Teachers may be wary of presenting material biased by personal beliefs, and students often feel inhibited speaking about moral issues in a large group. Yet, to ignore what is happening "out there"…

  12. Stem Cells of Dental Origin: Current Research Trends and Key Milestones towards Clinical Application

    Directory of Open Access Journals (Sweden)

    Athina Bakopoulou

    2016-01-01

    Full Text Available Dental Mesenchymal Stem Cells (MSCs, including Dental Pulp Stem Cells (DPSCs, Stem Cells from Human Exfoliated Deciduous teeth (SHED, and Stem Cells From Apical Papilla (SCAP, have been extensively studied using highly sophisticated in vitro and in vivo systems, yielding substantially improved understanding of their intriguing biological properties. Their capacity to reconstitute various dental and nondental tissues and the inherent angiogenic, neurogenic, and immunomodulatory properties of their secretome have been a subject of meticulous and costly research by various groups over the past decade. Key milestone achievements have exemplified their clinical utility in Regenerative Dentistry, as surrogate therapeutic modules for conventional biomaterial-based approaches, offering regeneration of damaged oral tissues instead of simply “filling the gaps.” Thus, the essential next step to validate these immense advances is the implementation of well-designed clinical trials paving the way for exploiting these fascinating research achievements for patient well-being: the ultimate aim of this ground breaking technology. This review paper presents a concise overview of the major biological properties of the human dental MSCs, critical for the translational pathway “from bench to clinic.”

  13. RNAi Technique in Stem Cell Research: Current Status and Future Perspectives.

    Science.gov (United States)

    Zou, Gang-Ming

    2017-01-01

    RNAi is a mechanism displayed by most eukaryotic cells to rid themselves of foreign double-strand RNA molecules. In the 18 years since the initial report, RNAi has now been demonstrated to function in mammalian cells to alter gene expression and has been used as a means for genetic discovery as well as a possible strategy for genetic correction and genetic therapy in cancer and other disease. The aim of this review is to provide a general overview of how RNAi suppresses gene expression and to examine some published RNAi approaches that have resulted in changes in stem cell function and suggest the possible clinical relevance of this work in cancer therapy through targeting cancer stem cells.

  14. Mammary gland stem cells

    DEFF Research Database (Denmark)

    Fridriksdottir, Agla J R; Petersen, Ole W; Rønnov-Jessen, Lone

    2011-01-01

    Distinct subsets of cells, including cells with stem cell-like properties, have been proposed to exist in normal human breast epithelium and breast carcinomas. The cellular origins of epithelial cells contributing to gland development, tissue homeostasis and cancer are, however, still poorly...... and differences between mouse and human gland development with particular emphasis on the identity and localization of stem cells, and the influence of the surrounding microenvironment. It is concluded that while recent advances in the field have contributed immense insight into how the normal mammary gland...... develops and is maintained, significant discrepancies exist between the mouse and human gland which should be taken into consideration in current and future models of mammary stem cell biology....

  15. Myeloproliferative neoplasm stem cells.

    Science.gov (United States)

    Mead, Adam J; Mullally, Ann

    2017-03-23

    Myeloproliferative neoplasms (MPNs) arise in the hematopoietic stem cell (HSC) compartment as a result of the acquisition of somatic mutations in a single HSC that provides a selective advantage to mutant HSC over normal HSC and promotes myeloid differentiation to engender a myeloproliferative phenotype. This population of somatically mutated HSC, which initiates and sustains MPNs, is termed MPN stem cells. In >95% of cases, mutations that drive the development of an MPN phenotype occur in a mutually exclusive manner in 1 of 3 genes: JAK2 , CALR , or MPL The thrombopoietin receptor, MPL, is the key cytokine receptor in MPN development, and these mutations all activate MPL-JAK-STAT signaling in MPN stem cells. Despite common biological features, MPNs display diverse disease phenotypes as a result of both constitutional and acquired factors that influence MPN stem cells, and likely also as a result of heterogeneity in the HSC in which MPN-initiating mutations arise. As the MPN clone expands, it exerts cell-extrinsic effects on components of the bone marrow niche that can favor the survival and expansion of MPN stem cells over normal HSC, further sustaining and driving malignant hematopoiesis. Although developed as targeted therapies for MPNs, current JAK2 inhibitors do not preferentially target MPN stem cells, and as a result, rarely induce molecular remissions in MPN patients. As the understanding of the molecular mechanisms underlying the clonal dominance of MPN stem cells advances, this will help facilitate the development of therapies that preferentially target MPN stem cells over normal HSC. © 2017 by The American Society of Hematology.

  16. Tissue Engineering in Osteoarthritis: Current Status and Prospect of Mesenchymal Stem Cell Therapy.

    Science.gov (United States)

    Im, Gun-Il

    2018-04-27

    Osteoarthritis (OA) is the most common form of arthritis. Over the last 20 years, attempts have been made to regenerate articular cartilage to overcome the limitations of conventional treatments. As OA is generally associated with larger and diffuse involvement of articular surfaces and alteration of joint homeostasis, a tissue engineering approach for cartilage regeneration is more difficult than in simple chondral defects. Autologous and allogeneic mesenchymal stem cells (MSCs) have rapidly emerged as investigational products for cartilage regeneration. This review outlines points to consider in MSC-based approaches for OA treatment, including allogeneic MSCs, sources of MSCs, dosages, feasibility of multiple injections, indication according to severity of OA lesion and patient age, and issues regarding implantation versus injection. We introduce possible mechanisms of action of implanted or injected MSCs as well as the immunological aspects of MSC therapy and provide a summary of clinical trials of MSCs in the treatment of OA. Given current knowledge, it is too early to draw conclusions on the ultimate effectiveness of intra-articular application of MSCs in terms of regenerative effects. Further radiological and histological data will be needed, with a larger pool of patients, before this question can be answered.

  17. Report of the International Stem Cell Banking Initiative Workshop Activity: Current Hurdles and Progress in Seed-Stock Banking of Human Pluripotent Stem Cells.

    Science.gov (United States)

    Kim, Jung-Hyun; Kurtz, Andreas; Yuan, Bao-Zhu; Zeng, Fanyi; Lomax, Geoff; Loring, Jeanne F; Crook, Jeremy; Ju, Ji Hyeon; Clarke, Laura; Inamdar, Maneesha S; Pera, Martin; Firpo, Meri T; Sheldon, Michael; Rahman, Nafees; O'Shea, Orla; Pranke, Patricia; Zhou, Qi; Isasi, Rosario; Rungsiwiwut, Ruttachuk; Kawamata, Shin; Oh, Steve; Ludwig, Tenneille; Masui, Tohru; Novak, Thomas J; Takahashi, Tsuneo; Fujibuchi, Wataru; Koo, Soo Kyung; Stacey, Glyn N

    2017-11-01

    This article summarizes the recent activity of the International Stem Cell Banking Initiative (ISCBI) held at the California Institute for Regenerative Medicine (CIRM) in California (June 26, 2016) and the Korean National Institutes for Health in Korea (October 19-20, 2016). Through the workshops, ISCBI is endeavoring to support a new paradigm for human medicine using pluripotent stem cells (hPSC) for cell therapies. Priority considerations for ISCBI include ensuring the safety and efficacy of a final cell therapy product and quality assured source materials, such as stem cells and primary donor cells. To these ends, ISCBI aims to promote global harmonization on quality and safety control of stem cells for research and the development of starting materials for cell therapies, with regular workshops involving hPSC banking centers, biologists, and regulatory bodies. Here, we provide a brief overview of two such recent activities, with summaries of key issues raised. Stem Cells Translational Medicine 2017;6:1956-1962. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  18. Involvement of plant stem cells or stem cell-like cells in dedifferentiation

    Directory of Open Access Journals (Sweden)

    Fangwei eJiang

    2015-11-01

    Full Text Available Dedifferentiation is the transformation of cells from a given differentiated state to a less differentiated or stem cell-like state. Stem cell-related genes play important roles in dedifferentiation, which exhibits similar histone modification and DNA methylation features to stem cell maintenance. Hence, stem cell-related factors possibly synergistically function to provide a specific niche beneficial to dedifferentiation. During callus formation in Arabidopsis petioles, cells adjacent to procambium cells (stem cell-like cells are dedifferentiated and survive more easily than other cell types. This finding indicates that stem cells or stem cell-like cells may influence the dedifferentiating niche. In this paper, we provide a brief overview of stem cell maintenance and dedifferentiation regulation. We also summarize current knowledge of genetic and epigenetic mechanisms underlying the balance between differentiation and dedifferentiation. Furthermore, we discuss the correlation of stem cells or stem cell-like cells with dedifferentiation.

  19. Targeting Cancer Stem Cells and Their Niche: Current Therapeutic Implications and Challenges in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Jiangang Zhao

    2017-01-01

    Full Text Available Cancer stem cells (CSCs have been identified as a subpopulation of stem-like cancer cells with the ability of self-renewal and differentiation in hematological malignancies and solid tumors. Pancreatic cancer is one of the most lethal cancers worldwide. CSCs are thought to be responsible for cancer initiation, progression, metastasis, chemoresistance, and recurrence in pancreatic cancer. In this review, we summarize the characteristics of pancreatic CSCs and discuss the mechanisms involved in resistance to chemotherapy, the interactions with the niche, and the potential role in cancer immunoediting. We propose that immunotherapy targeting pancreatic CSCs, in combination with targeting the niche components, may provide a novel treatment strategy to eradicate pancreatic CSCs and hence improve outcomes in pancreatic cancer.

  20. Haematopoietic stem cell transplantation as first-line treatment in myeloma: a global perspective of current concepts and future possibilities

    Directory of Open Access Journals (Sweden)

    Catriona Elizabeth Mactier

    2012-10-01

    Full Text Available Stem cell transplantation forms an integral part of the treatment for multiple myeloma. This paper reviews the current role of transplantation and the progress that has been made in order to optimize the success of this therapy. Effective induction chemotherapy is important and a combination regimen incorporating the novel agent bortezomib is now favorable. Adequate induction is a crucial adjunct to stem cell transplantation and in some cases may potentially postpone the need for transplant. Different conditioning agents prior to transplantation have been explored: high-dose melphalan is most commonly used and bortezomib is a promising additional agent. There is no well-defined superior transplantation protocol but single or tandem autologous stem cell transplantations are those most commonly used, with allogeneic transplantation only used in clinical trials. The appropriate timing of transplantation in the treatment plan is a matter of debate. Consolidation and maintenance chemotherapies, particularly thalidomide and bortezomib, aim to improve and prolong disease response to transplantation and delay recurrence. Prognostic factors for the outcome of stem cell transplant in myeloma have been highlighted. Despite good responses to chemotherapy and transplantation, the problem of disease recurrence persists. Thus, there is still much room for improvement. Treatments which harness the graft-versus-myeloma effect may offer a potential cure for this disease. Trials of novel agents are underway, including targeted therapies for specific antigens such as vaccines and monoclonal antibodies.

  1. Historical Perspective on the Current Renaissance for Hematopoietic Stem Cell Gene Therapy.

    Science.gov (United States)

    Kohn, Donald B

    2017-10-01

    Gene therapy using hematopoietic stem cells (HSC) has developed over the past 3 decades, with progressive improvements in the efficacy and safety. Autologous transplantation of HSC modified with murine gammaretroviral vectors first showed clinical benefits for patients with several primary immune deficiencies, but some of these patients suffered complications from vector-related genotoxicity. Lentiviral vectors have been used recently for gene addition to HSC and have yielded clinical benefits for primary immune deficiencies, metabolic diseases, and hemoglobinopathies, without vector-related complications. Gene editing using site-specific endonucleases is emerging as a promising technology for gene therapy and is moving into clinical trials. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Plant stem cell niches.

    Science.gov (United States)

    Stahl, Yvonne; Simon, Rüdiger

    2005-01-01

    Stem cells are required to support the indeterminate growth style of plants. Meristems are a plants stem cell niches that foster stem cell survival and the production of descendants destined for differentiation. In shoot meristems, stem cell fate is decided at the populational level. The size of the stem cell domain at the meristem tip depends on signals that are exchanged with cells of the organizing centre underneath. In root meristems, individual stem cells are controlled by direct interaction with cells of the quiescent centre that lie in the immediate neighbourhood. Analysis of the interactions and signaling processes in the stem cell niches has delivered some insights into the molecules that are involved and revealed that the two major niches for plant stem cells are more similar than anticipated.

  3. Stem cell therapy for inflammatory bowel disease

    NARCIS (Netherlands)

    Duijvestein, Marjolijn

    2012-01-01

    Hematopoietic stem cell transplantation (HSCT) and mesenchymal stromal (MSC) cell therapy are currently under investigation as novel therapies for inflammatory bowel diseases (IBD). Hematopoietic stem cells are thought to repopulate the immune system and reset the immunological response to luminal

  4. Mesenchymal Stem Cells and Cutaneous Wound Healing: Current Evidence and Future Potential

    Directory of Open Access Journals (Sweden)

    M. Isakson

    2015-01-01

    Full Text Available Human skin is a remarkable organ that sustains insult and injury throughout life. The ability of skin to expeditiously repair wounds is paramount to survival. With an aging global population, coupled with a rise in the prevalence of conditions such as diabetes, chronic wounds represent a significant biomedical burden. Mesenchymal stem cells (MSC, a progenitor cell population of the mesoderm lineage, have been shown to be significant mediators in inflammatory environments. Preclinical studies of MSC in various animal wound healing models point towards a putative therapy. This review examines the body of evidence suggesting that MSC accelerate wound healing in both clinical and preclinical studies and also the possible mechanisms controlling its efficacy. The delivery of a cellular therapy to the masses presents many challenges from a safety, ethical, and regulatory point of view. Some of the issues surrounding the introduction of MSC as a medicinal product are also delineated in this review.

  5. The use of mesenchymal (skeletal) stem cells for treatment of degenerative diseases: current status and future perspectives

    DEFF Research Database (Denmark)

    Abdallah, Basem; Kassem, Moustapha

    2009-01-01

    Human bone marrow derived-mesenchymal (skeletal) stem (MSC) cells are a group of non-hematopoietic stem cells residing in the perivascular niches in bone marrow. These cells have the capacity to differentiate mainly into mesoderm-type cells such as osteoblasts, chondrocytes and adipocytes and pos...

  6. Stem Cell Transplant

    Science.gov (United States)

    ... Graft-versus-host disease: A potential risk when stem cells come from donors If you receive a transplant ... medications and blood products into your body. Collecting stem cells for transplant If a transplant using your own ...

  7. Skin Stem Cells in Skin Cell Therapy

    Directory of Open Access Journals (Sweden)

    Mollapour Sisakht

    2015-12-01

    Full Text Available Context Preclinical and clinical research has shown that stem cell therapy is a promising therapeutic option for many diseases. This article describes skin stem cells sources and their therapeutic applications. Evidence Acquisition Compared with conventional methods, cell therapy reduces the surgical burden for patients because it is simple and less time-consuming. Skin cell therapy has been developed for variety of diseases. By isolation of the skin stem cell from the niche, in vitro expansion and transplantation of cells offers a surprising healing capacity profile. Results Stem cells located in skin cells have shown interesting properties such as plasticity, transdifferentiation, and specificity. Mesenchymal cells of the dermis, hypodermis, and other sources are currently being investigated to promote regeneration. Conclusions Because skin stem cells are highly accessible from autologous sources and their immunological profile is unique, they are ideal for therapeutic approaches. Optimization of administrative routes requires more investigation own to the lack of a standard protocol.

  8. Stem Cell Pathology.

    Science.gov (United States)

    Fu, Dah-Jiun; Miller, Andrew D; Southard, Teresa L; Flesken-Nikitin, Andrea; Ellenson, Lora H; Nikitin, Alexander Yu

    2018-01-24

    Rapid advances in stem cell biology and regenerative medicine have opened new opportunities for better understanding disease pathogenesis and the development of new diagnostic, prognostic, and treatment approaches. Many stem cell niches are well defined anatomically, thereby allowing their routine pathological evaluation during disease initiation and progression. Evaluation of the consequences of genetic manipulations in stem cells and investigation of the roles of stem cells in regenerative medicine and pathogenesis of various diseases such as cancer require significant expertise in pathology for accurate interpretation of novel findings. Therefore, there is an urgent need for developing stem cell pathology as a discipline to facilitate stem cell research and regenerative medicine. This review provides examples of anatomically defined niches suitable for evaluation by diagnostic pathologists, describes neoplastic lesions associated with them, and discusses further directions of stem cell pathology.

  9. Osteoblastic differentiation and stress response of human mesenchymal stem cells exposed to alternating current electric fields

    Directory of Open Access Journals (Sweden)

    Kaplan David L

    2011-01-01

    Full Text Available Abstract Background Electric fields are integral to many biological events, from maintaining cellular homeostasis to embryonic development to healing. The application of electric fields offers substantial therapeutic potential, while optimal dosing regimens and the underlying mechanisms responsible for the positive clinical impact are poorly understood. Methods The purpose of this study was to track the differentiation profile and stress response of human bone marrow derived mesenchymal stem cells (hMSCs undergoing osteogenic differentiation during exposure to a 20 mV/cm, 60 kHz electric field. Morphological and biochemical changes were imaged using endogenous two-photon excited fluorescence (TPEF and quantitatively assessed through eccentricity calculations and extraction of the redox ratio from NADH, FAD and lipofuscin contributions. Real time reverse transcriptase-polymerase chain reactions (RT-PCR were used to track osteogenic differentiation markers, namely alkaline phosphatase (ALP and collagen type 1 (col1, and stress response markers, such as heat shock protein 27 (hsp27 and heat shock protein 70 (hsp70. Comparisons of collagen deposition between the stimulated hMSCs and controls were examined through second harmonic generation (SHG imaging. Results Quantitative differences in cell morphology, as described through an eccentricity ratio, were found on days 2 and days 5 (p Conclusions Electrical stimulation is a useful tool to improve hMSC osteogenic differentiation, while heat shock proteins may reveal underlying mechanisms, and optical non-invasive imaging may be used to monitor the induced morphological and biochemical changes.

  10. Adipose stem cells for intervertebral disc regeneration: Current status and concepts for the future: Tissue Engineering Review Series

    NARCIS (Netherlands)

    Hoogendoorn, R.J.W.; Lu, Z.F.; Kroeze, R.J.; Bank, R.A.; Wuisman, P.I.; Helder, M.N.

    2008-01-01

    Introduction Degenerative disc disease and emerging biological treatment approaches Stem cell sources Integration of ASC-based regenerative medicine and surgery In vitro studies Animal models Cells in disc regeneration in vivo In vivo studies Perspective Conclusions Abstract New regenerative

  11. Dental pulp stem cells

    DEFF Research Database (Denmark)

    Ashri, N. Y.; Ajlan, S. A.; Aldahmash, Abdullah M.

    2015-01-01

    scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from...... an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors....

  12. Colorectal cancer stem cells.

    Science.gov (United States)

    Salama, Paul; Platell, Cameron

    2009-10-01

    Somatic stem cells reside at the base of the crypts throughout the colonic mucosa. These cells are essential for the normal regeneration of the colonic epithelium. The stem cells reside within a special 'niche' comprised of intestinal sub-epithelial myofibroblasts that tightly control their function. It has been postulated that mutations within these adult colonic stem cells may induce neoplastic changes. Such cells can then dissociate from the epithelium and travel into the mesenchyme and thus form invasive cancers. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumour. It is this group of cells that exhibits characteristics of colonic stem cells. Although anti-neoplastic agents can induce remissions by inhibiting cell division, the stem cells appear to be remarkably resistant to both standard chemotherapy and radiotherapy. These stem cells may therefore persist after treatment and form the nucleus for cancer recurrence. Hence, future treatment modalities should focus specifically on controlling the cancer stem cells. In this review, we discuss the biology of normal and malignant colonic stem cells.

  13. Aneuploidy in stem cells

    NARCIS (Netherlands)

    Garcia-Martinez, Jorge; Bakker, Bjorn; Schukken, Klaske M; Simon, Judith E; Foijer, Floris

    2016-01-01

    Stem cells hold enormous promise for regenerative medicine as well as for engineering of model systems to study diseases and develop new drugs. The discovery of protocols that allow for generating induced pluripotent stem cells (IPSCs) from somatic cells has brought this promise steps closer to

  14. Dazlin' pluripotent stem cells

    NARCIS (Netherlands)

    Welling, M.A.

    2014-01-01

    Pluripotent embryonic stem cells (ESCs) can be isolated from the inner cell mass (ICM) of blastocyst embryos and differentiate into all three germ layers in vitro. However, despite their similar origin, mouse embryonic stem cells represent a more naïve ICM-like pluripotent state whereas human

  15. Setting FIRES to Stem Cell Research

    Science.gov (United States)

    Miller, Roxanne Grietz

    2005-01-01

    The goal of this lesson is to present the basic scientific knowledge about stem cells, the promise of stem cell research to medicine, and the ethical considerations and arguments involved. One of the challenges of discussing stem cell research is that the field is constantly evolving and the most current information changes almost daily. Few…

  16. Stem Cells: What They Are and What They Do

    Science.gov (United States)

    Stem cells: What they are and what they do Stem cells and derived products offer great promise for new medical treatments. Learn about stem cell types, current and possible uses, ethical issues, and ...

  17. Stem Cell Research: Unlocking the Mystery of Disease

    Science.gov (United States)

    ... Home Current Issue Past Issues From the Director: Stem Cell Research: Unlocking the Mystery of Disease Past Issues / ... Zerhouni, NIH Director, described the need for expanding stem cell research. Recently, he spoke about stem cell research ...

  18. Current practices for screening, consent and care of related donors in France: Haematopoietic stem cell transplantation coordinator nurses' perceptions.

    Science.gov (United States)

    Polomeni, A; Bompoint, C; Gomez, A; Brissot, E; Ruggeri, A; Belhocine, R; Mohty, M

    2017-11-01

    Haematopoietic stem cell transplantation-coordinating nurses (HSCT-CNs) play an important role in informing related donors (RDs) and in organising human leucocyte antigen (HLA) tests, pre-donation workup and stem cells collection. Our pilot study aimed to explore French HSCT-CNs' perceptions of RD care issues. Twenty-nine French HSCT adult units were sent a questionnaire on the subject of donation procedures, HSCT-CNs' data and their professional experience of related donation issues. Twenty-two HSCT-CNs returned a completed questionnaire, and 90% of HSCT units were involved to some degree in both patient and donor care. Responses indicated that the provision of information to potential donors prior to HLA tests was insufficient, while donors were given a medical consultation only during the pre-donation workup. Questions were raised about the consent and voluntary status of RDs. None of the HSCT teams organised a post-donation consultation, while 57% provided follow-up by phone or via a questionnaire. Our results draw attention to the conflict of interest experienced by HSCT-CNs when caring simultaneously for patients and donors. The specific psychosocial difficulties associated with becoming an RD are also highlighted. French HSCT-CNs' perceptions of related donation reveal many ethical and clinical problems that have yet to be fully explored. Data on this topic remain scarce, and our pilot study may contribute to the current debate on the organisation of RD care. © 2016 John Wiley & Sons Ltd.

  19. Culture of Mouse Neural Stem Cell Precursors

    OpenAIRE

    Currle, D. Spencer; Hu, Jia Sheng; Kolski-Andreaco, Aaron; Monuki, Edwin S.

    2007-01-01

    Primary neural stem cell cultures are useful for studying the mechanisms underlying central nervous system development. Stem cell research will increase our understanding of the nervous system and may allow us to develop treatments for currently incurable brain diseases and injuries. In addition, stem cells should be used for stem cell research aimed at the detailed study of mechanisms of neural differentiation and transdifferentiation and the genetic and environmental signals that direct the...

  20. The Current Status of STEM Education Research

    Science.gov (United States)

    Brown, Josh

    2012-01-01

    This paper explores the current Science, Technology, Engineering and Mathematics (STEM) education research base through an analysis of articles from eight journals focused on the STEM disciplines. Analyzed are both practitioner and research publications to determine the current scope of STEM education research, where current STEM education…

  1. Cancer stem cells revisited

    NARCIS (Netherlands)

    Batlle, Eduard; Clevers, Hans

    2017-01-01

    The cancer stem cell (CSC) concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It has gradually become clear that many tumors harbor CSCs in dedicated niches, and yet their

  2. Retinal stem cells and potential cell transplantation treatments

    Directory of Open Access Journals (Sweden)

    Tai-Chi Lin

    2014-11-01

    Full Text Available The retina, histologically composed of ten delicate layers, is responsible for light perception and relaying electrochemical signals to the secondary neurons and visual cortex. Retinal disease is one of the leading clinical causes of severe vision loss, including age-related macular degeneration, Stargardt's disease, and retinitis pigmentosa. As a result of the discovery of various somatic stem cells, advances in exploring the identities of embryonic stem cells, and the development of induced pluripotent stem cells, cell transplantation treatment for retinal diseases is currently attracting much attention. The sources of stem cells for retinal regeneration include endogenous retinal stem cells (e.g., neuronal stem cells, Müller cells, and retinal stem cells from the ciliary marginal zone and exogenous stem cells (e.g., bone mesenchymal stem cells, adipose-derived stem cells, embryonic stem cells, and induced pluripotent stem cells. The success of cell transplantation treatment depends mainly on the cell source, the timing of cell harvesting, the protocol of cell induction/transplantation, and the microenvironment of the recipient's retina. This review summarizes the different sources of stem cells for regeneration treatment in retinal diseases and surveys the more recent achievements in animal studies and clinical trials. Future directions and challenges in stem cell transplantation are also discussed.

  3. Donating Peripheral Blood Stem Cells

    Science.gov (United States)

    ... Print this page My Cart Donating peripheral blood stem cells Peripheral blood stem cell (PBSC) donation is a nonsurgical procedure to collect ... Donating bone marrow Donor experiences videos Peripheral blood stem cell (PBSC) donation is one of two methods of ...

  4. Stem Cell Transplants (For Teens)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Stem Cell Transplants KidsHealth / For Teens / Stem Cell Transplants What's ... Take to Recover? Coping Print What Are Stem Cells? As you probably remember from biology class, every ...

  5. Skeletal (stromal) stem cells

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Kermani, Abbas Jafari; Zaher, Walid

    2015-01-01

    Skeletal (marrow stromal) stem cells (BMSCs) are a group of multipotent cells that reside in the bone marrow stroma and can differentiate into osteoblasts, chondrocytes and adipocytes. Studying signaling pathways that regulate BMSC differentiation into osteoblastic cells is a strategy....../preadipocyte factor 1 (Dlk1/Pref-1), the Wnt co-receptor Lrp5 and intracellular kinases. This article is part of a Special Issue entitled: Stem Cells and Bone....

  6. Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: update on defibrotide and other current investigational therapies.

    Science.gov (United States)

    Ho, V T; Revta, C; Richardson, P G

    2008-02-01

    Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), remains one of the most serious and common complications after myeloablative hematopoietic stem cell transplantation (HSCT). Clinical diagnosis of hepatic VOD is based on the clinical triad of (1) painful hepatomegaly, (2) hyperbilirubinemia and (3) unexplained fluid retention. While milder cases usually resolve spontaneously, severe VOD is associated with a grim prognosis. Defibrotide (DF), a polydisperse mixture of single-stranded oligonucleotide with antithrombotic and fibrinolytic effects on microvascular endothelium, has emerged as an effective and safe therapy for patients with severe VOD. Multiple studies, including a recent large international multicenter phase II clinical trial, have demonstrated 30-60% complete remission rates with DF, even among patients with severe VOD and multiorgan failure. This article will review our current understanding of hepatic VOD, and update the clinical trial experience with DF and other potential therapies for this feared transplant complication.

  7. What is a stem cell?

    Science.gov (United States)

    Slack, Jonathan M W

    2018-05-15

    The historical roots of the stem cell concept are traced with respect to its usage in embryology and in hematology. The modern consensus definition of stem cells, comprising both pluripotent stem cells in culture and tissue-specific stem cells in vivo, is explained and explored. Methods for identifying stem cells are discussed with respect to cell surface markers, telomerase, label retention and transplantability, and properties of the stem cell niche are explored. The CreER method for identifying stem cells in vivo is explained, as is evidence in favor of a stochastic rather than an obligate asymmetric form of cell division. In conclusion, it is found that stem cells do not possess any unique and specific molecular markers; and stem cell behavior depends on the environment of the cell as well as the stem cell's intrinsic qualities. Furthermore, the stochastic mode of division implies that stem cell behavior is a property of a cell population not of an individual cell. In this sense, stem cells do not exist in isolation but only as a part of multicellular system. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Tissue Stem Cells and Niches Adult Stem Cells, Tissue Renewal, and Regeneration > Methods and Principles Adult Stem Cells, Tissue Renewal, and Regeneration > Environmental Control of Stem Cells. © 2018 Wiley Periodicals, Inc.

  8. Stem Cell Therapy for Erectile Dysfunction.

    Science.gov (United States)

    Matz, Ethan L; Terlecki, Ryan; Zhang, Yuanyuan; Jackson, John; Atala, Anthony

    2018-04-06

    The prevalence of erectile dysfunction (ED) is substantial and continues to rise. Current therapeutics for ED consist of oral medications, intracavernosal injections, vacuum erection devices, and penile implants. While such options may manage the disease state, none of these modalities, however, restore function. Stem cell therapy has been evaluated for erectile restoration in animal models. These cells have been derived from multiple tissues, have varied potential, and may function via local engraftment or paracrine signaling. Bone marrow-derived stem cells (BMSC) and adipose-derived stem cells (ASC) have both been used in these models with noteworthy effects. Herein, we will review the pathophysiology of ED, animal models, current and novel stem-cell based therapeutics, clinical trials and areas for future research. The relevant literature and contemporary data using keywords, "stem cells and erectile dysfunction" was reviewed. Examination of evidence supporting the association between erectile dysfunction and adipose derived stem cells, bone marrow derived stem cells, placental stem cells, urine stem cells and stem cell therapy respectively. Placental-derived stem cells and urine-derived stem cells possess many similar properties as BMSC and ASC, but the methods of acquisition are favorable. Human clinical trials have already demonstrated successful use of stem cells for improvement of erectile function. The future of stem cell research is constantly being evaluated, although, the evidence suggests a place for stem cells in erectile dysfunction therapeutics. Matz EL, Terlecki R, Zhang Y, et al. Stem Cell Therapy for Erectile Dysfunction. Sex Med Rev 2018;XX:XXX-XXX. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  9. Stem cell plasticity.

    Science.gov (United States)

    Lakshmipathy, Uma; Verfaillie, Catherine

    2005-01-01

    The central dogma in stem cell biology has been that cells isolated from a particular tissue can renew and differentiate into lineages of the tissue it resides in. Several studies have challenged this idea by demonstrating that tissue specific cell have considerable plasticity and can cross-lineage restriction boundary and give rise to cell types of other lineages. However, the lack of a clear definition for plasticity has led to confusion with several reports failing to demonstrate that a single cell can indeed differentiate into multiple lineages at significant levels. Further, differences between results obtained in different labs has cast doubt on some results and several studies still await independent confirmation. In this review, we critically evaluate studies that report stem cell plasticity using three rigid criteria to define stem cell plasticity; differentiation of a single cell into multiple cell lineages, functionality of differentiated cells in vitro and in vivo, robust and persistent engraft of transplanted cells.

  10. Specific Intensity Direct Current (DC) Electric Field Improves Neural Stem Cell Migration and Enhances Differentiation towards βIII-Tubulin+ Neurons

    Science.gov (United States)

    Zhao, Huiping; Steiger, Amanda; Nohner, Mitch; Ye, Hui

    2015-01-01

    Control of stem cell migration and differentiation is vital for efficient stem cell therapy. Literature reporting electric field–guided migration and differentiation is emerging. However, it is unknown if a field that causes cell migration is also capable of guiding cell differentiation—and the mechanisms for these processes remain unclear. Here, we report that a 115 V/m direct current (DC) electric field can induce directional migration of neural precursor cells (NPCs). Whole cell patching revealed that the cell membrane depolarized in the electric field, and buffering of extracellular calcium via EGTA prevented cell migration under these conditions. Immunocytochemical staining indicated that the same electric intensity could also be used to enhance differentiation and increase the percentage of cell differentiation into neurons, but not astrocytes and oligodendrocytes. The results indicate that DC electric field of this specific intensity is capable of promoting cell directional migration and orchestrating functional differentiation, suggestively mediated by calcium influx during DC field exposure. PMID:26068466

  11. Mesenchymal Stem/Progenitor Cells Derived from Articular Cartilage, Synovial Membrane and Synovial Fluid for Cartilage Regeneration: Current Status and Future Perspectives.

    Science.gov (United States)

    Huang, Yi-Zhou; Xie, Hui-Qi; Silini, Antonietta; Parolini, Ornella; Zhang, Yi; Deng, Li; Huang, Yong-Can

    2017-10-01

    Large articular cartilage defects remain an immense challenge in the field of regenerative medicine because of their poor intrinsic repair capacity. Currently, the available medical interventions can relieve clinical symptoms to some extent, but fail to repair the cartilaginous injuries with authentic hyaline cartilage. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stem/progenitor cells with or without scaffolds. Mesenchymal stem/progenitor cells are promising graft cells for tissue regeneration, but the most suitable source of cells for cartilage repair remains controversial. The tissue origin of mesenchymal stem/progenitor cells notably influences the biological properties and therapeutic potential. It is well known that mesenchymal stem/progenitor cells derived from synovial joint tissues exhibit superior chondrogenic ability compared with those derived from non-joint tissues; thus, these cell populations are considered ideal sources for cartilage regeneration. In addition to the progress in research and promising preclinical results, many important research questions must be answered before widespread success in cartilage regeneration is achieved. This review outlines the biology of stem/progenitor cells derived from the articular cartilage, the synovial membrane, and the synovial fluid, including their tissue distribution, function and biological characteristics. Furthermore, preclinical and clinical trials focusing on their applications for cartilage regeneration are summarized, and future research perspectives are discussed.

  12. Stem Cell Lineages: Between Cell and Organism

    Directory of Open Access Journals (Sweden)

    Melinda Bonnie Fagan

    2017-01-01

    Full Text Available Ontologies of living things are increasingly grounded on the concepts and practices of current life science. Biological development is a process, undergone by living things, which begins with a single cell and (in an important class of cases ends with formation of a multicellular organism. The process of development is thus prima facie central for ideas about biological individuality and organismality. However, recent accounts of these concepts do not engage developmental biology. This paper aims to fill the gap, proposing the lineage view of stem cells as an ontological framework for conceptualizing organismal development. This account is grounded on experimental practices of stem cell research, with emphasis on new techniques for generating biological organization in vitro. On the lineage view, a stem cell is the starting point of a cell lineage with a specific organismal source, time-interval of existence, and ‘tree topology’ of branch-points linking the stem to developmental termini. The concept of ‘enkapsis’ accommodates the cell-organism relation within the lineage view; this hierarchical notion is further explicated by considering the methods and results of stem cell experiments. Results of this examination include a (partial characterization of stem cells’ developmental versatility, and the context-dependence of developmental processes involving stem cells.

  13. Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

    Horwood, Nicole J.; Dazzi, Francesco; Zaher, Walid

    2012-01-01

    Mesenchymal stem cells (MSC) are stem cell populations present among the bone marrow stroma and a number of other tissues that are capable of multi-lineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. MSC provide supportive stroma for growth...... and differentiation of hematopoietic stem cells (HSC) and hematopoiesis. These cells have been described as important immunoregulators due to their ability to suppress T cells proliferation. MSC can also directly contribute to tissue repair by migrating to sites of injury and providing a source of cells...... for differentiation and/or providing bystander support for resident stromal cells. This chapter discusses the cellular and molecular properties of MSC, the mechanisms by which they can modulate immune responses and the clinical applications of MSC in disorders such as graft-versus-host disease and aplastic anaemia...

  14. Extinction models for cancer stem cell therapy

    Science.gov (United States)

    Sehl, Mary; Zhou, Hua; Sinsheimer, Janet S.; Lange, Kenneth L.

    2012-01-01

    Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of cancer stem cells and normal stem cells) that must exist for the survival of an adequate number of normal stem cells. Our main tools are birth–death Markov chains in continuous time. In this framework, we investigate the extinction times of cancer stem cells and normal stem cells. Application of extreme value theory from mathematical statistics yields an accurate asymptotic distribution and corresponding moments for both extinction times. We compare these distributions for the two cell populations as a function of the killing rates. Perhaps a more telling comparison involves the number of normal stem cells NH at the extinction time of the cancer stem cells. Conditioning on the asymptotic time to extinction of the cancer stem cells allows us to calculate the asymptotic mean and variance of NH. The full distribution of NH can be retrieved by the finite Fourier transform and, in some parameter regimes, by an eigenfunction expansion. Finally, we discuss the impact of quiescence (the resting state) on stem cell dynamics. Quiescence can act as a sanctuary for cancer stem cells and imperils the proposed therapy. We approach the complication of quiescence via multitype branching process models and stochastic simulation. Improvements to the τ-leaping method of stochastic simulation make it a versatile tool in this context. We conclude that the proposed therapy must target quiescent cancer stem cells as well as actively dividing cancer stem cells. The current cancer models demonstrate the virtue of attacking the same quantitative questions from a variety of modeling, mathematical, and computational perspectives

  15. Stem cell heterogeneity revealed

    DEFF Research Database (Denmark)

    Andersen, Marianne S; Jensen, Kim B

    2016-01-01

    The skin forms a protective, water-impermeable barrier consisting of heavily crosslinked epithelial cells. However, the specific role of stem cells in sustaining this barrier remains a contentious issue. A detailed analysis of the interfollicular epidermis now proposes a model for how a composite...... of cells with different properties are involved in its maintenance....

  16. Stem cells and repair of lung injuries

    Directory of Open Access Journals (Sweden)

    Randell Scott H

    2004-07-01

    Full Text Available Abstract Fueled by the promise of regenerative medicine, currently there is unprecedented interest in stem cells. Furthermore, there have been revolutionary, but somewhat controversial, advances in our understanding of stem cell biology. Stem cells likely play key roles in the repair of diverse lung injuries. However, due to very low rates of cellular proliferation in vivo in the normal steady state, cellular and architectural complexity of the respiratory tract, and the lack of an intensive research effort, lung stem cells remain poorly understood compared to those in other major organ systems. In the present review, we concisely explore the conceptual framework of stem cell biology and recent advances pertinent to the lungs. We illustrate lung diseases in which manipulation of stem cells may be physiologically significant and highlight the challenges facing stem cell-related therapy in the lung.

  17. Stem cell facelift: between reality and fiction.

    Science.gov (United States)

    Atiyeh, Bishara S; Ibrahim, Amir E; Saad, Dibo A

    2013-03-01

    Stem cells are "big business" throughout medical technology, and their potential application in cosmetic procedures is no exception. One of the latest nonsurgical facial treatments (and new catchphrases) in plastic surgery is the "stem cell facelift." It is evident from the currently available scientific literature that the use of stem cell therapy for facial rejuvenation is limited to the theoretical induction of skin tightening and can in no way be equated to a facelift. In fact, what is advertised and promoted as a new and original technique of stem cell facelifting is mostly stem cell-enriched lipofilling. Despite encouraging data suggesting that adult stem cells hold promise for future applications, the data from clinical evidence available today do not substantiate the marketing and promotional claims being made to patients. To claim that the "stem cell facelift" is a complete facial rejuvenation procedure surgery is unethical.

  18. INVASIVE CANDIDA INFECTIONS IN PATIENTS WITH HAEMATOLOGICAL MALIGNANCIES AND HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS: CURRENT EPIDEMIOLOGY AND THERAPEUTIC OPTIONS.

    Directory of Open Access Journals (Sweden)

    Corrado Girmenia

    2011-03-01

    Full Text Available In the last decades, the global epidemiological impact of invasive candidiasis (IC in patients with hematologic malignancies (HM and in hematopoietic stem cell transplant (HSCT recipients has decreased and the incidence of invasive aspergillosis  exceeded that of Candida infections. The use of prevention strategies, first of all antifungal prophylaxis with triazoles,  contributed to the reduction of IC in these populations as demonstrated by several  epidemiological studies. However, relatively little is known about the current epidemiological patterns of IC in HM and HSCT populations, because recent epidemiological data almost exclusively derive from retrospective experiences and few prospective data are available. Several prospective, controlled studies in the prophylaxis of invasive fungal diseases have been conducted in both the HM and HSCT setting. On the contrary, most of the prospective controlled trials that demonstrated the efficacy of the antifungal drugs echinocandins and voriconazole in the treatment of candidemia and invasive candidiasis mainly involved  patients with underlying conditions other than HM or  HSCT.  For these reasons, international guidelines provided specific indications for the prophylaxis strategies in HM and HSCT patients, whereas the  recommendations on therapy of documented Candida infections are based on the results observed in the general population and should be considered with caution.

  19. Biomechanics of stem cells

    Science.gov (United States)

    Spector, A. A.; Yuan, D.; Somers, S.; Grayson, W. L.

    2018-04-01

    Stem cells play a key role in the healthy development and maintenance of organisms. They are also critically important in medical treatments of various diseases. It has been recently demonstrated that the mechanical factors such as forces, adhesion, stiffness, relaxation, etc. have significant effects on stem cell functions. Under physiological conditions, cells (stem cells) in muscles, heart, and blood vessels are under the action of externally applied strains. We consider the stem cell microenvironment and performance associated with their conversion (differentiation) into skeletal muscle cells. Two problems are studied by using mathematical models whose parameters are then optimized by fitting experiments. First, we present our analysis of the process of stem cell differentiation under the application of cyclic unidirectional strain. This process is interpreted as a transition through several (six) stages where each of them is defined in terms of expression of a set of factors typical to skeletal muscle cells. The stem cell evolution toward muscle cells is described by a system of nonlinear ODEs. The parameters of the model are determined by fitting the experimental data on the time course of expression of the factors under consideration. Second, we analyse the mechanical (relaxation) properties of a scaffold that serves as the microenvironment for stem cells differentiation into skeletal muscle cells. This scaffold (surrounded by a liquid solution) is composed of unidirectional fibers with pores between them. The relaxation properties of the scaffold are studied in an experiment where a long cylindrical specimen is loaded by the application of ramp displacement until the strain reaches a prescribed value. The magnitude of the corresponding load is recorded. The specimen is considered as transversely isotropic poroelastic cylinder whose force relaxation is associated with liquid diffusion through the pores. An analytical solution for the total force applied to

  20. Gastric stem cells and gastric cancer stem cells

    OpenAIRE

    Han, Myoung-Eun; Oh, Sae-Ock

    2013-01-01

    The gastric epithelium is continuously regenerated by gastric stem cells, which give rise to various kinds of daughter cells, including parietal cells, chief cells, surface mucous cells, mucous neck cells, and enteroendocrine cells. The self-renewal and differentiation of gastric stem cells need delicate regulation to maintain the normal physiology of the stomach. Recently, it was hypothesized that cancer stem cells drive the cancer growth and metastasis. In contrast to conventional clonal ev...

  1. Stem cells: sources and therapies

    Directory of Open Access Journals (Sweden)

    Manuela Monti

    2012-01-01

    Full Text Available The historical, lexical and conceptual issues embedded in stem cell biology are reviewed from technical, ethical, philosophical, judicial, clinical, economic and biopolitical perspectives. The mechanisms assigning the simultaneous capacity to self-renew and to differentiate to stem cells (immortal template DNA and asymmetric division are evaluated in the light of the niche hypothesis for the stemness state. The induction of cell pluripotency and the different stem cells sources are presented (embryonic, adult and cord blood. We highlight the embryonic and adult stem cell properties and possible therapies while we emphasize the particular scientific and social values of cord blood donation to set up cord blood banks. The current scientific and legal frameworks of cord blood banks are reviewed at an international level as well as allogenic, dedicated and autologous donations. The expectations and the challenges in relation to present-day targeted diseases like diabetes mellitus type I, Parkinson's disease and myocardial infarction are evaluated in the light of the cellular therapies for regenerative medicine.

  2. Engineering Stem Cells for Biomedical Applications

    Science.gov (United States)

    Yin, Perry T.; Han, Edward

    2018-01-01

    Stem cells are characterized by a number of useful properties, including their ability to migrate, differentiate, and secrete a variety of therapeutic molecules such as immunomodulatory factors. As such, numerous pre-clinical and clinical studies have utilized stem cell-based therapies and demonstrated their tremendous potential for the treatment of various human diseases and disorders. Recently, efforts have focused on engineering stem cells in order to further enhance their innate abilities as well as to confer them with new functionalities, which can then be used in various biomedical applications. These engineered stem cells can take on a number of forms. For instance, engineered stem cells encompass the genetic modification of stem cells as well as the use of stem cells for gene delivery, nanoparticle loading and delivery, and even small molecule drug delivery. The present Review gives an in-depth account of the current status of engineered stem cells, including potential cell sources, the most common methods used to engineer stem cells, and the utilization of engineered stem cells in various biomedical applications, with a particular focus on tissue regeneration, the treatment of immunodeficiency diseases, and cancer. PMID:25772134

  3. Engineering Stem Cells for Biomedical Applications.

    Science.gov (United States)

    Yin, Perry T; Han, Edward; Lee, Ki-Bum

    2016-01-07

    Stem cells are characterized by a number of useful properties, including their ability to migrate, differentiate, and secrete a variety of therapeutic molecules such as immunomodulatory factors. As such, numerous pre-clinical and clinical studies have utilized stem cell-based therapies and demonstrated their tremendous potential for the treatment of various human diseases and disorders. Recently, efforts have focused on engineering stem cells in order to further enhance their innate abilities as well as to confer them with new functionalities, which can then be used in various biomedical applications. These engineered stem cells can take on a number of forms. For instance, engineered stem cells encompass the genetic modification of stem cells as well as the use of stem cells for gene delivery, nanoparticle loading and delivery, and even small molecule drug delivery. The present Review gives an in-depth account of the current status of engineered stem cells, including potential cell sources, the most common methods used to engineer stem cells, and the utilization of engineered stem cells in various biomedical applications, with a particular focus on tissue regeneration, the treatment of immunodeficiency diseases, and cancer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Mesenchymal stem cells: cell biology and potential use in therapy

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Kristiansen, Malthe; Abdallah, Basem M

    2004-01-01

    Mesenchymal stem cells are clonogenic, non-haematopoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages e.g. osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages e.g. neuronal-like cells. Several methods...... are currently available for isolation of the mesenchymal stem cells based on their physical and immunological characteristics. Because of the ease of their isolation and their extensive differentiation potential, mesenchymal stem cells are among the first stem cell types to be introduced in the clinic. Recent...... studies have demonstrated that the life span of mesenchymal stem cells in vitro can be extended by increasing the levels of telomerase expression in the cells and thus allowing culture of large number of cells needed for therapy. In addition, it has been shown that it is possible to culture the cells...

  5. Stem Cells in Burn Eschar

    NARCIS (Netherlands)

    van der Veen, V. C.; Vlig, M.; van Milligen-Kummer, F.J.; de Vries, S.I.; Middelkoop, E.; Ulrich, M.

    2012-01-01

    This study compares mesenchymal cells isolated from excised burn wound eschar with adipose-derived stem cells (ASCs) and dermal fibroblasts in their ability to conform to the requirements for multipotent mesenchymal stem cells (MSCs). A population of multipotent stem cells in burn eschar could be an

  6. Stem cell organization in Arabidopsis

    NARCIS (Netherlands)

    Wendrich, J.R.

    2016-01-01

    Growth of plant tissues and organs depends on continuous production of new cells, by niches of stem cells. Stem cells typically divide to give rise to one differentiating daughter and one non-differentiating daughter. This constant process of self-renewal ensures that the niches of stem cells or

  7. Ca2+-currents in human induced pluripotent stem cell-derived cardiomyocytes - effects of two different culture conditions

    Directory of Open Access Journals (Sweden)

    Ahmet Umur Uzun

    2016-09-01

    Full Text Available Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM provide a unique opportunity to study human heart physiology and pharmacology and repair injured hearts. The suitability of hiPSC-CM critically depends on how closely they share physiological properties of human adult cardiomyocytes (CM. Here we investigated whether a 3D engineered heart tissue (EHT culture format favors maturation and addressed the L-type Ca2+-current (ICa,L as a readout. The results were compared with hiPSC-CM cultured in conventional monolayer (ML and to our previous data from human adult atrial and ventricular CM obtained when identical patch-clamp protocols were used. HiPSC-CM were 2-3 fold smaller than adult CM, independently of culture format (capacitance ML 45±1 pF (n=289, EHT 45±1 pF (n=460, atrial CM 87±3 pF (n=196, ventricular CM 126±8 pF (n=50. Only 88% of ML cells showed ICa, but all EHT. Basal ICa density was 10±1 pA/pF (n=207 for ML and 12±1 pA/pF (n=361 for EHT and was larger than in adult CM (7±1 pA/pF (p<0.05, n=196 for atrial CM and 6±1 pA/pF (p<0.05, n=47 for ventricular CM. However, ML and EHT showed robust T-type Ca2+-currents (ICa,T. While (--Bay K 8644, that activates ICa,L directly, increased ICa,L to the same extent in ML and EHT, β1- and β2-adrenoceptor effects were marginal in ML, but of same size as (--Bay K 8644 in EHT. The opposite was true for serotonin receptors. Sensitivity to β1 and β2-adrenoceptor stimulation was the same in EHT as in adult CM (-logEC50: 5.9 and 6.1 for norepinephrine (NE and epinephrine (Epi, respectively, but very low concentrations of Rp-8-Br-cAMPS were sufficient to suppress effects (-logEC50: 5.3 and 5.3 respectively for NE and Epi. Taken together, hiPSC-CM express ICa,L at the same density as human adult CM, but, in contrast, possess robust ICa,T. Increased effects of catecholamines in EHT suggest more efficient maturation.

  8. Stem cell therapy for diabetes

    Directory of Open Access Journals (Sweden)

    K O Lee

    2012-01-01

    Full Text Available Stem cell therapy holds immense promise for the treatment of patients with diabetes mellitus. Research on the ability of human embryonic stem cells to differentiate into islet cells has defined the developmental stages and transcription factors involved in this process. However, the clinical applications of human embryonic stem cells are limited by ethical concerns, as well as the potential for teratoma formation. As a consequence, alternative forms of stem cell therapies, such as induced pluripotent stem cells, umbilical cord stem cells and bone marrow-derived mesenchymal stem cells, have become an area of intense study. Recent advances in stem cell therapy may turn this into a realistic treatment for diabetes in the near future.

  9. Engineering stem cell niches in bioreactors

    OpenAIRE

    Liu, Meimei; Liu, Ning; Zang, Ru; Li, Yan; Yang, Shang-Tian

    2013-01-01

    Stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the body. Efficient differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as “ni...

  10. Fake news portrayals of stem cells and stem cell research.

    Science.gov (United States)

    Marcon, Alessandro R; Murdoch, Blake; Caulfield, Timothy

    2017-10-01

    This study examines how stem cells and stem cell research are portrayed on websites deemed to be purveyors of distorted and dubious information. Content analysis was conducted on 224 articles from 2015 to 2016, compiled by searching with the keywords 'stem cell(s)' on a list of websites flagged for containing either 'fake' or 'junk science' news. Articles contained various exaggerated positive and negative claims about stem cells and stem cell science, health and science related conspiracy theories, and statements promoting fear and mistrust of conventional medicine. Findings demonstrate the existence of organized misinformation networks, which may lead the public away from accurate information and facilitate a polarization of public discourse.

  11. Adult Stem Cell Therapy for Stroke: Challenges and Progress

    Science.gov (United States)

    Bang, Oh Young; Kim, Eun Hee; Cha, Jae Min; Moon, Gyeong Joon

    2016-01-01

    Stroke is one of the leading causes of death and physical disability among adults. It has been 15 years since clinical trials of stem cell therapy in patients with stroke have been conducted using adult stem cells like mesenchymal stem cells and bone marrow mononuclear cells. Results of randomized controlled trials showed that adult stem cell therapy was safe but its efficacy was modest, underscoring the need for new stem cell therapy strategies. The primary limitations of current stem cell therapies include (a) the limited source of engraftable stem cells, (b) the presence of optimal time window for stem cell therapies, (c) inherited limitation of stem cells in terms of growth, trophic support, and differentiation potential, and (d) possible transplanted cell-mediated adverse effects, such as tumor formation. Here, we discuss recent advances that overcome these hurdles in adult stem cell therapy for stroke. PMID:27733032

  12. [Progress in epidermal stem cells].

    Science.gov (United States)

    Wang, Li-Juan; Wang, You-Liang; Yang, Xiao

    2010-03-01

    Mammalian skin epidermis contains different epidermal stem cell pools which contribute to the homeostasis and repair of skin epithelium. Epidermal stem cells possess two essential features common to all stem cells: self-renewal and differentiation. Disturbing the balance between self-renewal and differentiation of epidermal stem cell often causes tumors or other skin diseases. Epidermal stem cell niches provide a special microenvironment that maintains a balance of stem cell quiescence and activity. This review primarily concentrates on the following points of the epidermal stem cells: the existing evidences, the self-renewal and differentiation, the division pattern, the signal pathways regulating self-renewal and differentiation, and the microenvironment (niche) and macroenvironment maintaining the homeostasis of stem cells.

  13. Porcine embryonic stem cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane

    2008-01-01

    The development of porcine embryonic stem cell lines (pESC) has received renewed interest given the advances being made in the production of immunocompatible transgenic pigs. However, difficulties are evident in the production of pESCs in-vitro. This may largely be attributable to differences...

  14. Materials as stem cell regulators

    Science.gov (United States)

    Murphy, William L.; McDevitt, Todd C.; Engler, Adam J.

    2014-01-01

    The stem cell/material interface is a complex, dynamic microenvironment in which the cell and the material cooperatively dictate one another's fate: the cell by remodelling its surroundings, and the material through its inherent properties (such as adhesivity, stiffness, nanostructure or degradability). Stem cells in contact with materials are able to sense their properties, integrate cues via signal propagation and ultimately translate parallel signalling information into cell fate decisions. However, discovering the mechanisms by which stem cells respond to inherent material characteristics is challenging because of the highly complex, multicomponent signalling milieu present in the stem cell environment. In this Review, we discuss recent evidence that shows that inherent material properties may be engineered to dictate stem cell fate decisions, and overview a subset of the operative signal transduction mechanisms that have begun to emerge. Further developments in stem cell engineering and mechanotransduction are poised to have substantial implications for stem cell biology and regenerative medicine. PMID:24845994

  15. Stem Cells for Skeletal Muscle Tissue Engineering.

    Science.gov (United States)

    Pantelic, Molly N; Larkin, Lisa M

    2018-04-19

    Volumetric muscle loss (VML) is a debilitating condition wherein muscle loss overwhelms the body's normal physiological repair mechanism. VML is particularly common among military service members who have sustained war injuries. Because of the high social and medical cost associated with VML and suboptimal current surgical treatments, there is great interest in developing better VML therapies. Skeletal muscle tissue engineering (SMTE) is a promising alternative to traditional VML surgical treatments that use autogenic tissue grafts, and rather uses isolated stem cells with myogenic potential to generate de novo skeletal muscle tissues to treat VML. Satellite cells are the native precursors to skeletal muscle tissue, and are thus the most commonly studied starting source for SMTE. However, satellite cells are difficult to isolate and purify, and it is presently unknown whether they would be a practical source in clinical SMTE applications. Alternative myogenic stem cells, including adipose-derived stem cells, bone marrow-derived mesenchymal stem cells, perivascular stem cells, umbilical cord mesenchymal stem cells, induced pluripotent stem cells, and embryonic stem cells, each have myogenic potential and have been identified as possible starting sources for SMTE, although they have yet to be studied in detail for this purpose. These alternative stem cell varieties offer unique advantages and disadvantages that are worth exploring further to advance the SMTE field toward highly functional, safe, and practical VML treatments. The following review summarizes the current state of satellite cell-based SMTE, details the properties and practical advantages of alternative myogenic stem cells, and offers guidance to tissue engineers on how alternative myogenic stem cells can be incorporated into SMTE research.

  16. Stem cells in psoriasis.

    Science.gov (United States)

    Hou, Ruixia; Li, Junqin; Niu, Xuping; Liu, Ruifeng; Chang, Wenjuan; Zhao, Xincheng; Wang, Qiang; Li, Xinhua; Yin, Guohua; Zhang, Kaiming

    2017-06-01

    Psoriasis is a complex chronic relapsing inflammatory disease. Although the exact mechanism remains unknown, it is commonly accepted that the development of psoriasis is a result of multi-system interactions among the epidermis, dermis, blood vessels, immune system, neuroendocrine system, metabolic system, and hematopoietic system. Many cell types have been confirmed to participate in the pathogenesis of psoriasis. Here, we review the stem cell abnormalities related to psoriasis that have been investigated recently. Copyright © 2016. Published by Elsevier B.V.

  17. International Society for Stem Cell Research

    Science.gov (United States)

    ... renowned stem cell and regenerative medicine community. More stem cell research Take a closer look Recent Blogs View ... story independent nonprofit organization & the voice of the stem cell research community The International Society for Stem Cell ...

  18. Stem cell-derived vascular endothelial cells and their potential application in regenerative medicine

    Science.gov (United States)

    Although a 'vascular stem cell' population has not been identified or generated, vascular endothelial and mural cells (smooth muscle cells and pericytes) can be derived from currently known pluripotent stem cell sources, including human embryonic stem cells and induced pluripotent stem cells. We rev...

  19. Biochemistry of epidermal stem cells.

    Science.gov (United States)

    Eckert, Richard L; Adhikary, Gautam; Balasubramanian, Sivaprakasam; Rorke, Ellen A; Vemuri, Mohan C; Boucher, Shayne E; Bickenbach, Jackie R; Kerr, Candace

    2013-02-01

    The epidermis is an important protective barrier that is essential for maintenance of life. Maintaining this barrier requires continuous cell proliferation and differentiation. Moreover, these processes must be balanced to produce a normal epidermis. The stem cells of the epidermis reside in specific locations in the basal epidermis, hair follicle and sebaceous glands and these cells are responsible for replenishment of this tissue. A great deal of effort has gone into identifying protein epitopes that mark stem cells, in identifying stem cell niche locations, and in understanding how stem cell populations are related. We discuss these studies as they apply to understanding normal epidermal homeostasis and skin cancer. An assortment of stem cell markers have been identified that permit assignment of stem cells to specific regions of the epidermis, and progress has been made in understanding the role of these cells in normal epidermal homeostasis and in conditions of tissue stress. A key finding is the multiple stem cell populations exist in epidermis that give rise to different structures, and that multiple stem cell types may contribute to repair in damaged epidermis. Understanding epidermal stem cell biology is likely to lead to important therapies for treating skin diseases and cancer, and will also contribute to our understanding of stem cells in other systems. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Bioreactor engineering of stem cell environments.

    Science.gov (United States)

    Tandon, Nina; Marolt, Darja; Cimetta, Elisa; Vunjak-Novakovic, Gordana

    2013-11-15

    Stem cells hold promise to revolutionize modern medicine by the development of new therapies, disease models and drug screening systems. Standard cell culture systems have limited biological relevance because they do not recapitulate the complex 3-dimensional interactions and biophysical cues that characterize the in vivo environment. In this review, we discuss the current advances in engineering stem cell environments using novel biomaterials and bioreactor technologies. We also reflect on the challenges the field is currently facing with regard to the translation of stem cell based therapies into the clinic. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. In Vitro Cardiomyogenic Potential of Human Amniotic Fluid Stem Cells

    OpenAIRE

    Guan, Xuan; Delo, Dawn M.; Atala, Anthony; Soker, Shay

    2011-01-01

    Stem cell therapy for damaged cardiac tissue is currently limited by a number of factors, including the inability to obtain sufficient cell numbers, the potential tumorigenicity of certain types of stem cells, and the possible link between stem cell therapy and the development of malignant arrhythmias. In this study, we investigated whether human amniotic fluid-derived stem (hAFS) cells could be a potential source of cells for cardiac cell therapy by testing the in vitro differentiation capab...

  2. Stem cell migration after irradiation

    International Nuclear Information System (INIS)

    Nothdurft, W.; Fliedner, T.M.

    1979-01-01

    The survival rate of irradiated rodents could be significantly improved by shielding only the small parts of hemopoietic tissues during the course of irradiation. The populations of circulating stem cells in adult organisms are considered to be of some importance for the homeostasis between the many sites of blood cell formation and for the necessary flexibility of hemopoietic response in the face of fluctuating demands. Pluripotent stem cells are migrating through peripheral blood as has been shown for several mammalian species. Under steady state conditions, the exchange of stem cells between the different sites of blood cell formation appears to be restricted. Their presence in blood and the fact that they are in balance with the extravascular stem cell pool may well be of significance for the surveilance of the integrity of local stem cell populations. Any decrease of stem cell population in blood below a critical size results in the rapid immigration of circulating stem cells in order to restore local stem cell pool size. Blood stem cells are involved in the regeneration after whole-body irradiation if the stem cell population in bone marrows is reduced to less than 10% of the normal state. In the animals subjected to partial-body irradiation, the circulating stem cells appear to be the only source for the repopulation of the heavily irradiated, aplastic sites of hemopoietic organs. (Yamashita, S.)

  3. Stem cell-based approaches in dentistry

    Directory of Open Access Journals (Sweden)

    TA Mitsiadis

    2011-11-01

    Full Text Available Repair of dental pulp and periodontal lesions remains a major clinical challenge. Classical dental treatments require the use of specialised tissue-adapted materials with still questionable efficacy and durability. Stem cell-based therapeutic approaches could offer an attractive alternative in dentistry since they can promise physiologically improved structural and functional outcomes. These therapies necessitate a sufficient number of specific stem cell populations for implantation. Dental mesenchymal stem cells can be easily isolated and are amenable to in vitro expansion while retaining their stemness. In vivo studies realised in small and large animals have evidenced the potential of dental mesenchymal stem cells to promote pulp and periodontal regeneration, but have also underlined new important challenges. The homogeneity of stem cell populations and their quality control, the delivery method, the quality of the regenerated dental tissues and their integration to the host tissue are some of the key challenges. The use of bioactive scaffolds that can elicit effective tissue repair response, through activation and mobilisation of endogenous stem cell populations, constitutes another emerging therapeutic strategy. Finally, the use of stem cells and induced pluripotent cells for the regeneration of entire teeth represents a novel promising alternative to dental implant treatment after tooth loss. In this mini-review, we present the currently applied techniques in restorative dentistry and the various attempts that are made to bridge gaps in knowledge regarding treatment strategies by translating basic stem cell research into the dental practice.

  4. [Perinatal sources of stem cells].

    Science.gov (United States)

    Piskorska-Jasiulewicz, Magdalena Maria; Witkowska-Zimny, Małgorzata

    2015-03-08

    Recently, stem cell biology has become an interesting topic. Several varieties of human stem cells have been isolated and identified in vivo and in vitro. Successful application of hematopoietic stem cells in hematology has led to the search for other sources of stem cells and expanding the scale of their application. Perinatal stem cells are a versatile cell population, and they are interesting for both scientific and practical objectives. Stem cells from perinatal tissue may be particularly useful in the clinic for autologous transplantation for fetuses and newborns, and after banking in later stages of life, as well as for in utero transplantation in the case of genetic disorders. In this review paper we focus on the extraction and therapeutic potential of stem cells derived from perinatal tissues such as the placenta, the amnion, amniotic fluid, umbilical cord blood and Wharton's jelly.

  5. Perinatal sources of stem cells

    Directory of Open Access Journals (Sweden)

    Magdalena Maria Piskorska-Jasiulewicz

    2015-03-01

    Full Text Available Recently, stem cell biology has become an interesting topic. Several varieties of human stem cells have been isolated and identified in vivo and in vitro. Successful application of hematopoietic stem cells in hematology has led to the search for other sources of stem cells and expanding the scale of their application. Perinatal stem cells are a versatile cell population, and they are interesting for both scientific and practical objectives. Stem cells from perinatal tissue may be particularly useful in the clinic for autologous transplantation for fetuses and newborns, and after banking in later stages of life, as well as for in utero transplantation in the case of genetic disorders. In this review paper we focus on the extraction and therapeutic potential of stem cells derived from perinatal tissues such as the placenta, the amnion, amniotic fluid, umbilical cord blood and Wharton’s jelly.

  6. Stem cell therapy for inflammatory bowel disease

    OpenAIRE

    Duijvestein, Marjolijn

    2012-01-01

    Hematopoietic stem cell transplantation (HSCT) and mesenchymal stromal (MSC) cell therapy are currently under investigation as novel therapies for inflammatory bowel diseases (IBD). Hematopoietic stem cells are thought to repopulate the immune system and reset the immunological response to luminal antigens. MSCs have the capacity to differentiate into a wide variety of distinct cell lineages and to suppress immune responses in vitro and in vivo. The main goal of this thesis was to study the s...

  7. Biomaterial-stem cell interactions and their impact on stem cell response

    NARCIS (Netherlands)

    Oziemlak-Schaap, Aneta M.; Kuhn, Philipp T.; van Kooten, Theo G.; van Rijn, Patrick

    2014-01-01

    In this review, current research in the field of biomaterial properties for directing stem cells are discussed and placed in a critical perspective. Regenerative medicine, in which stem cells play a crucial role, has become an interdisciplinary field between cell biology and materials science. New

  8. Potential Use of Stem Cells for Kidney Regeneration

    Directory of Open Access Journals (Sweden)

    Takashi Yokoo

    2011-01-01

    Full Text Available Significant advances have been made in stem cell research over the past decade. A number of nonhematopoietic sources of stem cells (or progenitor cells have been identified, including endothelial stem cells and neural stem cells. These discoveries have been a major step toward the use of stem cells for potential clinical applications of organ regeneration. Accordingly, kidney regeneration is currently gaining considerable attention to replace kidney dialysis as the ultimate therapeutic strategy for renal failure. However, due to anatomic complications, the kidney is believed to be the hardest organ to regenerate; it is virtually impossible to imagine such a complicated organ being completely rebuilt from pluripotent stem cells by gene or chemical manipulation. Nevertheless, several groups are taking on this big challenge. In this manuscript, current advances in renal stem cell research are reviewed and their usefulness for kidney regeneration discussed. We also reviewed the current knowledge of the emerging field of renal stem cell biology.

  9. Limbal Stem Cell Deficiency and Treatment with Stem Cell Transplantation.

    Science.gov (United States)

    Barut Selver, Özlem; Yağcı, Ayşe; Eğrilmez, Sait; Gürdal, Mehmet; Palamar, Melis; Çavuşoğlu, Türker; Ateş, Utku; Veral, Ali; Güven, Çağrı; Wolosin, Jose Mario

    2017-10-01

    The cornea is the outermost tissue of the eye and it must be transparent for the maintenance of good visual function. The superficial epithelium of the cornea, which is renewed continuously by corneal stem cells, plays a critical role in the permanence of this transparency. These stem cells are localized at the cornea-conjunctival transition zone, referred to as the limbus. When this zone is affected/destroyed, limbal stem cell deficiency ensues. Loss of limbal stem cell function allows colonization of the corneal surface by conjunctival epithelium. Over 6 million people worldwide are affected by corneal blindness, and limbal stem cell deficiency is one of the main causes. Fortunately, it is becoming possible to recover vision by autologous transplantation of limbal cells obtained from the contralateral eye in unilateral cases. Due to the potential risks to the donor eye, only a small amount of tissue can be obtained, in which only 1-2% of the limbal epithelial cells are actually limbal stem cells. Vigorous attempts are being made to expand limbal stem cells in culture to preserve or even enrich the stem cell population. Ex vivo expanded limbal stem cell treatment in limbal stem cell deficiency was first reported in 1997. In the 20 years since, various protocols have been developed for the cultivation of limbal epithelial cells. It is still not clear which method promotes effective stem cell viability and this remains a subject of ongoing research. The most preferred technique for limbal cell culture is the explant culture model. In this approach, a small donor eye limbal biopsy is placed as an explant onto a biocompatible substrate (preferably human amniotic membrane) for expansion. The outgrowth (cultivated limbal epithelial cells) is then surgically transferred to the recipient eye. Due to changing regulations concerning cell-based therapy, the implementation of cultivated limbal epithelial transplantation in accordance with Good Laboratory Practice using

  10. Stem cells in dentistry--part I: stem cell sources.

    Science.gov (United States)

    Egusa, Hiroshi; Sonoyama, Wataru; Nishimura, Masahiro; Atsuta, Ikiru; Akiyama, Kentaro

    2012-07-01

    Stem cells can self-renew and produce different cell types, thus providing new strategies to regenerate missing tissues and treat diseases. In the field of dentistry, adult mesenchymal stem/stromal cells (MSCs) have been identified in several oral and maxillofacial tissues, which suggests that the oral tissues are a rich source of stem cells, and oral stem and mucosal cells are expected to provide an ideal source for genetically reprogrammed cells such as induced pluripotent stem (iPS) cells. Furthermore, oral tissues are expected to be not only a source but also a therapeutic target for stem cells, as stem cell and tissue engineering therapies in dentistry continue to attract increasing clinical interest. Part I of this review outlines various types of intra- and extra-oral tissue-derived stem cells with regard to clinical availability and applications in dentistry. Additionally, appropriate sources of stem cells for regenerative dentistry are discussed with regard to differentiation capacity, accessibility and possible immunomodulatory properties. Copyright © 2012 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  11. Overcoming Multidrug Resistance in Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Karobi Moitra

    2015-01-01

    Full Text Available The principle mechanism of protection of stem cells is through the expression of ATP-binding cassette (ABC transporters. These transporters serve as the guardians of the stem cell population in the body. Unfortunately these very same ABC efflux pumps afford protection to cancer stem cells in tumors, shielding them from the adverse effects of chemotherapy. A number of strategies to circumvent the function of these transporters in cancer stem cells are currently under investigation. These strategies include the development of competitive and allosteric modulators, nanoparticle mediated delivery of inhibitors, targeted transcriptional regulation of ABC transporters, miRNA mediated inhibition, and targeting of signaling pathways that modulate ABC transporters. The role of ABC transporters in cancer stem cells will be explored in this paper and strategies aimed at overcoming drug resistance caused by these particular transporters will also be discussed.

  12. Fundamental Principles of Stem Cell Banking.

    Science.gov (United States)

    Sun, Changbin; Yue, Jianhui; He, Na; Liu, Yaqiong; Zhang, Xi; Zhang, Yong

    2016-01-01

    Stem cells are highly promising resources for application in cell therapy, regenerative medicine, drug discovery, toxicology and developmental biology research. Stem cell banks have been increasingly established all over the world in order to preserve their cellular characteristics, prevent contamination and deterioration, and facilitate their effective use in basic and translational research, as well as current and future clinical application. Standardization and quality control during banking procedures are essential to allow researchers from different labs to compare their results and to develop safe and effective new therapies. Furthermore, many stem cells come from once-in-a-life time tissues. Cord blood for example, thrown away in the past, can be used to treat many diseases such as blood cancers nowadays. Meanwhile, these cells stored and often banked for long periods can be immediately available for treatment when needed and early treatment can minimize disease progression. This paper provides an overview of the fundamental principles of stem cell banking, including: (i) a general introduction of the construction and architecture commonly used for stem cell banks; (ii) a detailed section on current quality management practices; (iii) a summary of questions we should consider for long-term storage, such as how long stem cells can be stored stably, how to prevent contamination during long term storage, etc.; (iv) the prospects for stem cell banking.

  13. Adipose-Derived Stem Cells in Aesthetic Surgery: A Mixed Methods Evaluation of the Current Clinical Trial, Intellectual Property, and Regulatory Landscape.

    Science.gov (United States)

    Arshad, Zeeshaan; Halioua-Haubold, Celine-Lea; Roberts, Mackenna; Urso-Baiarda, Fulvio; Branford, Oliver A; Brindley, David A; Davies, Benjamin M; Pettitt, David

    2018-02-17

    Adipose tissue, which can be readily harvested via a number of liposuction techniques, offers an easily accessible and abundant source of adipose-derived stem cells (ASCs). Consequently, ASCs have become an increasingly popular reconstructive option and a novel means of aesthetic soft tissue augmentation. This paper examines recent advances in the aesthetic surgery field, extending beyond traditional review formats to incorporate a comprehensive analysis of current clinical trials, adoption status, and the commercialization pathway. Keyword searches were carried out on clinical trial databases to search for trials using ASCs for aesthetic indications. An intellectual property landscape was created using commercial software (Thomson Reuters Thomson Innovation, New York, NY). Analysis of who is claiming what in respect of ASC use in aesthetic surgery for commercial purposes was analyzed by reviewing the patent landscape in relation to these techniques. Key international regulatory guidelines were also summarized. Completed clinical trials lacked robust controls, employed small sample sizes, and lacked long-term follow-up data. Ongoing clinical trials still do not address such issues. In recent years, claims to intellectual property ownership have increased in the "aesthetic stem cell" domain, reflecting commercial interest in the area. However, significant translational barriers remain including regulatory challenges and ethical considerations. Further rigorous randomized controlled trials are required to delineate long-term clinical efficacy and safety. Providers should consider the introduction of patient reported outcome metrics to facilitate clinical adoption. Robust regulatory and ethical policies concerning stem cells and aesthetic surgery should be devised to discourage further growth of "stem cell tourism." © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

  14. Application of Stem Cell Technology in Dental Regenerative Medicine.

    Science.gov (United States)

    Feng, Ruoxue; Lengner, Chistopher

    2013-07-01

    In this review, we summarize the current literature regarding the isolation and characterization of dental tissue-derived stem cells and address the potential of these cell types for use in regenerative cell transplantation therapy. Looking forward, platforms for the delivery of stem cells via scaffolds and the use of growth factors and cytokines for enhancing dental stem cell self-renewal and differentiation are discussed. We aim to understand the developmental origins of dental tissues in an effort to elucidate the molecular pathways governing the genesis of somatic dental stem cells. The advantages and disadvantages of several dental stem cells are discussed, including the developmental stage and specific locations from which these cells can be purified. In particular, stem cells from human exfoliated deciduous teeth may act as a very practical and easily accessibly reservoir for autologous stem cells and hold the most value in stem cell therapy. Dental pulp stem cells and periodontal ligament stem cells should also be considered for their triple lineage differentiation ability and relative ease of isolation. Further, we address the potentials and limitations of induced pluripotent stem cells as a cell source in dental regenerative. From an economical and a practical standpoint, dental stem cell therapy would be most easily applied in the prevention of periodontal ligament detachment and bone atrophy, as well as in the regeneration of dentin-pulp complex. In contrast, cell-based tooth replacement due to decay or other oral pathology seems, at the current time, an untenable approach.

  15. Aging, metabolism and stem cells: Spotlight on muscle stem cells.

    Science.gov (United States)

    García-Prat, Laura; Muñoz-Cánoves, Pura

    2017-04-15

    All tissues and organs undergo a progressive regenerative decline as they age. This decline has been mainly attributed to loss of stem cell number and/or function, and both stem cell-intrinsic changes and alterations in local niches and/or systemic environment over time are known to contribute to the stem cell aging phenotype. Advancing in the molecular understanding of the deterioration of stem cell cells with aging is key for targeting the specific causes of tissue regenerative dysfunction at advanced stages of life. Here, we revise exciting recent findings on why stem cells age and the consequences on tissue regeneration, with a special focus on regeneration of skeletal muscle. We also highlight newly identified common molecular pathways affecting diverse types of aging stem cells, such as altered proteostasis, metabolism, or senescence entry, and discuss the questions raised by these findings. Finally, we comment on emerging stem cell rejuvenation strategies, principally emanating from studies on muscle stem cells, which will surely burst tissue regeneration research for future benefit of the increasing human aging population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Curbing stem cell tourism in South Africa.

    Science.gov (United States)

    Meissner-Roloff, Madelein; Pepper, Michael S

    2013-12-01

    Stem cells have received much attention globally due in part to the immense therapeutic potential they harbor. Unfortunately, malpractice and exploitation (financial and emotional) of vulnerable patients have also drawn attention to this field as a result of the detrimental consequences experienced by some individuals that have undergone unproven stem cell therapies. South Africa has had limited exposure to stem cells and their applications and, while any exploitation is detrimental to the field of stem cells, South Africa is particularly vulnerable in this regard. The current absence of adequate legislation and the inability to enforce existing legislation, coupled to the sea of misinformation available on the Internet could lead to an increase in illegitimate stem cell practices in South Africa. Circumstances are already precarious because of a lack of understanding of concepts involved in stem cell applications. What is more, credible and easily accessible information is not available to the public. This in turn cultivates fears born out of existing superstitions, cultural beliefs, rituals and practices. Certain cultural or religious concerns could potentially hinder the effective application of stem cell therapies in South Africa and novel ways of addressing these concerns are necessary. Understanding how scientific progress and its implementation will affect each individual and, consequently, the community, will be of cardinal importance to the success of the fields of stem cell therapy and regenerative medicine in South Africa. A failure to understand the ethical, cultural or moral ramifications when new scientific concepts are introduced could hinder the efficacy and speed of bringing discoveries to the patient. Neglecting proper procedure for establishing the field would lead to long delays in gaining public support in South Africa. Understanding the dangers of stem cell tourism - where vulnerable patients are subjected to unproven stem cell therapies that

  17. Stem cell tourism and public education: the missing elements.

    Science.gov (United States)

    Master, Zubin; Robertson, Kelsey; Frederick, Daniel; Rachul, Christen; Caulfield, Timothy

    2014-09-04

    Stem cell tourism describes the Internet-based industry where in patients receive unproven stem cell interventions. To better inform the public, several organizations provide educational material on stem cell therapies and tourism; however, an assessment of the currently available resources reveals a lack of comprehensive information, suggesting that further efforts are needed. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Stem Cell Transplantation from Bench to Bedside

    Indian Academy of Sciences (India)

    Table of contents. Stem Cell Transplantation from Bench to Bedside · Slide 2 · Slide 3 · Slide 4 · Principles of an allogeneic stem cell transplant · Principle of an allogeneic stem cell transplant · Principle of an autologous Stem Cell Transplant · Slide 8 · Conditioning · Slide 10 · Slide 11 · Stem Cell Transplantation · Slide 13.

  19. Identification of Abnormal Stem Cells Using Raman Spectroscopy

    DEFF Research Database (Denmark)

    Harkness, Linda; Novikov, Sergey M; Beermann, Jonas

    2012-01-01

    The clinical use of stem cells in cell-based therapeutics for degenerative diseases requires development of criteria for defining normal stem cells to ensure safe transplantation. Currently, identification of abnormal from normal stem cells is based on extensive ex vivo and in vivo testing. Raman...... microscopy is a label-free method for rapid and sensitive detection of changes in cells' bio-molecular composition. Here, we report that by using Raman spectroscopy, we were able to map the distribution of different biomolecules within 2 types of stem cells: adult human bone marrow-derived stromal stem cells...... and human embryonic stem cells and to identify reproducible differences in Raman's spectral characteristics that distinguished genetically abnormal and transformed stem cells from their normal counterparts. Raman microscopy can be prospectively employed as a method for identifying abnormal stem cells in ex...

  20. Stem cell applications in military medicine.

    Science.gov (United States)

    Christopherson, Gregory T; Nesti, Leon J

    2011-10-19

    There are many similarities between health issues affecting military and civilian patient populations, with the exception of the relatively small but vital segment of active soldiers who experience high-energy blast injuries during combat. A rising incidence of major injuries from explosive devices in recent campaigns has further complicated treatment and recovery, highlighting the need for tissue regenerative options and intensifying interest in the possible role of stem cells for military medicine. In this review we outline the array of tissue-specific injuries typically seen in modern combat - as well as address a few complications unique to soldiers--and discuss the state of current stem cell research in addressing each area. Embryonic, induced-pluripotent and adult stem cell sources are defined, along with advantages and disadvantages unique to each cell type. More detailed stem cell sources are described in the context of each tissue of interest, including neural, cardiopulmonary, musculoskeletal and sensory tissues, with brief discussion of their potential role in regenerative medicine moving forward. Additional commentary is given to military stem cell applications aside from regenerative medicine, such as blood pharming, immunomodulation and drug screening, with an overview of stem cell banking and the unique opportunity provided by the military and civilian overlap of stem cell research.

  1. Assaying embryotoxicity in the test tube: current limitations of the embryonic stem cell test (EST) challenging its applicability domain.

    Science.gov (United States)

    Riebeling, Christian; Hayess, Katrin; Peters, Annelieke K; Steemans, Margino; Spielmann, Horst; Luch, Andreas; Seiler, Andrea E M

    2012-05-01

    Testing for embryotoxicity in vitro is an attractive alternative to animal experimentation. The embryonic stem cell test (EST) is such a method, and it has been formally validated by the European Centre for the Validation of Alternative Methods. A number of recent studies have underscored the potential of this method. However, the EST performed well below the 78% accuracy expected from the validation study using a new set of chemicals and pharmaceutical compounds, and also of toxicity criteria, tested to enlarge the database of the validated EST as part of the Work Package III of the ReProTect Project funded within the 6th Framework Programme of the European Union. To assess the performance and applicability domain of the EST we present a detailed review of the substances and their effects in the EST being nitrofen, ochratoxin A, D-penicillamine, methylazoxymethanol, lovastatin, papaverine, warfarin, β-aminopropionitrile, dinoseb, furosemide, doxylamine, pravastatin, and metoclopramide. By delineation of the molecular mechanisms of the substances we identify six categories of reasons for misclassifications. Some of these limitations might also affect other in vitro methods assessing embryotoxicity. Substances that fall into these categories need to be included in future validation sets and in validation guidelines for embryotoxicity testing. Most importantly, we suggest conceivable improvements and additions to the EST which will resolve most of the limitations.

  2. Human stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Aldahmash, Abdullah; Zaher, Walid; Al-Nbaheen, May

    2012-01-01

    Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self......-renewal and multi-lineage differentiation into mesoderm-type of cells, e.g., to osteoblasts, adipocytes, chondrocytes and possibly other cell types including hepatocytes and astrocytes. Due to their ease of culture and multipotentiality, hMSC are increasingly employed as a source for cells suitable for a number...

  3. Haematopoietic stem and progenitor cells from human pluripotent stem cells

    Science.gov (United States)

    Sugimura, Ryohichi; Jha, Deepak Kumar; Han, Areum; Soria-Valles, Clara; da Rocha, Edroaldo Lummertz; Lu, Yi-Fen; Goettel, Jeremy A.; Serrao, Erik; Rowe, R. Grant; Malleshaiah, Mohan; Wong, Irene; Sousa, Patricia; Zhu, Ted N.; Ditadi, Andrea; Keller, Gordon; Engelman, Alan N.; Snapper, Scott B.; Doulatov, Sergei; Daley, George Q.

    2018-01-01

    A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders. PMID:28514439

  4. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Shan Liu

    2016-06-01

    Full Text Available Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous. The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells, early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium, using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration, timing for cell therapy (immediate vs. a few days after injury, single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications.

  5. Advances in reprogramming somatic cells to induced pluripotent stem cells.

    Science.gov (United States)

    Patel, Minal; Yang, Shuying

    2010-09-01

    Traditionally, nuclear reprogramming of cells has been performed by transferring somatic cell nuclei into oocytes, by combining somatic and pluripotent cells together through cell fusion and through genetic integration of factors through somatic cell chromatin. All of these techniques changes gene expression which further leads to a change in cell fate. Here we discuss recent advances in generating induced pluripotent stem cells, different reprogramming methods and clinical applications of iPS cells. Viral vectors have been used to transfer transcription factors (Oct4, Sox2, c-myc, Klf4, and nanog) to induce reprogramming of mouse fibroblasts, neural stem cells, neural progenitor cells, keratinocytes, B lymphocytes and meningeal membrane cells towards pluripotency. Human fibroblasts, neural cells, blood and keratinocytes have also been reprogrammed towards pluripotency. In this review we have discussed the use of viral vectors for reprogramming both animal and human stem cells. Currently, many studies are also involved in finding alternatives to using viral vectors carrying transcription factors for reprogramming cells. These include using plasmid transfection, piggyback transposon system and piggyback transposon system combined with a non viral vector system. Applications of these techniques have been discussed in detail including its advantages and disadvantages. Finally, current clinical applications of induced pluripotent stem cells and its limitations have also been reviewed. Thus, this review is a summary of current research advances in reprogramming cells into induced pluripotent stem cells.

  6. Biophotonics sensor acclimatization to stem cells environment

    Science.gov (United States)

    Mohamad Shahimin, Mukhzeer

    2017-11-01

    The ability to discriminate, characterise and purify biological cells from heterogeneous population of cells is fundamental to numerous prognosis and diagnosis applications; often forming the basis for current and emerging clinical protocols in stem cell therapy. Current sorting approaches exploit differences in cell density, specific immunologic targets, or receptor-ligand interactions to isolate particular cells. Identification of novel properties by which different cell types may be discerned and of new ways for their selective manipulation are clearly fundamental components for improving sorting methodologies. Biophotonics sensor developed by our team are potentially capable of discriminating cells according to their refractive index (which is highly dependable on the organelles inside the cell), size (indicator to cell stage) and shape (in certain cases as an indicator to cell type). The sensor, which already discriminate particles efficiently, is modified to acclimatize into biological environment, especially for stem cell applications.

  7. Stem cells in pharmaceutical biotechnology.

    Science.gov (United States)

    Zuba-Surma, Ewa K; Józkowicz, Alicja; Dulak, Józef

    2011-11-01

    Multiple populations of stem cells have been indicated to potentially participate in regeneration of injured organs. Especially, embryonic stem cells (ESC) and recently inducible pluripotent stem cells (iPS) receive a marked attention from scientists and clinicians for regenerative medicine because of their high proliferative and differentiation capacities. Despite that ESC and iPS cells are expected to give rise into multiple regenerative applications when their side effects are overcame during appropriate preparation procedures, in fact their most recent application of human ESC may, however, reside in their use as a tool in drug development and disease modeling. This review focuses on the applications of stem cells in pharmaceutical biotechnology. We discuss possible relevance of pluripotent cell stem populations in developing physiological models for any human tissue cell type useful for pharmacological, metabolic and toxicity evaluation necessary in the earliest steps of drug development. The present models applied for preclinical drug testing consist of primary cells or immortalized cell lines that show limitations in terms of accessibility or relevance to their in vivo counterparts. The availability of renewable human cells with functional similarities to their in vivo counterparts is the first landmark for a new generation of cell-based assays. We discuss the approaches for using stem cells as valuable physiological targets of drug activity which may increase the strength of target validation and efficacy potentially resulting in introducing new safer remedies into clinical trials and the marketplace. Moreover, we discuss the possible applications of stem cells for elucidating mechanisms of disease pathogenesis. The knowledge about the mechanisms governing the development and progression of multitude disorders which would come from the cellular models established based on stem cells, may give rise to new therapeutical strategies for such diseases. All

  8. Bioprinting for stem cell research

    Science.gov (United States)

    Tasoglu, Savas; Demirci, Utkan

    2012-01-01

    Recently, there has been a growing interest to apply bioprinting techniques to stem cell research. Several bioprinting methods have been developed utilizing acoustics, piezoelectricity, and lasers to deposit living cells onto receiving substrates. Using these technologies, spatially defined gradients of immobilized proteins can be engineered to direct stem cell differentiation into multiple subpopulations of different lineages. Stem cells can also be patterned in a high-throughput manner onto flexible implementation patches for tissue regeneration or onto substrates with the goal of accessing encapsulated stem cell of interest for genomic analysis. Here, we review recent achievements with bioprinting technologies in stem cell research, and identify future challenges and potential applications including tissue engineering and regenerative medicine, wound healing, and genomics. PMID:23260439

  9. Stem Cells and Tissue Engineering

    CERN Document Server

    Pavlovic, Mirjana

    2013-01-01

    Stem cells are the building blocks for all other cells in an organism. The human body has about 200 different types of cells and any of those cells can be produced by a stem cell. This fact emphasizes the significance of stem cells in transplantational medicine, regenerative therapy and bioengineering. Whether embryonic or adult, these cells can be used for the successful treatment of a wide range of diseases that were not treatable before, such as osteogenesis imperfecta in children, different forms of leukemias, acute myocardial infarction, some neural damages and diseases, etc. Bioengineering, e.g. successful manipulation of these cells with multipotential capacity of differentiation toward appropriate patterns and precise quantity, are the prerequisites for successful outcome and treatment. By combining in vivo and in vitro techniques, it is now possible to manage the wide spectrum of tissue damages and organ diseases. Although the stem-cell therapy is not a response to all the questions, it provides more...

  10. Technology advancement for integrative stem cell analyses.

    Science.gov (United States)

    Jeong, Yoon; Choi, Jonghoon; Lee, Kwan Hyi

    2014-12-01

    Scientists have endeavored to use stem cells for a variety of applications ranging from basic science research to translational medicine. Population-based characterization of such stem cells, while providing an important foundation to further development, often disregard the heterogeneity inherent among individual constituents within a given population. The population-based analysis and characterization of stem cells and the problems associated with such a blanket approach only underscore the need for the development of new analytical technology. In this article, we review current stem cell analytical technologies, along with the advantages and disadvantages of each, followed by applications of these technologies in the field of stem cells. Furthermore, while recent advances in micro/nano technology have led to a growth in the stem cell analytical field, underlying architectural concepts allow only for a vertical analytical approach, in which different desirable parameters are obtained from multiple individual experiments and there are many technical challenges that limit vertically integrated analytical tools. Therefore, we propose--by introducing a concept of vertical and horizontal approach--that there is the need of adequate methods to the integration of information, such that multiple descriptive parameters from a stem cell can be obtained from a single experiment.

  11. Time to Reconsider Stem Cell Induction Strategies

    Directory of Open Access Journals (Sweden)

    Hans-Werner Denker

    2012-12-01

    Full Text Available Recent developments in stem cell research suggest that it may be time to reconsider the current focus of stem cell induction strategies. During the previous five years, approximately, the induction of pluripotency in somatic cells, i.e., the generation of so-called ‘induced pluripotent stem cells’ (iPSCs, has become the focus of ongoing research in many stem cell laboratories, because this technology promises to overcome limitations (both technical and ethical seen in the production and use of embryonic stem cells (ESCs. A rapidly increasing number of publications suggest, however, that it is now possible to choose instead other, alternative ways of generating stem and progenitor cells bypassing pluripotency. These new strategies may offer important advantages with respect to ethics, as well as to safety considerations. The present communication discusses why these strategies may provide possibilities for an escape from the dilemma presented by pluripotent stem cells (self-organization potential, cloning by tetraploid complementation, patenting problems and tumor formation risk.

  12. Stem cell bioprocessing: fundamentals and principles.

    Science.gov (United States)

    Placzek, Mark R; Chung, I-Ming; Macedo, Hugo M; Ismail, Siti; Mortera Blanco, Teresa; Lim, Mayasari; Cha, Jae Min; Fauzi, Iliana; Kang, Yunyi; Yeo, David C L; Ma, Chi Yip Joan; Polak, Julia M; Panoskaltsis, Nicki; Mantalaris, Athanasios

    2009-03-06

    In recent years, the potential of stem cell research for tissue engineering-based therapies and regenerative medicine clinical applications has become well established. In 2006, Chung pioneered the first entire organ transplant using adult stem cells and a scaffold for clinical evaluation. With this a new milestone was achieved, with seven patients with myelomeningocele receiving stem cell-derived bladder transplants resulting in substantial improvements in their quality of life. While a bladder is a relatively simple organ, the breakthrough highlights the incredible benefits that can be gained from the cross-disciplinary nature of tissue engineering and regenerative medicine (TERM) that encompasses stem cell research and stem cell bioprocessing. Unquestionably, the development of bioprocess technologies for the transfer of the current laboratory-based practice of stem cell tissue culture to the clinic as therapeutics necessitates the application of engineering principles and practices to achieve control, reproducibility, automation, validation and safety of the process and the product. The successful translation will require contributions from fundamental research (from developmental biology to the 'omics' technologies and advances in immunology) and from existing industrial practice (biologics), especially on automation, quality assurance and regulation. The timely development, integration and execution of various components will be critical-failures of the past (such as in the commercialization of skin equivalents) on marketing, pricing, production and advertising should not be repeated. This review aims to address the principles required for successful stem cell bioprocessing so that they can be applied deftly to clinical applications.

  13. Skin appendage-derived stem cells: cell biology and potential for wound repair

    OpenAIRE

    Xie, Jiangfan; Yao, Bin; Han, Yutong; Huang, Sha; Fu, Xiaobing

    2016-01-01

    Stem cells residing in the epidermis and skin appendages are imperative for skin homeostasis and regeneration. These stem cells also participate in the repair of the epidermis after injuries, inducing restoration of tissue integrity and function of damaged tissue. Unlike epidermis-derived stem cells, comprehensive knowledge about skin appendage-derived stem cells remains limited. In this review, we summarize the current knowledge of skin appendage-derived stem cells, including their fundament...

  14. Counting stem cells : methodological constraints

    NARCIS (Netherlands)

    Bystrykh, Leonid V.; Verovskaya, Evgenia; Zwart, Erik; Broekhuis, Mathilde; de Haan, Gerald

    The number of stem cells contributing to hematopoiesis has been a matter of debate. Many studies use retroviral tagging of stem cells to measure clonal contribution. Here we argue that methodological factors can impact such clonal analyses. Whereas early studies had low resolution, leading to

  15. Stem cell function and maintenance

    Indian Academy of Sciences (India)

    Stem cell research holds a promise to treat and prevent age-related degenerative changes in humans. Literature is replete with studies showing that stem cell function declines with aging, especially in highly proliferative tissues/organs. Among others, telomerase and telomere damage is one of the intrinsic physical ...

  16. Clinical grade adult stem cell banking.

    Science.gov (United States)

    Thirumala, Sreedhar; Goebel, W Scott; Woods, Erik J

    2009-07-01

    There has been a great deal of scientific interest recently generated by the potential therapeutic applications of adult stem cells in human care but there are several challenges regarding quality and safety in clinical applications and a number of these challenges relate to the processing and banking of these cells ex-vivo. As the number of clinical trials and the variety of adult cells used in regenerative therapy increases, safety remains a primary concern. This has inspired many nations to formulate guidelines and standards for the quality of stem cell collection, processing, testing, banking, packaging and distribution. Clinically applicable cryopreservation and banking of adult stem cells offers unique opportunities to advance the potential uses and widespread implementation of these cells in clinical applications. Most current cryopreservation protocols include animal serum proteins and potentially toxic cryoprotectant additives (CPAs) that prevent direct use of these cells in human therapeutic applications. Long term cryopreservation of adult stem cells under good manufacturing conditions using animal product free solutions is critical to the widespread clinical implementation of ex-vivo adult stem cell therapies. Furthermore, to avoid any potential cryoprotectant related complications, reduced CPA concentrations and efficient post-thaw washing to remove CPA are also desirable. The present review focuses on the current strategies and important aspects of adult stem cell banking for clinical applications. These include current good manufacturing practices (cGMPs), animal protein free freezing solutions, cryoprotectants, freezing & thawing protocols, viability assays, packaging and distribution. The importance and benefits of banking clinical grade adult stem cells are also discussed.

  17. Stem cells in endodontic therapy

    Directory of Open Access Journals (Sweden)

    Sita Rama Kumar M, Madhu Varma K, Kalyan Satish R, Manikya kumar Nanduri.R, Murali Krishnam Raju S, Mohan rao

    2014-11-01

    Full Text Available Stem cells have the remarkable potential to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person or animal is still alive. However, progress in stem cell biology and tissue engineering may present new options for replacing heavily damaged or lost teeth, or even individual tooth structures. The goal of this review is to discuss the potential impact of dental pulp stem cells on regenerative endodontics.

  18. Stem cells and respiratory diseases

    Energy Technology Data Exchange (ETDEWEB)

    Abreu, Soraia Carvalho; Maron-Gutierrez, Tatiana; Garcia, Cristiane Sousa Nascimento Baez; Morales, Marcelo Marcos; Rocco, Patricia Rieken Macedo [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Biofisica Carlos Chagas Filho. Lab. de Investigacao]. E-mail: prmrocco@biof.ufrj.br

    2008-12-15

    Stem cells have a multitude of clinical implications in the lung. This article is a critical review that includes clinical and experimental studies of MedLine and SciElo database in the last 10 years, where we highlight the effects of stem cell therapy in acute respiratory distress syndrome or more chronic disorders such as lung fibrosis and emphysema. Although, many studies have shown the beneficial effects of stem cells in lung development, repair and remodeling; some important questions need to be answered to better understand the mechanisms that control cell division and differentiation, therefore enabling the use of cell therapy in human respiratory diseases. (author)

  19. Stem cells and respiratory diseases

    International Nuclear Information System (INIS)

    Abreu, Soraia Carvalho; Maron-Gutierrez, Tatiana; Garcia, Cristiane Sousa Nascimento Baez; Morales, Marcelo Marcos; Rocco, Patricia Rieken Macedo

    2008-01-01

    Stem cells have a multitude of clinical implications in the lung. This article is a critical review that includes clinical and experimental studies of MedLine and SciElo database in the last 10 years, where we highlight the effects of stem cell therapy in acute respiratory distress syndrome or more chronic disorders such as lung fibrosis and emphysema. Although, many studies have shown the beneficial effects of stem cells in lung development, repair and remodeling; some important questions need to be answered to better understand the mechanisms that control cell division and differentiation, therefore enabling the use of cell therapy in human respiratory diseases. (author)

  20. Stem Cell Transplants (For Parents)

    Science.gov (United States)

    ... of Transplants Transplantation Recovery Coping Print en español Trasplantes de células madre Stem cells are cells in ... finding a match is called tissue typing (or HLA [human leukocyte antigen] typing). HLA is a protein ...

  1. Lasers, stem cells, and COPD

    Directory of Open Access Journals (Sweden)

    De Necochea-Campion Rosalia

    2010-02-01

    Full Text Available Abstract The medical use of low level laser (LLL irradiation has been occurring for decades, primarily in the area of tissue healing and inflammatory conditions. Despite little mechanistic knowledge, the concept of a non-invasive, non-thermal intervention that has the potential to modulate regenerative processes is worthy of attention when searching for novel methods of augmenting stem cell-based therapies. Here we discuss the use of LLL irradiation as a "photoceutical" for enhancing production of stem cell growth/chemoattractant factors, stimulation of angiogenesis, and directly augmenting proliferation of stem cells. The combination of LLL together with allogeneic and autologous stem cells, as well as post-mobilization directing of stem cells will be discussed.

  2. Human epithelial hair follicle stem cells and their progeny: current state of knowledge, the widening gap in translational research and future challenges.

    Science.gov (United States)

    Purba, Talveen S; Haslam, Iain S; Poblet, Enrique; Jiménez, Francisco; Gandarillas, Alberto; Izeta, Ander; Paus, Ralf

    2014-05-01

    Epithelial hair follicle stem cells (eHFSCs) are required to generate, maintain and renew the continuously cycling hair follicle (HF), supply cells that produce the keratinized hair shaft and aid in the reepithelialization of injured skin. Therefore, their study is biologically and clinically important, from alopecia to carcinogenesis and regenerative medicine. However, human eHFSCs remain ill defined compared to their murine counterparts, and it is unclear which murine eHFSC markers really apply to the human HF. We address this by reviewing current concepts on human eHFSC biology, their immediate progeny and their molecular markers, focusing on Keratin 15 and 19, CD200, CD34, PHLDA1, and EpCAM/Ber-EP4. After delineating how human eHFSCs may be selectively targeted experimentally, we close by defining as yet unmet key challenges in human eHFSC research. The ultimate goal is to transfer emerging concepts from murine epithelial stem cell biology to human HF physiology and pathology. © 2014 WILEY Periodicals, Inc.

  3. Stem cells and bone: a historical perspective.

    Science.gov (United States)

    Bianco, Paolo

    2015-01-01

    Bone physiology and stem cells were tightly intertwined with one another, both conceptually and experimentally, long before the current explosion of interest in stem cells and so-called regenerative medicine. Bone is home to the two best known and best characterized systems of postnatal stem cells, and it is the only organ in which two stem cells and their dependent lineages coordinate the overall adaptive responses of two major physiological systems. All along, the nature and the evolutionary significance of the interplay of bone and hematopoiesis have remained a major scientific challenge, but also allowed for some of the most spectacular developments in cell biology-based medicine, such as hematopoietic stem cell transplantation. This question recurs in novel forms at multiple turning points over time: today, it finds in the biology of the "niche" its popular phrasing. Entirely new avenues of investigation emerge as a new view of bone in physiology and medicine is progressively established. Looking at bone and stem cells in a historical perspective provides a unique case study to highlight the general evolution of science in biomedicine since the end of World War II to the present day. A paradigm shift in science and in its relation to society and policies occurred in the second half of the XXth century, with major implications thereof for health, industry, drug development, market and society. Current interest in stem cells in bone as in other fields is intertwined with that shift. New opportunities and also new challenges arise. This article is part of a Special Issue entitled "Stem cells and bone". Copyright © 2014. Published by Elsevier Inc.

  4. Nano scaffolds and stem cell therapy in liver tissue engineering

    Science.gov (United States)

    Montaser, Laila M.; Fawzy, Sherin M.

    2015-08-01

    Tissue engineering and regenerative medicine have been constantly developing of late due to the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Although stem cells hold great potential for the treatment of many injuries and degenerative diseases, several obstacles must be overcome before their therapeutic application can be realized. These include the development of advanced techniques to understand and control functions of micro environmental signals and novel methods to track and guide transplanted stem cells. A major complication encountered with stem cell therapies has been the failure of injected cells to engraft to target tissues. The application of nanotechnology to stem cell biology would be able to address those challenges. Combinations of stem cell therapy and nanotechnology in tissue engineering and regenerative medicine have achieved significant advances. These combinations allow nanotechnology to engineer scaffolds with various features to control stem cell fate decisions. Fabrication of Nano fiber cell scaffolds onto which stem cells can adhere and spread, forming a niche-like microenvironment which can guide stem cells to proceed to heal damaged tissues. In this paper, current and emergent approach based on stem cells in the field of liver tissue engineering is presented for specific application. The combination of stem cells and tissue engineering opens new perspectives in tissue regeneration for stem cell therapy because of the potential to control stem cell behavior with the physical and chemical characteristics of the engineered scaffold environment.

  5. Bone regeneration and stem cells

    Science.gov (United States)

    Arvidson, K; Abdallah, B M; Applegate, L A; Baldini, N; Cenni, E; Gomez-Barrena, E; Granchi, D; Kassem, M; Konttinen, Y T; Mustafa, K; Pioletti, D P; Sillat, T; Finne-Wistrand, A

    2011-01-01

    Abstract This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed. PMID:21129153

  6. Bone regeneration and stem cells

    DEFF Research Database (Denmark)

    Arvidson, K; Abdallah, B M; Applegate, L A

    2011-01-01

    cells, use of platelet rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed.......This invited review covers research areas of central importance for orthopedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and fetal stem cells, effects of sex steroids on mesenchymal stem...

  7. Stem cells for tooth engineering

    Directory of Open Access Journals (Sweden)

    G Bluteau

    2008-07-01

    Full Text Available Tooth development results from sequential and reciprocal interactions between the oral epithelium and the underlying neural crest-derived mesenchyme. The generation of dental structures and/or entire teeth in the laboratory depends upon the manipulation of stem cells and requires a synergy of all cellular and molecular events that finally lead to the formation of tooth-specific hard tissues, dentin and enamel. Although mesenchymal stem cells from different origins have been extensively studied in their capacity to form dentin in vitro, information is not yet available concerning the use of epithelial stem cells. The odontogenic potential resides in the oral epithelium and thus epithelial stem cells are necessary for both the initiation of tooth formation and enamel matrix production. This review focuses on the different sources of stem cells that have been used for making teeth in vitro and their relative efficiency. Embryonic, post-natal or even adult stem cells were assessed and proved to possess an enormous regenerative potential, but their application in dental practice is still problematic and limited due to various parameters that are not yet under control such as the high risk of rejection, cell behaviour, long tooth eruption period, appropriate crown morphology and suitable colour. Nevertheless, the development of biological approaches for dental reconstruction using stem cells is promising and remains one of the greatest challenges in the dental field for the years to come.

  8. Embryos, Clones, and Stem Cells: A Scientific Primer

    Directory of Open Access Journals (Sweden)

    Kenyon S. Tweedell

    2004-01-01

    Full Text Available This article is intended to give the nonspecialist an insight into the nuances of “clones”, cloning, and stem cells. It distinguishes embryonic and adult stem cells, their normal function in the organism, their origin, and how they are recovered to produce stem cell lines in culture. As background, the fundamental processes of embryo development are reviewed and defined, since the manipulation of stem cell lines into desired specialized cells employs many of the same events. Stem cells are defined and characterized and shown how they function in the intact organism during early development and later during cell regeneration in the adult. The complexity of stem cell recovery and their manipulation into specific cells and tissue is illustrated by reviewing current experimentation on both embryonic and adult stem cells in animals and limited research on human stem cell lines. The current and projected use of stem cells for human diseases and repair, along with the expanding methodology for the recovery of human embryonic stem cells, is described. An assessment on the use of human embryonic stem cells is considered from ethical, legal, religious, and political viewpoints.

  9. A Promising Tool in Retina Regeneration: Current Perspectives and Challenges When Using Mesenchymal Progenitor Stem Cells in Veterinary and Human Ophthalmological Applications.

    Science.gov (United States)

    Cislo-Pakuluk, Anna; Marycz, Krzysztof

    2017-10-01

    Visual impairment is a common ailment of the current world population, with more exposure to CCD screens and fluorescent lighting, approximately 285 billion people suffer from this deficiency and 13% of those are considered clinically blind. More common causes for visual impairment include age-related macular degeneration (AMD), glaucoma and diabetic retinopathy (Zhu et al. Molecular Medicine Reports, 2015; Kolb et al. 2007; Machalińska et al. Current Eye Research, 34(9),748-760, 2009) among a few. As cases of retinal and optic nerve diseases rise, it is vital to find a treatment, which has led to investigation of the therapeutic potential of various stem cells types (Bull et al. Investigative Opthalmology & Visual Science, 50(9), 4244, 2009; Bull et al. Investigative Opthalmology & Visual Science, 49(8), 3449, 2008; Yu et al. Biochemical and Biophysical Research Communications, 344(4), 1071-1079, 2006; Na et al. Graefe's Archive for Clinical and Experimental Ophthalmology, 247(4), 503-514, 2008). In previous studies, some of the stem cell variants used include human Muller SCs and bone marrow derived SCs. Some of the regenerative potential characteristics of mesenchymal progenitor stem cells (MSCs) include their multilineage differentiation potential, their immunomodulatory effects, their high proliferative activity, they can be easily cultured in vitro, and finally their potential to synthesize and secrete membrane derived vesicles rich in growth factors, mRNA and miRNA which possibly aid in regulation of tissue damage regeneration. These facts alone, explain why MSCs are so widely used in clinical trials, 350 up to date (Switonski, Reproductive Biology, 14(1), 44-50, 2014). Animal studies have demonstrated that sub-retinal transplantation of MSCs delays retinal degeneration and preserves retinal function through trophic response (Inoue et al. Experimental Eye Research, 85(2), 234-241, 2007). Umbilical cord derived MSCs (UC/MSCs) have also been shown to contain

  10. Stem cell technology for drug discovery and development.

    Science.gov (United States)

    Hook, Lilian A

    2012-04-01

    Stem cells have enormous potential to revolutionise the drug discovery process at all stages, from target identification through to toxicology studies. Their ability to generate physiologically relevant cells in limitless supply makes them an attractive alternative to currently used recombinant cell lines or primary cells. However, realisation of the full potential of stem cells is currently hampered by the difficulty in routinely directing stem cell differentiation to reproducibly and cost effectively generate pure populations of specific cell types. In this article we discuss how stem cells have already been used in the drug discovery process and how novel technologies, particularly in relation to stem cell differentiation, can be applied to attain widespread adoption of stem cell technology by the pharmaceutical industry. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Stem Cells in Regenerative Medicine

    OpenAIRE

    Sykova, Eva; Forostyak, Serhiy

    2013-01-01

    Background: A number of cardiovascular, neurological, musculoskeletal and other diseases have a limited capacity for repair and only a modest progress has been made in treatment of brain diseases. The discovery of stem cells has opened new possibilities for the treatment of these maladies, and cell therapy now stands at the cutting-edge of modern regenerative medicine and tissue engineering. Experimental data and the first clinical trials employing stem cells have shown their broad therapeuti...

  12. Mesenchymal stem cell-mediated functional tooth regeneration in swine.

    Directory of Open Access Journals (Sweden)

    Wataru Sonoyama

    2006-12-01

    Full Text Available Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla. Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance.

  13. Stem cells in retinal regeneration: past, present and future.

    Science.gov (United States)

    Ramsden, Conor M; Powner, Michael B; Carr, Amanda-Jayne F; Smart, Matthew J K; da Cruz, Lyndon; Coffey, Peter J

    2013-06-01

    Stem cell therapy for retinal disease is under way, and several clinical trials are currently recruiting. These trials use human embryonic, foetal and umbilical cord tissue-derived stem cells and bone marrow-derived stem cells to treat visual disorders such as age-related macular degeneration, Stargardt's disease and retinitis pigmentosa. Over a decade of analysing the developmental cues involved in retinal generation and stem cell biology, coupled with extensive surgical research, have yielded differing cellular approaches to tackle these retinopathies. Here, we review these various stem cell-based approaches for treating retinal diseases and discuss future directions and challenges for the field.

  14. Overview of the current issues and advances in haemopoietic stem cell transplantation for β-thalassemia major

    Directory of Open Access Journals (Sweden)

    S.S. Anak

    2011-12-01

    Full Text Available Bone marrow transplantation (BMT is the only possible curative treatment for β-thalassemia major. The largest experience occurred in Pesaro, Italy, where the BMT was applied after a standard risk assessment. The patients were divided into 3 risk classes based on liver size by physical examination, the presence or absence of fibrosis by liver biopsy, and adherence to regular iron chelation. Outcomes were mainly affected by the risk status. After modifications to the conditioning regimens, the risk of transplantation-related complications in highrisk recipients reduced considerably. As a result, outcomes after transplantation have become more similar across risk categories. For BMT, most centers use bone marrow instead of peripheral blood in thalassemia. Some studies showed that peripheral blood stem cell transplantation (PBSCT is better than BMT with regard to hematologic recovery, hospitalization period, leukemia-free survival, overall survival (OS, and transplant-related mortality (TRM. No significant differences were seen in grade II to IV acute GVHD (aGVHD; but the incidence of chronic GVHD (cGVHD was significantly higher in the PBSCT group. BMT from unrelated donors may offer similar results to those obtained using HLA-identical family donors, at least for patients who are not fully compliant with conventional treatment and do not yet show severe complications of iron overload. All studies conclude that MUD BMT might be a good alternative for patients with less risk factors. Another study concluded that, at present, due to high graft failure and GVHD rates, BMT from alternative donors should be restricted to patients who have poor life expectancies because they cannot receive adequate conventional treatment or because of alloimmunization to minor blood antigens. In another study unrelated cord blood transplantation (CBT was compared to related donor transplantation for children with β-thalassemia. The results were comparable to the

  15. Cell Cycle Regulation of Stem Cells by MicroRNAs.

    Science.gov (United States)

    Mens, Michelle M J; Ghanbari, Mohsen

    2018-06-01

    MicroRNAs (miRNAs) are a class of small non-coding RNA molecules involved in the regulation of gene expression. They are involved in the fine-tuning of fundamental biological processes such as proliferation, differentiation, survival and apoptosis in many cell types. Emerging evidence suggests that miRNAs regulate critical pathways involved in stem cell function. Several miRNAs have been suggested to target transcripts that directly or indirectly coordinate the cell cycle progression of stem cells. Moreover, previous studies have shown that altered expression levels of miRNAs can contribute to pathological conditions, such as cancer, due to the loss of cell cycle regulation. However, the precise mechanism underlying miRNA-mediated regulation of cell cycle in stem cells is still incompletely understood. In this review, we discuss current knowledge of miRNAs regulatory role in cell cycle progression of stem cells. We describe how specific miRNAs may control cell cycle associated molecules and checkpoints in embryonic, somatic and cancer stem cells. We further outline how these miRNAs could be regulated to influence cell cycle progression in stem cells as a potential clinical application.

  16. Placenta-an alternative source of stem cells

    International Nuclear Information System (INIS)

    Matikainen, Tiina; Laine, Jarmo

    2005-01-01

    The two most promising practical applications of human stem cells are cellular replacement therapies in human disease and toxicological screening of candidate drug molecules. Both require a source of human stem cells that can be isolated, purified, expanded in number and differentiated into the cell type of choice in a controlled manner. Currently, uses of both embryonic and adult stem cells are investigated. While embryonic stem cells are pluripotent and can differentiate into any specialised cell type, their use requires establishment of embryonic stem cell lines using the inner cell mass of an early pre-implantation embryo. As the blastocyst is destroyed during the process, ethical issues need to be carefully considered. The use of embryonic stem cells is also limited by the difficulties in growing large numbers of the cells without inducing spontaneous differentiation, and the problems in controlling directed differentiation of the cells. The use of adult stem cells, typically derived from bone marrow, but also from other tissues, is ethically non-controversial but their differentiation potential is more limited than that of the embryonic stem cells. Since human cord blood, umbilical cord, placenta and amnion are normally discarded at birth, they provide an easily accessible alternative source of stem cells. We review the potential and current status of the use of adult stem cells derived from the placenta or umbilical cord in therapeutic and toxicological applications

  17. Stem cells: Concepts and prospects

    Indian Academy of Sciences (India)

    development exemplified by murine experiments motivated the ... from specific regions of the brain, cardiac stem cells from atrial ..... have also been shown to integrate and differentiate .... to vascular network structures in three dimensional.

  18. Stem cell therapy for ischemic heart diseases.

    Science.gov (United States)

    Yu, Hong; Lu, Kai; Zhu, Jinyun; Wang, Jian'an

    2017-01-01

    Ischemic heart diseases, especially the myocardial infarction, is a major hazard problem to human health. Despite substantial advances in control of risk factors and therapies with drugs and interventions including bypass surgery and stent placement, the ischemic heart diseases usually result in heart failure (HF), which could aggravate social burden and increase the mortality rate. The current therapeutic methods to treat HF stay at delaying the disease progression without repair and regeneration of the damaged myocardium. While heart transplantation is the only effective therapy for end-stage patients, limited supply of donor heart makes it impossible to meet the substantial demand from patients with HF. Stem cell-based transplantation is one of the most promising treatment for the damaged myocardial tissue. Key recent published literatures and ClinicalTrials.gov. Stem cell-based therapy is a promising strategy for the damaged myocardial tissue. Different kinds of stem cells have their advantages for treatment of Ischemic heart diseases. The efficacy and potency of cell therapies vary significantly from trial to trial; some clinical trials did not show benefit. Diverged effects of cell therapy could be affected by cell types, sources, delivery methods, dose and their mechanisms by which delivered cells exert their effects. Understanding the origin of the regenerated cardiomyocytes, exploring the therapeutic effects of stem cell-derived exosomes and using the cell reprogram technology to improve the efficacy of cell therapy for cardiovascular diseases. Recently, stem cell-derived exosomes emerge as a critical player in paracrine mechanism of stem cell-based therapy. It is promising to exploit exosomes-based cell-free therapy for ischemic heart diseases in the future. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

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

    Science.gov (United States)

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

    2015-06-01

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

  20. The promises of stem cells: stem cell therapy for movement disorders.

    Science.gov (United States)

    Mochizuki, Hideki; Choong, Chi-Jing; Yasuda, Toru

    2014-01-01

    Despite the multitude of intensive research, the exact pathophysiological mechanisms underlying movement disorders including Parkinson's disease, multiple system atrophy and Huntington's disease remain more or less elusive. Treatments to halt these disease progressions are currently unavailable. With the recent induced pluripotent stem cells breakthrough and accomplishment, stem cell research, as the vast majority of scientists agree, holds great promise for relieving and treating debilitating movement disorders. As stem cells are the precursors of all cells in the human body, an understanding of the molecular mechanisms that govern how they develop and work would provide us many fundamental insights into human biology of health and disease. Moreover, stem-cell-derived neurons may be a renewable source of replacement cells for damaged neurons in movement disorders. While stem cells show potential for regenerative medicine, their use as tools for research and drug testing is thought to have more immediate impact. The use of stem-cell-based drug screening technology could be a big boost in drug discovery for these movement disorders. Particular attention should also be given to the involvement of neural stem cells in adult neurogenesis so as to encourage its development as a therapeutic option. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Development of hematopoietic stem and progenitor cells from human pluripotent stem cells.

    Science.gov (United States)

    Chen, Tong; Wang, Fen; Wu, Mengyao; Wang, Zack Z

    2015-07-01

    Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), provide a new cell source for regenerative medicine, disease modeling, drug discovery, and preclinical toxicity screening. Understanding of the onset and the sequential process of hematopoietic cells from differentiated hPSCs will enable the achievement of personalized medicine and provide an in vitro platform for studying of human hematopoietic development and disease. During embryogenesis, hemogenic endothelial cells, a specified subset of endothelial cells in embryonic endothelium, are the primary source of multipotent hematopoietic stem cells. In this review, we discuss current status in the generation of multipotent hematopoietic stem and progenitor cells from hPSCs via hemogenic endothelial cells. We also review the achievements in direct reprogramming from non-hematopoietic cells to hematopoietic stem and progenitor cells. Further characterization of hematopoietic differentiation in hPSCs will improve our understanding of blood development and expedite the development of hPSC-derived blood products for therapeutic purpose. © 2015 Wiley Periodicals, Inc.

  2. Human embryonic stem cells handbook

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2013-03-01

    Full Text Available After the Nobel prize in physiology or medicine was awarded jointly to Sir John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent it became imperative to write down the review for a book entirely devoted to human embryonic stem cells (hES, those cells that are a urgent need for researchers, those cells that rekindle the ethical debates and finally, last but not least, those cells whose study paved the way to obtain induced pluripotent stem cells by the OSKC’s Yamanaka method (the OSKC acronim refers, for those not familiar with the topic, to the four stemness genes used to transfect somatic fibroblasts: Oct4, Sox2, Klf4 and c-Myc....

  3. Plasticity of spermatogonial stem cells

    Directory of Open Access Journals (Sweden)

    Paul S Cooke

    2015-06-01

    Full Text Available There have been significant breakthroughs over the past decade in the development and use of pluripotent stem cells as a potential source of cells for applications in regenerative medicine. It is likely that this methodology will begin to play an important role in human clinical medicine in the years to come. This review describes the plasticity of one type of pluripotent cell, spermatogonial stem cells (SSCs, and their potential therapeutic applications in regenerative medicine and male infertility. Normally, SSCs give rise to sperm when in the testis. However, both human and murine SSCs can give rise to cells with embryonic stem (ES cell-like characteristics that can be directed to differentiate into tissues of all three embryonic germ layers when placed in an appropriate inductive microenvironment, which is in contrast to other postnatal stem cells. Previous studies have reported that SSCs expressed an intermediate pluripotent phenotype before differentiating into a specific cell type and that extended culture was necessary for this to occur. However, recent studies from our group using a tissue recombination model demonstrated that SSCs differentiated rapidly into another tissue, in this case, prostatic epithelium, without expression of pluripotent ES cell markers before differentiation. These results suggest that SSCs are capable of directly differentiating into other cell types without going through an intermediate ES cell-like stage. Because SSCs do not require reprogramming to achieve a pluripotent state, they are an attractive source of pluripotent cells for use in regenerative medicine.

  4. Direct reprogramming of somatic cells into neural stem cells or neurons for neurological disorders.

    Science.gov (United States)

    Hou, Shaoping; Lu, Paul

    2016-01-01

    Direct reprogramming of somatic cells into neurons or neural stem cells is one of the most important frontier fields in current neuroscience research. Without undergoing the pluripotency stage, induced neurons or induced neural stem cells are a safer and timelier manner resource in comparison to those derived from induced pluripotent stem cells. In this prospective, we review the recent advances in generation of induced neurons and induced neural stem cells in vitro and in vivo and their potential treatments of neurological disorders.

  5. Genetic modification of stem cells for transplantation.

    Science.gov (United States)

    Phillips, M Ian; Tang, Yao Liang

    2008-01-14

    Gene modification of cells prior to their transplantation, especially stem cells, enhances their survival and increases their function in cell therapy. Like the Trojan horse, the gene-modified cell has to gain entrance inside the host's walls and survive and deliver its transgene products. Using cellular, molecular and gene manipulation techniques the transplanted cell can be protected in a hostile environment from immune rejection, inflammation, hypoxia and apoptosis. Genetic engineering to modify cells involves constructing modules of functional gene sequences. They can be simple reporter genes or complex cassettes with gene switches, cell specific promoters and multiple transgenes. We discuss methods to deliver and construct gene cassettes with viral and non-viral delivery, siRNA, and conditional Cre/Lox P. We review the current uses of gene-modified stem cells in cardiovascular disease, diabetes, neurological diseases, (including Parkinson's, Alzheimer's and spinal cord injury repair), bone defects, hemophilia, and cancer.

  6. Stem cells therapy for ALS.

    Science.gov (United States)

    Mazzini, Letizia; Vescovi, Angelo; Cantello, Roberto; Gelati, Maurizio; Vercelli, Alessandro

    2016-01-01

    Despite knowledge on the molecular basis of amyotrophic lateral sclerosis (ALS) having quickly progressed over the last few years, such discoveries have not yet translated into new therapeutics. With the advancement of stem cell technologies there is hope for stem cell therapeutics as novel treatments for ALS. We discuss in detail the therapeutic potential of different types of stem cells in preclinical and clinical works. Moreover, we address many open questions in clinical translation. SC therapy is a potentially promising new treatment for ALS and the need to better understand how to develop cell-based experimental treatments, and how to implement them in clinical trials, becomes more pressing. Mesenchymal stem cells and neural fetal stem cells have emerged as safe and potentially effective cell types, but there is a need to carry out appropriately designed experimental studies to verify their long-term safety and possibly efficacy. Moreover, the cost-benefit analysis of the results must take into account the quality of life of the patients as a major end point. It is our opinion that a multicenter international clinical program aime d at fine-tuning and coordinating transplantation procedures and protocols is mandatory.

  7. Road for understanding cancer stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Erzik, Can

    2007-01-01

    There is increasing evidence suggesting that stem cells are susceptive to carcinogenesis and, consequently, can be the origin of many cancers. Recently, the neoplastic potential of stem cells has been supported by many groups showing the existence of subpopulations with stem cell characteristics...... in tumor biopsies such as brain and breast. Evidence supporting the cancer stem cell hypothesis has gained impact due to progress in stem cell biology and development of new models to validate the self-renewal potential of stem cells. Recent evidence on the possible identification of cancer stem cells may...... offer an opportunity to use these cells as future therapeutic targets. Therefore, model systems in this field have become very important and useful. This review will focus on the state of knowledge on cancer stem cell research, including cell line models for cancer stem cells. The latter will, as models...

  8. The role of purinergic receptors in stem cell differentiation

    Directory of Open Access Journals (Sweden)

    Constanze Kaebisch

    2015-01-01

    Full Text Available A major challenge modern society has to face is the increasing need for tissue regeneration due to degenerative diseases or tumors, but also accidents or warlike conflicts. There is great hope that stem cell-based therapies might improve current treatments of cardiovascular diseases, osteochondral defects or nerve injury due to the unique properties of stem cells such as their self-renewal and differentiation potential. Since embryonic stem cells raise severe ethical concerns and are prone to teratoma formation, adult stem cells are still in the focus of research. Emphasis is placed on cellular signaling within these cells and in between them for a better understanding of the complex processes regulating stem cell fate. One of the oldest signaling systems is based on nucleotides as ligands for purinergic receptors playing an important role in a huge variety of cellular processes such as proliferation, migration and differentiation. Besides their natural ligands, several artificial agonists and antagonists have been identified for P1 and P2 receptors and are already used as drugs. This review outlines purinergic receptor expression and signaling in stem cells metabolism. We will briefly describe current findings in embryonic and induced pluripotent stem cells as well as in cancer-, hematopoietic-, and neural crest-derived stem cells. The major focus will be placed on recent findings of purinergic signaling in mesenchymal stem cells addressed in in vitro and in vivo studies, since stem cell fate might be manipulated by this system guiding differentiation towards the desired lineage in the future.

  9. Therapeutic strategies involving uterine stem cells in reproductive medicine.

    Science.gov (United States)

    Simoni, Michael; Taylor, Hugh S

    2018-04-12

    The current review provides an update on recent advances in stem cell biology relevant to female reproduction. Stem cells are undifferentiated cells that often serve as a reservoir of cells to regenerate tissue in settings or injury or cell loss. The endometrium has progenitor stem cells that can replace all of the endometrium during each menstrual cycle. In addition, multipotent endometrial cells replace these progenitor cells when depleted. Recruitment of stem cells from outside of the uterus occurs in setting of increased demand such as ischemia or injury. Bone marrow-derived multipotent stem cells are recruited to the uterus by estrogen or injury-induced expression of the chemokine CXCL12. In the setting of overwhelming injury, especially in the setting of low estrogen levels, there may be insufficient stem cell recruitment to adequately repair the uterus resulting in conditions such as Asherman syndrome or other endometrial defects. In contrast, excessive recruitment of stem cells underlies endometriosis. Enhanced understanding of stem-cell mobilization, recruitment, and engraftment has created the possibility of improved therapy for endometrial defects and endometriosis through enhanced manipulation of stem-cell trafficking. Further, the normal endometrium is a rich source of multipotent stem cells that can be used for numerous applications in regenerative medicine beyond reproduction. A better understanding of reproductive stem-cell biology may allow improved treatment of endometrial disease such as Asherman syndrome and other endometrial receptivity defects. Inhibiting stem-cell mobilization may also be helpful in endometriosis therapy. Finally, endometrial derived multipotent stem cells may play a crucial role in cell therapy for regenerative medicine.

  10. Stem Cell Therapies in Retinal Disorders

    Directory of Open Access Journals (Sweden)

    Aakriti Garg

    2017-02-01

    Full Text Available Stem cell therapy has long been considered a promising mode of treatment for retinal conditions. While human embryonic stem cells (ESCs have provided the precedent for regenerative medicine, the development of induced pluripotent stem cells (iPSCs revolutionized this field. iPSCs allow for the development of many types of retinal cells, including those of the retinal pigment epithelium, photoreceptors, and ganglion cells, and can model polygenic diseases such as age-related macular degeneration. Cellular programming and reprogramming technology is especially useful in retinal diseases, as it allows for the study of living cells that have genetic variants that are specific to patients’ diseases. Since iPSCs are a self-renewing resource, scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Challenges in the use of stem cells are present from the scientific, ethical, and political realms. These include transplant complications leading to anatomically incorrect placement, concern for tumorigenesis, and incomplete targeting of differentiation leading to contamination by different types of cells. Despite these limitations, human ESCs and iPSCs specific to individual patients can revolutionize the study of retinal disease and may be effective therapies for conditions currently considered incurable.

  11. Recent Advances in Intestinal Stem Cells.

    Science.gov (United States)

    McCabe, Laura R; Parameswaran, Narayanan

    2017-09-01

    The intestine is a dynamic organ with rapid stem cell division generating epithelial cells that mature and apoptose in 3-5 days. Rapid turnover maintains the epithelial barrier and homeostasis. Current insights on intestinal stem cells (ISCs) and their regulation are discussed here. The Lgr5+ ISCs maintain intestinal homeostasis by dividing asymmetrically, but also divide symmetrically to extinguish or replace ISCs. Following radiation or mucosal injury, reserve BMI1+ ISCs as well as other crypt cells can de-differentiate into Lgr5+ ISCs. ISC niche cells, including Paneth, immune and myofibroblast cells secrete factors that regulate ISC proliferation. Finally, several studies indicate that the microbiome metabolites regulate ISC growth. ISC cells can be plastic and integrate a complexity of environmental/niche cues to trigger or suppress proliferation as needed.

  12. Cancer stem cells in solid tumors: elusive or illusive?

    Directory of Open Access Journals (Sweden)

    Lehrach Hans R

    2010-05-01

    Full Text Available Abstract During the past years in vivo transplantation experiments and in vitro colony-forming assays indicated that tumors arise only from rare cells. These cells were shown to bear self-renewal capacities and the ability to recapitulate all cell types within an individual tumor. Due to their phenotypic resemblance to normal stem cells, the term "cancer stem cells" is used. However, some pieces of the puzzle are missing: (a a stringent definition of cancer stem cells in solid tumors (b specific markers that only target cells that meet the criteria for a cancer stem cell in a certain type of tumor. These missing parts started an ongoing debate about which is the best method to identify and characterize cancer stem cells, or even if their mere existence is just an artifact caused by the experimental procedures. Recent findings query the cancer stem cell hypothesis for solid tumors itself since it was shown in xenograft transplantation experiments that under appropriate conditions tumor-initiating cells are not rare. In this review we critically discuss the challenges and prospects of the currently used major methods to identify cancer stem cells. Further on, we reflect the present discussion about the existence of cancer stem cells in solid tumors as well as the amount and characteristics of tumor-initiating cells and finally provide new perspectives like the correlation of cancer stem cells and induced pluripotent cells.

  13. Dental Stem Cell in Tooth Development and Advances of Adult Dental Stem Cell in Regenerative Therapies.

    Science.gov (United States)

    Tan, Jiali; Xu, Xin; Lin, Jiong; Fan, Li; Zheng, Yuting; Kuang, Wei

    2015-01-01

    Stem cell-based therapies are considered as a promising treatment for many clinical usage such as tooth regeneration, bone repairation, spinal cord injury, and so on. However, the ideal stem cell for stem cell-based therapy still remains to be elucidated. In the past decades, several types of stem cells have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs) and stem cells from apical papilla (SCAP), which may be a good source for stem cell-based therapy in certain disease, especially when they origin from neural crest is considered. In this review, the specific characteristics and advantages of the adult dental stem cell population will be summarized and the molecular mechanisms of the differentiation of dental stem cell during tooth development will be also discussed.

  14. Stem cell therapy: MRI guidance and monitoring.

    Science.gov (United States)

    Kraitchman, Dara L; Gilson, Wesley D; Lorenz, Christine H

    2008-02-01

    With the recent advances in magnetic resonance (MR) labeling of cellular therapeutics, it is natural that interventional MRI techniques for targeting would be developed. This review provides an overview of the current methods of stem cell labeling and the challenges that are created with respect to interventional MRI administration. In particular, stem cell therapies will require specialized, MR-compatible devices as well as integration of graphical user interfaces with pulse sequences designed for interactive, real-time delivery in many organs. Specific applications that are being developed will be reviewed as well as strategies for future translation to the clinical realm. (Copyright) 2008 Wiley-Liss, Inc.

  15. Epigenetics in cancer stem cells.

    Science.gov (United States)

    Toh, Tan Boon; Lim, Jhin Jieh; Chow, Edward Kai-Hua

    2017-02-01

    Compelling evidence have demonstrated that bulk tumors can arise from a unique subset of cells commonly termed "cancer stem cells" that has been proposed to be a strong driving force of tumorigenesis and a key mechanism of therapeutic resistance. Recent advances in epigenomics have illuminated key mechanisms by which epigenetic regulation contribute to cancer progression. In this review, we present a discussion of how deregulation of various epigenetic pathways can contribute to cancer initiation and tumorigenesis, particularly with respect to maintenance and survival of cancer stem cells. This information, together with several promising clinical and preclinical trials of epigenetic modulating drugs, offer new possibilities for targeting cancer stem cells as well as improving cancer therapy overall.

  16. Large Scale Production of Stem Cells and Their Derivatives

    Science.gov (United States)

    Zweigerdt, Robert

    Stem cells have been envisioned to become an unlimited cell source for regenerative medicine. Notably, the interest in stem cells lies beyond direct therapeutic applications. They might also provide a previously unavailable source of valuable human cell types for screening platforms, which might facilitate the development of more efficient and safer drugs. The heterogeneity of stem cell types as well as the numerous areas of application suggests that differential processes are mandatory for their in vitro culture. Many of the envisioned applications would require the production of a high number of stem cells and their derivatives in scalable, well-defined and potentially clinical compliant manner under current good manufacturing practice (cGMP). In this review we provide an overview on recent strategies to develop bioprocesses for the expansion, differentiation and enrichment of stem cells and their progenies, presenting examples for adult and embryonic stem cells alike.

  17. Multifaceted Roles of Connexin 43 in Stem Cell Niches.

    Science.gov (United States)

    Genet, Nafiisha; Bhatt, Neha; Bourdieu, Antonin; Hirschi, Karen K

    2018-01-01

    Considerable progress has been made in the field of stem cell research; nonetheless, the use of stem cells for regenerative medicine therapies, for either endogenous tissue repair or cellular grafts post injury, remains a challenge. To better understand how to maintain stem cell potential in vivo and promote differentiation ex vivo, it is fundamentally important to elucidate the interactions between stem cells and their surrounding partners within their distinct niches. Among the vast array of proteins depicted as mediators for cell-to-cell interactions, connexin-comprised gap junctions play pivotal roles in the regulation of stem cell fate both in vivo and in vitro. This review summarizes and illustrates the current knowledge regarding the multifaceted roles of Cx43, specifically, in various stem cell niches.

  18. Mismatch repair deficient hematopoietic stem cells are preleukemic stem cells.

    Directory of Open Access Journals (Sweden)

    Yulan Qing

    Full Text Available Whereas transformation events in hematopoietic malignancies may occur at different developmental stages, the initial mutation originates in hematopoietic stem cells (HSCs, creating a preleukemic stem cell (PLSC. Subsequent mutations at either stem cell or progenitor cell levels transform the PLSC into lymphoma/leukemia initiating cells (LIC. Thymic lymphomas have been thought to develop from developing thymocytes. T cell progenitors are generated from HSCs in the bone marrow (BM, but maturation and proliferation of T cells as well as T-lymphomagenesis depends on both regulatory mechanisms and microenvironment within the thymus. We studied PLSC linked to thymic lymphomas. In this study, we use MSH2-/- mice as a model to investigate the existence of PLSC and the evolution of PLSC to LIC. Following BM transplantation, we found that MSH2-/- BM cells from young mice are able to fully reconstitute multiple hematopoietic lineages of lethally irradiated wild-type recipients. However, all recipients developed thymic lymphomas within three and four months post transplantation. Transplantation of different fractions of BM cells or thymocytes from young health MSH2-/- mice showed that an HSC enriched fraction always reconstituted hematopoiesis followed by lymphoma development. In addition, lymphomas did not occur in thymectomized recipients of MSH2-/- BM. These results suggest that HSCs with DNA repair defects such as MSH2-/- are PLSCs because they retain hematopoietic function, but also carry an obligate lymphomagenic potential within their T-cell progeny that is dependent on the thymic microenvironment.

  19. Stem cells and regenerative medicine

    Czech Academy of Sciences Publication Activity Database

    Syková, Eva

    2005-01-01

    Roč. 3, - (2005), s. 45-46 ISSN 1214-021X. [Cells VI - Biological Days /18./. 24.10.2005-26.10.2005, České Budějovice] R&D Projects: GA MŠk(CZ) 1M0538 Institutional research plan: CEZ:AV0Z5039906 Keywords : stem cells Subject RIV: FH - Neurology

  20. Stem Cells in Regenerative Medicine

    Czech Academy of Sciences Publication Activity Database

    Syková, Eva; Forostyak, Serhiy

    2013-01-01

    Roč. 22, č. 2 (2013), s. 87-92 ISSN 0898-5901 R&D Projects: GA ČR(CZ) GAP304/11/0189; GA ČR(CZ) GBP304/12/G069 Institutional research plan: CEZ:AV0Z50390703 Institutional support: RVO:68378041 Keywords : cell therapy * stem cells * clinical study Subject RIV: FH - Neurology

  1. The spermatogonial stem cell niche

    NARCIS (Netherlands)

    de Rooij, Dirk G.

    2009-01-01

    Spermatogonial stem cells (SSCs; A(s) spermatogonia) and their direct descendants (A(pr) and A(al) spermatogonia) are preferentially located in those areas of the seminiferous tubules that border on the interstitial tissue. Fewer of these cells are present in tubule areas directly bordering on

  2. Methods in Molecular Biology: Germline Stem Cells | Center for Cancer Research

    Science.gov (United States)

    The protocols in Germline Stem Cells are intended to present selected genetic, molecular, and cellular techniques used in germline stem cell research. The book is divided into two parts. Part I covers germline stem cell identification and regulation in model organisms. Part II covers current techniques used in in vitro culture and applications of germline stem cells.

  3. Suspension culture of pluripotent stem cells: effect of shear on stem cell fate.

    Science.gov (United States)

    Keller, Kevin C; Rodrigues, Beatriz; zur Nieden, Nicole I

    2014-01-01

    Despite significant promise, the routine usage of suspension cell culture to manufacture stem cell-derived differentiated cells has progressed slowly. Suspension culture is an innovative way of either expanding or differentiating cells and sometimes both are combined into a single bioprocess. Its advantages over static 2D culturing include a homogeneous and controllable culture environment and producing a large quantity of cells in a fraction of time. This feature makes suspension cell culture ideal for use in stem cell research and eventually ideal in the large-scale production of differentiated cells for regenerative medicine. Because of their tremendous differentiation capacities and unlimited growth properties, pluripotent stem cells (PSCs) in particular are considered potential sources for future cell-replacement therapies. Currently, expansion of PSCs is accomplished in 2D, which only permits a limited amount of cell growth per culture flask before cells need to be passaged. However, before stem cells can be applied clinically, several aspects of their expansion, such as directed growth, but also differentiation, need to be better controlled. This review will summarize recent advantages in suspension culture of PSCs, while at the same time highlighting current challenges.

  4. Isolation and Culture of Postnatal Stem Cells from Deciduous Teeth

    OpenAIRE

    Olávez, Daniela; Facultad de Odontología Universidad de Los Andes; Salmen, Siham; Instituto de Inmunología Clínica, Universidad de Los Andes.; Padrón, Karla; Facultad de Odontología. Univerisdad de Los Andes.; Lobo, Carmine; Facultad de Odontología. Univerisdad de Los Andes.; Díaz, Nancy; Facultad de Odontología, Universidad de Los Andes.; Berrueta, Lisbeth; Doctora en Inmunología por Instituto Venezolano de Investigaciones Científicas (IVIC). Instituto de Inmunología Clínica, Facultad de Medicina, Universidad de Los Andes, Venezuela.; Solorzanio, Eduvigis; Facultad de Odontología, Universidad de Los Andes.

    2014-01-01

    Background: Currently, degenerative diseases represent a public health problem; therefore, the development and implementation of strategies to fully or partially recover of damaged tissues has a special interest in the biomedical field. Therapeutic strategies based on mesenchymal stem cells transplantation from dental pulp have been proposed as an alternative. Purpose: To develop a mesenchymal stem cells culture isolated from dental pulp of deciduous teeth. Methods: The mesenchymal stem cells...

  5. Multifaceted Interpretation of Colon Cancer Stem Cells.

    Science.gov (United States)

    Hatano, Yuichiro; Fukuda, Shinya; Hisamatsu, Kenji; Hirata, Akihiro; Hara, Akira; Tomita, Hiroyuki

    2017-07-05

    Colon cancer is one of the leading causes of cancer-related deaths worldwide, despite recent advances in clinical oncology. Accumulating evidence sheds light on the existence of cancer stem cells and their role in conferring therapeutic resistance. Cancer stem cells are a minor fraction of cancer cells, which enable tumor heterogeneity and initiate tumor formation. In addition, these cells are resistant to various cytotoxic factors. Therefore, elimination of cancer stem cells is difficult but essential to cure the malignant foci completely. Herein, we review the recent evidence for intestinal stem cells and colon cancer stem cells, methods to detect the tumor-initiating cells, and clinical significance of cancer stem cell markers. We also describe the emerging problems of cancer stem cell theory, including bidirectional conversion and intertumoral heterogeneity of stem cell phenotype.

  6. Cancer stem cells, cancer cell plasticity and radiation therapy.

    Science.gov (United States)

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Cord Blood-Derived Hematopoietic Stem/Progenitor Cells: Current Challenges in Engraftment, Infection, and Ex Vivo Expansion

    Directory of Open Access Journals (Sweden)

    Katsuhiro Kita

    2011-01-01

    Full Text Available Umbilical cord blood has served as an alternative to bone marrow for hematopoietic transplantation since the late 1980s. Numerous clinical studies have proven the efficacy of umbilical cord blood. Moreover, the possible immaturity of cells in umbilical cord blood gives more options to recipients with HLA mismatch and allows for the use of umbilical cord blood from unrelated donors. However, morbidity and mortality rates associated with hematopoietic malignancies still remain relatively high, even after cord blood transplantation. Infections and relapse are the major causes of death after cord blood transplantation in patients with hematopoietic diseases. Recently, new strategies have been introduced to improve these major problems. Establishing better protocols for simple isolation of primitive cells and ex vivo expansion will also be very important. In this short review, we discuss several recent promising findings related to the technical improvement of cord blood transplantation.

  8. Turnover of circulating hematopoietic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Dorie, M J; Maloney, M A; Patt, H M

    1979-10-01

    Short-term parabiosis of male and female CBA/CaJ mice was used to investigate the turnover of circulating hematopoietic stem cells. The change and subsequent disappearance of donor stem cells were monitored by spleen colony assay and chromosome analysis of individual colonies. The results revealed an exponential disappearance of pluripotent stem cells from blood with a characteristic half time of 1.7 h. Blood-borne stem cells were shown to be equilibrated with a subpopulation of marrow stem cells exhibiting a disappearance half time of 9.5 h. Splenectomy did not change the apparent rate of stem cell removal from the blood.

  9. Stem cell biology and cell transplantation therapy in the retina.

    Science.gov (United States)

    Osakada, Fumitaka; Hirami, Yasuhiko; Takahashi, Masayo

    2010-01-01

    Embryonic stem (ES) cells, which are derived from the inner cell mass of mammalian blastocyst stage embryos, have the ability to differentiate into any cell type in the body and to grow indefinitely while maintaining pluripotency. During development, cells undergo progressive and irreversible differentiation into specialized adult cell types. Remarkably, in spite of this restriction in potential, adult somatic cells can be reprogrammed and returned to the naive state of pluripotency found in the early embryo simply by forcing expression of a defined set of transcription factors. These induced pluripotent stem (iPS) cells are molecularly and functionally equivalent to ES cells and provide powerful in vitro models for development, disease, and drug screening, as well as material for cell replacement therapy. Since functional impairment results from cell loss in most central nervous system (CNS) diseases, recovery of lost cells is an important treatment strategy. Although adult neurogenesis occurs in restricted regions, the CNS has poor potential for regeneration to compensate for cell loss. Thus, cell transplantation into damaged or diseased CNS tissues is a promising approach to treating various neurodegenerative disorders. Transplantation of photoreceptors or retinal pigment epithelium cells derived from human ES cells can restore some visual function. Patient-specific iPS cells may lead to customized cell therapy. However, regeneration of retinal function will require a detailed understanding of eye development, visual system circuitry, and retinal degeneration pathology. Here, we review the current progress in retinal regeneration, focusing on the therapeutic potential of pluripotent stem cells.

  10. 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.

  11. Stem Cell Banking for Regenerative and Personalized Medicine

    Science.gov (United States)

    Harris, David T.

    2014-01-01

    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. PMID:28548060

  12. Development of New Technologies for Stem Cell Research

    Directory of Open Access Journals (Sweden)

    Xibo Ma

    2012-01-01

    Full Text Available Since the 1960s, the stem cells have been extensively studied including embryonic stem cells, neural stem cells, bone marrow hematopoietic stem cells, and mesenchymal stem cells. In the recent years, several stem cells have been initially used in the treatment of diseases, such as in bone marrow transplant. At the same time, isolation and culture experimental technologies for stem cell research have been widely developed in recent years. In addition, molecular imaging technologies including optical molecular imaging, positron emission tomography, single-photon emission computed tomography, and computed tomography have been developed rapidly in recent the 10 years and have also been used in the research on disease mechanism and evaluation of treatment of disease related with stem cells. This paper will focus on recent typical isolation, culture, and observation techniques of stem cells followed by a concise introduction. Finally, the current challenges and the future applications of the new technologies in stem cells are given according to the understanding of the authors, and the paper is then concluded.

  13. Advances in Bone Marrow Stem Cell Therapy for Retinal Dysfunction

    Science.gov (United States)

    Park, Susanna S.; Moisseiev, Elad; Bauer, Gerhard; Anderson, Johnathon D.; Grant, Maria B.; Zam, Azhar; Zawadzki, Robert J.; Werner, John S.; Nolta, Jan A.

    2016-01-01

    The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue. Since the paracrine trophic effects can have regenerative effects on multiple cells in the retina, the use of this cell therapy is not limited to a particular retinal condition. Autologous bone marrow-derived stem cells are being explored in early clinical trials as therapy for various retinal conditions. These bone marrow stem cells include mesenchymal stem cells, mononuclear cells and CD34+ cells. Autologous therapy requires no systemic immunosuppression or donor matching. Intravitreal delivery of CD34+ cells and mononuclear cells appears to be tolerated and is being explored since some of these cells can home into the damaged retina after intravitreal administration. The safety of intravitreal delivery of mesenchymal stem cells has not been well established. This review provides an update of the current evidence in support of the use of bone marrow stem cells as treatment for retinal dysfunction. The potential limitations and complications of using certain forms of bone marrow stem cells as therapy are discussed. Future directions of research include methods to optimize the therapeutic potential of these stem cells, non-cellular alternatives using extracellular vesicles, and in vivo high-resolution retinal imaging to detect cellular changes in the retina following cell therapy. PMID:27784628

  14. Organizing Organoids: Stem Cells Branch Out.

    Science.gov (United States)

    Davies, Jamie A

    2017-12-07

    In this issue of Cell Stem Cell, Taguchi and Nishinakamura (2017) describe a carefully optimized method for making a branch-competent ureteric bud, a tissue fundamental to kidney development, from mouse embryonic stem cells and human induced pluripotent stem cells. The work illuminates embryology and has important implications for making more realistic kidney organoids. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. nduced pluripotent stem cells and cell therapy

    Directory of Open Access Journals (Sweden)

    Banu İskender

    2013-12-01

    Full Text Available Human embryonic stem cells are derived from the inner cell mass of a blastocyst-stage embryo. They hold a huge promise for cell therapy with their self-renewing ability and pluripotency, which is known as the potential to differentiate into all cell types originating from three embryonic germ layers. However, their unique pluripotent feature could not be utilised for therapeutic purposes due to the ethical and legal problems during derivation. Recently, it was shown that the cells from adult tissues could be reverted into embryonic state, thereby restoring their pluripotent feature. This has strenghtened the possiblity of directed differentition of the reprogrammed somatic cells into the desired cell types in vitro and their use in regenerative medicine. Although these cells were termed as induced pluripotent cells, the mechanism of pluripotency has yet to be understood. Still, induced pluripotent stem cell technology is considered to be significant by proposing novel approaches in disease modelling, drug screening and cell therapy. Besides their self-renewing ability and their potential to differentiate into all cell types in a human body, they arouse a great interest in scientific world by being far from the ethical concerns regarding their embryonic counterparts and their unique feature of being patient-specific in prospective cell therapies. In this review, induced pluripotent stem cell technology and its role in cell-based therapies from past to present will be discussed. J Clin Exp Invest 2013; 4 (4: 550-561

  16. Characterization and comparison of osteoblasts derived from mouse embryonic stem cells and induced pluripotent stem cells

    NARCIS (Netherlands)

    Ma, Ming San; Kannan, Vishnu; de Vries, Anneriek E; Czepiel, Marcin; Wesseling, Evelyn; Balasubramaniyan, Veerakumar; Kuijer, Roelof; Vissink, Arjan; Copray, Sjef; Raghoebar, Gerry

    New developments in stem cell biology offer alternatives for the reconstruction of critical-sized bone defects. One of these developments is the use of induced pluripotent stem (iPS) cells. These stem cells are similar to embryonic stem (ES) cells, but can be generated from adult somatic cells and

  17. Electrical Guidance of Human Stem Cells in the Rat Brain

    Directory of Open Access Journals (Sweden)

    Jun-Feng Feng

    2017-07-01

    Full Text Available Limited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies.

  18. Systems Biology and Stem Cell Pluripotency

    DEFF Research Database (Denmark)

    Mashayekhi, Kaveh; Hall, Vanessa Jane; Freude, Kristine

    2016-01-01

    Recent breakthroughs in stem cell biology have accelerated research in the area of regenerative medicine. Over the past years, it has become possible to derive patient-specific stem cells which can be used to generate different cell populations for potential cell therapy. Systems biological...... modeling of stem cell pluripotency and differentiation have largely been based on prior knowledge of signaling pathways, gene regulatory networks, and epigenetic factors. However, there is a great need to extend the complexity of the modeling and to integrate different types of data, which would further...... improve systems biology and its uses in the field. In this chapter, we first give a general background on stem cell biology and regenerative medicine. Stem cell potency is introduced together with the hierarchy of stem cells ranging from pluripotent embryonic stem cells (ESCs) and induced pluripotent stem...

  19. Atrial Fibrillation in Hematologic Malignancies, Especially After Autologous Hematopoietic Stem Cell Transplantation: Review of Risk Factors, Current Management, and Future Directions.

    Science.gov (United States)

    Mathur, Pankaj; Paydak, Hakan; Thanendrarajan, Sharmilan; van Rhee, Frits

    2016-02-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with significant morbidity and mortality worldwide. In addition to well-established risk factors, cancer has been increasingly associated with the development of AF. Its increased occurrence in those with hematologic malignancies has been attributed to chemotherapeutic agents and autologous hematopoietic stem cell transplantation (AHSCT). Recently, a few studies have attempted to define the etiopathogenesis of AF in hematologic malignancies. The management of AF in these patients is challenging because of the concurrent complicating factors, such as thrombocytopenia, orthostatic hypotension, and cardiac amyloidosis. More studies are needed to define the management of AF, especially rate versus rhythm control and anticoagulation. Arrhythmias, in particular, AF, have been associated with an increased length of stay, increased intensive care unit admissions, and greater cardiovascular mortality. In the present review, we describe AF in patients with hematologic malignancies, the risk factors, especially after AHSCT, and the current management of AF. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Renal stem cells: fact or science fiction?

    Science.gov (United States)

    McCampbell, Kristen K; Wingert, Rebecca A

    2012-06-01

    The kidney is widely regarded as an organ without regenerative abilities. However, in recent years this dogma has been challenged on the basis of observations of kidney recovery following acute injury, and the identification of renal populations that demonstrate stem cell characteristics in various species. It is currently speculated that the human kidney can regenerate in some contexts, but the mechanisms of renal regeneration remain poorly understood. Numerous controversies surround the potency, behaviour and origins of the cell types that are proposed to perform kidney regeneration. The present review explores the current understanding of renal stem cells and kidney regeneration events, and examines the future challenges in using these insights to create new clinical treatments for kidney disease.

  1. Stem cells: a plant biology perspective

    NARCIS (Netherlands)

    Scheres, B.J.G.

    2005-01-01

    A recent meeting at the Juan March Foundation in Madrid, Spain brought together plant biologists to discuss the characteristics of plant stem cells that are unique and those that are shared by stem cells from the animal kingdom

  2. FDA Warns About Stem Cell Therapies

    Science.gov (United States)

    ... Home For Consumers Consumer Updates FDA Warns About Stem Cell Therapies Share Tweet Linkedin Pin it More sharing ... see the boxed section below for more advice. Stem Cell Uses and FDA Regulation The FDA has the ...

  3. Stem Cell Transplant Patients and Fungal Infections

    Science.gov (United States)

    ... Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch Stem Cell Transplant Patients and Fungal Infections Recommend on Facebook ... Mold . Top of Page Preventing fungal infections in stem cell transplant patients Fungi are difficult to avoid because ...

  4. Blood-Forming Stem Cell Transplants

    Science.gov (United States)

    ... to Ask about Your Treatment Research Blood-Forming Stem Cell Transplants On This Page What are bone marrow ... Considering becoming a bone marrow or a blood stem cell donor? View this video on YouTube. Follow a ...

  5. Molecular mechanisms of adult stem cell aging

    National Research Council Canada - National Science Library

    Rudolph, K. Lenhard

    2010-01-01

    "There is growing evidence that adult stem cells age. This process can result in alterations in the number and function of stem cells, leading to distinct phenotypic outcomes in different organ systems...

  6. Innovative diagnostics and treatment nanorobotics and stem cells

    CERN Document Server

    Jadczyk, Tomasz; Mishra, Sachin; Jędrzejek, Marek; Bołoz, Marta; Padmanabhan, Parasuraman; Wojakowski, Wojciech; Stárek, Zdeněk; Martel, Sylvain; Gulyás, Balázs

    2017-01-01

    This book focuses on nanorobotic agents and stem cells for biomedical applications.It is intended for researchers and clinicians interested in innovative diagnostic and therapeutic strategies based on nanorobots and stem cells.It presents current advances in the field of molecular machines, which could be applied to generate novel therapeutic-diagnostic systems.

  7. CIRM Alpha Stem Cell Clinics: Collaboratively Addressing Regenerative Medicine Challenges.

    Science.gov (United States)

    Jamieson, Catriona H M; Millan, Maria T; Creasey, Abla A; Lomax, Geoff; Donohoe, Mary E; Walters, Mark C; Abedi, Mehrdad; Bota, Daniela A; Zaia, John A; Adams, John S

    2018-06-01

    The California Institute for Regenerative Medicine (CIRM) Alpha Stem Cell Clinic (ASCC) Network was launched in 2015 to address a compelling unmet medical need for rigorous, FDA-regulated, stem cell-related clinical trials for patients with challenging, incurable diseases. Here, we describe our multi-center experiences addressing current and future challenges. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Autologous stem cells in neurology: is there a future?

    NARCIS (Netherlands)

    de Munter, J.P.J.M.; Wolters, E.C.

    2013-01-01

    Stem cells seem very promising in the treatment of degenerative neurological diseases for which there are currently no or limited therapeutic strategies. However, their clinical application meets many regulatory hurdles. This article gives an overview of stem cells, their potential healing

  9. Adipose-Derived Stem Cells

    NARCIS (Netherlands)

    Gathier, WA; Türktas, Z; Duckers, HJ

    2015-01-01

    Until recently bone marrow was perceived to be the only significant reservoir of stem cells in the body. However, it is now recognized that there are other and perhaps even more abundant sources, which include adipose tissue. Subcutaneous fat is readily available in most patients, and can easily be

  10. Stem cell therapy for severe autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Marmont Alberto M.

    2002-01-01

    Full Text Available Intense immunosuppresion followed by alogenic or autogenic hematopoietic stem cell transplantation is a relatively recent procedure which was used for the first time in severe, refractory cases of systemic lupus erythematosus. Currently three agressive procedures are used in the treatment of autoimmune diseases: high dose chemotherapy without stem cell rescue, intense immunosuppression with subsequent infusion of the alogenic hematopoietic stem cell transplantation combined with or without the selection of CD34+ cells, and the autogenic hematopoietic stem cell transplantation. Proof of the graft-versus-leukemia effect observed define SCT as a form of immunotherapy, with additional evidence of an similar Graft-vs-Autoimmunity effect which is suggestive of a cure for autoimmune diseases in this type of therapy. The use of alogenic SCT improved due to its safety compared to autogenic transplantations. In this report, data of multiply sclerosis and systemic lupus erythematosus are reported, with the conclusion that Immunoablation followed by SCT is clearly indicated in such cases.

  11. Pluripotent Stem Cells for Schwann Cell Engineering

    NARCIS (Netherlands)

    Ma, Ming-San; Boddeke, Erik; Copray, Sjef

    Tissue engineering of Schwann cells (SCs) can serve a number of purposes, such as in vitro SC-related disease modeling, treatment of peripheral nerve diseases or peripheral nerve injury, and, potentially, treatment of CNS diseases. SCs can be generated from autologous stem cells in vitro by

  12. [Genetic regulation of plant shoot stem cells].

    Science.gov (United States)

    Al'bert, E V; Ezhova, T A

    2013-02-01

    This article describes the main features of plant stem cells and summarizes the results of studies of the genetic control of stem cell maintenance in the apical meristem of the shoot. It is demonstrated that the WUS-CLV gene system plays a key role in the maintenance of shoot apical stem cells and the formation of adventitious buds and somatic embryos. Unconventional concepts of plant stem cells are considered.

  13. College Students' Conceptions of Stem Cells, Stem Cell Research, and Cloning

    Science.gov (United States)

    Concannon, James P.; Siegel, Marcelle A.; Halverson, Kristy; Freyermuth, Sharyn

    2010-01-01

    In this study, we examined 96 undergraduate non-science majors' conceptions of stem cells, stem cell research, and cloning. This study was performed at a large, Midwest, research extensive university. Participants in the study were asked to answer 23 questions relating to stem cells, stem cell research, and cloning in an on-line assessment before…

  14. Nine Things to Know About Stem Cell Treatments

    Science.gov (United States)

    ... Search Toggle Nav Nine Things To Know About Stem Cell Treatments Home > Stem Cells and Medicine > Nine Things ... Know About Stem Cell Treatments Many clinics offering stem cell treatments make claims that are not supported by ...

  15. Dental pulp stem cells in regenerative dentistry.

    Science.gov (United States)

    Casagrande, Luciano; Cordeiro, Mabel M; Nör, Silvia A; Nör, Jacques E

    2011-01-01

    Stem cells constitute the source of differentiated cells for the generation of tissues during development, and for regeneration of tissues that are diseased or injured postnatally. In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that span from Alzheimer's disease to cardiac ischemia to bone or tooth loss. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental pulp is considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that dental pulp stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. The dental pulp stem cells are highly proliferative. This characteristic facilitates ex vivo expansion and enhances the translational potential of these cells. Notably, the dental pulp is arguably the most accessible source of postnatal stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental pulp an attractive source of mesenchymal stem cells for tissue regeneration. This review discusses fundamental concepts of stem cell biology and tissue engineering within the context of regenerative dentistry.

  16. Methods for Stem Cell Production and Therapy

    Science.gov (United States)

    Valluri, Jagan V. (Inventor); Claudio, Pier Paolo (Inventor)

    2015-01-01

    The present invention relates to methods for rapidly expanding a stem cell population with or without culture supplements in simulated microgravity conditions. The present invention relates to methods for rapidly increasing the life span of stem cell populations without culture supplements in simulated microgravity conditions. The present invention also relates to methods for increasing the sensitivity of cancer stem cells to chemotherapeutic agents by culturing the cancer stem cells under microgravity conditions and in the presence of omega-3 fatty acids. The methods of the present invention can also be used to proliferate cancer cells by culturing them in the presence of omega-3 fatty acids. The present invention also relates to methods for testing the sensitivity of cancer cells and cancer stem cells to chemotherapeutic agents by culturing the cancer cells and cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce tissue for use in transplantation by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors to promote differentiation of cancer stem cells under microgravity conditions.

  17. Cancer stem cells and differentiation therapy.

    Science.gov (United States)

    Jin, Xiong; Jin, Xun; Kim, Hyunggee

    2017-10-01

    Cancer stem cells can generate tumors from only a small number of cells, whereas differentiated cancer cells cannot. The prominent feature of cancer stem cells is its ability to self-renew and differentiate into multiple types of cancer cells. Cancer stem cells have several distinct tumorigenic abilities, including stem cell signal transduction, tumorigenicity, metastasis, and resistance to anticancer drugs, which are regulated by genetic or epigenetic changes. Like normal adult stem cells involved in various developmental processes and tissue homeostasis, cancer stem cells maintain their self-renewal capacity by activating multiple stem cell signaling pathways and inhibiting differentiation signaling pathways during cancer initiation and progression. Recently, many studies have focused on targeting cancer stem cells to eradicate malignancies by regulating stem cell signaling pathways, and products of some of these strategies are in preclinical and clinical trials. In this review, we describe the crucial features of cancer stem cells related to tumor relapse and drug resistance, as well as the new therapeutic strategy to target cancer stem cells named "differentiation therapy."

  18. [Embryonic stem cells. Future perspectives].

    Science.gov (United States)

    Groebner, M; David, R; Franz, W M

    2006-05-01

    Embryonic stem cells (ES cells) are able to differentiate into any cell type, and therefore represent an excellent source for cellular replacement therapies in the case of widespread diseases, for example heart failure, diabetes, Parkinson's disease and spinal cord injury. A major prerequisite for their efficient and safe clinical application is the availability of pure populations for direct cell transplantation or tissue engineering as well as the immunological compatibility of the transplanted cells. The expression of human surface markers under the control of cell type specific promoters represents a promising approach for the selection of cardiomyocytes and other cell types for therapeutic applications. The first human clinical trial using ES cells will start in the United States this year.

  19. Nuclear Mechanics and Stem Cell Differentiation.

    Science.gov (United States)

    Mao, Xinjian; Gavara, Nuria; Song, Guanbin

    2015-12-01

    Stem cells are characterized by their self-renewal and multi-lineage differentiation potential. Stem cell differentiation is a prerequisite for the application of stem cells in regenerative medicine and clinical therapy. In addition to chemical stimulation, mechanical cues play a significant role in regulating stem cell differentiation. The integrity of mechanical sensors is necessary for the ability of cells to respond to mechanical signals. The nucleus, the largest and stiffest cellular organelle, interacts with the cytoskeleton as a key mediator of cell mechanics. Nuclear mechanics are involved in the complicated interactions of lamins, chromatin and nucleoskeleton-related proteins. Thus, stem cell differentiation is intimately associated with nuclear mechanics due to its indispensable role in mechanotransduction and mechanical response. This paper reviews several main contributions of nuclear mechanics, highlights the hallmarks of the nuclear mechanics of stem cells, and provides insight into the relationship between nuclear mechanics and stem cell differentiation, which may guide clinical applications in the future.

  20. Some applications of nanotechnologies in stem cells research

    International Nuclear Information System (INIS)

    Belicchi, M.; Cancedda, R.; Cedola, A.; Fiori, F.; Gavina, M.; Giuliani, A.; Komlev, V.S.; Lagomarsino, S.; Mastrogiacomo, M.; Renghini, C.; Rustichelli, F.

    2009-01-01

    Stem cell based tissue engineering therapies involve the administration of ex vivo manipulated stem cell populations with the purpose of repairing and regenerating damaged or diseased tissue. Currently available methods of monitoring transplanted cells are quite limited. To monitor the outcomes of stem cell therapy longitudinally requires the development of non-destructive strategies that are capable of identifying the location, magnitude, and duration of cellular survival and fate. The recent development of imaging techniques offers great potential to address these critical issues by non-invasively tracking the fate of the transplanted cells. This review offers a focused presentation of some examples of the use of imaging techniques connected to the nanotechnological world in research areas related to stem cells. In particular investigations will be considered concerning tissue-engineered bone, treatment of intervertebral disc degeneration, treatment by human stem cells of muscular dystrophy of Duchenne in small animal models and the repair of spinal cord injuries.

  1. Stem Cell Extracellular Vesicles: Extended Messages of Regeneration

    Science.gov (United States)

    Riazifar, Milad; Pone, Egest J.; Lötvall, Jan; Zhao, Weian

    2017-01-01

    Stem cells are critical to maintaining steady-state organ homeostasis and regenerating injured tissues. Recent intriguing reports implicate extracellular vesicles (EVs) as carriers for the distribution of morphogens and growth and differentiation factors from tissue parenchymal cells to stem cells, and conversely, stem cell–derived EVs carrying certain proteins and nucleic acids can support healing of injured tissues. We describe approaches to make use of engineered EVs as technology platforms in therapeutics and diagnostics in the context of stem cells. For some regenerative therapies, natural and engineered EVs from stem cells may be superior to single-molecule drugs, biologics, whole cells, and synthetic liposome or nanoparticle formulations because of the ease of bioengineering with multiple factors while retaining superior biocompatibility and biostability and posing fewer risks for abnormal differentiation or neoplastic transformation. Finally, we provide an overview of current challenges and future directions of EVs as potential therapeutic alternatives to cells for clinical applications. PMID:27814025

  2. Some applications of nanotechnologies in stem cells research

    Energy Technology Data Exchange (ETDEWEB)

    Belicchi, M. [Fondazione IRCCS Ospedale Policlinico di Milano, Via Francesco Sforza, Milano 20122 (Italy); Cancedda, R. [Istituto Nazionale per la Ricerca sul Cancro and Dipartimento di Oncologia Biologia e Genetica - Universita di Genova, Largo R. Benzi 10, Genova 16132 (Italy); Cedola, A. [Istituto di Fotonica e Nanotecnologie - CNR, Via Cinto Romano 42, Roma 00156 (Italy); Fiori, F. [Dipartimento S.A.I.F.E.T. Sezione di Scienze Fisiche - Universita' Politecnica delle Marche, Via Brecce Bianche, Ancona 60131 (Italy); INBB - Istituto Nazionale Biostrutture e Biosistemi (Italy); CNISM - Matec (Ancona) (Italy); Gavina, M. [Fondazione IRCCS Ospedale Policlinico di Milano, Via Francesco Sforza, Milano 20122 (Italy); Giuliani, A. [Dipartimento S.A.I.F.E.T. Sezione di Scienze Fisiche - Universita' Politecnica delle Marche, Via Brecce Bianche, Ancona 60131 (Italy); CNISM - Matec (Ancona) (Italy); Komlev, V.S. [Dipartimento S.A.I.F.E.T. Sezione di Scienze Fisiche - Universita' Politecnica delle Marche, Via Brecce Bianche, Ancona 60131 (Italy); Institute for Physical Chemistry of Ceramics, Russian Academy of Sciences, Ozernaya 48, 119361 Moscow (Russian Federation); Lagomarsino, S. [Istituto di Fotonica e Nanotecnologie - CNR, Via Cinto Romano 42, Roma 00156 (Italy); Mastrogiacomo, M. [Istituto Nazionale per la Ricerca sul Cancro and Dipartimento di Oncologia Biologia e Genetica - Universita di Genova, Largo R. Benzi 10, Genova 16132 (Italy); Renghini, C. [Dipartimento S.A.I.F.E.T. Sezione di Scienze Fisiche - Universita' Politecnica delle Marche, Via Brecce Bianche, Ancona 60131 (Italy); INBB - Istituto Nazionale Biostrutture e Biosistemi (Italy); CNISM - Matec (Ancona) (Italy); Rustichelli, F., E-mail: f.rustichelli@univpm.i [Dipartimento S.A.I.F.E.T. Sezione di Scienze Fisiche - Universita' Politecnica delle Marche, Via Brecce Bianche, Ancona 60131 (Italy); INBB - Istituto Nazionale Biostrutture e Biosistemi (Italy); CNISM - Matec (Ancona) (Italy)

    2009-12-15

    Stem cell based tissue engineering therapies involve the administration of ex vivo manipulated stem cell populations with the purpose of repairing and regenerating damaged or diseased tissue. Currently available methods of monitoring transplanted cells are quite limited. To monitor the outcomes of stem cell therapy longitudinally requires the development of non-destructive strategies that are capable of identifying the location, magnitude, and duration of cellular survival and fate. The recent development of imaging techniques offers great potential to address these critical issues by non-invasively tracking the fate of the transplanted cells. This review offers a focused presentation of some examples of the use of imaging techniques connected to the nanotechnological world in research areas related to stem cells. In particular investigations will be considered concerning tissue-engineered bone, treatment of intervertebral disc degeneration, treatment by human stem cells of muscular dystrophy of Duchenne in small animal models and the repair of spinal cord injuries.

  3. Viscoelastic and dynamic properties of embryonic stem cells

    DEFF Research Database (Denmark)

    Ritter, Christine

    Stem cells are often referred to as the ‘holy grail’ of regenerative medicine, because they possessthe ability to develop into any cell type. The use of stem cells within medicine is currently limited bythe effectivity of differentiation and cell reprogramming protocols, making it therefore...... imperative tounderstand stem cells’ differentiation mechanisms better. Studies have shown that mechanical cuescan have an influence on stem cell fate decision. However, in order to understand the reaction of stemcells to mechanical input, one should first investigate and understand the mechanical properties...... ofthe cells themselves. In this thesis, the viscoelastic properties of mouse embryonic stem cells primedeither toward the epiblast (Epi) or the primitive endoderm (PrE) lineage were investigated.Optical tweezers were used to measure the fluctuations of endogenous lipid granules and therebydraw...

  4. Stem Cell Technology in Cardiac Regeneration: A Pluripotent Stem Cell Promise.

    Science.gov (United States)

    Duelen, Robin; Sampaolesi, Maurilio

    2017-02-01

    Despite advances in cardiovascular biology and medical therapy, heart disorders are the leading cause of death worldwide. Cell-based regenerative therapies become a promising treatment for patients affected by heart failure, but also underline the need for reproducible results in preclinical and clinical studies for safety and efficacy. Enthusiasm has been tempered by poor engraftment, survival and differentiation of the injected adult stem cells. The crucial challenge is identification and selection of the most suitable stem cell type for cardiac regenerative medicine. Human pluripotent stem cells (PSCs) have emerged as attractive cell source to obtain cardiomyocytes (CMs), with potential applications, including drug discovery and toxicity screening, disease modelling and innovative cell therapies. Lessons from embryology offered important insights into the development of stem cell-derived CMs. However, the generation of a CM population, uniform in cardiac subtype, adult maturation and functional properties, is highly recommended. Moreover, hurdles regarding tumorigenesis, graft cell death, immune rejection and arrhythmogenesis need to be overcome in clinical practice. Here we highlight the recent progression in PSC technologies for the regeneration of injured heart. We review novel strategies that might overcome current obstacles in heart regenerative medicine, aiming at improving cell survival and functional integration after cell transplantation. Copyright © 2017. Published by Elsevier B.V.

  5. Stem Cell Technology in Cardiac Regeneration: A Pluripotent Stem Cell Promise

    Directory of Open Access Journals (Sweden)

    Robin Duelen

    2017-02-01

    Full Text Available Despite advances in cardiovascular biology and medical therapy, heart disorders are the leading cause of death worldwide. Cell-based regenerative therapies become a promising treatment for patients affected by heart failure, but also underline the need for reproducible results in preclinical and clinical studies for safety and efficacy. Enthusiasm has been tempered by poor engraftment, survival and differentiation of the injected adult stem cells. The crucial challenge is identification and selection of the most suitable stem cell type for cardiac regenerative medicine. Human pluripotent stem cells (PSCs have emerged as attractive cell source to obtain cardiomyocytes (CMs, with potential applications, including drug discovery and toxicity screening, disease modelling and innovative cell therapies. Lessons from embryology offered important insights into the development of stem cell-derived CMs. However, the generation of a CM population, uniform in cardiac subtype, adult maturation and functional properties, is highly recommended. Moreover, hurdles regarding tumorigenesis, graft cell death, immune rejection and arrhythmogenesis need to be overcome in clinical practice. Here we highlight the recent progression in PSC technologies for the regeneration of injured heart. We review novel strategies that might overcome current obstacles in heart regenerative medicine, aiming at improving cell survival and functional integration after cell transplantation.

  6. Ethical clinical translation of stem cell interventions for neurologic disease

    DEFF Research Database (Denmark)

    Cote, David J; Bredenoord, Annelien L; Smith, Timothy R

    2017-01-01

    The application of stem cell transplants in clinical practice has increased in frequency in recent years. Many of the stem cell transplants in neurologic diseases, including stroke, Parkinson disease, spinal cord injury, and demyelinating diseases, are unproven-they have not been tested...... in prospective, controlled clinical trials and have not become accepted therapies. Stem cell transplant procedures currently being carried out have therapeutic aims, but are frequently experimental and unregulated, and could potentially put patients at risk. In some cases, patients undergoing such operations...... are not included in a clinical trial, and do not provide genuinely informed consent. For these reasons and others, some current stem cell interventions for neurologic diseases are ethically dubious and could jeopardize progress in the field. We provide discussion points for the evaluation of new stem cell...

  7. Synovium-derived stem cells: a tissue-specific stem cell for cartilage engineering and regeneration.

    Science.gov (United States)

    Jones, Brendan A; Pei, Ming

    2012-08-01

    Articular cartilage is difficult to heal once injury or disease occurs. Autologous chondrocyte transplantation is a biological treatment with good prognosis, but donor site morbidity and limited cell source are disadvantages. Currently, mesenchymal stem cells (MSCs) are a promising approach for cartilage regeneration. Despite there being various sources, the best candidate for cartilage regeneration is the one with the greatest chondrogenic potential and the least hypertrophic differentiation. These properties are able to insure that the regenerated tissue is hyaline cartilage of high quality. This review article will summarize relevant literature to justify synovium-derived stem cells (SDSCs) as a tissue-specific stem cell for chondrogenesis by comparing synovium and cartilage with respect to anatomical location and functional structure, comparing the growth characterization and chondrogenic capacity of SDSCs and MSCs, evaluating the application of SDSCs in regenerative medicine and diseases, and discussing potential future directions.

  8. Recent advances in hematopoietic stem cell biology

    DEFF Research Database (Denmark)

    Bonde, Jesper; Hess, David A; Nolta, Jan A

    2004-01-01

    PURPOSE OF REVIEW: Exciting advances have been made in the field of hematopoietic stem cell biology during the past year. This review summarizes recent progress in the identification, culture, and in vivo tracking of hematopoietic stem cells. RECENT FINDINGS: The roles of Wnt and Notch proteins...... in regulating stem cell renewal in the microenvironment, and how these molecules can be exploited in ex vivo stem cell culture, are reviewed. The importance of identification of stem cells using functional as well as phenotypic markers is discussed. The novel field of nanotechnology is then discussed...... in the context of stem cell tracking in vivo. This review concludes with a section on the unexpected potential of bone marrow-derived stem cells to contribute to the repair of damaged tissues. The contribution of cell fusion to explain the latter phenomenon is discussed. SUMMARY: Because of exciting discoveries...

  9. Dormancy activation mechanism of oral cavity cancer stem cells.

    Science.gov (United States)

    Chen, Xiang; Li, Xin; Zhao, Baohong; Shang, Dehao; Zhong, Ming; Deng, Chunfu; Jia, Xinshan

    2015-07-01

    Radiotherapy and chemotherapy are targeted primarily at rapidly proliferating cancer cells and are unable to eliminate cancer stem cells in the G0 phase. Thus, these treatments cannot prevent the recurrence and metastasis of cancer. Understanding the mechanisms by which cancer stem cells are maintained in the dormant G0 phase, and how they become active is key to developing new cancer therapies. The current study found that the anti-cancer drug 5-fluorouracil, acting on the oral squamous cell carcinoma KB cell line, selectively killed proliferating cells while sparing cells in the G0 phase. Bisulfite sequencing PCR showed that demethylation of the Sox2 promoter led to the expression of Sox2. This then resulted in the transformation of cancer stem cells from the G0 phase to the division stage and suggested that the transformation of cancer stem cells from the G0 phase to the division stage is closely related to an epigenetic modification of the cell.

  10. Challenges for heart disease stem cell therapy

    Directory of Open Access Journals (Sweden)

    Hoover-Plow J

    2012-02-01

    Full Text Available Jane Hoover-Plow, Yanqing GongDepartments of Cardiovascular Medicine and Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USAAbstract: Cardiovascular diseases (CVDs are the leading cause of death worldwide. The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI is an important emerging therapeutic strategy. However, recent reviews of clinical trials of stem cell therapy for MI and ischemic heart disease recovery report that less than half of the trials found only small improvements in cardiac function. In clinical trials, bone marrow, peripheral blood, or umbilical cord blood cells were used as the source of stem cells delivered by intracoronary infusion. Some trials administered only a stem cell mobilizing agent that recruits endogenous sources of stem cells. Important challenges to improve the effectiveness of stem cell therapy for CVD include: (1 improved identification, recruitment, and expansion of autologous stem cells; (2 identification of mobilizing and homing agents that increase recruitment; and (3 development of strategies to improve stem cell survival and engraftment of both endogenous and exogenous sources of stem cells. This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress.Keywords: mobilization, expansion, homing, survival, engraftment

  11. Cancer Stem Cells in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J., E-mail: christiane.bruns@med.uni-muenchen.de [Department of Surgery, Ludwig Maximilian University of Munich, Klinikum Grosshadern, Marchioninistr. 15, D-81377, Munich (Germany)

    2010-08-19

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

  12. Cancer Stem Cells in Pancreatic Cancer

    Science.gov (United States)

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J.

    2010-01-01

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer. PMID:24281178

  13. Cancer Stem Cells in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Karl-Walter Jauch

    2010-08-01

    Full Text Available Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs. Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

  14. Combination cell therapy with mesenchymal stem cells and neural stem cells for brain stroke in rats.

    Science.gov (United States)

    Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

    2015-05-01

    Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

  15. Klotho, stem cells, and aging.

    Science.gov (United States)

    Bian, Ao; Neyra, Javier A; Zhan, Ming; Hu, Ming Chang

    2015-01-01

    Aging is an inevitable and progressive biological process involving dysfunction and eventually destruction of every tissue and organ. This process is driven by a tightly regulated and complex interplay between genetic and acquired factors. Klotho is an antiaging gene encoding a single-pass transmembrane protein, klotho, which serves as an aging suppressor through a wide variety of mechanisms, such as antioxidation, antisenescence, antiautophagy, and modulation of many signaling pathways, including insulin-like growth factor and Wnt. Klotho deficiency activates Wnt expression and activity contributing to senescence and depletion of stem cells, which consequently triggers tissue atrophy and fibrosis. In contrast, the klotho protein was shown to suppress Wnt-signaling transduction, and inhibit cell senescence and preserve stem cells. A better understanding of the potential effects of klotho on stem cells could offer novel insights into the cellular and molecular mechanisms of klotho deficiency-related aging and disease. The klotho protein may be a promising therapeutic agent for aging and aging-related disorders.

  16. Stem cells: progressions and applications in clinical medicine

    Directory of Open Access Journals (Sweden)

    Ali Hosseini Bereshneh

    2016-05-01

    of them in transferring gene into different cells. Today, this method have had considerable progress in the treatment of many disease. In this review study, some aspect of stem cells like types and characteristic, origin, derivation techniques, storage conditions and differentiation to target tissues, current clinical usage and their therapeutic capabilities will be discussed.

  17. Strategies for future histocompatible stem cell therapy

    DEFF Research Database (Denmark)

    Nehlin, Jan; Barington, Torben

    2009-01-01

    Stem cell therapy based on the safe and unlimited self-renewal of human pluripotent stem cells is envisioned for future use in tissue or organ replacement after injury or disease. A gradual decline of regenerative capacity has been documented among the adult stem cell population in some body organs...... during the aging process. Recent progress in human somatic cell nuclear transfer and inducible pluripotent stem cell technologies has shown that patient-derived nuclei or somatic cells can be reprogrammed in vitro to become pluripotent stem cells, from which the three germ layer lineages can be generated......, genetically identical to the recipient. Once differentiation protocols and culture conditions can be defined and optimized, patient-histocompatible pluripotent stem cells could be directed towards virtually every cell type in the human body. Harnessing this capability to enrich for given cells within...

  18. The Stem Cell Club: a model for unrelated stem cell donor recruitment.

    Science.gov (United States)

    Fingrut, Warren; Parmar, Simran; Cuperfain, Ari; Rikhraj, Kiran; Charman, Erin; Ptak, Emilie; Kahlon, Manjot; Graham, Alice; Luong, Susan; Wang, Yongjun George; Yu, Janice; Arora, Neha; Suppiah, Roopa; Li, Edward W; Lee, Anna; Welsh, Christopher; Benzaquen, Menachem; Thatcher, Alicia; Baharmand, Iman; Ladd, Aedan; Petraszko, Tanya; Allan, David; Messner, Hans

    2017-12-01

    Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non-Caucasian males ages 17 to 35 years represent only 8.8% of listed donors. The Stem Cell Club is a non-profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada. To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor-database. Of the recruited registrants, 58.3% were male; 60.3% of males self-reported as non-Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality. The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor-database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world. © 2017 AABB.

  19. Stem Cells, Science, and Public Reasoning

    Science.gov (United States)

    Hurlbut, J. Benjamin; Robert, Jason Scott

    2012-01-01

    These are interesting days in the scientific, social, and political debates about human embryonic stem cell research. Pluripotent stem cells--cells that can, in principle, give rise to the body's full range of cell types--were previously derivable only from human embryos that were destroyed in the process. Now, a variety of somatic cell types can…

  20. Epithelial cell polarity, stem cells and cancer

    DEFF Research Database (Denmark)

    Martin-Belmonte, Fernando; Perez-Moreno, Mirna

    2011-01-01

    , deregulation of adhesion and polarity proteins can cause misoriented cell divisions and increased self-renewal of adult epithelial stem cells. In this Review, we highlight some advances in the understanding of how loss of epithelial cell polarity contributes to tumorigenesis.......After years of extensive scientific discovery much has been learned about the networks that regulate epithelial homeostasis. Loss of expression or functional activity of cell adhesion and cell polarity proteins (including the PAR, crumbs (CRB) and scribble (SCRIB) complexes) is intricately related...

  1. Modelling Neurodegenerative Diseases Using Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane

    2016-01-01

    Neurodegenerative diseases are being modelled in-vitro using human patient-specific, induced pluripotent stem cells and transgenic embryonic stem cells to determine more about disease mechanisms, as well as to discover new treatments for patients. Current research in modelling Alzheimer’s disease......, frontotemporal dementia and Parkinson’s disease using pluripotent stem cells is described, along with the advent of gene-editing, which has been the complimentary tool for the field. Current methods used to model these diseases are predominantly dependent on 2D cell culture methods. Outcomes reveal that only...... that includes studying more complex 3D cell cultures, as well as accelerating aging of the neurons, may help to yield stronger phenotypes in the cultured cells. Thus, the use and application of pluripotent stem cells for modelling disease have already shown to be a powerful approach for discovering more about...

  2. The pluripotency of hair follicle stem cells.

    Science.gov (United States)

    Hoffman, Robert M

    2006-02-01

    The hair follicle bulge area is an abundant, easily accessible source of actively growing, pluripotent adult stem cells. Nestin, a protein marker for neural stem cells, is also expressed in follicle stem cells as well as their immediate differentiated progeny. The nestin-expressing hair follicle stem cells differentiated into neurons, glial cells, keratinocytes and smooth muscle cells in vitro. Hair-follicle stem cells were implanted into the gap region of a severed sciatic nerve. The hair follicle stem cells greatly enhanced the rate of nerve regeneration and the restoration of nerve function. The follicle stem cells transdifferentiated largely into Schwann cells which are known to support neuron regrowth. Function of the rejoined sciatic nerve was measured by contraction of the gastrocnemius muscle upon electrical stimulation. After severing the tibial nerve and subsequent transplantation of hair-follicle stem cells, the transplanted mice recovered the ability to walk normally. These results suggest that hair-follicle stem cells provide an important accessible, autologous source of adult stem cells for regenerative medicine.

  3. Stem Cell Therapies in Orthopaedic Trauma

    OpenAIRE

    Marcucio, Ralph S.; Nauth, Aaron; Giannoudis, Peter V.; Bahney, Chelsea; Piuzzi, Nicolas S.; Muschler, George; Miclau, Theodore

    2015-01-01

    Stem cells offer great promise to help understand the normal mechanisms of tissue renewal, regeneration, and repair, and also for development of cell-based therapies to treat patients after tissue injury. Most adult tissues contain stem cells and progenitor cells that contribute to homeostasis, remodeling and repair. Multiple stem and progenitor cell populations in bone are found in the marrow, the endosteum, and the periosteum. They contribute to the fracture healing process after injury and...

  4. When nano meets stem: the impact of nanotechnology in stem cell biology.

    Science.gov (United States)

    Kaur, Savneet; Singhal, Barkha

    2012-01-01

    Nanotechnology and biomedical treatments using stem cells are among the latest conduits of biotechnological research. Even more recently, scientists have begun finding ways to mate these two specialties of science. The advent of nanotechnology has paved the way for an explicit understanding of stem cell therapy in vivo and by recapitulation of such in vivo environments in the culture, this technology seems to accommodate a great potential in providing new vistas to stem cell research. Nanotechnology carries in its wake, the development of highly stable, efficient and specific gene delivery systems for both in vitro and in vivo genetic engineering of stem cells, use of nanoscale systems (such as microarrays) for investigation of gene expression in stem cells, creation of dynamic three-dimensional nano-environments for in vitro and in vivo maintenance and differentiation of stem cells and development of extremely sensitive in vivo detection systems to gain insights into the mechanisms of stem cell differentiation and apoptosis in different disease models. The present review presents an overview of the current applications and future prospects for the use of nanotechnology in stem cell biology. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  5. Legal implications of translational promises of unproven stem cell ...

    African Journals Online (AJOL)

    2015-08-02

    Aug 2, 2015 ... multipotent stem cells are haematopoietic stem cells (HSCs), which give rise ... include diseases such as arthritis, heart attacks, multiple sclerosis, diabetes ... regard to autologous stem cell therapy, where a patient's own stem.

  6. Stem cell factor supports migration in canine mesenchymal stem cells.

    Science.gov (United States)

    Enciso, Nathaly; Ostronoff, Luciana L K; Mejías, Guillermo; León, Leticia G; Fermín, María Luisa; Merino, Elena; Fragio, Cristina; Avedillo, Luis; Tejero, Concepción

    2018-03-01

    Adult Mesenchymal Stem Cells (MSC) are cells that can be defined as multipotent cells able to differentiate into diverse lineages, under appropriate conditions. These cells have been widely used in regenerative medicine, both in preclinical and clinical settings. Initially discovered in bone marrow, MSC can now be isolated from a wide spectrum of adult and foetal tissues. Studies to evaluate the therapeutic potential of these cells are based on their ability to arrive to damaged tissues. In this paper we have done a comparative study analyzing proliferation, surface markers and OCT4, SOX9, RUNX2, PPARG genes expression in MSC cells from Bone marrow (BMMSC) and Adipose tissue (ASC). We also analyzed the role of Stem Cell Factor (SCF) on MSC proliferation and on ASCs metalloproteinases MMP-2, MMP-9 secretion. Healthy dogs were used as BMMSC donors, and ASC were collected from omentum during elective ovariohysterectomy surgery. Both cell types were cultured in IMDM medium with or without SCF, 10% Dog Serum (DS), and incubated at 38 °C with 5% CO2. Growth of BMMSCs and ASCs was exponential until 25-30 days. Flow citometry of MSCs revealed positive results for CD90 and negative for CD34, CD45 and MCH-II. Genes were evaluated by RT-PCR and metalloproteinases by zymografy. Our findings indicate morphological and immunological similarities as well as expression of genes from both origins on analyzed cells. Furthermore, SCF did not affect proliferation of MSCs, however it up-regulated MMP-2 and MMP-9 secretion in ASCs. These results suggest that metalloproteinases are possibly essential molecules pivoting migration.

  7. Redox regulation of plant stem cell fate.

    Science.gov (United States)

    Zeng, Jian; Dong, Zhicheng; Wu, Haijun; Tian, Zhaoxia; Zhao, Zhong

    2017-10-02

    Despite the importance of stem cells in plant and animal development, the common mechanisms of stem cell maintenance in both systems have remained elusive. Recently, the importance of hydrogen peroxide (H 2 O 2 ) signaling in priming stem cell differentiation has been extensively studied in animals. Here, we show that different forms of reactive oxygen species (ROS) have antagonistic roles in plant stem cell regulation, which were established by distinct spatiotemporal patterns of ROS-metabolizing enzymes. The superoxide anion (O2·-) is markedly enriched in stem cells to activate WUSCHEL and maintain stemness, whereas H 2 O 2 is more abundant in the differentiating peripheral zone to promote stem cell differentiation. Moreover, H 2 O 2 negatively regulates O2·- biosynthesis in stem cells, and increasing H 2 O 2 levels or scavenging O2·- leads to the termination of stem cells. Our results provide a mechanistic framework for ROS-mediated control of plant stem cell fate and demonstrate that the balance between O2·- and H 2 O 2 is key to stem cell maintenance and differentiation. © 2017 The Authors.

  8. Femtosecond laser pulses for chemical-free embryonic and mesenchymal stem cell differentiation

    CSIR Research Space (South Africa)

    Mthunzi, P

    2011-08-01

    Full Text Available Owing to their self renewal and pluripotency properties, stem cells can efficiently advance current therapies in tissue regeneration and/or engineering. Under appropriate culture conditions in vitro, pluripotent stem cells can be primed...

  9. Stem cells in dentistry: A study regarding awareness of stem cells among dental professionals

    OpenAIRE

    Parita K Chitroda; Girish Katti; Nikhat M Attar; Syed Shahbaz; G Sreenivasarao; Ambika Patil

    2017-01-01

    Background: Dental stem cell, a type of adult stem cell, exhibits multipotent differentiation capacity and is drawing worldwide attention because of its numerous applications. The advances in applications of dental stem cells seem to be unsurpassed in the near future, for which specialized skills and knowledge in this arena are of prime significance. Hence, there is a need to acquire more knowledge about dental stem cells to obtain maximum benefits from it in the coming years. Dental stem cel...

  10. Proliferative capacity of murine hematopoietic stem cells

    International Nuclear Information System (INIS)

    Hellman, S.; Botnick, L.E.; Hannon, E.C.; Vigneulle, R.M.

    1978-01-01

    The present study demonstrates a decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells. Production of differentiated cell progeny is maintained longer than stem cell self-renewal. In normal animals the capacity for self-renewal is not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appears to be proliferatively quiescent. After apparent recovery from the alkylating agent busulfan, the probability of stem cell self-renewal is decreased, there is a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells are proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity. Cells progress in the continuum in one direction and such progression is not reversible

  11. Therapeutic application of multipotent stem cells

    DEFF Research Database (Denmark)

    Mirzaei, Hamed; Sahebkar, Amirhossein; Sichani, Laleh Shiri

    2018-01-01

    Cell therapy is an emerging fields in the treatment of various diseases such as cardiovascular, pulmonary, hepatic, and neoplastic diseases. Stem cells are an integral tool for cell therapy. Multipotent stem cells are an important class of stem cells which have the ability to self-renew through...... been showed that multipotent stem cells exert their therapeutic effects via inhibition/activation of a sequence of cellular and molecular pathways. Although the advantages of multipotent stem cells are numerous, further investigation is still necessary to clarify the biology and safety of these cells...... before they could be considered as a potential treatment for different types of diseases. This review summarizes different features of multipotent stem cells including isolation, differentiation, and therapeutic applications....

  12. Therapeutic potential of adult stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Keith, W. Nicol

    2006-01-01

    is the necessity to be able to identify, select, expand and manipulate cells outside the body. Recent advances in adult stem cell technologies and basic biology have accelerated therapeutic opportunities aimed at eventual clinical applications. Adult stem cells with the ability to differentiate down multiple...... lineages are an attractive alternative to human embryonic stem cells (hES) in regenerative medicine. In many countries, present legislation surrounding hES cells makes their use problematic, and indeed the origin of hES cells may represent a controversial issue for many communities. However, adult stem...... cells are not subject to these issues. This review will therefore focus on adult stem cells. Based on their extensive differentiation potential and, in some cases, the relative ease of their isolation, adult stem cells are appropriate for clinical development. Recently, several observations suggest...

  13. New Advanced Technologies in Stem Cell Therapy

    Science.gov (United States)

    2014-11-01

    James, J. N. Zara , M. Corselli et al., “An abundant perivascular source of stem cells for bone tissue engineering,” Stem Cells Translational Medicine...vol. 1, no. 9, pp. 673–684, 2012. [89] A.W. James, J. N. Zara , X. Zhang et al., “Perivascular stem cells: a prospectively purified mesenchymal stem...1, pp. 54–63, 2009. [176] A. Askarinam, A. W. James, J. N. Zara et al., “Human perivas- cular stem cells show enhanced osteogenesis and

  14. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Varga, Nora [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Vereb, Zoltan; Rajnavoelgyi, Eva [Department of Immunology, Medical and Health Science Centre, University of Debrecen, Debrecen (Hungary); Nemet, Katalin; Uher, Ferenc; Sarkadi, Balazs [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Apati, Agota, E-mail: apati@kkk.org.hu [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary)

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer MSC like cells were derived from hESC by a simple and reproducible method. Black-Right-Pointing-Pointer Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. Black-Right-Pointing-Pointer MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  15. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

    International Nuclear Information System (INIS)

    Varga, Nóra; Veréb, Zoltán; Rajnavölgyi, Éva; Német, Katalin; Uher, Ferenc; Sarkadi, Balázs; Apáti, Ágota

    2011-01-01

    Highlights: ► MSC like cells were derived from hESC by a simple and reproducible method. ► Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. ► MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  16. Skeletal Muscle Cell Induction from Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Yusaku Kodaka

    2017-01-01

    Full Text Available Embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs have the potential to differentiate into various types of cells including skeletal muscle cells. The approach of converting ESCs/iPSCs into skeletal muscle cells offers hope for patients afflicted with the skeletal muscle diseases such as the Duchenne muscular dystrophy (DMD. Patient-derived iPSCs are an especially ideal cell source to obtain an unlimited number of myogenic cells that escape immune rejection after engraftment. Currently, there are several approaches to induce differentiation of ESCs and iPSCs to skeletal muscle. A key to the generation of skeletal muscle cells from ESCs/iPSCs is the mimicking of embryonic mesodermal induction followed by myogenic induction. Thus, current approaches of skeletal muscle cell induction of ESCs/iPSCs utilize techniques including overexpression of myogenic transcription factors such as MyoD or Pax3, using small molecules to induce mesodermal cells followed by myogenic progenitor cells, and utilizing epigenetic myogenic memory existing in muscle cell-derived iPSCs. This review summarizes the current methods used in myogenic differentiation and highlights areas of recent improvement.

  17. Research on human placenta-derived mesenchymal stem cells ...

    African Journals Online (AJOL)

    Research on human placenta-derived mesenchymal stem cells transfected with pIRES2-EGFP-VEGF165 using liposome. ... African Journal of Biotechnology. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue ...

  18. Targeting cancer stem cells in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    He AR

    2014-12-01

    Full Text Available Aiwu Ruth He,1 Daniel C Smith,1 Lopa Mishra2 1Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 2Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The poor outcome of patients with hepatocellular carcinoma (HCC is attributed to recurrence of the disease after curative treatment and the resistance of HCC cells to conventional chemotherapy, which may be explained partly by the function of liver cancer stem cells (CSCs. Liver CSCs have emerged as an important therapeutic target against HCC. Numerous surface markers for liver CSCs have been identified, and include CD133, CD90, CD44, CD13, and epithelial cell adhesion molecules. These surface markers serve not only as tools for identifying and isolating liver CSCs but also as therapeutic targets for eradicating these cells. In studies of animal models and large-scale genomic analyses of human HCC samples, many signaling pathways observed in normal stem cells have been found to be altered in liver CSCs, which accounts for the stemness and aggressive behavior of these cells. Antibodies and small molecule inhibitors targeting the signaling pathways have been evaluated at different levels of preclinical and clinical development. Another strategy is to promote the differentiation of liver CSCs to less aggressive HCC that is sensitive to conventional chemotherapy. Disruption of the tumor niche essential for liver CSC homeostasis has become a novel strategy in cancer treatment. To overcome the challenges in developing treatment for liver CSCs, more research into the genetic makeup of patient tumors that respond to treatment may lead to more effective therapy. Standardization of HCC CSC tumor markers would be helpful for measuring the CSC response to these agents. Herein, we review the current strategies for developing treatment to eradicate liver CSCs and to improve the outcome for patients with

  19. Stem cell treatment for chronic lung diseases.

    Science.gov (United States)

    Tzouvelekis, Argyris; Ntolios, Paschalis; Bouros, Demosthenes

    2013-01-01

    Chronic lung diseases such as idiopathic pulmonary fibrosis and cystic fibrosis or chronic obstructive pulmonary disease and asthma are leading causes of morbidity and mortality worldwide with a considerable human, societal and financial burden. In view of the current disappointing status of available pharmaceutical agents, there is an urgent need for alternative more effective therapeutic approaches that will not only help to relieve patient symptoms but will also affect the natural course of the respective disease. Regenerative medicine represents a promising option with several fruitful therapeutic applications in patients suffering from chronic lung diseases. Nevertheless, despite relative enthusiasm arising from experimental data, application of stem cell therapy in the clinical setting has been severely hampered by several safety concerns arising from the major lack of knowledge on the fate of exogenously administered stem cells within chronically injured lung as well as the mechanisms regulating the activation of resident progenitor cells. On the other hand, salient data arising from few 'brave' pilot investigations of the safety of stem cell treatment in chronic lung diseases seem promising. The main scope of this review article is to summarize the current state of knowledge regarding the application status of stem cell treatment in chronic lung diseases, address important safety and efficacy issues and present future challenges and perspectives. In this review, we argue in favor of large multicenter clinical trials setting realistic goals to assess treatment efficacy. We propose the use of biomarkers that reflect clinically inconspicuous alterations of the disease molecular phenotype before rigid conclusions can be safely drawn. Copyright © 2013 S. Karger AG, Basel.

  20. Stepwise development of hematopoietic stem cells from embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Kenji Matsumoto

    Full Text Available The cellular ontogeny of hematopoietic stem cells (HSCs remains poorly understood because their isolation from and their identification in early developing small embryos are difficult. We attempted to dissect early developmental stages of HSCs using an in vitro mouse embryonic stem cell (ESC differentiation system combined with inducible HOXB4 expression. Here we report the identification of pre-HSCs and an embryonic type of HSCs (embryonic HSCs as intermediate cells between ESCs and HSCs. Both pre-HSCs and embryonic HSCs were isolated by their c-Kit(+CD41(+CD45(- phenotype. Pre-HSCs did not engraft in irradiated adult mice. After co-culture with OP9 stromal cells and conditional expression of HOXB4, pre-HSCs gave rise to embryonic HSCs capable of engraftment and long-term reconstitution in irradiated adult mice. Blast colony assays revealed that most hemangioblast activity was detected apart from the pre-HSC population, implying the early divergence of pre-HSCs from hemangioblasts. Gene expression profiling suggests that a particular set of transcripts closely associated with adult HSCs is involved in the transition of pre-HSC to embryonic HSCs. We propose an HSC developmental model in which pre-HSCs and embryonic HSCs sequentially give rise to adult types of HSCs in a stepwise manner.

  1. Combination stem cell therapy for heart failure

    Directory of Open Access Journals (Sweden)

    Ichim Thomas E

    2010-04-01

    Full Text Available Abstract Patients with congestive heart failure (CHF that are not eligible for transplantation have limited therapeutic options. Stem cell therapy such as autologous bone marrow, mobilized peripheral blood, or purified cells thereof has been used clinically since 2001. To date over 1000 patients have received cellular therapy as part of randomized trials, with the general consensus being that a moderate but statistically significant benefit occurs. Therefore, one of the important next steps in the field is optimization. In this paper we discuss three ways to approach this issue: a increasing stem cell migration to the heart; b augmenting stem cell activity; and c combining existing stem cell therapies to recapitulate a "therapeutic niche". We conclude by describing a case report of a heart failure patient treated with a combination stem cell protocol in an attempt to augment beneficial aspects of cord blood CD34 cells and mesenchymal-like stem cells.

  2. Cellular Mechanisms of Somatic Stem Cell Aging

    Science.gov (United States)

    Jung, Yunjoon

    2014-01-01

    Tissue homeostasis and regenerative capacity rely on rare populations of somatic stem cells endowed with the potential to self-renew and differentiate. During aging, many tissues show a decline in regenerative potential coupled with a loss of stem cell function. Cells including somatic stem cells have evolved a series of checks and balances to sense and repair cellular damage to maximize tissue function. However, during aging the mechanisms that protect normal cell function begin to fail. In this review, we will discuss how common cellular mechanisms that maintain tissue fidelity and organismal lifespan impact somatic stem cell function. We will highlight context-dependent changes and commonalities that define aging, by focusing on three age-sensitive stem cell compartments: blood, neural, and muscle. Understanding the interaction between extrinsic regulators and intrinsic effectors that operate within different stem cell compartments is likely to have important implications for identifying strategies to improve health span and treat age-related degenerative diseases. PMID:24439814

  3. Stem cell biology meets systems biology

    OpenAIRE

    Roeder, I.; Radtke, F.

    2009-01-01

    Stem cells and their descendents are the building blocks of life. How stem cell populations guarantee their maintenance and/or self-renewal, and how individual stem cells decide to transit from one cell stage to another to generate different cell types are long-standing and fascinating questions in the field. Here, we review the discussions that took place at a recent EMBO conference in Cambridge, UK, in which these questions were placed in the context of the latest advances in stem cell biol...

  4. Stem cells: limitations and opportunities in Peru

    OpenAIRE

    Amiel-Pérez, José; Laboratorio de Cultivos Celulares, Universidad Científica del Sur. Lima, Perú.; Casado, Fanny; Stem Cell and Cancer Research Institute, McMaster University. Hamilton, Canadá.

    2015-01-01

    Stem cells are defined as rare cells that are characterized by asymmetric division, a process known as self-renewal, and the potential to differentiate into more than one type of terminally differentiated cell. There is a diversity of stem cells including embryonic stem cells, which exist only during the first stages of human development, and many adult stem cells depending on the specific tissues from where they derive or the ones derived from mesenchymal or stromal tissues. On the other han...

  5. Stem cell therapy to treat heart ischaemia

    DEFF Research Database (Denmark)

    Ali Qayyum, Abbas; Mathiasen, Anders Bruun; Kastrup, Jens

    2014-01-01

    (CABG), morbidity and mortality is still high in patients with CAD. Along with PCI and CABG or in patients without options for revascularization, stem cell regenerative therapy in controlled trials is a possibility. Stem cells are believed to exert their actions by angiogenesis and regeneration...... of cardiomyocytes. Recently published clinical trials and meta-analysis of stem cell studies have shown encouraging results with increased left ventricle ejection fraction and reduced symptoms in patients with CAD and heart failure. There is some evidence of mesenchymal stem cell being more effective compared...... to other cell types and cell therapy may be more effective in patients with known diabetes mellitus. However, further investigations are warranted....

  6. Molecular Imaging in Stem Cell Therapy for Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Fahuan Song

    2014-01-01

    Full Text Available Spinal cord injury (SCI is a serious disease of the center nervous system (CNS. It is a devastating injury with sudden loss of motor, sensory, and autonomic function distal to the level of trauma and produces great personal and societal costs. Currently, there are no remarkable effective therapies for the treatment of SCI. Compared to traditional treatment methods, stem cell transplantation therapy holds potential for repair and functional plasticity after SCI. However, the mechanism of stem cell therapy for SCI remains largely unknown and obscure partly due to the lack of efficient stem cell trafficking methods. Molecular imaging technology including positron emission tomography (PET, magnetic resonance imaging (MRI, optical imaging (i.e., bioluminescence imaging (BLI gives the hope to complete the knowledge concerning basic stem cell biology survival, migration, differentiation, and integration in real time when transplanted into damaged spinal cord. In this paper, we mainly review the molecular imaging technology in stem cell therapy for SCI.

  7. Mesenchymal dental stem cells in regenerative dentistry.

    Science.gov (United States)

    Rodríguez-Lozano, Francisco-Javier; Insausti, Carmen-Luisa; Iniesta, Francisca; Blanquer, Miguel; Ramírez, María-del-Carmen; Meseguer, Luis; Meseguer-Henarejos, Ana-Belén; Marín, Noemí; Martínez, Salvador; Moraleda, José-María

    2012-11-01

    In the last decade, tissue engineering is a field that has been suffering an enormous expansion in the regenerative medicine and dentistry. The use of cells as mesenchymal dental stem cells of easy access for dentist and oral surgeon, immunosuppressive properties, high proliferation and capacity to differentiate into odontoblasts, cementoblasts, osteoblasts and other cells implicated in the teeth, suppose a good perspective of future in the clinical dentistry. However, is necessary advance in the known of growth factors and signalling molecules implicated in tooth development and regeneration of different structures of teeth. Furthermore, these cells need a fabulous scaffold that facility their integration, differentiation, matrix synthesis and promote multiple specific interactions between cells. In this review, we give a brief description of tooth development and anatomy, definition and classification of stem cells, with special attention of mesenchymal stem cells, commonly used in the cellular therapy for their trasdifferentiation ability, non ethical problems and acceptable results in preliminary clinical trials. In terms of tissue engineering, we provide an overview of different types of mesenchymal stem cells that have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHEDs), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs), and stem cells from apical papilla (SCAPs), growth factors implicated in regeneration teeth and types of scaffolds for dental tissue regeneration.

  8. Stem cells and respiratory diseases

    Directory of Open Access Journals (Sweden)

    Soraia Carvalho Abreu

    2008-12-01

    Full Text Available Stem cells have a multitude of clinical implications in the lung. This article is a critical review that includes clinical and experimental studies of MedLine and SciElo database in the last 10 years, where we highlight the effects of stem cell therapy in acute respiratory distress syndrome or more chronic disorders such as lung fibrosis and emphysema. Although, many studies have shown the beneficial effects of stem cells in lung development, repair and remodeling; some important questions need to be answered to better understand the mechanisms that control cell division and differentiation, therefore enabling the use of cell therapy in human respiratory diseases.As células-tronco têm uma infinidade de implicações clínicas no pulmão. Este artigo é uma revisão crítica que inclui estudos clínicos e experimentais advindos do banco de dados do MEDLINE e SciElo nos últimos 10 anos, onde foram destacados os efeitos da terapia celular na síndrome do desconforto respiratório agudo ou doenças mais crônicas, como fibrose pulmonar e enfisema. Apesar de muitos estudos demonstrarem os efeitos benéficos das células-tronco no desenvolvimento, reparo e remodelamento pulmonar; algumas questões ainda precisam ser respondidas para um melhor entendimento dos mecanismos que controlam a divisão celular e diferenciação, permitindo o uso da terapia celular nas doenças respiratórias.

  9. Isolation, characterization, and differentiation of stem cells for cartilage regeneration.

    Science.gov (United States)

    Beane, Olivia S; Darling, Eric M

    2012-10-01

    The goal of tissue engineering is to create a functional replacement for tissues damaged by injury or disease. In many cases, impaired tissues cannot provide viable cells, leading to the investigation of stem cells as a possible alternative. Cartilage, in particular, may benefit from the use of stem cells since the tissue has low cellularity and cannot effectively repair itself. To address this need, researchers are investigating the chondrogenic capabilities of several multipotent stem cell sources, including adult and extra-embryonic mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Comparative studies indicate that each cell type has advantages and disadvantages, and while direct comparisons are difficult to make, published data suggest some sources may be more promising for cartilage regeneration than others. In this review, we identify current approaches for isolating and chondrogenically differentiating MSCs from bone marrow, fat, synovium, muscle, and peripheral blood, as well as cells from extra-embryonic tissues, ESCs, and iPSCs. Additionally, we assess chondrogenic induction with growth factors, identifying standard cocktails used for each stem cell type. Cell-only (pellet) and scaffold-based studies are also included, as is a discussion of in vivo results.

  10. Stem Cell Therapy: An emerging science

    International Nuclear Information System (INIS)

    Khan, Muhammad M.

    2007-01-01

    The research on stem cells is advancing knowledge about the development of an organism from a single cell and to how healthy cells replace damaged cells in adult organisms. Stem cell therapy is emerging rapidly nowadays as a technical tool for tissue repair and replacement. The purpose of this review to provide a framework of understanding for the challenges behind translating fundamental stem cell biology and its potential use into clinical therapies, also to give an overview on stem cell research to the scientists of Saudi Arabia in general. English language MEDLINE publications from 1980 through January 2007 for experimental, observational and clinical studies having relation with stem cells with different diseases were reviewed. Approximately 85 publications were reviewed based on the relevance, strength and quality of design and methods, 36 publications were selected for inclusion. Stem cells reside in a specific area of each tissue where they may remain undivided for several years until they are activated by disease or tissue injury. The embryonic stem cells are typically derived from four or five days old embryos and they are pluripotent. The adult tissues reported to contain stem cells brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin and liver. The promise of stem cell therapies is an exciting one, but significant technical hurdles remain that will only be overcome through years of intensive research. (author)

  11. Stem Cells and Herbal Acupuncture Therapy

    Directory of Open Access Journals (Sweden)

    Ki Rok Kwon

    2005-12-01

    Full Text Available Stem cell therapy implies the birth of regenerative medicine. Regenerative medicine signify treatment through regeneration of cells which was impossible by existing medicine. Stem cell is classified into embryonic stem cell and adult stem cell and they have distinctive benefits and limitations. Researches on stem cell are already under active progression and is expected to be commercially available in the near future. One may not relate the stem cell treatment with Oriental medicine, but can be interpreted as the fundamental treatment action of Oriental medicine is being investigated in more concrete manner. When it comes to difficult to cure diseases, there is no boundary between eastern and western medicine, and one must be ready to face and overcome changes lying ahead.

  12. Transplantation? Peripheral Stem Cell/Bone Marrow/Cord Blood

    Directory of Open Access Journals (Sweden)

    Itır Sirinoglu Demiriz

    2012-01-01

    Full Text Available The introduction of peripheral stem cell (PSC and cord blood (CB as an alternative to bone marrow (BM recently has caused important changes on hematopoietic stem cell transplantation (HSCT practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

  13. Stem cell therapy: From bench to bedside

    International Nuclear Information System (INIS)

    Tamarat, R.; Lataillade, J. J.; Bey, E.; Gourmelon, P.; Benderitter, M.

    2012-01-01

    Several countries have increased efforts to develop medical countermeasures to protect against radiation toxicity due to acts of bio-terrorism as well as cancer treatment. Both acute radiation injuries and delayed effects such as cutaneous effects and impaired wound repair depend, to some extent, on angiogenesis deficiency. Vascular damage influences levels of nutrients, oxygen available to skin tissue and epithelial cell viability. Consequently, the evolution of radiation lesions often becomes uncontrolled and surgery is the final option-amputation leading to a disability. Therefore, the development of strategies designed to promote healing of radiation injuries is a major therapeutic challenge. Adult mesenchymal stem cell therapy has been combined with surgery in some cases and not in others and successfully applied in patients with accidental radiation injuries. Although research in the field of radiation skin injury management has made substantial progress in the past 10 y, several strategies are still needed in order to enhance the beneficial effect of stem cell therapy and to counteract the deleterious effect of an irradiated tissue environment. This review summarises the current and evolving advances concerning basic and translational research based on stem cell therapy for the management of radiological burns. (authors)

  14. Mesenchymal Stem Cells in Cardiology

    Science.gov (United States)

    White, Ian A.; Sanina, Cristina; Balkan, Wayne; Hare, Joshua M.

    2017-01-01

    Cardiovascular disease (CVD) accounts for more deaths globally than any other single disease. There are on average 1.5 million episodes of myocardial infarction (heart attack) each year in the United States alone with roughly one third resulting in death. There is therefore a major need for developing new and effective strategies to promote cardiac repair. Intramyocardial transplantation of mesenchymal stem cells (MSCs) has emerged as a leading contender in the pursuit of clinical intervention and therapy. MSCs are potent mediators of cardiac repair and are therefore an attractive tool in the development of pre-clinical and clinical trials. MSCs are capable of secreting a large array of soluble factors, which have had demonstrated effects on pathogenic cardiac remolding, fibrosis, immune activation and cardiac stem cell proliferation within the damaged heart. MSCs are also capable of differentiation into cardiomyocytes, endothelial cells and vascular smooth muscle cells, although the relative contribution of trilineage differentiation and paracrine effectors on cardiac repair remains the subject of active investigation. PMID:27236666

  15. Generation of male differentiated germ cells from various types of stem cells.

    Science.gov (United States)

    Hou, Jingmei; Yang, Shi; Yang, Hao; Liu, Yang; Liu, Yun; Hai, Yanan; Chen, Zheng; Guo, Ying; Gong, Yuehua; Gao, Wei-Qiang; Li, Zheng; He, Zuping

    2014-06-01

    Infertility is a major and largely incurable disease caused by disruption and loss of germ cells. It affects 10-15% of couples, and male factor accounts for half of the cases. To obtain human male germ cells 'especially functional spermatids' is essential for treating male infertility. Currently, much progress has been made on generating male germ cells, including spermatogonia, spermatocytes, and spermatids, from various types of stem cells. These germ cells can also be used in investigation of the pathology of male infertility. In this review, we focused on advances on obtaining male differentiated germ cells from different kinds of stem cells, with an emphasis on the embryonic stem (ES) cells, the induced pluripotent stem (iPS) cells, and spermatogonial stem cells (SSCs). We illustrated the generation of male differentiated germ cells from ES cells, iPS cells and SSCs, and we summarized the phenotype for these stem cells, spermatocytes and spermatids. Moreover, we address the differentiation potentials of ES cells, iPS cells and SSCs. We also highlight the advantages, disadvantages and concerns on derivation of the differentiated male germ cells from several types of stem cells. The ability of generating mature and functional male gametes from stem cells could enable us to understand the precise etiology of male infertility and offer an invaluable source of autologous male gametes for treating male infertility of azoospermia patients. © 2014 Society for Reproduction and Fertility.

  16. Skin appendage-derived stem cells: cell biology and potential for wound repair.

    Science.gov (United States)

    Xie, Jiangfan; Yao, Bin; Han, Yutong; Huang, Sha; Fu, Xiaobing

    2016-01-01

    Stem cells residing in the epidermis and skin appendages are imperative for skin homeostasis and regeneration. These stem cells also participate in the repair of the epidermis after injuries, inducing restoration of tissue integrity and function of damaged tissue. Unlike epidermis-derived stem cells, comprehensive knowledge about skin appendage-derived stem cells remains limited. In this review, we summarize the current knowledge of skin appendage-derived stem cells, including their fundamental characteristics, their preferentially expressed biomarkers, and their potential contribution involved in wound repair. Finally, we will also discuss current strategies, future applications, and limitations of these stem cells, attempting to provide some perspectives on optimizing the available therapy in cutaneous repair and regeneration.

  17. Adipose stem cells for bone tissue repair

    OpenAIRE

    Ciuffi, Simone; Zonefrati, Roberto; Brandi, Maria Luisa

    2017-01-01

    Adipose-derived stem/stromal cells (ASCs), together with adipocytes, vascular endothelial cells, and vascular smooth muscle cells, are contained in fat tissue. ASCs, like the human bone marrow stromal/stem cells (BMSCs), can differentiate into several lineages (adipose cells, fibroblast, chondrocytes, osteoblasts, neuronal cells, endothelial cells, myocytes, and cardiomyocytes). They have also been shown to be immunoprivileged, and genetically stable in long-term cultures. Nevertheless, unlik...

  18. Reprogramming stem cells is a microenvironmental task

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina J; Inman, Jamie

    2008-10-14

    That tumor cells for all practical purposes are unstable and plastic could be expected. However, the astonishing ability of the nuclei from cells of normal adult tissues to be reprogrammed - given the right embryonic context - found its final truth even for mammals in the experiments that allowed engineering Dolly (1). The landmark experiments showed that nuclei originating from cells of frozen mammary tissues were capable of being reprogrammed by the embryonic cytoplasm and its microenvironment to produce a normal sheep. The rest is history. However, whether microenvironments other than those of the embryos can also reprogram adult cells of different tissue origins still containing their cytoplasm is of obvious interest. In this issue of PNAS, the laboratory of Gilbert Smith (2) reports on how the mammary gland microenvironment can reprogram both embryonic and adult stem neuronal cells. The work is a follow-up to their previous report on testis stem cells that were reprogrammed by the mammary microenvironment (3). They demonstrated that cells isolated from the seminiferous tubules of the mature testis, mixed with normal mammary epithelial cells, contributed a sizable number of epithelial progeny to normal mammary outgrowths in transplanted mammary fat pads. However, in those experiments they were unable to distinguish which subpopulation of the testis cells contributed progeny to the mammary epithelial tree. The current work adds new, compelling, and provocative information to our understanding of stem cell plasticity. Booth et al. (2) use neuronal stem cells (NSCs) isolated from WAP-cre/R26R mice combined with unlabeled mammary epithelial cells that subsequently are implanted in cleared mammary fat pads. In this new microenvironment, the NSCs that are incorporated into the branching mammary tree make chimeric glands (Fig. 1) that remarkably can also express the milk protein {beta}-casein, progesterone receptor, and estrogen receptor {alpha}. Remarkably, the

  19. Stem cells and cancer: A review

    Directory of Open Access Journals (Sweden)

    Najeeb Ullah

    2016-05-01

    Full Text Available Stem cells are the small units of multicellular creature. Regeneration and self-renewal are the ability of the stem cells. Each tissue is having particular stem cells, specific to it. These normal stem cells are converted into cancer stem cells through mutations in it. Although the expression of oncogenes is enhanced a lot, the tumor-supressing gene is lessened. Cancer stem cells are isolated and visualized through different techniques like immunocytochemical staining, spectral karyotyping, immunohistochemistry, induction method and dissection measures, then are performed histological procedures which include fascination, immunohistochemistry, dispensation, in situ hybridization and also quantitative examination of tissue flow cytometric analysis. For the analysis of quantization, statistical tests are also performed as two-sample t-test, Chi-square test, SD and arithmetic mean. Tumor cells generate glioma spheres. These are used in cancer study. Axin 1 is the gene suppressing cancer. Its removal causes the generation of liver cancer. Curcumin is the most effective for suppressing cancer as it increases the normal stem cell function and decreases the cancer stem cell function. Brahma-related gene 1 is crucial for the safeguarding of the stem cell residents in tissue-specific comportment. Different types of cancers originate through genetic mutation, tissue disorganization and cell proliferation. Tumor configuration is produced by the alteration in original cell culture having stem cells and progenitor cell populations. The developmental facets about cancer cells and cancer stem cells as well as their personal natal functions sustain an intricate steadiness to settle on their personal donations to the efficacy or harmfulness of the biological organization.

  20. Steady advance of stem cell therapies: report from the 2011 World Stem Cell Summit, Pasadena, California, October 3-5.

    Science.gov (United States)

    Swan, Melanie

    2011-12-01

    Stem cell research and related therapies (including regenerative medicine and cellular therapies) could have a significant near-term impact on worldwide public health and aging. One reason is the industry's strong linkage between policy, science, industry, and patient advocacy, as was clear in the attendance and programming at the 7(th) annual World Stem Cell Summit held in Pasadena, California, October 3-5, 2011. A special conference session sponsored by the SENS Foundation discussed how stem cell therapies are being used to extend healthy life span. Stem cells are useful not only in cell-replacement therapies, but also in disease modeling, drug discovery, and drug toxicity screening. Stem cell therapies are currently being applied to over 50 diseases, including heart, lung, neurodegenerative, and eye disease, cancer, and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Dozens of companies are developing therapeutic solutions that are in different stages of clinical use and clinical trials. Some high-profile therapies include Dendreon's Provenge for prostate cancer, Geron's first-ever embryonic stem cell trials for spinal cord injury, Fibrocell's laViv cellular therapy for wrinkles, and well-established commercial skin substitutes (Organogenesis' Apligraf and Advanced BioHealing's Dermagraft). Stem cell policy issues under consideration include medical tourism, standards for large-scale stem cell manufacturing, and lingering ethical debates over the use of embryonic stem cells. Contemporary stem cell science advances include a focus on techniques for the direct reprogramming of cells from one lineage to another without returning to pluripotency as an intermediary step, improved means of generating and characterizing induced pluripotent cells, and progress in approaches to neurodegenerative disease.

  1. Basic Science and Clinical Application of Stem Cells in Veterinary Medicine

    Science.gov (United States)

    Ribitsch, I.; Burk, J.; Delling, U.; Geißler, C.; Gittel, C.; Jülke, H.; Brehm, W.

    Stem cells play an important role in veterinary medicine in different ways. Currently several stem cell therapies for animal patients are being developed and some, like the treatment of equine tendinopathies with mesenchymal stem cells (MSCs), have already successfully entered the market. Moreover, animal models are widely used to study the properties and potential of stem cells for possible future applications in human medicine. Therefore, in the young and emerging field of stem cell research, human and veterinary medicine are intrinsically tied to one another. Many of the pioneering innovations in the field of stem cell research are achieved by cooperating teams of human and veterinary medical scientists.

  2. Of Microenvironments and Mammary Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    LaBarge, Mark A; Petersen, Ole W; Bissell, Mina J

    2007-06-01

    In most adult tissues there reside pools of stem and progenitor cells inside specialized microenvironments referred to as niches. The niche protects the stem cells from inappropriate expansion and directs their critical functions. Thus guided, stem cells are able to maintain tissue homeostasis throughout the ebb and flow of metabolic and physical demands encountered over a lifetime. Indeed, a pool of stem cells maintains mammary gland structure throughout development, and responds to the physiological demands associated with pregnancy. This review discusses how stem cells were identified in both human and mouse mammary glands; each requiring different techniques that were determined by differing biological needs and ethical constraints. These studies together create a robust portrait of mammary gland biology and identify the location of the stem cell niche, elucidate a developmental hierarchy, and suggest how the niche might be manipulated for therapeutic benefit.

  3. Application of mesenchymal stem cells in paediatrics

    Directory of Open Access Journals (Sweden)

    Wawryk-Gawda Ewelina

    2017-09-01

    Full Text Available Mesenchymal stem cells (MSC were described by Friedenstein in the 1970s as being a group of bone marrow non-hematopoietic cells that are the source of fibroblasts. Since then, knowledge about the therapeutic potential of MSCs has significantly increased. MSCs are currently used for the treatment of many diseases, both in adults and children. MSCs are used successfully in the case of autoimmune diseases, including rheumatic diseases, diabetes mellitus type 1, gastroenterological and neurological diseases. Moreover, treatment of such organ disorders as damage or hypoxia through application of MSC therapy has shown to be satisfactory. In addition, there are some types of congenital disorders, including osteogenesis imperfecta and Spinal Muscular Atrophy, that may be treated with cellular therapy. Most studies showed no other adverse effects than fever. Our study is an analysis that particularly focuses on the registered trials and results of MSCs application to under 18 patients with acute, chronic, recurrent, resistance and corticosteroids types of Graft-versus-Host Disease (GvHD. Stem cells currently play an important role in the treatment of many diseases. Long-term studies conducted on animals have shown that cell therapy is both effective and safe. The number of indications for use of these cells in the course of treatment of people is constantly increasing. The results of subsequent studies provide important data justifying the application of MSCs in the course of treatment of many diseases whose treatment is ineffective when utilizing other approaches.

  4. MicroRNA expression profiles of cancer stem cells in head and neck squamous cell carcinoma

    OpenAIRE

    YATA, KAZUYA; BEDER, LEVENT BEKIR; TAMAGAWA, SHUNJI; HOTOMI, MUNEKI; HIROHASHI, YOSHIHIKO; GRENMAN, REIDAR; YAMANAKA, NOBORU

    2015-01-01

    Increasing evidence indicates that cancer stem cells have essential roles in tumor initiation, progression, metastasis and resistance to chemo-radiation. Recent research has pointed out biological importance of microRNAs in cancer stem cell dysregulation. Total number of mature microRNAs in human genome increased to more than 2,500 with the recent up-date of the database. However, currently no information is available regarding microRNA expression profiles of cancer stem cells in head and nec...

  5. [Bioethical challenges of stem cell tourism].

    Science.gov (United States)

    Ventura-Juncá, Patricio; Erices, Alejandro; Santos, Manuel J

    2013-08-01

    Stem cells have drawn extraordinary attention from scientists and the general public due to their potential to generate effective therapies for incurable diseases. At the same time, the production of embryonic stem cells involves a serious ethical issue concerning the destruction of human embryos. Although adult stem cells and induced pluripotential cells do not pose this ethical objection, there are other bioethical challenges common to all types of stem cells related particularly to the clinical use of stem cells. Their clinical use should be based on clinical trials, and in special situations, medical innovation, both of which have particular ethical dimensions. The media has raised unfounded expectations in patients and the public about the real clinical benefits of stem cells. At the same time, the number of unregulated clinics is increasing around the world, making direct offers through Internet of unproven stem cell therapies that attract desperate patients that have not found solutions in standard medicine. This is what is called stem cells tourism. This article reviews this situation, its consequences and the need for international cooperation to establish effective regulations to prevent the exploitation of patients and to endanger the prestige of legitimate stem cell research.

  6. Stem cells and chronic wound healing: state of the art

    Directory of Open Access Journals (Sweden)

    Leavitt T

    2016-03-01

    Full Text Available Tripp Leavitt, Michael S Hu, Clement D Marshall, Leandra A Barnes, Michael T Longaker, H Peter Lorenz Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA Abstract: Currently available treatments for chronic wounds are inadequate. A clearly effective therapy does not exist, and treatment is often supportive. This is largely because the cellular and molecular processes underlying failure of wound repair are still poorly understood. With an increase in comorbidities, such as diabetes and vascular disease, as well as an aging population, the incidence of these intractable wounds is expected to rise. As such, chronic wounds, which are already costly, are rapidly growing as a tremendous burden to the health-care system. Stem cells have garnered much interest as a therapy for chronic wounds due to their inherent ability to differentiate into multiple lineages and promote regeneration. Herein, we discuss the types of stem cells used for chronic wound therapy, as well as the proposed means by which they do so. In particular, we highlight mesenchymal stem cells (including adipose-derived stem cells, endothelial progenitor cells, and induced pluripotent stem cells. We include the results of recent in vitro and in vivo studies in both animal models and human clinical trials. Finally, we discuss the current studies to improve stem cell therapies and the limitations of stem cell-based therapeutics. Stem cells promise improved therapies for healing chronic wounds, but further studies that are well-designed with standardized protocols are necessary for fruition. Keywords: stem cells, chronic wounds, cell therapy, wound healing

  7. Update on small intestinal stem cells

    OpenAIRE

    Tesori, Valentina; Puglisi, Maria Ausiliatrice; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio

    2013-01-01

    Among somatic stem cells, those residing in the intestine represent a fascinating and poorly explored research field. Particularly, somatic stem cells reside in the small intestine at the level of the crypt base, in a constant balance between self-renewal and differentiation. Aim of the present review is to delve into the mechanisms that regulate the delicate equilibrium through which intestinal stem cells orchestrate intestinal architecture. To this aim, special focus will be addressed to id...

  8. Ethical Issues in Stem Cell Research

    OpenAIRE

    Lo, Bernard; Parham, Lindsay

    2009-01-01

    Stem cell research offers great promise for understanding basic mechanisms of human development and differentiation, as well as the hope for new treatments for diseases such as diabetes, spinal cord injury, Parkinson’s disease, and myocardial infarction. However, human stem cell (hSC) research also raises sharp ethical and political controversies. The derivation of pluripotent stem cell lines from oocytes and embryos is fraught with disputes about the onset of human personhood. The reprogramm...

  9. Stem cell aging: Survival of the laziest?

    OpenAIRE

    Muller-Sieburg, Christa; Sieburg, Hans B.

    2008-01-01

    The question whether stem cells age remains an enigma. Traditionally, aging was thought to change the properties of hematopoietic stem cells (HSC). We discuss here a new model of stem cell aging that challenges this view. It is now well-established that the HSC compartment is heterogeneous, consisting of epigenetically fixed subpopulations of HSC that differ in self-renewal and differentiation capacity. New data show that the representation of these HSC subsets changes during aging. HSC that ...

  10. Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy.

    Science.gov (United States)

    Naderi-Meshkin, Hojjat; Bahrami, Ahmad Reza; Bidkhori, Hamid Reza; Mirahmadi, Mahdi; Ahmadiankia, Naghmeh

    2015-01-01

    Stem/progenitor cell-based therapeutic approach in clinical practice has been an elusive dream in medical sciences, and improvement of stem cell homing is one of major challenges in cell therapy programs. Stem/progenitor cells have a homing response to injured tissues/organs, mediated by interactions of chemokine receptors expressed on the cells and chemokines secreted by the injured tissue. For improvement of directed homing of the cells, many techniques have been developed either to engineer stem/progenitor cells with higher amount of chemokine receptors (stem cell-based strategies) or to modulate the target tissues to release higher level of the corresponding chemokines (target tissue-based strategies). This review discusses both of these strategies involved in the improvement of stem cell homing focusing on mesenchymal stem cells as most frequent studied model in cellular therapies. © 2014 International Federation for Cell Biology.

  11. Stem cells for brain repair in neonatal hypoxia-ischemia.

    Science.gov (United States)

    Chicha, L; Smith, T; Guzman, R

    2014-01-01

    Neonatal hypoxic-ischemic insults are a significant cause of pediatric encephalopathy, developmental delays, and spastic cerebral palsy. Although the developing brain's plasticity allows for remarkable self-repair, severe disruption of normal myelination and cortical development upon neonatal brain injury are likely to generate life-persisting sensory-motor and cognitive deficits in the growing child. Currently, no treatments are available that can address the long-term consequences. Thus, regenerative medicine appears as a promising avenue to help restore normal developmental processes in affected infants. Stem cell therapy has proven effective in promoting functional recovery in animal models of neonatal hypoxic-ischemic injury and therefore represents a hopeful therapy for this unmet medical condition. Neural stem cells derived from pluripotent stem cells or fetal tissues as well as umbilical cord blood and mesenchymal stem cells have all shown initial success in improving functional outcomes. However, much still remains to be understood about how those stem cells can safely be administered to infants and what their repair mechanisms in the brain are. In this review, we discuss updated research into pathophysiological mechanisms of neonatal brain injury, the types of stem cell therapies currently being tested in this context, and the potential mechanisms through which exogenous stem cells might interact with and influence the developing brain.

  12. Stem cell treatment of degenerative eye disease

    Directory of Open Access Journals (Sweden)

    Ben Mead

    2015-05-01

    Full Text Available Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs has so far been reliant on mesenchymal stem cells (MSC. Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs, MSC derived from bone marrow (BMSC, adipose tissues (ADSC and dental pulp (DPSC, together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment.

  13. Hematopoietic stem cell expansion : challenges and opportunities

    NARCIS (Netherlands)

    Walasek, Marta A.; van Os, Ronald; de Haan, Gerald; Kanz, L; Fibbe, WE; Lengerke, C; Dick, JE

    2012-01-01

    Attempts to improve hematopoietic reconstitution and engraftment potential of ex vivo-expanded hematopoietic stem and progenitor cells (HSPCs) have been largely unsuccessful due to the inability to generate sufficient stem cell numbers and to excessive differentiation of the starting cell

  14. Stem cell treatment of degenerative eye disease.

    Science.gov (United States)

    Mead, Ben; Berry, Martin; Logan, Ann; Scott, Robert A H; Leadbeater, Wendy; Scheven, Ben A

    2015-05-01

    Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs) and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE) cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs) has so far been reliant on mesenchymal stem cells (MSC). Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs), MSC derived from bone marrow (BMSC), adipose tissues (ADSC) and dental pulp (DPSC), together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment. Copyright © 2015. Published by Elsevier B.V.

  15. Single-cell sequencing in stem cell biology.

    Science.gov (United States)

    Wen, Lu; Tang, Fuchou

    2016-04-15

    Cell-to-cell variation and heterogeneity are fundamental and intrinsic characteristics of stem cell populations, but these differences are masked when bulk cells are used for omic analysis. Single-cell sequencing technologies serve as powerful tools to dissect cellular heterogeneity comprehensively and to identify distinct phenotypic cell types, even within a 'homogeneous' stem cell population. These technologies, including single-cell genome, epigenome, and transcriptome sequencing technologies, have been developing rapidly in recent years. The application of these methods to different types of stem cells, including pluripotent stem cells and tissue-specific stem cells, has led to exciting new findings in the stem cell field. In this review, we discuss the recent progress as well as future perspectives in the methodologies and applications of single-cell omic sequencing technologies.

  16. Stem cell therapy for retinal diseases

    Science.gov (United States)

    Garcia, José Mauricio; Mendonça, Luisa; Brant, Rodrigo; Abud, Murilo; Regatieri, Caio; Diniz, Bruno

    2015-01-01

    In this review, we discuss about current knowledge about stem cell (SC) therapy in the treatment of retinal degeneration. Both human embryonic stem cell and induced pluripotent stem cell has been growth in culture for a long time, and started to be explored in the treatment of blinding conditions. The Food and Drug Administration, recently, has granted clinical trials using SC retinal therapy to treat complex disorders, as Stargardt’s dystrophy, and patients with geographic atrophy, providing good outcomes. This study’s intent is to overview the critical regeneration of the subretinal anatomy through retinal pigment epithelium transplantation, with the goal of reestablish important pathways from the retina to the occipital cortex of the brain, as well as the differentiation from pluripotent quiescent SC to adult retina, and its relationship with a primary retinal injury, different techniques of transplantation, management of immune rejection and tumorigenicity, its potential application in improving patients’ vision, and, finally, approaching future directions and challenges for the treatment of several conditions. PMID:25621115

  17. Stem cells and cancer of the stomach and intestine.

    Science.gov (United States)

    Vries, Robert G J; Huch, Meritxell; Clevers, Hans

    2010-10-01

    Cancer in the 21st century has become the number one cause of death in developed countries. Although much progress has been made in improving patient survival, tumour relapse is one of the important causes of cancer treatment failure. An early observation in the study of cancer was the heterogeneity of tumours. Traditionally, this was explained by a combination of genomic instability of tumours and micro environmental factors leading to diverse phenotypical characteristics. It was assumed that cells in a tumour have an equal capacity to propagate the cancer. This model is currently known as the stochastic model. Recently, the Cancer stem cell model has been proposed to explain the heterogeneity of a tumour and its progression. According to this model, the heterogeneity of tumours is the result of aberrant differentiation of tumour cells into the cells of the tissue the tumour originated from. Tumours were suggested to contain stem cell-like cells, the cancer stem cells or tumour-initiating cells, which are uniquely capable of propagating a tumour much like normal stem cells fuel proliferation and differentiation in normal tissue. In this review we discuss the normal stem cell biology of the stomach and intestine followed by both the stochastic and cancer stem cell models in light of recent findings in the gastric and intestinal systems. The molecular pathways underlying normal and tumourigenic growth have been well studied, and recently the stem cells of the stomach and intestine have been identified. Furthermore, intestinal stem cells were identified as the cells-of-origin of colon cancer upon loss of the tumour suppressor APC. Lastly, several studies have proposed the positive identification of a cancer stem cell of human colon cancer. At the end we compare the cancer stem cell model and the stochastic model. We conclude that clonal evolution of tumour cells resulting from genetic mutations underlies tumour initiation and progression in both cancer models. This

  18. O transplante de células-tronco hematopoéticas na infância: situação atual e perspectivas Hematopoietic stem cell transplantation in childhood: current status and perspectives

    Directory of Open Access Journals (Sweden)

    Adriana Seber

    2009-05-01

    Full Text Available O transplante de células-tronco hematopoéticas (TCTH é uma opção terapêutica para um grande número de crianças com doenças malignas e não malignas. O objetivo deste artigo é apresentar a situação atual dos TCTH em pediatria para o tratamento de doenças hematológicas malignas, incluindo dados de nosso país e perspectivas futuras.Hematopoietic stem cell transplantation is a treatment option for a large number of children with malignant and non-malignant diseases. The objective of this article is to present the current status of hematopoietic stem cell transplantation in the treatment of malignant hematological diseases in pediatrics, including results in Brazil, and future perspectives.

  19. Hardwiring Stem Cell Communication through Tissue Structure.

    Science.gov (United States)

    Xin, Tianchi; Greco, Valentina; Myung, Peggy

    2016-03-10

    Adult stem cells across diverse organs self-renew and differentiate to maintain tissue homeostasis. How stem cells receive input to preserve tissue structure and function largely relies on their communication with surrounding cellular and non-cellular elements. As such, how tissues are organized and patterned not only reflects organ function, but also inherently hardwires networks of communication between stem cells and their environment to direct tissue homeostasis and injury repair. This review highlights how different methods of stem cell communication reflect the unique organization and function of diverse tissues. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Nanomaterials for Engineering Stem Cell Responses.

    Science.gov (United States)

    Kerativitayanan, Punyavee; Carrow, James K; Gaharwar, Akhilesh K

    2015-08-05

    Recent progress in nanotechnology has stimulated the development of multifunctional biomaterials for tissue engineering applications. Synergistic interactions between nanomaterials and stem cell engineering offer numerous possibilities to address some of the daunting challenges in regenerative medicine, such as controlling trigger differentiation, immune reactions, limited supply of stem cells, and engineering complex tissue structures. Specifically, the interactions between stem cells and their microenvironment play key roles in controlling stem cell fate, which underlines therapeutic success. However, the interactions between nanomaterials and stem cells are not well understood, and the effects of the nanomaterials shape, surface morphology, and chemical functionality on cellular processes need critical evaluation. In this Review, focus is put on recent development in nanomaterial-stem cell interactions, with specific emphasis on their application in regenerative medicine. Further, the emerging technologies based on nanomaterials developed over the past decade for stem cell engineering are reviewed, as well as the potential applications of these nanomaterials in tissue regeneration, stem cell isolation, and drug/gene delivery. It is anticipated that the enhanced understanding of nanomaterial-stem cell interactions will facilitate improved biomaterial design for a range of biomedical and biotechnological applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. The Patentability of Stem Cells in Australia.

    Science.gov (United States)

    Petering, Jenny; Cowin, Prue

    2015-07-01

    The potential therapeutic applications of stem cells are unlimited. However, the ongoing political and social debate surrounding the intellectual property and patenting considerations of stem cell research has led to the implementation of strict legislative regulations. In Australia the patent landscape surrounding stem cells has evolved considerably over the past 20 years. The Australian Patents Act 1990 includes a specific exclusion to the patentability of human beings and of biological processes for their generation. However, this exclusion has received no judicial consideration to date, and so its scope and potential impact on stem cell patents is unclear. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  2. Hardwiring stem cell communication through tissue structure

    Science.gov (United States)

    Xin, Tianchi; Greco, Valentina; Myung, Peggy

    2016-01-01

    Adult stem cells across diverse organs self-renew and differentiate to maintain tissue homeostasis. How stem cells receive input to preserve tissue structure and function largely relies on their communication with surrounding cellular and non-cellular elements. As such, how tissues are organized and patterned not only reflects organ function but also inherently hardwires networks of communication between stem cells and their environment to direct tissue homeostasis and injury repair. This review highlights how different methods of stem cell communication reflect the unique organization and function of diverse tissues. PMID:26967287

  3. Pulp tissue from primary teeth: new source of stem cells

    Directory of Open Access Journals (Sweden)

    Paloma Dias Telles

    2011-06-01

    Full Text Available SHED (stem cells from human exfoliated deciduous teeth represent a population of postnatal stem cells capable of extensive proliferation and multipotential differentiation. Primary teeth may be an ideal source of postnatal stem cells to regenerate tooth structures and bone, and possibly to treat neural tissue injury or degenerative diseases. SHED are highly proliferative cells derived from an accessible tissue source, and therefore hold potential for providing enough cells for clinical applications. In this review, we describe the current knowledge about dental pulp stem cells and discuss tissue engineering approaches that use SHED to replace irreversibly inflamed or necrotic pulps with a healthy and functionally competent tissue that is capable of forming new dentin.

  4. Therapeutic Application of Pluripotent Stem Cells: Challenges and Risks

    Directory of Open Access Journals (Sweden)

    Ulrich Martin

    2017-12-01

    Full Text Available Stem-cell-based therapies are considered to be promising and innovative but complex approaches. Induced pluripotent stem cells (iPSCs combine the advantages of adult stem cells with the hitherto unique characteristics of embryonic stem cells (ESCs. Major progress has already been achieved with regard to reprogramming technology, but also regarding targeted genome editing and scalable expansion and differentiation of iPSCs and ESCs, in some cases yielding highly enriched preparations of well-defined cell lineages at clinically required dimensions. It is noteworthy, however, that for many applications critical requirements such as the targeted specification into distinct cellular subpopulations and a proper cell maturation remain to be achieved. Moreover, current hurdles such as low survival rates and insufficient functional integration of cellular transplants remain to be overcome. Nevertheless, PSC technologies obviously have come of age and matured to a stage where various clinical applications of PSC-based cellular therapies have been initiated and are conducted.

  5. Perspectives of stem cell use in reconstructive maxillofacial surgery

    Directory of Open Access Journals (Sweden)

    Mikhail G. Semyonov

    2016-12-01

    Full Text Available The discovery of stem cells is one of the greatest achievements of molecular and cell biology, and associated research has confirmed the possibility of self-renewal and differentiation into specialized tissue stem cells. The use of cellular technologies is an important trend in modern medicine. The aim of this article is to briefly review current findings on the use of stem cells in cardiology, endocrinology, neurology, traumatology, and maxillofacial surgery. All data were retrieved from experimental and clinical studies using various cell technologies. The material is part of ongoing maxillofacial surgery research to investigate the possible use of stem cells in reconstructive maxillofacial surgery for jaw bone pathologies in children. Present tissue engineering methods provide some opportunities for solving difficult clinical problems in oral and maxillofacial surgery. Despite some international achievements of effective application of IC in various diseases, clinical use in reconstructive surgery requires further investigation.

  6. Stem cells in the human breast

    DEFF Research Database (Denmark)

    Petersen, Ole William; Polyak, Kornelia

    2010-01-01

    The origins of the epithelial cells participating in the development, tissue homeostasis, and cancer of the human breast are poorly understood. However, emerging evidence suggests a role for adult tissue-specific stem cells in these processes. In a hierarchical manner, these generate the two main...... mammary cell lineages, producing an increasing number of cells with distinct properties. Understanding the biological characteristics of human breast stem cells and their progeny is crucial in attempts to compare the features of normal stem cells and cancer precursor cells and distinguish these from...... nonprecursor cells and cells from the bulk of a tumor. A historical overview of research on human breast stem cells in primary tissue and in culture reveals the progress that has been made in this area, whereas a focus on the cell-of-origin and reprogramming that occurs during neoplastic conversion provides...

  7. Pluripotent stem cell-derived neural stem cells: From basic research to applications

    OpenAIRE

    Otsu, Masahiro; Nakayama, Takashi; Inoue, Nobuo

    2014-01-01

    Basic research on pluripotent stem cells is designed to enhance understanding of embryogenesis, whereas applied research is designed to develop novel therapies and prevent diseases. Attainment of these goals has been enhanced by the establishment of embryonic stem cell lines, the technological development of genomic reprogramming to generate induced-pluripotent stem cells, and improvements in vitro techniques to manipulate stem cells. This review summarizes the techniques required to generate...

  8. Stem cells in bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Jeong Min [Department of Preventive and Social Dentistry and Institute of Oral Biology, College of Dentistry, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Kim, Byung-Chul; Park, Jae-Hong; Kwon, Il Keun; Hwang, Yu-Shik [Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, College of Dentistry, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Mantalaris, Anathathios, E-mail: yshwang@khu.ac.k [Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ (United Kingdom)

    2010-12-15

    Bone tissue engineering has been one of the most promising areas of research, providing a potential clinical application to cure bone defects. Recently, various stem cells including embryonic stem cells (ESCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs), adipose tissue-derived stem cells (ADSCs), muscle-derived stem cells (MDSCs) and dental pulp stem cells (DPSCs) have received extensive attention in the field of bone tissue engineering due to their distinct biological capability to differentiate into osteogenic lineages. The application of these stem cells to bone tissue engineering requires inducing in vitro differentiation of these cells into bone forming cells, osteoblasts. For this purpose, efficient in vitro differentiation towards osteogenic lineage requires the development of well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source for application to bone tissue engineering therapies. This review provides a critical examination of the various experimental strategies that could be used to direct the differentiation of ESC, BM-MSC, UCB-MSC, ADSC, MDSC and DPSC towards osteogenic lineages and their potential applications in tissue engineering, particularly in the regeneration of bone. (topical review)

  9. Stem cells in bone tissue engineering

    International Nuclear Information System (INIS)

    Seong, Jeong Min; Kim, Byung-Chul; Park, Jae-Hong; Kwon, Il Keun; Hwang, Yu-Shik; Mantalaris, Anathathios

    2010-01-01

    Bone tissue engineering has been one of the most promising areas of research, providing a potential clinical application to cure bone defects. Recently, various stem cells including embryonic stem cells (ESCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs), adipose tissue-derived stem cells (ADSCs), muscle-derived stem cells (MDSCs) and dental pulp stem cells (DPSCs) have received extensive attention in the field of bone tissue engineering due to their distinct biological capability to differentiate into osteogenic lineages. The application of these stem cells to bone tissue engineering requires inducing in vitro differentiation of these cells into bone forming cells, osteoblasts. For this purpose, efficient in vitro differentiation towards osteogenic lineage requires the development of well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source for application to bone tissue engineering therapies. This review provides a critical examination of the various experimental strategies that could be used to direct the differentiation of ESC, BM-MSC, UCB-MSC, ADSC, MDSC and DPSC towards osteogenic lineages and their potential applications in tissue engineering, particularly in the regeneration of bone. (topical review)

  10. Cell culture density affects the stemness gene expression of adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Kim, Dae Seong; Lee, Myoung Woo; Lee, Tae-Hee; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

    2017-03-01

    The results of clinical trials using mesenchymal stem cells (MSCs) are controversial due to the heterogeneity of human MSCs and differences in culture conditions. In this regard, it is important to identify gene expression patterns according to culture conditions, and to determine how the cells are expanded and when they should be clinically used. In the current study, stemness gene expression was investigated in adipose tissue-derived MSCs (AT-MSCs) harvested following culture at different densities. AT-MSCs were plated at a density of 200 or 5,000 cells/cm 2 . After 7 days of culture, stemness gene expression was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The proliferation rate of AT-MSCs harvested at a low density (~50% confluent) was higher than that of AT-MSCs harvested at a high density (~90% confluent). Although there were differences in the expression levels of stemness gene, such as octamer-binding transcription factor 4, nanog homeobox ( Nanog ), SRY-box 2, Kruppel like factor 4, v-myc avian myelocytomatosis viral oncogene homolog ( c-Myc ), and lin-28 homolog A, in the AT-MSCs obtained from different donors, RT-qPCR analysis demonstrated differential gene expression patterns according to the cell culture density. Expression levels of stemness genes, particularly Nanog and c-Myc , were upregulated in AT-MSCs harvested at a low density (~50% confluent) in comparison to AT-MSCs from the same donor harvested at a high density (~90% confluent). These results imply that culture conditions, such as the cell density at harvesting, modulate the stemness gene expression and proliferation of MSCs.

  11. Silent Waters Run Deep. Quiescent stem cells in homeostasis and cancer

    NARCIS (Netherlands)

    S.G. Roth (Sabrina)

    2012-01-01

    markdownabstract__Abstract__ The Introduction summarizes the current literature on quiescence in adult stem cell niches and the various methods for the isolation of quiescent stem cells, outlines the complexity of the intestinal stem cell niche, and formulates the hypothesis that quiescent

  12. Functional dysregulation of stem cells during aging: a focus on skeletal muscle stem cells.

    Science.gov (United States)

    García-Prat, Laura; Sousa-Victor, Pedro; Muñoz-Cánoves, Pura

    2013-09-01

    Aging of an organism is associated with the functional decline of tissues and organs, as well as a sharp decline in the regenerative capacity of stem cells. A prevailing view holds that the aging rate of an individual depends on the ratio of tissue attrition to tissue regeneration. Therefore, manipulations that favor the balance towards regeneration may prevent or delay aging. Skeletal muscle is a specialized tissue composed of postmitotic myofibers that contract to generate force. Satellite cells are the adult stem cells responsible for skeletal muscle regeneration. Recent studies on the biology of skeletal muscle and satellite cells in aging have uncovered the critical impact of systemic and niche factors on stem cell functionality and demonstrated the capacity of aged satellite cells to rejuvenate and increase their regenerative potential when exposed to a youthful environment. Here we review the current literature on the coordinated relationship between cell extrinsic and intrinsic factors that regulate the function of satellite cells, and ultimately determine tissue homeostasis and repair during aging, and which encourage the search for new anti-aging strategies. © 2013 The Authors Journal compilation © 2013 FEBS.

  13. Autologous Mesenchymal Stem Cells in Chronic Stroke

    Directory of Open Access Journals (Sweden)

    Ashu Bhasin

    2011-12-01

    Full Text Available Background: Cell transplantation is a ‘hype and hope’ in the current scenario. It is in the early stage of development with promises to restore function in chronic diseases. Mesenchymal stem cell (MSC transplantation in stroke patients has shown significant improvement by reducing clinical and functional deficits. They are feasible and multipotent and have homing characteristics. This study evaluates the safety, feasibility and efficacy of autologous MSC transplantation in patients with chronic stroke using clinical scores and functional imaging (blood oxygen level-dependent and diffusion tensor imaging techniques. Methods: Twelve chronic stroke patients were recruited; inclusion criteria were stroke lasting 3 months to 1 year, motor strength of hand muscles of at least 2, and NIHSS of 4–15, and patients had to be conscious and able to comprehend. Fugl Meyer (FM, modified Barthel index (mBI, MRC, Ashworth tone grade scale scores and functional imaging scans were assessed at baseline, and after 8 and 24 weeks. Bone marrow was aspirated under aseptic conditions and expansion of MSC took 3 weeks with animal serum-free media (Stem Pro SFM. Six patients were administered a mean of 50–60 × 106 cells i.v. followed by 8 weeks of physiotherapy. Six patients served as controls. This was a non-randomized experimental controlled trial. Results: Clinical and radiological scanning was normal for the stem cell group patients. There was no mortality or cell-related adverse reaction. The laboratory tests on days 1, 3, 5 and 7 were also normal in the MSC group till the last follow-up. The FM and mBI showed a modest increase in the stem cell group compared to controls. There was an increased number of cluster activation of Brodmann areas BA 4 and BA 6 after stem cell infusion compared to controls, indicating neural plasticity. Conclusion: MSC therapy aiming to restore function in stroke is safe and feasible. Further randomized controlled trials are needed

  14. Nonclinical safety strategies for stem cell therapies

    Energy Technology Data Exchange (ETDEWEB)

    Sharpe, Michaela E., E-mail: michaela_sharpe@yahoo.com [Investigative Toxicology, Drug Safety Research and Development, Pfizer Ltd, Ramsgate Road, Sandwich, CT13 9NJ (United Kingdom); Morton, Daniel [Exploratory Drug Safety, Drug Safety Research and Development, Pfizer Inc, Cambridge, 02140 (United States); Rossi, Annamaria [Investigative Toxicology, Drug Safety Research and Development, Pfizer Ltd, Ramsgate Road, Sandwich, CT13 9NJ (United Kingdom)

    2012-08-01

    Recent breakthroughs in stem cell biology, especially the development of the induced pluripotent stem cell techniques, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Stem cell therapies are being considered for the treatment of degenerative diseases, inflammatory conditions, cancer and repair of damaged tissue. The safety of a stem cell therapy depends on many factors including the type of cell therapy, the differentiation status and proliferation capacity of the cells, the route of administration, the intended clinical location, long term survival of the product and/or engraftment, the need for repeated administration, the disease to be treated and the age of the population. Understanding the product profile of the intended therapy is crucial to the development of the nonclinical safety study design.

  15. Nonclinical safety strategies for stem cell therapies

    International Nuclear Information System (INIS)

    Sharpe, Michaela E.; Morton, Daniel; Rossi, Annamaria

    2012-01-01

    Recent breakthroughs in stem cell biology, especially the development of the induced pluripotent stem cell techniques, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Stem cell therapies are being considered for the treatment of degenerative diseases, inflammatory conditions, cancer and repair of damaged tissue. The safety of a stem cell therapy depends on many factors including the type of cell therapy, the differentiation status and proliferation capacity of the cells, the route of administration, the intended clinical location, long term survival of the product and/or engraftment, the need for repeated administration, the disease to be treated and the age of the population. Understanding the product profile of the intended therapy is crucial to the development of the nonclinical safety study design.

  16. Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells

    NARCIS (Netherlands)

    D. ten Berge (Derk); D. Kurek (Dorota); T. Blauwkamp (Tim); W. Koole (Wouter); A. Maas (Alex); E. Eroglu (Elif); R.K. Siu (Ronald); R. Nusse (Roel)

    2011-01-01

    textabstractPluripotent stem cells exist in naive and primed states, epitomized by mouse embryonic stem cells (ESCs) and the developmentally more advanced epiblast stem cells (EpiSCs; ref.). In the naive state of ESCs, the genome has an unusual open conformation and possesses a minimum of repressive

  17. Sensing radiosensitivity of human epidermal stem cells

    International Nuclear Information System (INIS)

    Rachidi, Walid; Harfourche, Ghida; Lemaitre, Gilles; Amiot, Franck; Vaigot, Pierre; Martin, Michele T.

    2007-01-01

    Purpose: Radiosensitivity of stem cells is a matter of debate. For mouse somatic stem cells, both radiosensitive and radioresistant stem cells have been described. By contrast, the response of human stem cells to radiation has been poorly studied. As epidermis is a radiosensitive tissue, we evaluated in the present work the radiosensitivity of cell populations enriched for epithelial stem cells of human epidermis. Methods and materials: The total keratinocyte population was enzymatically isolated from normal human skin. We used flow cytometry and antibodies against cell surface markers to isolate basal cell populations from human foreskin. Cell survival was measured after a dose of 2 Gy with the XTT assay at 72 h after exposure and with a clonogenic assay at 2 weeks. Transcriptome analysis using oligonucleotide microarrays was performed to assess the genomic cell responses to radiation. Results: Cell sorting based on two membrane proteins, α6 integrin and the transferrin receptor CD71, allowed isolation of keratinocyte populations enriched for the two types of cells found in the basal layer of epidermis: stem cells and progenitors. Both the XTT assay and the clonogenic assay showed that the stem cells were radioresistant whereas the progenitors were radiosensitive. We made the hypothesis that upstream DNA damage signalling might be different in the stem cells and used microarray technology to test this hypothesis. The stem cells exhibited a much more reduced gene response to a dose of 2 Gy than the progenitors, as we found that 6% of the spotted genes were regulated in the stem cells and 20% in the progenitors. Using Ingenuity Pathway Analysis software, we found that radiation exposure induced very specific pathways in the stem cells. The most striking responses were the repression of a network of genes involved in apoptosis and the induction of a network of cytokines and growth factors. Conclusion: These results show for the first time that keratinocyte

  18. The stem cell secretome and its role in brain repair.

    Science.gov (United States)

    Drago, Denise; Cossetti, Chiara; Iraci, Nunzio; Gaude, Edoardo; Musco, Giovanna; Bachi, Angela; Pluchino, Stefano

    2013-12-01

    Compelling evidence exists that non-haematopoietic stem cells, including mesenchymal (MSCs) and neural/progenitor stem cells (NPCs), exert a substantial beneficial and therapeutic effect after transplantation in experimental central nervous system (CNS) disease models through the secretion of immune modulatory or neurotrophic paracrine factors. This paracrine hypothesis has inspired an alternative outlook on the use of stem cells in regenerative neurology. In this paradigm, significant repair of the injured brain may be achieved by injecting the biologics secreted by stem cells (secretome), rather than implanting stem cells themselves for direct cell replacement. The stem cell secretome (SCS) includes cytokines, chemokines and growth factors, and has gained increasing attention in recent years because of its multiple implications for the repair, restoration or regeneration of injured tissues. Thanks to recent improvements in SCS profiling and manipulation, investigators are now inspired to harness the SCS as a novel alternative therapeutic option that might ensure more efficient outcomes than current stem cell-based therapies for CNS repair. This review discusses the most recent identification of MSC- and NPC-secreted factors, including those that are trafficked within extracellular membrane vesicles (EVs), and reflects on their potential effects on brain repair. It also examines some of the most convincing advances in molecular profiling that have enabled mapping of the SCS. Copyright © 2013 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  19. [Cancer stem cells as the therapeutic target of tomorrow].

    Science.gov (United States)

    Hatina, Jiří

    2017-02-01

    The concept of hierarchical organization of tumour cell population, with cancer stem cells positioned at the apex of the cell hierarchy, can explain at least some crucial aspects of biological and clinical behaviour of cancer, like its propensity to relapse as well as the development of therapeutic resistance. The underlying biological properties of cancer stem cells are crucially dependent on various signals, inhibition of which provides an attractive opportunity to attack pharmacologically cancer stem cells. Currently, a lot of such stemness-inhibitors undergo various phases of clinical testing. Interestingly, numerous old drugs that are in routine use in human and veterinary medicine for non-oncological indications appear to be able to specifically target cancer stem cells as well. As cancer stem cells, at least for most tumours, represent usually only a minor tumour cell fraction, it is quite probable that the main focus of the clinical use of the stemness inhibitors would consist in their rational combinations with traditional anticancer treatment modalities. A highly important goal for the future research is to identify reliable and clinically applicable predictive markers that would allow to apply these novel anticancer drugs on the individual basis within the context of personalized medicine.

  20. Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0644 TITLE: Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells PRINCIPAL INVESTIGATOR: Chun-Ju...Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0644 5c. PROGRAM ELEMENT...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Cancer stem cells (CSCs), a cell population with acquired perpetuating self-renewal properties which

  1. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-14-1-0115 TITLE: Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas PRINCIPAL INVESTIGATOR: Kyuson Yun...CA130273 - Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0115 5c. PROGRAM...hypothesis, we originally proposed to transform neural stem cells (NSCs) and neural progenitor cells (NPCs) in vivo by expressing an activated form

  2. Induced Pluripotent Stem Cells for Regenerative Medicine

    OpenAIRE

    Hirschi, Karen K.; Li, Song; Roy, Krishnendu

    2014-01-01

    With the discovery of induced pluripotent stem (iPS) cells, it is now possible to convert differentiated somatic cells into multipotent stem cells that have the capacity to generate all cell types of adult tissues. Thus, there is a wide variety of applications for this technology, including regenerative medicine, in vitro disease modeling, and drug screening/discovery. Although biological and biochemical techniques have been well established for cell reprogramming, bioengineering technologies...

  3. Cancer stem cells: a metastasizing menace!

    International Nuclear Information System (INIS)

    Bandhavkar, Saurabh

    2016-01-01

    Cancer is one of the leading causes of death worldwide, and is estimated to be a reason of death of more than 18 billion people in the coming 5 years. Progress has been made in diagnosis and treatment of cancer; however, a sound understanding of the underlying cell biology still remains an unsolved mystery. Current treatments include a combination of radiation, surgery, and/or chemotherapy. However, these treatments are not a complete cure, aimed simply at shrinking the tumor and in majority of cases, there is a relapse of tumor. Several evidences suggest the presence of cancer stem cells (CSCs) or tumor-initiating stem-like cells, a small population of cells present in the tumor, capable of self-renewal and generation of differentiated progeny. The presence of these CSCs can be attributed to the failure of cancer treatments as these cells are believed to exhibit therapy resistance. As a result, increasing attention has been given to CSC research to resolve the therapeutic problems related to cancer. Progress in this field of research has led to the development of novel strategies to treat several malignancies and has become a hot topic of discussion. In this review, we will briefly focus on the main characteristics, therapeutic implications, and perspectives of CSCs in cancer therapy

  4. Cancer stem cells: a metastasizing menace!

    Science.gov (United States)

    Bandhavkar, Saurabh

    2016-04-01

    Cancer is one of the leading causes of death worldwide, and is estimated to be a reason of death of more than 18 billion people in the coming 5 years. Progress has been made in diagnosis and treatment of cancer; however, a sound understanding of the underlying cell biology still remains an unsolved mystery. Current treatments include a combination of radiation, surgery, and/or chemotherapy. However, these treatments are not a complete cure, aimed simply at shrinking the tumor and in majority of cases, there is a relapse of tumor. Several evidences suggest the presence of cancer stem cells (CSCs) or tumor-initiating stem-like cells, a small population of cells present in the tumor, capable of self-renewal and generation of differentiated progeny. The presence of these CSCs can be attributed to the failure of cancer treatments as these cells are believed to exhibit therapy resistance. As a result, increasing attention has been given to CSC research to resolve the therapeutic problems related to cancer. Progress in this field of research has led to the development of novel strategies to treat several malignancies and has become a hot topic of discussion. In this review, we will briefly focus on the main characteristics, therapeutic implications, and perspectives of CSCs in cancer therapy. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  5. Cancer stem cells of the digestive system.

    Science.gov (United States)

    Colvin, Hugh S; Nishida, Naohiro; Koseki, Jun; Konno, Masamitsu; Kawamoto, Koichi; Tsunekuni, Kenta; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi

    2014-12-01

    Stem cells of the digestive system are ideal in many ways for research, given they are abundant, highly proliferative and have a uniform structural arrangement. This in turn has enormously aided the research of cancer stem cells of the digestive system, which is now shaping our understanding of cancer stem cells. In this review, the recent advances in the understanding of cancer stem cells of the digestive system have been summarized, including aspects such as their identification, origin, cell-cycle dormancy, relationship with epithelial-mesenchymal transition, cellular metabolism and the underlying molecular mechanisms. Newly acquired knowledge concerning cancer stem cells have led to the development of novel cancer therapeutics with provisional yet encouraging results. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Cell cycle regulation in human embryonic stem cells: links to adaptation to cell culture.

    Science.gov (United States)

    Barta, Tomas; Dolezalova, Dasa; Holubcova, Zuzana; Hampl, Ales

    2013-03-01

    Cell cycle represents not only a tightly orchestrated mechanism of cell replication and cell division but it also plays an important role in regulation of cell fate decision. Particularly in the context of pluripotent stem cells or multipotent progenitor cells, regulation of cell fate decision is of paramount importance. It has been shown that human embryonic stem cells (hESCs) show unique cell cycle characteristics, such as short doubling time due to abbreviated G1 phase; these properties change with the onset of differentiation. This review summarizes the current understanding of cell cycle regulation in hESCs. We discuss cell cycle properties as well as regulatory machinery governing cell cycle progression of undifferentiated hESCs. Additionally, we provide evidence that long-term culture of hESCs is accompanied by changes in cell cycle properties as well as configuration of several cell cycle regulatory molecules.

  7. Modulating the stem cell niche for tissue regeneration

    Science.gov (United States)

    Lane, Steven W; Williams, David A; Watt, Fiona M

    2015-01-01

    The field of regenerative medicine holds considerable promise for treating diseases that are currently intractable. Although many researchers are adopting the strategy of cell transplantation for tissue repair, an alternative approach to therapy is to manipulate the stem cell microenvironment, or niche, to facilitate repair by endogenous stem cells. The niche is highly dynamic, with multiple opportunities for intervention. These include administration of small molecules, biologics or biomaterials that target specific aspects of the niche, such as cell-cell and cell–extracellular matrix interactions, to stimulate expansion or differentiation of stem cells, or to cause reversion of differentiated cells to stem cells. Nevertheless, there are several challenges in targeting the niche therapeutically, not least that of achieving specificity of delivery and responses. We envisage that successful treatments in regenerative medicine will involve different combinations of factors to target stem cells and niche cells, applied at different times to effect recovery according to the dynamics of stem cell–niche interactions. PMID:25093887

  8. Stem cells show promising results for lymphoedema treatment

    DEFF Research Database (Denmark)

    Toyserkani, Navid Mohamadpour; Quaade, Marlene Louise; Sheikh, Søren Paludan

    2015-01-01

    Abstract Lymphoedema is a debilitating condition, manifesting in excess lymphatic fluid and swelling of subcutaneous tissues. Lymphoedema is as of yet still an incurable condition and current treatment modalities are not satisfactory. The capacity of mesenchymal stem cells to promote angiogenesis......, secrete growth factors, regulate the inflammatory process, and differentiate into multiple cell types make them a potential ideal therapy for lymphoedema. Adipose tissue is the richest and most accessible source of mesenchymal stem cells and they can be harvested, isolated, and used for therapy...... in a single stage procedure as an autologous treatment. The aim of this paper was to review all studies using mesenchymal stem cells for lymphoedema treatment with a special focus on the potential use of adipose-derived stem cells. A systematic search was performed and five preclinical and two clinical...

  9. Banking on cord blood stem cells.

    Science.gov (United States)

    Sullivan, Michael J

    2008-07-01

    Umbilical cord blood gifted to non-profit public cord blood banks is now routinely used as an alternative source of haematopoietic stem cells for allogeneic transplantation for children and adults with cancer, bone marrow failure syndromes, haemoglobinopathies and many genetic metabolic disorders. Because of the success and outcomes of public cord banking, many companies now provide private cord banking services. However, in the absence of any published transplant evidence to support autologous and non-directed family banking, commercial cord banks currently offer a superfluous service.

  10. The potential application of stem cell in dentistry

    Directory of Open Access Journals (Sweden)

    Ketut Suardita

    2006-12-01

    Full Text Available Stem cells are generally defined as cells that have the capacity to self-renewal and differentiate to specialize cell. There are two kinds of stem cell, embryonic stem cell and adult stem cells. Stem cell therapy has been used to treat diseases including Parkinson’s and Alzheimer’s diseases, spinal cord injury, stroke, burns, heart diseases, diabetes, osteoarthritis, and rheumatoid arthritis. Stem cells were found in dental pulp, periodontal ligament, and alveolar bone marrow. Because of their potential in medical therapy, stem cells were used to regenerate lost or damage teeth and periodontal structures. This article discusses the potential application of stem cells for dental field.

  11. Isolation and characterization of exosome from human embryonic stem cell-derived c-myc-immortalized mesenchymal stem cells

    NARCIS (Netherlands)

    Lai, Ruenn Chai; Yeo, Ronne Wee Yeh; Padmanabhan, Jayanthi; Choo, Andre; De Kleijn, Dominique P V; Lim, Sai Kiang

    2016-01-01

    Mesenchymal stem cells (MSC) are currently the cell type of choice in many cell therapy trials. The number of therapeutic applications for MSCs registered as product IND submissions with the FDA and initiation of registered clinical trials has increased substantially in recent years, in particular

  12. Stem cell research in pakistan; past, present and future.

    Science.gov (United States)

    Zahra, Sayeda Anum; Muzavir, Sayed Raheel; Ashraf, Sadia; Ahmad, Aftab

    2015-05-01

    Stem cells have proved to have great therapeutic potential as stem cell treatment is replacing traditional ways of treatment in different disorders like cancer, aplastic anemia, stroke, heart disorders. The developed and developing countries are investing differently in this area of research so research output and clinical translation of research greatly vary among developed and developing countries. Present study was done to investigate the current status of stem cells research in Pakistan and ways to improve it. Many advanced countries (USA, UK and Canada etc.) are investing heavily in stem cell research and treatment. Different developing countries like Iran, Turkey and India are also following the developed countries and investing a lot in stem cells research. Pakistan is also making efforts in establishing this field to get desired benefits but unfortunately the progress is at very low pace. If Government plays an active role along with private sector, stem cell research in Pakistan can be boosted up. The numbers of publications from Pakistan are very less compared to developed and neighboring countries and Pakistan also has very less number of institutes working in this area of research. Stem cells research is at its initial stages in Pakistan and there is great need to bring Government, academia and industry together so they could make serious efforts to promote research in this very important field. This will help millions of patients suffering from incurable disorders and will also reduce economic loss.

  13. Oncolytic viral therapy: targeting cancer stem cells

    Directory of Open Access Journals (Sweden)

    Smith TT

    2014-02-01

    Full Text Available Tyrel T Smith,1 Justin C Roth,1 Gregory K Friedman,1 G Yancey Gillespie2 1Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Neurosurgery, The University of Alabama at Birmingham, Birmingham, AL, USA Abstract: Cancer stem cells (CSCs are defined as rare populations of tumor-initiating cancer cells that are capable of both self-renewal and differentiation. Extensive research is currently underway to develop therapeutics that target CSCs for cancer therapy, due to their critical role in tumorigenesis, as well as their resistance to chemotherapy and radiotherapy. To this end, oncolytic viruses targeting unique CSC markers, signaling pathways, or the pro-tumor CSC niche offer promising potential as CSCs-destroying agents/therapeutics. We provide a summary of existing knowledge on the biology of CSCs, including their markers and their niche thought to comprise the tumor microenvironment, and then we provide a critical analysis of the potential for targeting CSCs with oncolytic viruses, including herpes simplex virus-1, adenovirus, measles virus, reovirus, and vaccinia virus. Specifically, we review current literature regarding first-generation oncolytic viruses with their innate ability to replicate in CSCs, as well as second-generation viruses engineered to enhance the oncolytic effect and CSC-targeting through transgene expression. Keywords: oncolytic virotherapy, cancer stem cell niche

  14. Comparison of Teratoma Formation between Embryonic Stem Cells and Parthenogenetic Embryonic Stem Cells by Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Hongyan Tao

    2018-01-01

    Full Text Available With their properties of self-renewal and differentiation, embryonic stem (ES cells hold great promises for regenerative therapy. However, teratoma formation and ethical concerns of ES cells may restrict their potential clinical applications. Currently, parthenogenetic embryonic stem (pES cells have attracted the interest of researchers for its self-renewing and pluripotent differentiation while eliciting less ethic concerns. In this study, we established a model with ES and pES cells both stably transfected with a double-fusion reporter gene containing renilla luciferase (Rluc and red fluorescent protein (RFP to analyze the mechanisms of teratoma formation. Transgenic Vegfr2-luc mouse, which expresses firefly luciferase (Fluc under the promoter of vascular endothelial growth factor receptor 2 (Vegfr2-luc, was used to trace the growth of new blood vessel recruited by transplanted cells. Bioluminescence imaging (BLI of Rluc/Fluc provides an effective tool in estimating the growth and angiogenesis of teratoma in vivo. We found that the tumorigenesis and angiogenesis capacity of ES cells were higher than those of pES cells, in which VEGF/VEGFR2 signal pathway plays an important role. In conclusion, pES cells have the decreased potential of teratoma formation but meanwhile have similar differentiating capacity compared with ES cells. These data demonstrate that pES cells provide an alternative source for ES cells with the risk reduction of teratoma formation and without ethical controversy.

  15. Physiology of stem cell-derived cardiomyocytes

    NARCIS (Netherlands)

    Boer, T.P. de

    2007-01-01

    All chapters in this thesis revolve around the general theme, stem cells and their electrophysiological characteristics and capacity to induce pro-arrhythmia. The first part of this thesis focusses on key aspects that are relevant to possible pro-arrhythmic effects of stem cell transplantation. An

  16. Stem Cell Research and Health Education

    Science.gov (United States)

    Eve, David J.; Marty, Phillip J.; McDermott, Robert J.; Klasko, Stephen K.; Sanberg, Paul R.

    2008-01-01

    Stem cells are being touted as the greatest discovery for the potential treatment of a myriad of diseases in the new millennium, but there is still much research to be done before it will be known whether they can live up to this description. There is also an ethical debate over the production of one of the most valuable types of stem cell: the…

  17. Cerebral toxoplasmosis after haematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Agnieszka Zaucha-Prażmo

    2017-05-01

    Full Text Available Toxoplasmosis is an opportunistic infection caused by the parasite Toxoplasma gondii. The infection is severe and difficult to diagnose in patients receiving allogeneic haematopoietic stem cell transplantation (HSCT. It frequently involves the central nervous system. The case is presented of cerebral toxoplasmosis in a 17-year-old youth with Fanconi anaemia treated with haematopoietic stem cell transplantation (HSCT

  18. Pathological modifications of plant stem cell destiny

    Science.gov (United States)

    In higher plants, the shoot apex contains undifferentiated stem cells that give rise to various tissues and organs. The fate of these stem cells determines the pattern of plant growth as well as reproduction; and such fate is genetically preprogrammed. We found that a bacterial infection can derai...

  19. Stem Cell Transplants in Cancer Treatment

    Science.gov (United States)

    Stem cell transplants are procedures that restore blood-forming stem cells in cancer patients who have had theirs destroyed by very high doses of chemotherapy or radiation therapy. Learn about the types of transplants and side effects that may occur.

  20. Representations of stem cell clinics on Twitter.

    Science.gov (United States)

    Kamenova, Kalina; Reshef, Amir; Caulfield, Timothy

    2014-12-01

    The practice of travelling abroad to receive unproven and unregulated stem cell treatments has become an increasingly problematic global phenomenon known as 'stem cell tourism'. In this paper, we examine representations of nine major clinics and providers of such treatments on the microblogging network Twitter. We collected and conducted a content analysis of Twitter posts (n = 363) by these establishments and by other users mentioning them, focusing specifically on marketing claims about treatment procedures and outcomes, discussions of safety and efficacy of stem cell transplants, and specific representations of patients' experiences. Our analysis has shown that there were explicit claims or suggestions of benefits associated with unproven stem cell treatments in approximately one third of the tweets and that patients' experiences, whenever referenced, were presented as invariably positive and as testimonials about the efficacy of stem cell transplants. Furthermore, the results indicated that the tone of most tweets (60.2 %) was overwhelmingly positive and there were rarely critical discussions about significant health risks associated with unproven stem cell therapies. When placed in the context of past research on the problems associated with the marketing of unproven stem cell therapies, this analysis of representations on Twitter suggests that discussions in social media have also remained largely uncritical of the stem cell tourism phenomenon, with inaccurate representations of risks and benefits for patients.

  1. Molecular regulation of human hematopoietic stem cells

    NARCIS (Netherlands)

    van Galen, P.L.J.

    2014-01-01

    Peter van Galen focuses on understanding the determinants that maintain the stem cell state. Using human hematopoietic stem cells (HSCs) as a model, processes that govern self-renewal and tissue regeneration were investigated. Specifically, a role for microRNAs in balancing the human HSC

  2. A MODEL FOR POSTRADIATION STEM CELL KINETICS,

    Science.gov (United States)

    In polycythemic rats observed for 17 days postradiation (300 R, 250 KVP X-rays) it was noted that stem cell release diminished to 8 percent of the...correlate these findings with a kinetic model of erythropoiesis. It was suggested that the initial depression in stem cell release might be due to cellular

  3. Mesenchymal stem cells in oral reconstructive surgery

    DEFF Research Database (Denmark)

    Jakobsen, C; Sørensen, J A; Kassem, M

    2013-01-01

    This study evaluated clinical outcomes following intraoperative use of adult mesenchymal stem cells (MSCs) in various oral reconstructive procedures. PubMed was searched without language restrictions from 2000 to 2011 using the search words stem cell, oral surgery, tissue engineering, sinus lift...

  4. Skeletal stem cells in space and time

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Bianco, Paolo

    2015-01-01

    The nature, biological characteristics, and contribution to organ physiology of skeletal stem cells are not completely determined. Chan et al. and Worthley et al. demonstrate that a stem cell for skeletal tissues, and a system of more restricted, downstream progenitors, can be identified in mice...

  5. Targeting cancer stem cells: emerging role of Nanog transcription factor

    Directory of Open Access Journals (Sweden)

    Wang ML

    2013-09-01

    Full Text Available Mong-Lien Wang,1 Shih-Hwa Chiou,2,3 Cheng-Wen Wu1,4–61Institute of Biochemistry and Molecular Biology, 2Institute of Pharmacology, National Yang Ming University, Taipei, Taiwan; 3Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan; 4Institute of Microbiology and Immunology, 5Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan; 6Institute of Biomedical Science, Academia Sinica, Taipei, TaiwanAbstract: The involvement of stemness factors in cancer initiation and progression has drawn much attention recently, especially after the finding that introducing four stemness factors in somatic cells is able to reprogram the cells back to an embryonic stem cell-like state. Following accumulating data revealing abnormal elevated expression levels of key stemness factors, like Nanog, Oct4, and Sox2, in several types of cancer stem cells; the importance and therapeutic potential of targeting these stemness regulators in cancers has turned to research focus. Nanog determines cell fate in both embryonic and cancer stem cells; activating Nanog at an inappropriate time would result in cancer stem cells rather than normal pluripotent stem cells or differentiated somatic cells. Upregulated Nanog is correlated with poor survival outcome of patients with various types of cancer. The discoveries of downstream regulatory pathways directly or indirectly mediated by Nanog indicate that Nanog regulates several aspects of cancer development such as tumor cell proliferation, self-renewal, motility, epithelial-mesenchymal transition, immune evasion, and drug-resistance, which are all defined features for cancer stem cells. The current review paper illustrates the central role of Nanog in the regulatory networks of cancer malignant development and stemness acquirement, as well as in the communication between cancer cells and the surrounding stroma. Though a more defined model is needed to test the

  6. Amniotic fluid-derived mesenchymal stem cells as a novel ...

    African Journals Online (AJOL)

    CLEMENTINA

    2012-06-28

    Jun 28, 2012 ... stem cells (AFMSCs) have many advantages over other stem cells: avoiding much ethical controversy ... showed that induced pluripotent stem cells (iPSCs) have ... disadvantages of ESCs, BM-MSCs and iPSCs have.

  7. Spermatogonial stem cells: Progress and prospects

    Directory of Open Access Journals (Sweden)

    Mitsuru Komeya

    2015-01-01

    Full Text Available Twenty years ago, the transplantation of spermatogonial stem cells (SSCs from a mouse to other recipient mice was shown to be feasible, which clearly demonstrated the functional identity of SSCs. Since then, several important new findings and other technical developments have followed, which included a new hypothesis on their cell kinetics and spermatogonial hierarchy in the testis, a culture method allowing their self-renewal and proliferation, a testis tissue organ culture method, which induced their complete differentiation up to sperm, and the in vitro induction of germ cells from embryonic stem cells and induced pluripotent stem cells. These advancements reinforced or advanced our understanding of this unique cell. Nonetheless, there are many unresolved questions in the study of spermatogonial stem cells and a long road remains until these cells can be used clinically in reproductive medicine.

  8. Stem cell responses to plasma surface modified electrospun polyurethane scaffolds.

    Science.gov (United States)

    Zandén, Carl; Hellström Erkenstam, Nina; Padel, Thomas; Wittgenstein, Julia; Liu, Johan; Kuhn, H Georg

    2014-07-01

    The topographical effects from functional materials on stem cell behavior are currently of interest in tissue engineering and regenerative medicine. Here we investigate the influence of argon, oxygen, and hydrogen plasma surface modification of electrospun polyurethane fibers on human embryonic stem cell (hESC) and rat postnatal neural stem cell (NSC) responses. The plasma gases were found to induce three combinations of fiber surface functionalities and roughness textures. On randomly oriented fibers, plasma treatments lead to substantially increased hESC attachment and proliferation as compared to native fibers. Argon plasma was found to induce the most optimal combination of surface functionality and roughness for cell expansion. Contact guided migration of cells and alignment of cell processes were observed on aligned fibers. Neuronal differentiation around 5% was found for all samples and was not significantly affected by the induced variations of surface functional group distribution or individual fiber topography. In this study the influence of argon, oxygen, and hydrogen plasma surface modification of electrospun polyurethane fibers on human embryonic stem cell and rat postnatal neural stem cell (NSC) responses is studied with the goal of clarifying the potential effects of functional materials on stem cell behavior, a topic of substantial interest in tissue engineering and regenerative medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Nanotopographical Control of Stem Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Laura E. McNamara

    2010-01-01

    Full Text Available Stem cells have the capacity to differentiate into various lineages, and the ability to reliably direct stem cell fate determination would have tremendous potential for basic research and clinical therapy. Nanotopography provides a useful tool for guiding differentiation, as the features are more durable than surface chemistry and can be modified in size and shape to suit the desired application. In this paper, nanotopography is examined as a means to guide differentiation, and its application is described in the context of different subsets of stem cells, with a particular focus on skeletal (mesenchymal stem cells. To address the mechanistic basis underlying the topographical effects on stem cells, the likely contributions of indirect (biochemical signal-mediated and direct (force-mediated mechanotransduction are discussed. Data from proteomic research is also outlined in relation to topography-mediated fate determination, as this approach provides insight into the global molecular changes at the level of the functional effectors.

  10. Biophysical regulation of stem cell differentiation.

    Science.gov (United States)

    Govey, Peter M; Loiselle, Alayna E; Donahue, Henry J

    2013-06-01

    Bone adaptation to its mechanical environment, from embryonic through adult life, is thought to be the product of increased osteoblastic differentiation from mesenchymal stem cells. In parallel with tissue-scale loading, these heterogeneous populations of multipotent stem cells are subject to a variety of biophysical cues within their native microenvironments. Bone marrow-derived mesenchymal stem cells-the most broadly studied source of osteoblastic progenitors-undergo osteoblastic differentiation in vitro in response to biophysical signals, including hydrostatic pressure, fluid flow and accompanying shear stress, substrate strain and stiffness, substrate topography, and electromagnetic fields. Furthermore, stem cells may be subject to indirect regulation by mechano-sensing osteocytes positioned to more readily detect these same loading-induced signals within the bone matrix. Such paracrine and juxtacrine regulation of differentiation by osteocytes occurs in vitro. Further studies are needed to confirm both direct and indirect mechanisms of biophysical regulation within the in vivo stem cell niche.

  11. Cytokine signalling in embryonic stem cells

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Kalisz, Mark; Nielsen, Jens Høiriis

    2006-01-01

    Cytokines play a central role in maintaining self-renewal in mouse embryonic stem (ES) cells through a member of the interleukin-6 type cytokine family termed leukemia inhibitory factor (LIF). LIF activates the JAK-STAT3 pathway through the class I cytokine receptor gp130, which forms a trimeric...... pathways seem to converge on c-myc as a common target to promote self-renewal. Whereas LIF does not seem to stimulate self-renewal in human embryonic stem cells it cannot be excluded that other cytokines are involved. The pleiotropic actions of the increasing number of cytokines and receptors signalling...... via JAKs, STATs and SOCS exhibit considerable redundancy, compensation and plasticity in stem cells in accordance with the view that stem cells are governed by quantitative variations in strength and duration of signalling events known from other cell types rather than qualitatively different stem...

  12. Safety and immune regulatory properties of canine induced pluripotent stem cell-derived mesenchymal stem cells.

    Science.gov (United States)

    Chow, Lyndah; Johnson, Valerie; Regan, Dan; Wheat, William; Webb, Saiphone; Koch, Peter; Dow, Steven

    2017-12-01

    Mesenchymal stem cells (MSCs) exhibit broad immune modulatory activity in vivo and can suppress T cell proliferation and dendritic cell activation in vitro. Currently, most MSC for clinical usage are derived from younger donors, due to ease of procurement and to the superior immune modulatory activity. However, the use of MSC from multiple unrelated donors makes it difficult to standardize study results and compare outcomes between different clinical trials. One solution is the use of MSC derived from induced pluripotent stem cells (iPSC); as iPSC-derived MSC have nearly unlimited proliferative potential and exhibit in vitro phenotypic stability. Given the value of dogs as a spontaneous disease model for pre-clinical evaluation of stem cell therapeutics, we investigated the functional properties of canine iPSC-derived MSC (iMSC), including immune modulatory properties and potential for teratoma formation. We found that canine iMSC downregulated expression of pluripotency genes and appeared morphologically similar to conventional MSC. Importantly, iMSC retained a stable phenotype after multiple passages, did not form teratomas in immune deficient mice, and did not induce tumor formation in dogs following systemic injection. We concluded therefore that iMSC were phenotypically stable, immunologically potent, safe with respect to tumor formation, and represented an important new source of cells for therapeutic modulation of inflammatory disorders. Copyright © 2017. Published by Elsevier B.V.

  13. Clinical trials for stem cell transplantation: when are they needed?

    Science.gov (United States)

    Van Pham, Phuc

    2016-04-27

    In recent years, both stem cell research and the clinical application of these promising cells have increased rapidly. About 1000 clinical trials using stem cells have to date been performed globally. More importantly, more than 10 stem cell-based products have been approved in some countries. With the rapid growth of stem cell applications, some countries have used clinical trials as a tool to diminish the rate of clinical stem cell applications. However, the point at which stem cell clinical trials are essential remains unclear. This commentary discusses when stem cell clinical trials are essential for stem cell transplantation therapies.

  14. Skeletal Stem Cells: Origins, Functions and Uncertainties.

    Science.gov (United States)

    Mohamed, Fatma F; Franceschi, Renny T

    2017-12-01

    The development and maintenance of the skeleton requires a steady source of skeletal progenitors to provide the osteoblasts and chondrocytes necessary for bone and cartilage growth and development. The current model for skeletal stem cells (SSCs) posits that SSC/progenitor cells are present in bone marrow (BM) and other osteogenic sites such as cranial sutures where they undergo self-renewal and differentiation to give rise to the main skeletal tissues. SSCs hold great promise for understanding skeletal biology and genetic diseases of bone as well as for the advancement of bone tissue engineering and regenerative medicine strategies. In the past few years, a considerable effort has been devoted to identifying and purifying skeletal stem cells and determining their contribution to bone formation and homeostasis. Here, we review recent progress in this area with particular emphasis on the discovery of specific SSC markers, their use in tracking the progression of cell populations along specific lineages and the regulation of SSCs in both the appendicular and cranial skeleton.

  15. Glucocorticoids and hemopoietic stem cells

    International Nuclear Information System (INIS)

    Romashko, O.O.; Berin, G.I.

    1978-01-01

    Analyzing the data of home and foreign investigators the problems of the glucocorticoid effect on blood and bone marrow of experimental (including irradiated ones) animals are discussed. Considered are a character and mechanism of the adrenal cortex hormones effect on blood formation, as well as the effect of pharmacological doses of corticosteroids on CFU, their erythropoietic effect in physiological doses on a morphological picture of bone marrow after irradiation and subsequent introduction of hormones and the hormone effect on intensity of erythropoiesis recovery in irradiated mice. Presented are the experimental data on studying the effect of endogenic hypercorticoidism and a reduced level of endogenic corticosteroids on blood-forming stem cells in the irradiated mice and the data on the ACTH injection effect on CFU migration after irradiation. Evaluated are already available data and further investigations to ground advisability and conditions of using corticosteroids as well as determining rational therapeutic effects on secretion of endogenic glucocorticoids when treating blood system diseases

  16. Connecting Mitochondria, Metabolism, and Stem Cell Fate

    Science.gov (United States)

    Wanet, Anaïs; Arnould, Thierry; Najimi, Mustapha

    2015-01-01

    As sites of cellular respiration and energy production, mitochondria play a central role in cell metabolism. Cell differentiation is associated with an increase in mitochondrial content and activity and with a metabolic shift toward increased oxidative phosphorylation activity. The opposite occurs during reprogramming of somatic cells into induced pluripotent stem cells. Studies have provided evidence of mitochondrial and metabolic changes during the differentiation of both embryonic and somatic (or adult) stem cells (SSCs), such as hematopoietic stem cells, mesenchymal stem cells, and tissue-specific progenitor cells. We thus propose to consider those mitochondrial and metabolic changes as hallmarks of differentiation processes. We review how mitochondrial biogenesis, dynamics, and function are directly involved in embryonic and SSC differentiation and how metabolic and sensing pathways connect mitochondria and metabolism with cell fate and pluripotency. Understanding the basis of the crosstalk between mitochondria and cell fate is of critical importance, given the promising application of stem cells in regenerative medicine. In addition to the development of novel strategies to improve the in vitro lineage-directed differentiation of stem cells, understanding the molecular basis of this interplay could lead to the identification of novel targets to improve the treatment of degenerative diseases. PMID:26134242

  17. Stem Cell: Past, Present and Future- A Review Article | Avasthi ...

    African Journals Online (AJOL)

    Stem cells are basic cells of all multicellular organisms having the potency to differentiate into wide range of adult cells. Self renewal and totipotency are characteristic of stem cells. Though totipotency is shown by very early embryonic stem cells, the adult stem cells possess multipotency and differential plasticity which can ...

  18. Stem Cells and Engineered Scaffolds for Regenerative Wound Healing

    Directory of Open Access Journals (Sweden)

    Biraja C. Dash

    2018-03-01

    Full Text Available The normal wound healing process involves a well-organized cascade of biological pathways and any failure in this process leads to wounds becoming chronic. Non-healing wounds are a burden on healthcare systems and set to increase with aging population and growing incidences of obesity and diabetes. Stem cell-based therapies have the potential to heal chronic wounds but have so far seen little success in the clinic. Current research has been focused on using polymeric biomaterial systems that can act as a niche for these stem cells to improve their survival and paracrine activity that would eventually promote wound healing. Furthermore, different modification strategies have been developed to improve stem cell survival and differentiation, ultimately promoting regenerative wound healing. This review focuses on advanced polymeric scaffolds that have been used to deliver stem cells and have been tested for their efficiency in preclinical animal models of wounds.

  19. Stem Cells and Engineered Scaffolds for Regenerative Wound Healing.

    Science.gov (United States)

    Dash, Biraja C; Xu, Zhenzhen; Lin, Lawrence; Koo, Andrew; Ndon, Sifon; Berthiaume, Francois; Dardik, Alan; Hsia, Henry

    2018-03-09

    The normal wound healing process involves a well-organized cascade of biological pathways and any failure in this process leads to wounds becoming chronic. Non-healing wounds are a burden on healthcare systems and set to increase with aging population and growing incidences of obesity and diabetes. Stem cell-based therapies have the potential to heal chronic wounds but have so far seen little success in the clinic. Current research has been focused on using polymeric biomaterial systems that can act as a niche for these stem cells to improve their survival and paracrine activity that would eventually promote wound healing. Furthermore, different modification strategies have been developed to improve stem cell survival and differentiation, ultimately promoting regenerative wound healing. This review focuses on advanced polymeric scaffolds that have been used to deliver stem cells and have been tested for their efficiency in preclinical animal models of wounds.

  20. Nano-regenerative medicine towards clinical outcome of stem cell and tissue engineering in humans

    Science.gov (United States)

    Arora, Pooja; Sindhu, Annu; Dilbaghi, Neeraj; Chaudhury, Ashok; Rajakumar, Govindasamy; Rahuman, Abdul Abdul

    2012-01-01

    Nanotechnology is a fast growing area of research that aims to create nanomaterials or nanostructures development in stem cell and tissue-based therapies. Concepts and discoveries from the fields of bio nano research provide exciting opportunities of using stem cells for regeneration of tissues and organs. The application of nanotechnology to stem-cell biology would be able to address the challenges of disease therapeutics. This review covers the potential of nanotechnology approaches towards regenerative medicine. Furthermore, it focuses on current aspects of stem- and tissue-cell engineering. The magnetic nanoparticles-based applications in stem-cell research open new frontiers in cell and tissue engineering. PMID:22260258

  1. Epidermal stem cells - role in normal, wounded and pathological psoriatic and cancer skin

    DEFF Research Database (Denmark)

    Kamstrup, M.; Faurschou, A.; Gniadecki, R.

    2008-01-01

    In this review we focus on epidermal stem cells in the normal regeneration of the skin as well as in wounded and psoriatic skin. Furthermore, we discuss current data supporting the idea of cancer stem cells in the pathogenesis of skin carcinoma and malignant melanoma. Epidermal stem cells present...... or transit amplifying cells constitute a primary pathogenetic factor in the epidermal hyperproliferation seen in psoriasis. In cutaneous malignancies mounting evidence supports a stem cell origin in skin carcinoma and malignant melanoma and a possible existence of cancer stem cells Udgivelsesdato: 2008/5...

  2. Stem cells technology: a powerful tool behind new brain treatments.

    Science.gov (United States)

    Duru, Lucienne N; Quan, Zhenzhen; Qazi, Talal Jamil; Qing, Hong

    2018-06-18

    Stem cell research has recently become a hot research topic in biomedical research due to the foreseen unlimited potential of stem cells in tissue engineering and regenerative medicine. For many years, medicine has been facing intense challenges, such as an insufficient number of organ donations that is preventing clinicians to fulfill the increasing needs. To try and overcome this regrettable matter, research has been aiming at developing strategies to facilitate the in vitro culture and study of stem cells as a tool for tissue regeneration. Meanwhile, new developments in the microfluidics technology brought forward emerging cell culture applications that are currently allowing for a better chemical and physical control of cellular microenvironment. This review presents the latest developments in stem cell research that brought new therapies to the clinics and how the convergence of the microfluidics technology with stem cell research can have positive outcomes on the fields of regenerative medicine and high-throughput screening. These advances will bring new translational solutions for drug discovery and will upgrade in vitro cell culture to a new level of accuracy and performance. We hope this review will provide new insights into the understanding of new brain treatments from the perspective of stem cell technology especially regarding regenerative medicine and tissue engineering.

  3. Update on small intestinal stem cells.

    Science.gov (United States)

    Tesori, Valentina; Puglisi, Maria Ausiliatrice; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio

    2013-08-07

    Among somatic stem cells, those residing in the intestine represent a fascinating and poorly explored research field. Particularly, somatic stem cells reside in the small intestine at the level of the crypt base, in a constant balance between self-renewal and differentiation. Aim of the present review is to delve into the mechanisms that regulate the delicate equilibrium through which intestinal stem cells orchestrate intestinal architecture. To this aim, special focus will be addressed to identify the integrating signals from the surrounding niche, supporting a model whereby distinct cell populations facilitate homeostatic vs injury-induced regeneration.

  4. Stem cell migration - Methods and protocols

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2012-03-01

    Full Text Available The trafficking of stem cells is something unconsciously clear to any biologists (e.g., developmental biologists and physicians (e.g., all those taking care of hematopoietic and bone diseases and traumas; neverthless it is a phenomenon coming out as a hot topic just in these last years. Likely, the difficulties to track stem cells migration in vivo and the understanding of the elusive homing signals matching the circulating stem cells properties that makes these cells to stop and to start multiplication and differentiation....

  5. Differentiation of oligodendrocyte progenitor cells from dissociated monolayer and feeder-free cultured pluripotent stem cells.

    Science.gov (United States)

    Yamashita, Tomoko; Miyamoto, Yuki; Bando, Yoshio; Ono, Takashi; Kobayashi, Sakurako; Doi, Ayano; Araki, Toshihiro; Kato, Yosuke; Shirakawa, Takayuki; Suzuki, Yutaka; Yamauchi, Junji; Yoshida, Shigetaka; Sato, Naoya

    2017-01-01

    Oligodendrocytes myelinate axons and form myelin sheaths in the central nervous system. The development of therapies for demyelinating diseases, including multiple sclerosis and leukodystrophies, is a challenge because the pathogenic mechanisms of disease remain poorly understood. Primate pluripotent stem cell-derived oligodendrocytes are expected to help elucidate the molecular pathogenesis of these diseases. Oligodendrocytes have been successfully differentiated from human pluripotent stem cells. However, it is challenging to prepare large amounts of oligodendrocytes over a short amount of time because of manipulation difficulties under conventional primate pluripotent stem cell culture methods. We developed a proprietary dissociated monolayer and feeder-free culture system to handle pluripotent stem cell cultures. Because the dissociated monolayer and feeder-free culture system improves the quality and growth of primate pluripotent stem cells, these cells could potentially be differentiated into any desired functional cells and consistently cultured in large-scale conditions. In the current study, oligodendrocyte progenitor cells and mature oligodendrocytes were generated within three months from monkey embryonic stem cells. The embryonic stem cell-derived oligodendrocytes exhibited in vitro myelinogenic potency with rat dorsal root ganglion neurons. Additionally, the transplanted oligodendrocyte progenitor cells differentiated into myelin basic protein-positive mature oligodendrocytes in the mouse corpus callosum. This preparative method was used for human induced pluripotent stem cells, which were also successfully differentiated into oligodendrocyte progenitor cells and mature oligodendrocytes that were capable of myelinating rat dorsal root ganglion neurons. Moreover, it was possible to freeze, thaw, and successfully re-culture the differentiating cells. These results showed that embryonic stem cells and human induced pluripotent stem cells maintained in a

  6. Pluripotent stem cells and reprogrammed cells in farm animals.

    Science.gov (United States)

    Nowak-Imialek, Monika; Kues, Wilfried; Carnwath, Joseph W; Niemann, Heiner

    2011-08-01

    Pluripotent cells are unique because of their ability to differentiate into the cell lineages forming the entire organism. True pluripotent stem cells with germ line contribution have been reported for mice and rats. Human pluripotent cells share numerous features of pluripotentiality, but confirmation of their in vivo capacity for germ line contribution is impossible due to ethical and legal restrictions. Progress toward derivation of embryonic stem cells from domestic species has been made, but the derived cells were not able to produce germ line chimeras and thus are termed embryonic stem-like cells. However, domestic animals, in particular the domestic pig (Sus scrofa), are excellent large animals models, in which the clinical potential of stem cell therapies can be studied. Reprogramming technologies for somatic cells, including somatic cell nuclear transfer, cell fusion, in vitro culture in the presence of cell extracts, in vitro conversion of adult unipotent spermatogonial stem cells into germ line derived pluripotent stem cells, and transduction with reprogramming factors have been developed with the goal of obtaining pluripotent, germ line competent stem cells from domestic animals. This review summarizes the present state of the art in the derivation and maintenance of pluripotent stem cells in domestic animals.

  7. [Role of stem cell transplantation in treatment of primary cutaneous T‑cell lymphoma].

    Science.gov (United States)

    Stranzenbach, R; Theurich, S; Schlaak, M

    2017-09-01

    Within the heterogeneous group of cutaneous T‑cell lymphomas (CTCL) the therapeutic options for advanced and progressive forms are particularly limited. The therapeutic value of hematopoietic stem cell transplantation in CTCL was analyzed. A literature search using the keywords "hematopoietic stem cell transplantation" and "cutaneous T‑cell lymphoma" was performed in PubMed. Studies between 1990 and 2017 were taken into account. The studies identified were analyzed for relevance and being up to date. After reviewing the currently available literature no prospective randomized studies were found. Wu et al. showed a superiority of allogeneic transplantation in a comparison of autologous and allogeneic stem cell transplantation for cutaneous lymphoma. The graft-versus-lymphoma effect plays a significant role in a prolonged progression-free survival after allogeneic transplantation. By using a non-myeloablative conditioning regimen, stem cell transplantation can also be an option for elderly patients. The most extensive long-term data after allogeneic stem cell transplantation were reported by Duarte et al. in 2014. Autologous stem cell transplantation does not currently represent a therapeutic option, whereas allogeneic stem cell transplantation for advanced cutaneous T‑cell lymphoma, using a non-myeloablative conditioning scheme, does represent a therapeutic option. However, there is no consensus on the appropriate patients and the right timing. Morbidity and mortality of complications should be taken into account. Thus, this procedure is currently subject to an individual case decision.

  8. The Fountain of Stem Cell-Based Youth? Online Portrayals of Anti-Aging Stem Cell Technologies.

    Science.gov (United States)

    Rachul, Christen M; Percec, Ivona; Caulfield, Timothy

    2015-08-01

    The hype surrounding stem cell science has created a market opportunity for the cosmetic industry. Cosmetic and anti-aging products and treatments that make claims regarding stem cell technology are increasingly popular, despite a lack of evidence for safety and efficacy of such products. This study explores how stem cell-based products and services are portrayed to the public through online sources, in order to gain insight into the key messages available to consumers. A content analysis of 100 web pages was conducted to examine the portrayals of stem cell-based cosmetic and anti-aging products and treatments. A qualitative discourse analysis of one web page further examined how language contributes to the portrayals of these products and treatments to public audiences. The majority of web pages portrayed stem cell-based products as ready for public use. Very few web pages substantiated claims with scientific evidence, and even fewer mentioned any risks or limitations associated with stem cell science. The discourse analysis revealed that the framing and use of metaphor obscures the certainty of the efficacy of and length of time for stem cell-based anti-aging technology to be publicly available. This study highlights the need to educate patients and the public on the current limits of stem cell applications in this context. In addition, generating scientific evidence for stem cell-based anti-aging and aesthetic applications is needed for optimizing benefits and minimizing adverse effects for the public. Having more evidence on efficacy and risks will help to protect patients who are eagerly seeking out these treatments. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  9. Muscle Stem Cells: A Model System for Adult Stem Cell Biology.

    Science.gov (United States)

    Cornelison, Ddw; Perdiguero, Eusebio

    2017-01-01

    Skeletal muscle stem cells, originally termed satellite cells for their position adjacent to differentiated muscle fibers, are absolutely required for the process of skeletal muscle repair and regeneration. In the last decade, satellite cells have become one of the most studied adult stem cell systems and have emerged as a standard model not only in the field of stem cell-driven tissue regeneration but also in stem cell dysfunction and aging. Here, we provide background in the field and discuss recent advances in our understanding of muscle stem cell function and dysfunction, particularly in the case of aging, and the potential involvement of muscle stem cells in genetic diseases such as the muscular dystrophies.

  10. Immunological characteristics of mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Cíntia de Vasconcellos Machado

    2013-01-01

    Full Text Available Although bone marrow is the main source, mesenchymal stem cells have already been isolated from various other tissues, such as the liver, pancreas, adipose tissue, peripheral blood and dental pulp. These plastic adherent cells are morphologically similar to fibroblasts and have a high proliferative potential. This special group of cells possesses two essential characteristics: self-renewal and differentiation, with appropriate stimuli, into various cell types. Mesenchymal stem cells are considered immunologically privileged, since they do not express costimulatory molecules, required for complete T cell activation, on their surface. Several studies have shown that these cells exert an immunosuppressive effect on cells from both innate and acquired immunity systems. Mesenchymal stem cells can regulate the immune response in vitro by inhibiting the maturation of dendritic cells, as well as by suppressing the proliferation and function of T and B lymphocytes and natural killer cells. These special properties of mesenchymal stem cells make them a promising strategy in the treatment of immune mediated disorders, such as graft-versus-host disease and autoimmune diseases, as well as in regenerative medicine. The understanding of immune regulation mechanisms of mesenchymal stem cells, and also those involved in the differentiation of these cells in various lineages is primordial for their successful and safe application in different areas of medicine.

  11. TOPICAL REVIEW: Stem cells engineering for cell-based therapy

    Science.gov (United States)

    Taupin, Philippe

    2007-09-01

    Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

  12. Stem cells engineering for cell-based therapy.

    Science.gov (United States)

    Taupin, Philippe

    2007-09-01

    Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

  13. Müller stem cell dependent retinal regeneration.

    Science.gov (United States)

    Chohan, Annu; Singh, Usha; Kumar, Atul; Kaur, Jasbir

    2017-01-01

    Müller Stem cells to treat ocular diseases has triggered enthusiasm across all medical and scientific communities. Recent development in the field of stem cells has widened the prospects of applying cell based therapies to regenerate ocular tissues that have been irreversibly damaged by disease or injury. Ocular tissues such as the lens and the retina are now known to possess cell having remarkable regenerative abilities. Recent studies have shown that the Müller glia, a cell found in all vertebrate retinas, is the primary source of new neurons, and therefore are considered as the cellular basis for retinal regeneration in mammalian retinas. Here, we review the current status of retinal regeneration of the human eye by Müller stem cells. This review elucidates the current status of retinal regeneration by Müller stem cells, along with major retinal degenerative diseases where these stem cells play regenerative role in retinal repair and replacement. Copyright © 2016. Published by Elsevier B.V.

  14. Clinical trials for stem cell therapies

    Directory of Open Access Journals (Sweden)

    Lomax Geoff

    2011-05-01

    Full Text Available Abstract In recent years, clinical trials with stem cells have taken the emerging field in many new directions. While numerous teams continue to refine and expand the role of bone marrow and cord blood stem cells for their vanguard uses in blood and immune disorders, many others are looking to expand the uses of the various types of stem cells found in bone marrow and cord blood, in particular mesenchymal stem cells, to uses beyond those that could be corrected by replacing cells in their own lineage. Early results from these trials have produced mixed results often showing minor or transitory improvements that may be attributed to extracellular factors. More research teams are accelerating the use of other types of adult stem cells, in particular neural stem cells for diseases where beneficial outcome could result from either in-lineage cell replacement or extracellular factors. At the same time, the first three trials using cells derived from pluripotent cells have begun.

  15. The role of bone marrow derived mesenchymal stem cells in ...

    African Journals Online (AJOL)

    Stroke is the third most common cause of death, and a leading cause of physical disability in adults. Recovery after a major stroke is usually limited, but cell therapy, especially by application of mesenchymal stem cells (MSCs) is emerging with fixed neurologic deficits. The aim of the current study was directed to isolation ...

  16. The Stem Cell Hypothesis of Aging

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2010-04-01

    Full Text Available BACKGROUND: There is probably no single way to age. Indeed, so far there is no single accepted explanation or mechanisms of aging (although more than 300 theories have been proposed. There is an overall decline in tissue regenerative potential with age, and the question arises as to whether this is due to the intrinsic aging of stem cells or rather to the impairment of stem cell function in the aged tissue environment. CONTENT: Recent data suggest that we age, in part, because our self-renewing stem cells grow old as a result of heritable intrinsic events, such as DNA damage, as well as extrinsic forces, such as changes in their supporting niches. Mechanisms that suppress the development of cancer, such as senescence and apoptosis, which rely on telomere shortening and the activities of p53 and p16INK4a may also induce an unwanted consequence: a decline in the replicative function of certain stem cells types with advancing age. This decrease regenerative capacity appears to pointing to the stem cell hypothesis of aging. SUMMARY: Recent evidence suggested that we grow old partly because of our stem cells grow old as a result of mechanisms that suppress the development of cancer over a lifetime. We believe that a further, more precise mechanistic understanding of this process will be required before this knowledge can be translated into human anti-aging therapies. KEYWORDS: stem cells, senescence, telomere, DNA damage, epigenetic, aging.

  17. Adult Stem Cells and Diseases of Aging

    Directory of Open Access Journals (Sweden)

    Lisa B. Boyette

    2014-01-01

    Full Text Available Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan.

  18. Periarteriolar Glioblastoma Stem Cell Niches Express Bone Marrow Hematopoietic Stem Cell Niche Proteins

    NARCIS (Netherlands)

    Hira, Vashendriya V. V.; Wormer, Jill R.; Kakar, Hala; Breznik, Barbara; van der Swaan, Britt; Hulsbos, Renske; Tigchelaar, Wikky; Tonar, Zbynek; Khurshed, Mohammed; Molenaar, Remco J.; van Noorden, Cornelis J. F.

    2018-01-01

    In glioblastoma, a fraction of malignant cells consists of therapy-resistant glioblastoma stem cells (GSCs) residing in protective niches that recapitulate hematopoietic stem cell (HSC) niches in bone marrow. We have previously shown that HSC niche proteins stromal cell-derived factor-1α (SDF-1α),

  19. Induced pluripotent stem (iPS) cells from human fetal stem cells

    OpenAIRE

    Guillot, P. V.

    2016-01-01

    Pluripotency defines the ability of stem cells to differentiate into all the lineages of the three germ layers and self-renew indefinitely. Somatic cells can regain the developmental potential of embryonic stem cells following ectopic expression of a set of transcription factors or, in certain circumstances, via modulation of culture conditions and supplementation with small molecule, that is, induced pluripotent stem (iPS) cells. Here, we discuss the use of fetal tissues for reprogramming, f...

  20. PrPC from stem cells to cancer

    Directory of Open Access Journals (Sweden)

    Séverine eMartin-Lannerée

    2014-09-01

    Full Text Available The cellular prion protein PrPC was initially discovered as the normal counterpart of the pathological scrapie prion protein PrPSc, the main component of the infectious agent of Transmissible Spongiform Encephalopathies. While clues as to the physiological function of this ubiquitous protein were greatly anticipated from the development of knock-out animals, PrP-null mice turned out to be viable and to develop without major phenotypic abnormalities. Notwithstanding, the discovery that hematopoietic stem cells from PrP-null mice have impaired long-term repopulating potential has set the stage for investigating into the role of PrPC in stem cell biology. A wealth of data have now exemplified that PrPC is expressed in distinct types of stem cells and regulates their self-renewal as well as their differentiation potential. A role for PrPC in the fate restriction of embryonic stem cells has further been proposed. Paralleling these observations, an overexpression of PrPC has been documented in various types of tumours. In line with the contribution of PrPC to stemness and to the proliferation of cancer cells, PrPC was recently found to be enriched in subpopulations of tumour-initiating cells. In the present review, we summarize the current knowledge of the role played by PrPC in stem cell biology and discuss how the subversion of its function may contribute to cancer progression.

  1. Functionalized scaffolds to control dental pulp stem cell fate

    Science.gov (United States)

    Piva, Evandro; Silva, Adriana F.; Nör, Jacques E.

    2014-01-01

    Emerging understanding about interactions between stem cells, scaffolds and morphogenic factors has accelerated translational research in the field of dental pulp tissue engineering. Dental pulp stem cells constitute a sub-population of cells endowed with self-renewal and multipotency. Dental pulp stem cells seeded in biodegradable scaffolds and exposed to dentin-derived morphogenic signals give rise to a pulp-like tissue capable of generating new dentin. Notably, dentin-derived proteins are sufficient to induce dental pulp stem cell differentiation into odontoblasts. Ongoing work is focused on developing ways of mobilizing dentin-derived proteins and disinfecting the root canal of necrotic teeth without compromising the morphogenic potential of these signaling molecules. On the other hand, dentin by itself does not appear to be capable of inducing endothelial differentiation of dental pulp stem cells, despite the well known presence of angiogenic factors in dentin. This is particularly relevant in the context of dental pulp tissue engineering in full root canals, where access to blood supply is limited to the apical foramina. To address this challenge, scientists are looking at ways to use the scaffold as a controlled release device for angiogenic factors. The aim of this manuscript is to present and discuss current strategies to functionalize injectable scaffolds and customize them for dental pulp tissue engineering. The long-term goal of this work is to develop stem cell-based therapies that enable the engineering of functional dental pulps capable of generating new tubular dentin in humans. PMID:24698691

  2. In vitro regeneration of kidney from pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Osafune, Kenji, E-mail: osafu@cira.kyoto-u.ac.jp [Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan); JST Yamanaka iPS Cell Special Project, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan)

    2010-10-01

    Although renal transplantation has proved a successful treatment for the patients with end-stage renal failure, the therapy is hampered by the problem of serious shortage of donor organs. Regenerative medicine using stem cells, including cell transplantation therapy, needs to be developed to solve the problem. We previously identified the multipotent progenitor cells in the embryonic mouse kidney that can give rise to several kinds of epithelial cells found in adult kidney, such as glomerular podocytes and renal tubular epithelia. Establishing the method to generate the progenitors from human pluripotent stem cells that have the capacity to indefinitely proliferate in vitro is required for the development of kidney regeneration strategy. We review the current status of the research on the differentiation of pluripotent stem cells into renal lineages and describe cues to promote this research field.

  3. In vitro regeneration of kidney from pluripotent stem cells

    International Nuclear Information System (INIS)

    Osafune, Kenji

    2010-01-01

    Although renal transplantation has proved a successful treatment for the patients with end-stage renal failure, the therapy is hampered by the problem of serious shortage of donor organs. Regenerative medicine using stem cells, including cell transplantation therapy, needs to be developed to solve the problem. We previously identified the multipotent progenitor cells in the embryonic mouse kidney that can give rise to several kinds of epithelial cells found in adult kidney, such as glomerular podocytes and renal tubular epithelia. Establishing the method to generate the progenitors from human pluripotent stem cells that have the capacity to indefinitely proliferate in vitro is required for the development of kidney regeneration strategy. We review the current status of the research on the differentiation of pluripotent stem cells into renal lineages and describe cues to promote this research field.

  4. From here to there, progenitor cells and stem cells are everywhere in lung vascular remodeling

    Directory of Open Access Journals (Sweden)

    Rebecca L. Heise

    2016-08-01

    Full Text Available The field of stem cell biology, cell therapy and regenerative medicine has expanded almost exponentially in the last decade. Clinical trials are evaluating the potential therapeutic use of stem cells in many adult and pediatric lung diseases with vascular component, such as bronchopulmonary dysplasia (BPD, chronic obstructive pulmonary disease (COPD, idiopathic pulmonary fibrosis (IPF or pulmonary arterial hypertension (PAH. Extensive research activity is exploring lung resident and circulating progenitor cells and their contribution to vascular complications of chronic lung diseases, and researchers hope to use resident or circulating stem/progenitor cells to treat chronic lung diseases and their vascular complications. It is becoming more and more clear that progress in mechanobiology will help to understand the various influences of physical forces and extracellular matrix composition on the phenotype and features of the progenitor cells and stem cells. The current review provides an overview of current concepts in the field.

  5. Cancer stem cells and personalized cancer nanomedicine.

    Science.gov (United States)

    Gener, Petra; Rafael, Diana Fernandes de Sousa; Fernández, Yolanda; Ortega, Joan Sayós; Arango, Diego; Abasolo, Ibane; Videira, Mafalda; Schwartz, Simo

    2016-02-01

    Despite the progress in cancer treatment over the past years advanced cancer is still an incurable disease. Special attention is pointed toward cancer stem cell (CSC)-targeted therapies, because this minor cell population is responsible for the treatment resistance, metastatic growth and tumor recurrence. The recently described CSC dynamic phenotype and interconversion model of cancer growth hamper even more the possible success of current cancer treatments in advanced cancer stages. Accordingly, CSCs can be generated through dedifferentiation processes from non-CSCs, in particular, when CSC populations are depleted after treatment. In this context, the use of targeted CSC nanomedicines should be considered as a promising tool to increase CSC sensitivity and efficacy of specific anti-CSC therapies.

  6. Hematopoietic Stem Cell Transplantation and History

    Directory of Open Access Journals (Sweden)

    Atila Tanyeli

    2014-02-01

    Full Text Available Attemps to employ marrow stem cell for therapeutic purpose began in 1940’s. Marrow transplantation might be of use not only in irradiation protection, but also with therapeutic aim to marrow aplasia, leukemia and other diseases. The use and defining tissue antigens in humans were crucial to the improving of transplantation. The administration of methotrexate for GVHD improved the long term survival. Conditioning regimens for myeloablation designed according to diseases. Cord blood and peripheral blood stem cells were used for transplantion after 1980’s. Cord blood and bone marrow stem cell banks established to find HLA matched donor.

  7. Concise Review: Quiescence in Adult Stem Cells

    DEFF Research Database (Denmark)

    Rumman, M; Dhawan, J; Kassem, Moustapha

    2015-01-01

    Adult stem cells (ASCs) are tissue resident stem cells responsible for tissue homeostasis and regeneration following injury. In uninjured tissues, ASCs exist in a nonproliferating, reversibly cell cycle-arrested state known as quiescence or G0. A key function of the quiescent state is to preserve...... stemness in ASCs by preventing precocious differentiation, and thus maintaining a pool of undifferentiated ASCs. Recent evidences suggest that quiescence is an actively maintained state and that excessive or defective quiescence may lead to compromised tissue regeneration or tumorigenesis. The aim...

  8. Stem cells and the evolving notion of cellular identity

    OpenAIRE

    Daley, George Q.

    2015-01-01

    Stem cells are but one class of the myriad types of cells within an organism. With potential to self-renew and capacity to differentiate, stem cells play essential roles at multiple stages of development. In the early embryo, pluripotent stem cells represent progenitors for all tissues while later in development, tissue-restricted stem cells give rise to cells with highly specialized functions. As best understood in the blood, skin and gut, stem cells are the seeds that sustain tissue homeost...

  9. Autologous blood cell therapies from pluripotent stem cells

    Science.gov (United States)

    Lengerke, Claudia; Daley, George Q.

    2010-01-01

    Summary The discovery of human embryonic stem cells (hESCs) raised promises for a universal resource for cell based therapies in regenerative medicine. Recently, fast-paced progress has been made towards the generation of pluripotent stem cells (PSCs) amenable for clinical applications, culminating in reprogramming of adult somatic cells to autologous PSCs that can be indefinitely expanded in vitro. However, besides the efficient generation of bona fide, clinically safe PSCs (e.g. without the use of oncoproteins and gene transfer based on viruses inserting randomly into the genome), a major challenge in the field remains how to efficiently differentiate PSCs to specific lineages and how to select for cells that will function normally upon transplantation in adults. In this review, we analyse the in vitro differentiation potential of PSCs to the hematopoietic lineage discussing blood cell types that can be currently obtained, limitations in derivation of adult-type HSCs and prospects for clinical application of PSCs-derived blood cells. PMID:19910091

  10. HLA engineering of human pluripotent stem cells.

    Science.gov (United States)

    Riolobos, Laura; Hirata, Roli K; Turtle, Cameron J; Wang, Pei-Rong; Gornalusse, German G; Zavajlevski, Maja; Riddell, Stanley R; Russell, David W

    2013-06-01

    The clinical use of human pluripotent stem cells and their derivatives is limited by the rejection of transplanted cells due to differences in their human leukocyte antigen (HLA) genes. This has led to the proposed use of histocompatible, patient-specific stem cells; however, the preparation of many different stem cell lines for clinical use is a daunting task. Here, we develop two distinct genetic engineering approaches that address this problem. First, we use a combination of gene targeting and mitotic recombination to derive HLA-homozygous embryonic stem cell (ESC) subclones from an HLA-heterozygous parental line. A small bank of HLA-homozygous stem cells with common haplotypes would match a significant proportion of the population. Second, we derive HLA class I-negative cells by targeted disruption of both alleles of the Beta-2 Microglobulin (B2M) gene in ESCs. Mixed leukocyte reactions and peptide-specific HLA-restricted CD8(+) T cell responses were reduced in class I-negative cells that had undergone differentiation in embryoid bodies. These B2M(-/-) ESCs could act as universal donor cells in applications where the transplanted cells do not express HLA class II genes. Both approaches used adeno-associated virus (AAV) vectors for efficient gene targeting in the absence of potentially genotoxic nucleases, and produced pluripotent, transgene-free cell lines.

  11. HLA Engineering of Human Pluripotent Stem Cells

    Science.gov (United States)

    Riolobos, Laura; Hirata, Roli K; Turtle, Cameron J; Wang, Pei-Rong; Gornalusse, German G; Zavajlevski, Maja; Riddell, Stanley R; Russell, David W

    2013-01-01

    The clinical use of human pluripotent stem cells and their derivatives is limited by the rejection of transplanted cells due to differences in their human leukocyte antigen (HLA) genes. This has led to the proposed use of histocompatible, patient-specific stem cells; however, the preparation of many different stem cell lines for clinical use is a daunting task. Here, we develop two distinct genetic engineering approaches that address this problem. First, we use a combination of gene targeting and mitotic recombination to derive HLA-homozygous embryonic stem cell (ESC) subclones from an HLA-heterozygous parental line. A small bank of HLA-homozygous stem cells with common haplotypes would match a significant proportion of the population. Second, we derive HLA class I–negative cells by targeted disruption of both alleles of the Beta-2 Microglobulin (B2M) gene in ESCs. Mixed leukocyte reactions and peptide-specific HLA-restricted CD8+ T cell responses were reduced in class I–negative cells that had undergone differentiation in embryoid bodies. These B2M−/− ESCs could act as universal donor cells in applications where the transplanted cells do not express HLA class II genes. Both approaches used adeno-associated virus (AAV) vectors for efficient gene targeting in the absence of potentially genotoxic nucleases, and produced pluripotent, transgene-free cell lines. PMID:23629003

  12. Microencapsulation of Stem Cells for Therapy.

    Science.gov (United States)

    Leslie, Shirae K; Kinney, Ramsey C; Schwartz, Zvi; Boyan, Barbara D

    2017-01-01

    An increasing demand to regenerate tissues from patient-derived sources has led to the development of cell-based therapies using autologous stem cells, thereby decreasing immune rejection of scaffolds coupled with allogeneic stem cells or allografts. Adult stem cells are multipotent and are readily available in tissues such as fat and bone marrow. They possess the ability to repair and regenerate tissue through the production of therapeutic factors, particularly vasculogenic proteins. A major challenge in cell-based therapies is localizing the delivered stem cells to the target site. Microencapsulation of cells provides a porous polymeric matrix that can provide a protected environment, localize the cells to one area, and maintain their viability by enabling the exchange of nutrients and waste products between the encapsulated cells and the surrounding tissue. In this chapter, we describe a method to produce injectable microbeads containing a tunable number of stem cells using the biopolymer alginate. The microencapsulation process involves extrusion of the alginate suspension containing cells from a microencapsulator, a syringe pump to control its flow rate, an electrostatic potential to overcome capillary forces and a reduced Ca ++ cross-linking solution containing a nutrient osmolyte, to form microbeads. This method allows the encapsulated cells to remain viable up to three weeks in culture and up to three months in vivo and secrete growth factors capable of supporting tissue regeneration.

  13. Stem cell dynamics in the hair follicle niche

    Science.gov (United States)

    Rompolas, Panteleimon; Greco, Valentina

    2014-01-01

    Hair follicles are skin appendages of the mammalian skin that have the ability to periodically and stereotypically regenerate in order to continuously produce new hair over our lifetime. The ability of the hair follicle to regenerate is due to the presence of stem cells that along with other cell populations and non-cellular components, including molecular signals and extracellular material, make up a niche microenvironment. Mounting evidence suggests that the niche is critical for regulating stem cell behavior and thus the process of regeneration. Here we review the literature concerning past and current studies that have utilized mouse genetic models, combined with other approaches to dissect the molecular and cellular composition of the hair follicle niche. We also discuss our current understanding of how stem cells operate within the niche during the process of tissue regeneration and the factors that regulate their behavior. PMID:24361866

  14. Translational findings from cardiovascular stem cell research.

    Science.gov (United States)

    Mazhari, Ramesh; Hare, Joshua M

    2012-01-01

    The possibility of using stem cells to regenerate damaged myocardium has been actively investigated since the late 1990s. Consistent with the traditional view that the heart is a "postmitotic" organ that possesses minimal capacity for self-repair, much of the preclinical and clinical work has focused exclusively on introducing stem cells into the heart, with the hope of differentiation of these cells into functioning cardiomyocytes. This approach is ongoing and retains promise but to date has yielded inconsistent successes. More recently, it has become widely appreciated that the heart possesses endogenous repair mechanisms that, if adequately stimulated, might regenerate damaged cardiac tissue from in situ cardiac stem cells. Accordingly, much recent work has focused on engaging and enhancing endogenous cardiac repair mechanisms. This article reviews the literature on stem cell-based myocardial regeneration, placing emphasis on the mutually enriching interaction between basic and clinical research. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Hematopoietic stem cell origin of connective tissues.

    Science.gov (United States)

    Ogawa, Makio; Larue, Amanda C; Watson, Patricia M; Watson, Dennis K

    2010-07-01

    Connective tissue consists of "connective tissue proper," which is further divided into loose and dense (fibrous) connective tissues and "specialized connective tissues." Specialized connective tissues consist of blood, adipose tissue, cartilage, and bone. In both loose and dense connective tissues, the principal cellular element is fibroblasts. It has been generally believed that all cellular elements of connective tissue, including fibroblasts, adipocytes, chondrocytes, and bone cells, are generated solely by mesenchymal stem cells. Recently, a number of studies, including those from our laboratory based on transplantation of single hematopoietic stem cells, strongly suggested a hematopoietic stem cell origin of these adult mesenchymal tissues. This review summarizes the experimental evidence for this new paradigm and discusses its translational implications. Copyright 2010 ISEH - Society for Hematology and Stem Cells. All rights reserved.

  16. Bioprinting and Differentiation of Stem Cells

    Directory of Open Access Journals (Sweden)

    Scott A. Irvine

    2016-09-01

    Full Text Available The 3D bioprinting of stem cells directly into scaffolds offers great potential for the development of regenerative therapies; in particular for the fabrication of organ and tissue substitutes. For this to be achieved; the lineage fate of bioprinted stem cell must be controllable. Bioprinting can be neutral; allowing culture conditions to trigger differentiation or alternatively; the technique can be designed to be stimulatory. Such factors as the particular bioprinting technique; bioink polymers; polymer cross-linking mechanism; bioink additives; and mechanical properties are considered. In addition; it is discussed that the stimulation of stem cell differentiation by bioprinting may lead to the remodeling and modification of the scaffold over time matching the concept of 4D bioprinting. The ability to tune bioprinting properties as an approach to fabricate stem cell bearing scaffolds and to also harness the benefits of the cells multipotency is of considerable relevance to the field of biomaterials and bioengineering.

  17. STEM CELL RESEARCH-CONCEPT AND CONTROVERSIES

    African Journals Online (AJOL)

    Dr. E. P. Gharoro

    cells, heart cells, brain cells, etc.). Some researchers regard them as offering the greatest potential for the .... anaemia, heart damage, corneal damage, etc. To be useful for transplant purposes, stem cells must ... activity in the brain was demonstrated contradicting caja's “no new neurons” dogma. However, research into.

  18. The Androgen Receptor Bridges Stem Cell-Associated Signaling Nodes in Prostate Stem Cells

    Directory of Open Access Journals (Sweden)

    Alastair H. Davies

    2016-01-01

    Full Text Available The therapeutic potential of stem cells relies on dissecting the complex signaling networks that are thought to regulate their pluripotency and self-renewal. Until recently, attention has focused almost exclusively on a small set of “core” transcription factors for maintaining the stem cell state. It is now clear that stem cell regulatory networks are far more complex. In this review, we examine the role of the androgen receptor (AR in coordinating interactions between signaling nodes that govern the balance of cell fate decisions in prostate stem cells.

  19. Prion potency in stem cells biology.

    Science.gov (United States)

    Lopes, Marilene H; Santos, Tiago G

    2012-01-01

    Prion protein (PrP) can be considered a pivotal molecule because it interacts with several partners to perform a diverse range of critical biological functions that might differ in embryonic and adult cells. In recent years, there have been major advances in elucidating the putative role of PrP in the basic biology of stem cells in many different systems. Here, we review the evidence indicating that PrP is a key molecule involved in driving different aspects of the potency of embryonic and tissue-specific stem cells in self-perpetuation and differentiation in many cell types. It has been shown that PrP is involved in stem cell self-renewal, controlling pluripotency gene expression, proliferation, and neural and cardiomyocyte differentiation. PrP also has essential roles in distinct processes that regulate tissue-specific stem cell biology in nervous and hematopoietic systems and during muscle regeneration. Results from our own investigations have shown that PrP is able to modulate self-renewal and proliferation in neural stem cells, processes that are enhanced by PrP interactions with stress inducible protein 1 (STI1). Thus, the available data reveal the influence of PrP in acting upon the maintenance of pluripotent status or the differentiation of stem cells from the early embryogenesis through adulthood.

  20. Ethical and Safety Issues of Stem Cell-Based Therapy.

    Science.gov (United States)

    Volarevic, Vladislav; Markovic, Bojana Simovic; Gazdic, Marina; Volarevic, Ana; Jovicic, Nemanja; Arsenijevic, Nebojsa; Armstrong, Lyle; Djonov, Valentin; Lako, Majlinda; Stojkovic, Miodrag

    2018-01-01

    Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns. In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine. We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies. With previous derivation of induced pluripotent stem cells (iPSCs) this problem has been overcome, however current perspectives regarding clinical translation of iPSCs still remain. Unlimited differentiation potential of iPSCs which can be used in human reproductive cloning, as a risk for generation of genetically engineered human embryos and human-animal chimeras, is major ethical issue, while undesired differentiation and malignant transformation are major safety issues. Although clinical application of mesenchymal stem cells (MSCs) has shown beneficial effects in the therapy of autoimmune and chronic inflammatory diseases, the ability to promote tumor growth and metastasis and overestimated therapeutic potential of MSCs still provide concerns for the field of regenerative medicine. This review offers stem cell scientists, clinicians and patient's useful information and could be used as a starting point for more in-depth analysis of ethical and safety issues related to clinical application of stem cells.

  1. Therapeutic potential of stem cells in auditory hair cell repair

    Directory of Open Access Journals (Sweden)

    Ryuji Hata

    2009-01-01

    Full Text Available The prevalence of acquired hearing loss is very high. About 10% of the total population and more than one third of the population over 65 years suffer from debilitating hearing loss. The most common type of hearing loss in adults is idiopathic sudden sensorineural hearing loss (ISSHL. In the majority of cases, ISSHL is permanent and typically associated with loss of sensory hair cells in the organ of Corti. Following the loss of sensory hair cells, the auditory neurons undergo secondary degeneration. Sensory hair cells and auditory neurons do not regenerate throughout life, and loss of these cells is irreversible and cumulative. However, recent advances in stem cell biology have gained hope that stem cell therapy comes closer to regenerating sensory hair cells in humans. A major advance in the prospects for the use of stem cells to restore normal hearing comes with the recent discovery that hair cells can be generated ex vivo from embryonic stem (ES cells, adult inner ear stem cells and neural stem cells. Furthermore, there is increasing evidence that stem cells can promote damaged cell repair in part by secreting diffusible molecules such as growth factors. These results suggest that stem-cell-based treatment regimens can be applicable to the damaged inner ear as future clinical applications.Previously we have established an animal model of cochlear ischemia in gerbils and showed progressive hair cell loss up to 4 days after ischemia. Auditory brain stem response (ABR recordings have demonstrated that this gerbil model displays severe deafness just after cochlear ischemia and gradually recovers thereafter. These pathological findings and clinical manifestations are reminiscent of ISSHL in humans. In this study, we have shown the effectiveness of stem cell therapy by using this animal model of ISSHL.

  2. Radiopharmaceutical Stem Cell Tracking for Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Paulo Henrique Rosado-de-Castro

    2014-01-01

    Full Text Available Although neurological ailments continue to be some of the main causes of disease burden in the world, current therapies such as pharmacological agents have limited potential in the restoration of neural functions. Cell therapies, firstly applied to treat different hematological diseases, are now being investigated in preclinical and clinical studies for neurological illnesses. However, the potential applications and mechanisms for such treatments are still poorly comprehended and are the focus of permanent research. In this setting, noninvasive in vivo imaging allows better understanding of several aspects of stem cell therapies. Amongst the various methods available, radioisotope cell labeling has become one of the most promising since it permits tracking of cells after injection by different routes to investigate their biodistribution. A significant increase in the number of studies utilizing this method has occurred in the last years. Here, we review the different radiopharmaceuticals, imaging techniques, and findings of the preclinical and clinical reports published up to now. Moreover, we discuss the limitations and future applications of radioisotope cell labeling in the field of cell transplantation for neurological diseases.

  3. Stem cell clinics online: the direct-to-consumer portrayal of stem cell medicine.

    Science.gov (United States)

    Lau, Darren; Ogbogu, Ubaka; Taylor, Benjamin; Stafinski, Tania; Menon, Devidas; Caulfield, Timothy

    2008-12-04

    Despite the immature state of stem cell medicine, patients are seeking and accessing putative stem cell therapies in an "early market" in which direct-to-consumer advertising via the internet likely plays an important role. We analyzed stem cell clinic websites and appraised the relevant published clinical evidence of stem cell therapies to address three questions about the direct-to-consumer portrayal of stem cell medicine in this early market: What sorts of therapies are being offered? How are they portrayed? Is there clinical evidence to support the use of these therapies? We found that the portrayal of stem cell medicine on provider websites is optimistic and unsubstantiated by peer-reviewed literature.

  4. Stem cell tracking using iron oxide nanoparticles

    Directory of Open Access Journals (Sweden)

    Bull E

    2014-03-01

    Full Text Available Elizabeth Bull,1 Seyed Yazdan Madani,1 Roosey Sheth,1 Amelia Seifalian,1 Mark Green,2 Alexander M Seifalian1,31UCL Centre for Nanotechnology and Regenerative Medicine, Division of Surgery and Interventional Science, University College London, London, 2Department of Physics, King’s College London, Strand Campus, London, UK; 3Royal Free London National Health Service Foundation Trust Hospital, London, UKAbstract: Superparamagnetic iron oxide nanoparticles (SPIONs are an exciting advancement in the field of nanotechnology. They expand the possibilities of noninvasive analysis and have many useful properties, making them potential candidates for numerous novel applications. Notably, they have been shown that they can be tracked by magnetic resonance imaging (MRI and are capable of conjugation with various cell types, including stem cells. In-depth research has been undertaken to establish these benefits, so that a deeper level of understanding of stem cell migratory pathways and differentiation, tumor migration, and improved drug delivery can be achieved. Stem cells have the ability to treat and cure many debilitating diseases with limited side effects, but a main problem that arises is in the noninvasive tracking and analysis of these stem cells. Recently, researchers have acknowledged the use of SPIONs for this purpose and have set out to establish suitable protocols for coating and attachment, so as to bring MRI tracking of SPION-labeled stem cells into common practice. This review paper explains the manner in which SPIONs are produced, conjugated, and tracked using MRI, as well as a discussion on their limitations. A concise summary of recently researched magnetic particle coatings is provided, and the effects of SPIONs on stem cells are evaluated, while animal and human studies investigating the role of SPIONs in stem cell tracking will be explored.Keywords: stem cells, nanoparticle, magnetic

  5. Glial origin of mesenchymal stem cells in a tooth model system

    NARCIS (Netherlands)

    Kaukua, Nina; Shahidi, Maryam Khatibi; Konstantinidou, Chrysoula; Dyachuk, Vyacheslav; Kaucka, Marketa; Furlan, Alessandro; An, Zhengwen; Wang, Longlong; Hultman, Isabell; Ahrlund-Richter, Lars; Blom, Hans; Brismar, Hjalmar; Lopes, Natalia Assaife; Pachnis, Vassilis; Suter, Ueli; Clevers, Hans; Thesleff, Irma; Sharpe, Paul; Ernfors, Patrik; Fried, Kaj; Adameyko, Igor

    2014-01-01

    Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair. The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells

  6. The Controversial Clinicobiological Role of Breast Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Claudia Casarsa

    2008-01-01

    Full Text Available Breast cancer remains a leading cause of morbidity and mortality in women mainly because of the propensity of primary breast tumors to metastasize. Growing experimental evidence suggests that cancer stem cells (CSCs may contribute to tumor progression and metastasis spread. However, despite the tremendous clinical potential of such cells and their possible therapeutic management, the real nature of CSCs remains to be elucidated. Starting from what is currently known about normal mammary stem/progenitor cells, to better define the cell that originates a tumor or is responsible for metastatic spread, this review will discuss experimental evidence of breast cancer stem cells and speculate about the clinical importance and implications of their evaluation.

  7. Allogeneic Peripheral Blood Stem Cell Harvest

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Allogeneic Peripheral Blood Stem Cell Harvest. Mobilization protocol. G-CSF 10 mcg/Kg / day for 5 days. Pheresis. Cobe Spectra; Haemonetics mcs+. Enumeration. CD34 counts; Cfu-GM assays.

  8. Mesenchymal stem cell therapy for laryngotracheal stenosis

    DEFF Research Database (Denmark)

    Jakobsen, Kathrine Kronberg; Grønhøj, Christian; Jensen, David H

    2017-01-01

    BACKGROUND: Laryngotracheal stenosis (LTS) can be either congenital or acquired. Laryngeal stenosis is most often encountered after prolonged intubation. The mechanism for stenosis following intubation is believed to be hypertrophic scarring. Mesenchymal stem cells (MSCs) therapy has shown...

  9. Guidelines for human embryonic stem cell research

    National Research Council Canada - National Science Library

    Committee on Guidelines for Human Embryonic Stem Cell Research, National Research Council

    2005-01-01

    Since 1998, the volume of research being conducted using human embryonic stem (hES) cells has expanded primarily using private funds because of restrictions on the use of federal funds for such research...

  10. Stomach development, stem cells and disease

    Science.gov (United States)

    Kim, Tae-Hee; Shivdasani, Ramesh A.

    2016-01-01

    The stomach, an organ derived from foregut endoderm, secretes acid and enzymes and plays a key role in digestion. During development, mesenchymal-epithelial interactions drive stomach specification, patterning, differentiation and growth through selected signaling pathways and transcription factors. After birth, the gastric epithelium is maintained by the activity of stem cells. Developmental signals are aberrantly activated and stem cell functions are disrupted in gastric cancer and other disorders. Therefore, a better understanding of stomach development and stem cells can inform approaches to treating these conditions. This Review highlights the molecular mechanisms of stomach development and discusses recent findings regarding stomach stem cells and organoid cultures, and their roles in investigating disease mechanisms. PMID:26884394

  11. Generating pluripotent stem cells: Differential epigenetic changes during cellular reprogramming

    OpenAIRE

    Tobin, Stacey C.; Kim, Kitai

    2012-01-01

    Pluripotent stem cells hold enomous potential for therapuetic applications in tissue replacement therapy. Reprogramming somatic cells from a patient donor to generate pluripotent stem cells involves both ethical concerns inherent in the use of embryonic and oocyte-derived stem cells, as well as issues of histocompatibility. Among the various pluripotent stem cells, induced pluripotent stem cells (iPSC)—derived by ectopic expression of four reprogramming factors in donor somatic cells—are supe...

  12. Tracking of stem cells for treatment in cardiovascular disease

    International Nuclear Information System (INIS)

    Kang, Won Jun

    2005-01-01

    Various stem cells or progenitor cells are being used to treat cardiovascular disease. In ischemic heart disease, stem cell therapy is expected to regenerate damaged myocardium. To evaluate effects of stem cell treatment, the method to image stem cell location, distribution and differentiation is necessary. Optical imaging, MRI, nuclear imaging methods have been used for tracking stem cells. The methods and problems of each imaging technique are reviewed

  13. Mammary Stem Cells and Breast Cancer Stem Cells: Molecular Connections and Clinical Implications.

    Science.gov (United States)

    Celià-Terrassa, Toni

    2018-05-04

    Cancer arises from subpopulations of transformed cells with high tumor initiation and repopulation ability, known as cancer stem cells (CSCs), which share many similarities with their normal counterparts. In the mammary gland, several studies have shown common molecular regulators between adult mammary stem cells (MaSCs) and breast cancer stem cells (bCSCs). Cell plasticity and self-renewal are essential abilities for MaSCs to maintain tissue homeostasis and regenerate the gland after pregnancy. Intriguingly, these properties are similarly executed in breast cancer stem cells to drive tumor initiation, tumor heterogeneity and recurrence after chemotherapy. In addition, both stem cell phenotypes are strongly influenced by external signals from the microenvironment, immune cells and supportive specific niches. This review focuses on the intrinsic and extrinsic connections of MaSC and bCSCs with clinical implications for breast cancer progression and their possible therapeutic applications.

  14. THE GERMLINE STEM CELL NICHE UNIT IN MAMMALIAN TESTES

    Science.gov (United States)

    Oatley, Jon M.; Brinster, Ralph L.

    2014-01-01

    This review addresses current understanding of the germline stem cell niche unit in mammalian testes. Spermatogenesis is a classic model of tissue-specific stem cell function relying on self-renewal and differentiation of spermatogonial stem cells (SSCs). These fate decisions are influenced by a niche microenvironment composed of a growth factor milieu that is provided by several testis somatic support cell populations. Investigations over the last two decades have identified key determinants of the SSC niche including cytokines that regulate SSC functions and support cells providing these factors, adhesion molecules that influence SSC homing, and developmental heterogeneity of the niche during postnatal aging. Emerging evidence suggests that Sertoli cells are a key support cell population influencing the formation and function of niches by secreting soluble factors and possibly orchestrating contributions of other support cells. Investigations with mice have shown that niche influence on SSC proliferation differs during early postnatal development and adulthood. Moreover, there is mounting evidence of an age-related decline in niche function, which is likely influenced by systemic factors. Defining the attributes of stem cell niches is key to developing methods to utilize these cells for regenerative medicine. The SSC population and associated niche comprise a valuable model system for study that provides fundamental knowledge about the biology of tissue-specific stem cells and their capacity to sustain homeostasis of regenerating tissue lineages. While the stem cell is essential for maintenance of all self-renewing tissues and has received considerable attention, the role of niche cells is at least as important and may prove to be more receptive to modification in regenerative medicine. PMID:22535892

  15. The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent '+4' cell markers

    NARCIS (Netherlands)

    Muñoz, Javier; Stange, Daniel E.; Schepers, Arnout G.; van de Wetering, Marc; Koo, Bon-Kyoung; Itzkovitz, Shalev; Volckmann, Richard; Kung, Kevin S.; Koster, Jan; Radulescu, Sorina; Myant, Kevin; Versteeg, Rogier; Sansom, Owen J.; van Es, Johan H.; Barker, Nick; van Oudenaarden, Alexander; Mohammed, Shabaz; Heck, Albert J. R.; Clevers, Hans

    2012-01-01

    Two types of stem cells are currently defined in small intestinal crypts: cycling crypt base columnar (CBC) cells and quiescent '+4' cells. Here, we combine transcriptomics with proteomics to define a definitive molecular signature for Lgr5(+) CBC cells. Transcriptional profiling of FACS-sorted

  16. When stem cells grow old: phenotypes and mechanisms of stem cell aging

    Science.gov (United States)

    Schultz, Michael B.; Sinclair, David A.

    2016-01-01

    All multicellular organisms undergo a decline in tissue and organ function as they age. An attractive theory is that a loss in stem cell number and/or activity over time causes this decline. In accordance with this theory, aging phenotypes have been described for stem cells of multiple tissues, including those of the hematopoietic system, intestine, muscle, brain, skin and germline. Here, we discuss recent advances in our understanding of why adult stem cells age and how this aging impacts diseases and lifespan. With this increased understanding, it is feasible to design and test interventions that delay stem cell aging and improve both health and lifespan. PMID:26732838

  17. Radiobiology of intestinal epithelium stem cells

    International Nuclear Information System (INIS)

    Konoplyannikova, O.A.

    1988-01-01

    After a single or three-fold whole body irradiation of mice with a dose of 4 Gy and the time interval for the proliferation to be restored (5 days or 3 weeks) the survival curve for stem cells of small intestine epithelium with regard to radiation dose was the same as that for non-preirradiated mice. This indicated that the proliferative potential of stem cells in these experimental conditions was not reduced

  18. 3 CFR - Guidelines for Human Stem Cell Research

    Science.gov (United States)

    2010-01-01

    ... 3 The President 1 2010-01-01 2010-01-01 false Guidelines for Human Stem Cell Research Presidential Documents Other Presidential Documents Memorandum of July 30, 2009 Guidelines for Human Stem Cell Research..., scientifically worthy human stem cell research, including human embryonic stem cell research, to the extent...

  19. Stem cell therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease

    DEFF Research Database (Denmark)

    Fox, Ira J; Daley, George Q; Goldman, Steven A

    2014-01-01

    Pluripotent stem cells (PSCs) directed to various cell fates holds promise as source material for treating numerous disorders. The availability of precisely differentiated PSC-derived cells will dramatically affect blood component and hematopoietic stem cell therapies and should facilitate......, and industry is critical for generating new stem cell-based therapies....... treatment of diabetes, some forms of liver disease and neurologic disorders, retinal diseases, and possibly heart disease. Although an unlimited supply of specific cell types is needed, other barriers must be overcome. This review of the state of cell therapies highlights important challenges. Successful...

  20. A review on stem cell therapy for multiple sclerosis: special focus on human embryonic stem cells.

    Science.gov (United States)

    Shroff, Geeta

    2018-01-01

    Multiple sclerosis (MS), a complex disorder of the central nervous system (CNS), is characterized with axonal loss underlying long-term progressive disability. Currently available therapies for its management are able to slow down the progression but fail to treat it completely. Moreover, these therapies are associated with major CNS and cardiovascular adverse events, and prolonged use of these treatments may cause life-threatening diseases. Recent research has shown that cellular therapies hold a potential for CNS repair and may be able to provide protection from inflammatory damage caused after injury. Human embryonic stem cell (hESC) transplantation is one of the promising cell therapies; hESCs play an important role in remyelination and help in preventing demylenation of the axons. In this study, an overview of the current knowledge about the unique properties of hESC and their comparison with other cell therapies has been presented for the treatment of patients with MS.

  1. Stem Cell Treatment for Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Ming eLi

    2014-03-01

    Full Text Available Type 1 diabetes mellitus (T1DM is a common chronic disease in children, characterized by a loss of  cells, which results in defects in insulin secretion and hyperglycemia. Chronic hyperglycemia causes diabetic complications, including diabetic nephropathy, neuropathy and retinopathy. Curative therapies mainly include diet and insulin administration. Although hyperglycemia can be improved by insulin administration, exogenous insulin injection cannot successfully mimic the insulin secretion from normal  cells, which keeps blood glucose levels within the normal range all the time. Islet and pancreas transplantation achieves better glucose control, but there is a lack of organ donors. Cell based therapies have also been attempted to treat T1DM. Stem cells such as embryonic stem cells, induced pluripotent stem cells and tissue stem cells (TSCs such as bone marrow-, adipose tissue- and cord blood-derived stem cells, have been shown to generate insulin-producing cells. In this review, we summarize the most-recently available information about T1DM and the use of TSCs to treat T1DM.

  2. Wnt and BMP signaling crosstalk in regulating dental stem cells: Implications in dental tissue engineering

    Directory of Open Access Journals (Sweden)

    Fugui Zhang

    2016-12-01

    Full Text Available Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling. Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance, essential oral functions and the quality of life. Regenerative dentistry holds great promise in treating oral/dental disorders. The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells, along with the signaling mechanisms governing stem cell self-renewal and differentiation. In this review, we first summarize the biological characteristics of seven types of dental stem cells, including dental pulp stem cells, stem cells from apical papilla, stem cells from human exfoliated deciduous teeth, dental follicle precursor cells, periodontal ligament stem cells, alveolar bone-derived mesenchymal stem cells (MSCs, and MSCs from gingiva. We then focus on how these stem cells are regulated by bone morphogenetic protein (BMP and/or Wnt signaling by examining the interplays between these pathways. Lastly, we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways. We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications. Thus, we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade.

  3. Mesenchymal Stem Cell-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Ameliorate Diabetic Polyneuropathy in Mice

    Directory of Open Access Journals (Sweden)

    Tatsuhito Himeno

    2013-01-01

    Full Text Available Background. Although pathological involvements of diabetic polyneuropathy (DPN have been reported, no dependable treatment of DPN has been achieved. Recent studies have shown that mesenchymal stem cells (MSCs ameliorate DPN. Here we demonstrate a differentiation of induced pluripotent stem cells (iPSCs into MSC-like cells and investigate the therapeutic potential of the MSC-like cell transplantation on DPN. Research Design and Methods. For induction into MSC-like cells, GFP-expressing iPSCs were cultured with retinoic acid, followed by adherent culture for 4 months. The MSC-like cells, characterized with flow cytometry and RT-PCR analyses, were transplanted into muscles of streptozotocin-diabetic mice. Three weeks after the transplantation, neurophysiological functions were evaluated. Results. The MSC-like cells expressed MSC markers and angiogenic/neurotrophic factors. The transplanted cells resided in hindlimb muscles and peripheral nerves, and some transplanted cells expressed S100β in the nerves. Impairments of current perception thresholds, nerve conduction velocities, and plantar skin blood flow in the diabetic mice were ameliorated in limbs with the transplanted cells. The capillary number-to-muscle fiber ratios were increased in transplanted hindlimbs of diabetic mice. Conclusions. These results suggest that MSC-like cell transplantation might have therapeutic effects on DPN through secreting angiogenic/neurotrophic factors and differentiation to Schwann cell-like cells.

  4. [Stem and progenitor cells in biostructure of blood vessel walls].

    Science.gov (United States)

    Korta, Krzysztof; Kupczyk, Piotr; Skóra, Jan; Pupka, Artur; Zejler, Paweł; Hołysz, Marcin; Gajda, Mariusz; Nowakowska, Beata; Barć, Piotr; Dorobisz, Andrzej T; Dawiskiba, Tomasz; Szyber, Piotr; Bar, Julia

    2013-09-18

    Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, "anchored" in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC). Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as "subendothelial or vasculogenic zones". Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

  5. Stem and progenitor cells in biostructure of blood vessel walls

    Directory of Open Access Journals (Sweden)

    Krzysztof Korta

    2013-09-01

    Full Text Available Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, “anchored” in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC. Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as “subendothelial or vasculogenic zones”. Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

  6. Who Defends the Stem Cell's Citadel?

    Science.gov (United States)

    Strick-Marchand, Hélène; Durantel, David

    2018-03-01

    Recently in Cell, Wu et al. (2018) demonstrated that intrinsic expression of a subset of interferon stimulated genes confers resistance to viral infections in stem cells both in vitro and in vivo, while differentiated cells lose this intrinsic gatekeeper expression pattern in favor of inducible interferon responses. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Wnt signaling in the stem cell niche

    NARCIS (Netherlands)

    Rattis, Frédérique Marie; Voermans, Carlijn; Reya, Tannishtha

    2004-01-01

    All the cells present in the blood are derived from the hematopoietic stem cell (HSC). Because mature blood cells have a limited life span, HSCs must perpetuate themselves through self-renewal to maintain a functional hematopoietic compartment for the lifetime of an organism. This review focuses on

  8. Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-16-1-0260 TITLE: Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets PRINCIPAL INVESTIGATOR: Carla Kim... Cell Carcinoma Stem Cells as Immunotherapy Targets 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0260 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...SUPPLEMENTARY NOTES 14. ABSTRACT Lung squamous cell carcinoma (SCC) is the second most common type of lung cancer, and immunotherapy is a promising new

  9. In vivo stem cell transplantation using reduced cell numbers.

    Science.gov (United States)

    Tsutsui, Takeo W

    2015-01-01

    Dental pulp stem cell (DPSC) characterization is essential for regeneration of a dentin/pulp like complex in vivo. This is especially important for identifying the potential of DPSCs to function as stem cells. Previously reported DPSC transplantation methods have used with huge numbers of cells, along with hydroxyapatite/tricalcium phosphate (HA/TCP), gelatin and fibrin, and collagen scaffolds. This protocol describe a transplantation protocol that uses fewer cells and a temperature-responsive cell culture dish.

  10. Contribution of Mouse Embryonic Stem Cells and Induced Pluripotent Stem Cells to Chimeras through Injection and Coculture of Embryos

    OpenAIRE

    Guo, Jitong; Wu, Baojiang; Li, Shuyu; Bao, Siqin; Zhao, Lixia; Hu, Shuxiang; Sun, Wei; Su, Jie; Dai, Yanfeng; Li, Xihe

    2014-01-01

    Blastocyst injection and morula aggregation are commonly used to evaluate stem cell pluripotency based on chimeric contribution of the stem cells. To assess the protocols for generating chimeras from stem cells, 8-cell mouse embryos were either injected or cocultured with mouse embryonic stem cells and induced pluripotent stem cells, respectively. Although a significantly higher chimera rate resulted from blastocyst injection, the highest germline contribution resulted from injection of 8-cel...

  11. Autophagy regulates the stemness of cervical cancer stem cells

    Directory of Open Access Journals (Sweden)

    Yang Y

    2017-06-01

    Full Text Available Yi Yang,1,2 Li Yu,1 Jin Li,1 Ya Hong Yuan,1 Xiao Li Wang,1 Shi Rong Yan,1 Dong Sheng Li,1 Yan Ding1 1Hubei Key Laboratory of Embryonic Stem Cell Research, 2Reproductive Center, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China Abstract: Cancer stem cells (CSCs are a rare population of multipotent cells with the capacity to self-renew. It has been reported that there are CSCs in cervical cancer cells. Pluripotency-associated (PA transcription factors such as Oct4, Sox2, Nanog and CD44 have been used to isolate CSCs subpopulations. In this study, we showed that autophagy plays an important role in the biological behavior of cervical cancer cells. The expression of the autophagy protein Beclin 1 and LC3B was higher in tumorspheres established from human cervical cancers cell lines (and CaSki than in the parental adherent cells. It was also observed that the basal and starvation-induced autophagy flux was higher in tumorspheres than in the bulk population. Autophagy could regulate the expression level of PA proteins in cervical CSCs. In addition, CRISPR/Cas 9-mediated Beclin 1 knockout enhanced the malignancy of HeLa cells, leading to accumulation of PA proteins and promoted tumorsphere formation. Our findings suggest that autophagy modulates homeostasis of PA proteins, and Beclin 1 is critical for CSC maintenance and tumor development in nude mice. This demonstrates that a prosurvival autophagic pathway is critical for CSC maintenance. Keywords: cervical cancer, autophagy, cancer stem cell, LC3, Oct4

  12. Optical Imaging for Stem Cell Differentiation to Neuronal Lineage

    International Nuclear Information System (INIS)

    Hwang, Do Won; Lee, Dong Soo

    2012-01-01

    In regenerative medicine, the prospect of stem cell therapy hold great promise for the recovery of injured tissues and effective treatment of intractable diseases. Tracking stem cell fate provides critical information to understand and evaluate the success of stem cell therapy. The recent emergence of in vivo noninvasive molecular imaging has enabled assessment of the behavior of grafted stem cells in living subjects. In this review, we provide an overview of current optical imaging strategies based on cell or tissue specific reporter gene expression and of in vivo methods to monitor stem cell differentiation into neuronal lineages. These methods use optical reporters either regulated by neuron-specific promoters or containing neuron-specific microRNA binding sites. Both systems revealed dramatic changes in optical reporter imaging signals in cells differentiating a yeast GAL4 amplification system or an engineering-enhanced luciferase reported gene. Furthermore, we propose an advanced imaging system to monitor neuronal differentiation during neurogenesis that uses in vivo multiplexed imaging techniques capable of detecting several targets simultaneously

  13. Stem cell research: applicability in dentistry.

    Science.gov (United States)

    Mathur, Shivani; Chopra, Rahul; Pandit, I K; Srivastava, Nikhil; Gugnani, Neeraj

    2014-01-01

    In the face of extraordinary advances in the prevention, diagnosis, and treatment of human diseases, the inability of most tissues and organs to repair and regenerate after damage is a problem that needs to be solved. Stem cell research is being pursued in the hope of achieving major medical breakthroughs. Scientists are striving to create therapies that rebuild or replace damaged cells with tissues grown from stem cells that will offer hope to people suffering from various ailments. Regeneration of damaged periodontal tissue, bone, pulp, and dentin is a problem that dentists face today. Stem cells present in dental pulp, periodontal ligament, and alveolar bone marrow have the potential to repair and regenerate teeth and periodontal structures. These stem cells can be harvested from dental pulp, periodontal ligament, and/or alveolar bone marrow; expanded; embedded in an appropriate scaffold; and transplanted back into a defect to regenerate bone and tooth structures. These cells have the potential to regenerate dentin, periodontal ligament, and cementum and can also be used to restore bone defects. The kind of scaffold, the source of cells, the type of in vitro culturing, and the type of surgical procedure to be used all require careful consideration. The endeavor is clearly multidisciplinary in nature, and the practicing dental surgeon has a critical role in it. Playing this role in the most effective way requires awareness of the huge potential associated with the use of stem cells in a clinical setting, as well as a proper understanding of the related problems.

  14. Concise Review: Stem Cells in Osteoimmunology.

    Science.gov (United States)

    Fierro, Fernando A; Nolta, Jan A; Adamopoulos, Iannis E

    2017-06-01

    Bone remodeling is a lifelong process in which mature bone tissue is removed from the skeleton by bone resorption and is replenished by new during ossification or bone formation. The remodeling cycle requires both the differentiation and activation of two cell types with opposing functions; the osteoclast, which orchestrates bone resorption, and the osteoblast, which orchestrates bone formation. The differentiation of these cells from their respective precursors is a process which has been overshadowed by enigma, particularly because the precise osteoclast precursor has not been identified and because the identification of skeletal stem cells, which give rise to osteoblasts, is very recent. Latest advances in the area of stem cell biology have enabled us to gain a better understanding of how these differentiation processes occur in physiological and pathological conditions. In this review we postulate that modulation of stem cells during inflammatory conditions is a necessary prerequisite of bone remodeling and therefore an essential new component to the field of osteoimmunology. In this context, we highlight the role of transcription factor nuclear factor of activated T cells cytoplasmic 1 (NFATc1), because it directly links inflammation with differentiation of osteoclasts and osteoblasts. Stem Cells 2017;35:1461-1467. © 2017 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  15. Multipotent stem cells of mother's milk

    Directory of Open Access Journals (Sweden)

    Alessandra Reali

    2016-03-01

    Full Text Available In recent years the presence of stem cells (hBSCs: human breastmilk-derived stem cells and epithelial progenitors has been demonstrated in mother’s milk (MM. Stem cells present in samples of fresh MM exhibit a high degree of vitality and this makes possible the performance of cell cultures and to evaluate the differentiation capacity of the hBSCs. The most important datum that expresses the enormous potential of the use of MM stem cells is the presence of a cell population capable of differentiating into the three mesoderm, endoderm and ectoderm lines. The small number of studies and MM samples analyzed and the different sampling methods applied suggest standardization in the collection, analysis and culture of MM in future studies, in consideration of the well-known extreme variability of MM composition, also from the standpoint of cells.The analysis of literature data confirms the uniqueness of MM and its enormous potential.Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

  16. Tumour-initiating cells vs. cancer 'stem' cells and CD133: What's in the name?

    International Nuclear Information System (INIS)

    Neuzil, Jiri; Stantic, Marina; Zobalova, Renata; Chladova, Jaromira; Wang, Xiufang; Prochazka, Lubomir; Dong, Lanfeng; Andera, Ladislav; Ralph, Stephen J.

    2007-01-01

    Recent evidence suggests that a subset of cells within a tumour have 'stem-like' characteristics. These tumour-initiating cells, distinct from non-malignant stem cells, show low proliferative rates, high self-renewing capacity, propensity to differentiate into actively proliferating tumour cells, resistance to chemotherapy or radiation, and they are often characterised by elevated expression of the stem cell surface marker CD133. Understanding the molecular biology of the CD133 + cancer cells is now essential for developing more effective cancer treatments. These may include drugs targeting organelles, such as mitochondria or lysosomes, using highly efficient and selective inducers of apoptosis. Alternatively, agents or treatment regimens that enhance sensitivity of these therapy-resistant 'tumour stem cells' to the current or emerging anti-tumour drugs would be of interest as well

  17. Two subpopulations of stem cells for T cell lineage

    International Nuclear Information System (INIS)

    Katsura, Y.; Amagai, T.; Kina, T.; Sado, T.; Nishikawa, S.

    1985-01-01

    An assay system for the stem cell that colonizes the thymus and differentiates into T cells was developed, and by using this assay system the existence of two subpopulations of stem cells for T cell lineage was clarified. Part-body-shielded and 900-R-irradiated C57BL/6 (H-2b, Thy-1.2) recipient mice, which do not require the transfer of pluripotent stem cells for their survival, were transferred with cells from B10 X Thy-1.1 (H-2b, Thy-1.1) donor mice. The reconstitution of the recipient's thymus lymphocytes was accomplished by stem cells in the donor cells and those spared in the shielded portion of the recipient that competitively colonize the thymus. Thus, the stem cell activity of donor cells can be evaluated by determining the proportion of donor-type (Thy-1.1+) cells in the recipient's thymus. Bone marrow cells were the most potent source of stem cells. By contrast, when the stem cell activity was compared between spleen and bone marrow cells of whole-body-irradiated (800 R) C57BL/6 mice reconstituted with B10 X Thy-1.1 bone marrow cells by assaying in part-body-shielded and irradiated C57BL/6 mice, the activity of these two organs showed quite a different time course of development. The results strongly suggest that the stem cells for T cell lineage in the bone marrow comprise at least two subpopulations, spleen-seeking and bone marrow-seeking cells

  18. Socializing with the neighbors: stem cells and their niche.

    Science.gov (United States)

    Fuchs, Elaine; Tumbar, Tudorita; Guasch, Geraldine

    2004-03-19

    The potential of stem cells in regenerative medicine relies upon removing them from their natural habitat, propagating them in culture, and placing them into a foreign tissue environment. To do so, it is essential to understand how stem cells interact with their microenvironment, the so-called stem cell niche, to establish and maintain their properties. In this review, we examine adult stem cell niches and their impact on stem cell biology.

  19. Investigation progress of imaging techniques monitoring stem cell therapy

    International Nuclear Information System (INIS)

    Wu Jun; An Rui

    2006-01-01

    Recently stem cell therapy has showed potential clinical application in diabetes mellitus, cardiovascular diseases, malignant tumor and trauma. Efficient techniques of non-invasively monitoring stem cell transplants will accelerate the development of stem cell therapies. This paper briefly reviews the clinical practice of stem cell, in addition, makes a review of monitoring methods including magnetic resonance and radionuclide imaging which have been used in stem cell therapy. (authors)

  20. Therapeutic Approaches to Target Cancer Stem Cells

    International Nuclear Information System (INIS)

    Diaz, Arlhee; Leon, Kalet

    2011-01-01

    The clinical relevance of cancer stem cells (CSC) remains a major challenge for current cancer therapies, but preliminary findings indicate that specific targeting may be possible. Recent studies have shown that these tumor subpopulations promote tumor angiogenesis through the increased production of VEGF, whereas the VEGF neutralizing antibody bevacizumab specifically inhibits CSC growth. Moreover, nimotuzumab, a monoclonal antibody against the epidermal growth factor receptor (EGFR) with a potent antiangiogenic activity, has been shown by our group to reduce the frequency of CSC-like subpopulations in mouse models of brain tumors when combined with ionizing radiation. These studies and subsequent reports from other groups support the relevance of approaches based on molecular-targeted therapies to selectively attack CSC. This review discusses the relevance of targeting both the EGFR and angiogenic pathways as valid approaches to this aim. We discuss the relevance of identifying better molecular markers to develop drug screening strategies that selectively target CSC

  1. Genome Editing in Human Pluripotent Stem Cells.

    Science.gov (United States)

    Carlson-Stevermer, Jared; Saha, Krishanu

    2017-01-01

    Genome editing in human pluripotent stem cells (hPSCs) enables the generation of reporter lines and knockout cell lines. Zinc finger nucleases, transcription activator-like effector nucleases (TALENs), and CRISPR/Cas9 technology have recently increased the efficiency of proper gene editing by creating double strand breaks (DSB) at defined sequences in the human genome. These systems typically use plasmids to transiently transcribe nucleases within the cell. Here, we describe the process for preparing hPSCs for transient expression of nucleases via electroporation and subsequent analysis to create genetically modified stem cell lines.

  2. Evaluation of the osteogenic differentiation of gingiva-derived stem cells grown on culture plates or in stem cell spheroids: Comparison of two- and three-dimensional cultures.

    Science.gov (United States)

    Lee, Sung-Il; Ko, Youngkyung; Park, Jun-Beom

    2017-09-01

    Three-dimensional cell culture systems provide a convenient in vitro model for the study of complex cell-cell and cell-matrix interactions in the absence of exogenous substrates. The current study aimed to evaluate the osteogenic differentiation potential of gingiva-derived stem cells cultured in two-dimensional or three-dimensional systems. To the best of our knowledge, the present study is the first to compare the growth of gingiva-derived stem cells in monolayer culture to a three-dimensional culture system with microwells. For three-dimensional culture, gingiva-derived stem cells were isolated and seeded into polydimethylsiloxane-based concave micromolds. Alkaline phosphatase activity and alizarin red S staining assays were then performed to evaluate osteogenesis and the degree of mineralization, respectively. Stem cell spheroids had a significantly increased level of alkaline phosphatase activity and mineralization compared with cells from the two-dimensional culture. In addition, an increase in mineralized deposits was observed with an increase in the loading cell number. The results of present study indicate that gingiva-derived stem cell spheroids exhibit an increased osteogenic potential compared with stem cells from two-dimensional culture. This highlights the potential of three-dimensional culture systems using gingiva-derived stem cells for regenerative medicine applications requiring stem cells with osteogenic potential.

  3. Lymphoscintigraphy and autologous stem cell implantation

    International Nuclear Information System (INIS)

    Peña, Yamile; Batista, Juan F.; Perera, Alejandro; Torres, Leonel A.; Sánchez, Elvia L.; Sánchez, Yolaine; Ducat, Luis; Prats, Anais; Hernández, Porfirio; Romero, Susana; Goicochea, Pedro; Quintela, Ana M.

    2016-01-01

    Lymphoscintigraphy is the criterion standard technique for the diagnosis of lymphedema. Advances of the application of autologous hematopoietic stem cells in ischemic disorders of lower limbs have increased the attention of researchers in this field. Aim: To determine the usefulness of lymphoscintigraphy for the assessment the efficacy of autologous stem cell implantation in patients with chronic lymphedema of the upper and lower limbs. Methods: Sixty-five patients were included. Clinical evaluation and lymphoscintigraphy were performed before and six months after stem cells implantation. The stem cells implantations were carried out by multiple superficial and deep injections in the trajectory of the lymphatic vessels and also in the inguinal region. A volume of 0.75 to 1.00 mL of cell suspension (1.0-2.2 x 109 stem cells) was administered in each injection site. Lymphoscintigraphy: Whole-body scans were acquired at 20 minutes, 1 hour, and 3 hours after administration of 185 to 259 MBq (5–7mCi) of 99m Tc-albumin nanocolloids in the interdigital space of both limbs. The anatomy and function of the lymphatic system were evaluated. Results: Functional assessment before implantation of stem cells showed that 69.2% of the patients had severe lymphatic insufficiency. The 61.5% of patients showed clinical improvement, confirmed by the results of the lymphoscintigraphy. The 46.1% of the cases evaluated showed a clear improvement. The study showed that the isotopic lymphography can evaluate the therapeutic response and its intensity. Conclusion: Lymphoscintigraphy is a useful technique for the evaluation and monitoring of autologous stem cell transplantation in patients with chronic lymphedema. (author)

  4. Human stem cells for craniomaxillofacial reconstruction.

    Science.gov (United States)

    Jalali, Morteza; Kirkpatrick, William Niall Alexander; Cameron, Malcolm Gregor; Pauklin, Siim; Vallier, Ludovic

    2014-07-01

    Human stem cell research represents an exceptional opportunity for regenerative medicine and the surgical reconstruction of the craniomaxillofacial complex. The correct architecture and function of the vastly diverse tissues of this important anatomical region are critical for life supportive processes, the delivery of senses, social interaction, and aesthetics. Craniomaxillofacial tissue loss is commonly associated with inflammatory responses of the surrounding tissue, significant scarring, disfigurement, and psychological sequelae as an inevitable consequence. The in vitro production of fully functional cells for skin, muscle, cartilage, bone, and neurovascular tissue formation from human stem cells, may one day provide novel materials for the reconstructive surgeon operating on patients with both hard and soft tissue deficit due to cancer, congenital disease, or trauma. However, the clinical translation of human stem cell technology, including the application of human pluripotent stem cells (hPSCs) in novel regenerative therapies, faces several hurdles that must be solved to permit safe and effective use in patients. The basic biology of hPSCs remains to be fully elucidated and concerns of tumorigenicity need to be addressed, prior to the development of cell transplantation treatments. Furthermore, functional comparison of in vitro generated tissue to their in vivo counterparts will be necessary for confirmation of maturity and suitability for application in reconstructive surgery. Here, we provide an overview of human stem cells in disease modeling, drug screening, and therapeutics, while also discussing the application of regenerative medicine for craniomaxillofacial tissue deficit and surgical reconstruction.

  5. Stem Cell, Regenerative Medicine and Cancer | Center for Cancer Research

    Science.gov (United States)

    Of the estimated trillion cells that build up our bodies, only a little number can self-renew and give rise to many different cell types. These unspecialized cells are called stem cells. Stem cell division and differentiation is fundamental to the development of the mature organism. Stem cells have recently attracted significant attention largely due to their potential medical

  6. Differential marker expression by cultures rich in mesenchymal stem cells

    Science.gov (United States)

    2013-01-01

    Background Mesenchymal stem cells have properties that make them amenable to therapeutic use. However, the acceptance of mesenchymal stem cells in clinical practice requires standardized techniques for their specific isolation. To date, there are no conclusive marker (s) for the exclusive isolation of mesenchymal stem cells. Our aim was to identify markers differentially expressed between mesenchymal stem cell and non-stem cell mesenchymal cell cultures. We compared and contrasted the phenotype of tissue cultures in which mesenchymal stem cells are rich and rare. By initially assessing mesenchymal stem cell differentiation, we established that bone marrow and breast adipose cultures are rich in mesenchymal stem cells while, in our hands, foreskin fibroblast and olfactory tissue cultures contain rare mesenchymal stem cells. In particular, olfactory tissue cells represent non-stem cell mesenchymal cells. Subsequently, the phenotype of the tissue cultures were thoroughly assessed using immuno-fluorescence, flow-cytometry, proteomics, antibody arrays and qPCR. Results Our analysis revealed that all tissue cultures, regardless of differentiation potential, demonstrated remarkably similar phenotypes. Importantly, it was also observed that common mesenchymal stem cell markers, and fibroblast-associated markers, do not discriminate between mesenchymal stem cell and non-stem cell mesenchymal cell cultures. Examination and comparison of the phenotypes of mesenchymal stem cell and non-stem cell mesenchymal cell cultures revealed three differentially expressed markers – CD24, CD108 and CD40. Conclusion We indicate the importance of establishing differential marker expression between mesenchymal stem cells and non-stem cell mesenchymal cells in order to determine stem cell specific markers. PMID:24304471

  7. 1,5-Disubstituted benzimidazoles that direct cardiomyocyte differentiation from mouse embryonic stem cells.

    Science.gov (United States)

    Okolotowicz, Karl J; Bushway, Paul; Lanier, Marion; Gilley, Cynthia; Mercola, Mark; Cashman, John R

    2015-09-01

    Cardiomyopathy is the leading cause of death worldwide. Despite progress in medical treatments, heart transplantation is one of the only current options for those with infarcted heart muscle. Stem cell differentiation technology may afford cell-based therapeutics that may lead to the generation of new, healthy heart muscle cells from undifferentiated stem cells. Our approach is to use small molecules to stimulate stem cell differentiation. Herein, we describe a novel class of 1,5-disubstituted benzimidazoles that induce differentiation of stem cells into cardiac cells. We report on the evaluation in vitro for cardiomyocyte differentiation and describe structure-activity relationship results that led to molecules with drug-like properties. The results of this study show the promise of small molecules to direct stem cell lineage commitment, to probe signaling pathways and to develop compounds for the stimulation of stem cells to repair damaged heart tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Computational Tools for Stem Cell Biology.

    Science.gov (United States)

    Bian, Qin; Cahan, Patrick

    2016-12-01

    For over half a century, the field of developmental biology has leveraged computation to explore mechanisms of developmental processes. More recently, computational approaches have been critical in the translation of high throughput data into knowledge of both developmental and stem cell biology. In the past several years, a new subdiscipline of computational stem cell biology has emerged that synthesizes the modeling of systems-level aspects of stem cells with high-throughput molecular data. In this review, we provide an overview of this new field and pay particular attention to the impact that single cell transcriptomics is expected to have on our understanding of development and our ability to engineer cell fate. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Adipogenic placenta-derived mesenchymal stem cells are not lineage restricted by withdrawing extrinsic factors: developing a novel visual angle in stem cell biology.

    Science.gov (United States)

    Hu, C; Cao, H; Pan, X; Li, J; He, J; Pan, Q; Xin, J; Yu, X; Li, J; Wang, Y; Zhu, D; Li, L

    2016-03-17

    Current evidence implies that differentiated bone marrow mesenchymal stem cells (BMMSCs) can act as progenitor cells and transdifferentiate across lineage boundaries. However, whether this unrestricted lineage has specificities depending on the stem cell type is unknown. Placental-derived mesenchymal stem cells (PDMSCs), an easily accessible and less invasive source, are extremely useful materials in current stem cell therapies. No studies have comprehensively analyzed the transition in morphology, surface antigens, metabolism and multilineage potency of differentiated PDMSCs after their dedifferentiation. In this study, we showed that after withdrawing extrinsic factors, adipogenic PDMSCs reverted to a primitive cell population and retained stem cell characteristics. The mitochondrial network during differentiation and dedifferentiation may serve as a marker of absent or acquired pluripotency in various stem cell models. The new population proliferated faster than unmanipulated PDMSCs and could be differentiated into adipocytes, osteocytes and hepatocytes. The cell adhesion molecules (CAMs) signaling pathway and extracellular matrix (ECM) components modulate cell behavior and enable the cells to proliferate or differentiate during the differentiation, dedifferentiation and redifferentiation processes in our study. These observations indicate that the dedifferentiated PDMSCs are distinguishable from the original PDMSCs and may serve as a novel source in stem cell biology and cell-based therapeutic strategies. Furthermore, whether PDMSCs differentiated into other lineages can be dedifferentiated to a primitive cell population needs to be investigated.

  10. Pluripotent Stem Cells in Research and Treatment of Hemoglobinopathies

    Science.gov (United States)

    Arora, Natasha; Daley, George Q.

    2012-01-01

    Pluripotent stem cells (PSCs) hold great promise for research and treatment of hemoglobinopathies. In principle, patient-specific induced pluripotent stem cells could be derived from a blood sample, genetically corrected to repair the disease-causing mutation, differentiated into hematopoietic stem cells (HSCs), and returned to the patient to provide a cure through autologous gene and cell therapy. However, there are many challenges at each step of this complex treatment paradigm. Gene repair is currently inefficient in stem cells, but use of zinc finger nucleases and transcription activator-like effector nucleases appear to be a major advance. To date, no successful protocol exists for differentiating PSCs into definitive HSCs. PSCs can be directly differentiated into primitive red blood cells, but not yet in sufficient numbers to enable treating patients, and the cost of clinical scale differentiation is prohibitively expensive with current differentiation methods and efficiencies. Here we review the progress, promise, and remaining hurdles in realizing the potential of PSCs for cell therapy. PMID:22474618

  11. Organization of haemopoietic stem cells: the generation-age hypothesis

    International Nuclear Information System (INIS)

    Rosendaal, M.; Hodgson, G.S.; Bradley, T.R.

    1978-01-01

    This paper proposes that the previous division history of each stem cell is one determinant of the functional organisation of the haemopoietic stem cell population. Older stem cell are used to form blood before younger ones. The stem cells generating capacity of a lineage is finite, and cells are eventually lost to the system by forming two committed precursors of the cell lines, and the next oldest stem cell takes over. Hence the proposed term 'generation-age hypothesis', supported by experimental evidence. Older stem cells from normal bone marrow and 13 day foetal liver were stripped away with phase-specific drugs revealing a younger population of stem cells with three-to four-fold greater stem cell generating capacity. Normal stem cells aged by continuous irradiation and serial retransplantation had eight-fold reduced generating capacity. That of stem cells in the bloodstream was half to a quarter that of normal bone marrow stem cells. There were some circulating stem cells, identified by reaction to brain-associated antigen, positive for 75% of normal femoral stem cells but not their progeny, whose capacity for stem cell generation was an eighth to one fortieth that of normal cells. (U.K.)

  12. A functional model for adult stem cells in epithelial tissues.

    NARCIS (Netherlands)

    Verstappen, J.; Katsaros, C.; Torensma, R.; Hoff, J.W. Von den

    2009-01-01

    Tissue turnover, regeneration, and repair take place throughout life. Stem cells are key players in these processes. The characteristics and niches of the stem cell populations in different tissues, and even in related tissues, vary extensively. In this review, stem cell differentiation and stem

  13. System for tracking transplanted limbal epithelial stem cells in the treatment of corneal stem cell deficiency

    Science.gov (United States)

    Boadi, J.; Sangwal, V.; MacNeil, S.; Matcher, S. J.

    2015-03-01

    The prevailing hypothesis for the existence and healing of the avascular corneal epithelium is that this layer of cells is continually produced by stem cells in the limbus and transported onto the cornea to mature into corneal epithelium. Limbal Stem Cell Deficiency (LSCD), in which the stem cell population is depleted, can lead to blindness. LSCD can be caused by chemical and thermal burns to the eye. A popular treatment, especially in emerging economies such as India, is the transplantation of limbal stem cells onto damaged limbus with hope of repopulating the region. Hence regenerating the corneal epithelium. In order to gain insights into the success rates of this treatment, new imaging technologies are needed in order to track the transplanted cells. Optical Coherence Tomography (OCT) is well known for its high resolution in vivo images of the retina. A custom OCT system has been built to image the corneal surface, to investigate the fate of transplanted limbal stem cells. We evaluate two methods to label and track transplanted cells: melanin labelling and magneto-labelling. To evaluate melanin labelling, stem cells are loaded with melanin and then transplanted onto a rabbit cornea denuded of its epithelium. The melanin displays strongly enhanced backscatter relative to normal cells. To evaluate magneto-labelling the stem cells are loaded with magnetic nanoparticles (20-30nm in size) and then imaged with a custom-built, magneto-motive OCT system.

  14. Impact of genomic damage and ageing on stem cell function

    Science.gov (United States)

    Behrens, Axel; van Deursen, Jan M.; Rudolph, K. Lenhard; Schumacher, Björn

    2014-01-01

    Impairment of stem cell function contributes to the progressive deterioration of tissue maintenance and repair with ageing. Evidence is mounting that age-dependent accumulation of DNA damage in both stem cells and cells that comprise the stem cell microenvironment are partly responsible for stem cell dysfunction with ageing. Here, we review the impact of the various types of DNA damage that accumulate with ageing on stem cell functionality, as well as the development of cancer. We discuss DNA-damage-induced cell intrinsic and extrinsic alterations that influence these processes, and review recent advances in understanding systemic adjustments to DNA damage and how they affect stem cells. PMID:24576896

  15. Transformation of intestinal stem cells into gastric stem cells on loss of transcription factor Cdx2

    NARCIS (Netherlands)

    Simmini, Salvatore; Bialecka, Monika; Huch, Meritxell; Kester, Lennart; van de Wetering, Marc; Sato, Toshiro; Beck, Felix; van Oudenaarden, Alexander; Clevers, Hans; Deschamps, Jacqueline

    2014-01-01

    The endodermal lining of the adult gastro-intestinal tract harbours stem cells that are responsible for the day-to-day regeneration of the epithelium. Stem cells residing in the pyloric glands of the stomach and in the small intestinal crypts differ in their differentiation programme and in the gene

  16. Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss

    Science.gov (United States)

    2012-07-01

    Mesenchymal stem cell (MSC) differentiation towards the bone forming osteoblastic lineage decreases as a function of age and may contribute to age-related...problem of age-related reduced availability of MSC we propose to examine the bone anabolic potential of induced pluripotent stem cell (iPS) derived MSC

  17. Efficient and rapid derivation of primitive neural stem cells and generation of brain subtype neurons from human pluripotent stem cells.

    Science.gov (United States)

    Yan, Yiping; Shin, Soojung; Jha, Balendu Shekhar; Liu, Qiuyue; Sheng, Jianting; Li, Fuhai; Zhan, Ming; Davis, Janine; Bharti, Kapil; Zeng, Xianmin; Rao, Mahendra; Malik, Nasir; Vemuri, Mohan C

    2013-11-01

    Human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, are unique cell sources for disease modeling, drug discovery screens, and cell therapy applications. The first step in producing neural lineages from hPSCs is the generation of neural stem cells (NSCs). Current methods of NSC derivation involve the time-consuming, labor-intensive steps of an embryoid body generation or coculture with stromal cell lines that result in low-efficiency derivation of NSCs. In this study, we report a highly efficient serum-free pluripotent stem cell neural induction medium that can induce hPSCs into primitive NSCs (pNSCs) in 7 days, obviating the need for time-consuming, laborious embryoid body generation or rosette picking. The pNSCs expressed the neural stem cell markers Pax6, Sox1, Sox2, and Nestin; were negative for Oct4; could be expanded for multiple passages; and could be differentiated into neurons, astrocytes, and oligodendrocytes, in addition to the brain region-specific neuronal subtypes GABAergic, dopaminergic, and motor neurons. Global gene expression of the transcripts of pNSCs was comparable to that of rosette-derived and human fetal-derived NSCs. This work demonstrates an efficient method to generate expandable pNSCs, which can be further differentiated into central nervous system neurons and glia with temporal, spatial, and positional cues of brain regional heterogeneity. This method of pNSC derivation sets the stage for the scalable production of clinically relevant neural cells for cell therapy applications in good manufacturing practice conditions.

  18. Fine-tuning Hematopoiesis: Microenvironmental factors regulating self-renewal and differentiation of hematopoietic stem cells

    NARCIS (Netherlands)

    T.C. Luis (Tiago)

    2010-01-01

    markdownabstract__Abstract__ Hematopoietic stem cells (HSCs) have the ability to self renew and generate all lineages of blood cells. Although it is currently well established that hematopoietic stem cells (HSCs) regenerate the blood compartment, it was only in the 1960s that was introduced the

  19. Epigenetic control of embryonic stem cell fate

    DEFF Research Database (Denmark)

    Christophersen, Nicolaj Strøyer; Helin, Kristian

    2010-01-01

    Embryonic stem (ES) cells are derived from the inner cell mass of the preimplantation embryo and are pluripotent, as they are able to differentiate into all cell types of the adult organism. Once established, the pluripotent ES cells can be maintained under defined culture conditions, but can also...... be induced rapidly to differentiate. Maintaining this balance of stability versus plasticity is a challenge, and extensive studies in recent years have focused on understanding the contributions of transcription factors and epigenetic enzymes to the "stemness" properties of these cells. Identifying...... the molecular switches that regulate ES cell self-renewal versus differentiation can provide insights into the nature of the pluripotent state and enhance the potential use of these cells in therapeutic applications. Here, we review the latest models for how changes in chromatin methylation can modulate ES cell...

  20. Embryonic stem cells in pig and cattle

    DEFF Research Database (Denmark)

    Maddox-Hyttel, Poul; Wolf, Xenia Asbæk; Rasmussen, Mikkel Aabech

    2007-01-01

    Porcine and bovine cell lines derived from the inner cell mass (ICM) or epiblasts of blastocysts have been maintained over extended periods of time and characterized by morphology, identification of some stem cell markers and, in few cases, by production of chimaeric offspring. However, germ line...... transmission in chimaeras has never been obtained. Due to this incomplete characterization of the cell lines, the expression embryonic stem (ES)-like cells is presently used in pig and cattle. The ICM or epiblast can be isolated from the blastocyst by whole blastocyst culture, mechanical isolation......, or immunosurgery, and they are generally cultured on feeder cells. The resulting ES-like cells may be differentiated in vivo by chimaera and teratoma formation or in vitro by embryoid body formation and monolayer induction. It is likely that more well characterized and stable porcine and bovine ES cell lines...

  1. Deriving multipotent stem cells from mouse spermatogonial stem cells: a new tool for developmental and clinical research

    NARCIS (Netherlands)

    de Rooij, Dirk G.; Mizrak, S. Canan

    2008-01-01

    In recent years, embryonic stem (ES) cell-like cells have been obtained from cultured mouse spermatogonial stem cells (SSCs). These advances have shown that SSCs can transition from being the stem cell-producing cells of spermatogenesis to being multipotent cells that can differentiate into

  2. Mature lymphoid malignancies: origin, stem cells, and chronicity

    DEFF Research Database (Denmark)

    Husby, Simon; Grønbæk, Kirsten

    2017-01-01

    after treatment. Lately, the use of next-generation sequencing techniques has revealed essential information on the clonal evolution of lymphoid malignancies. Also, experimental xenograft transplantation point to the possible existence of an ancestral (stem) cell. Such a malignant lymphoid stem cell...... population could potentially evade current therapies and be the cause of chronicity and death in lymphoma patients; however, the evidence is divergent across disease entities and between studies. In this review we present an overview of genetic studies, case reports, and experimental evidence of the source...

  3. Fat, Stem Cells, and Platelet-Rich Plasma.

    Science.gov (United States)

    James, Isaac B; Coleman, Sydney R; Rubin, J Peter

    2016-07-01

    The ideal filler for aesthetic surgery is inexpensive and easy to obtain, natural in appearance and texture, immunologically compatible, and long lasting without risk of infection. By most metrics, autologous fat grafts meet these criteria perfectly. Although facial fat grafting is now a commonly accepted surgical procedure, there has been a wave of activity applying stem cells and platelet-rich plasma (PRP) therapies to aesthetic practice. This article addresses technical considerations in the use of autologous fat transfer for facial rejuvenation, and also explores the current evidence for these stem cell and PRP therapies in aesthetic practice. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Proteomic cornerstones of hematopoietic stem cell differentiation

    DEFF Research Database (Denmark)

    Klimmeck, Daniel; Hansson, Jenny; Raffel, Simon

    2012-01-01

    Regenerative tissues such as the skin epidermis, the intestinal mucosa or the hematopoietic system are organized in a hierarchical manner with stem cells building the top of this hierarchy. Somatic stem cells harbor the highest self-renewal activity and generate a series of multipotent progenitors...... which differentiate into lineage committed progenitors and subsequently mature cells. In this report, we applied an in-depth quantitative proteomic approach to analyze and compare the full proteomes of ex vivo isolated and FACS-sorted populations highly enriched for either multipotent hematopoietic stem....../progenitor cells (HSPCs, Lin(neg)Sca-1(+)c-Kit(+)) or myeloid committed precursors (Lin(neg)Sca-1(-)c-Kit(+)). By employing stable isotope dimethyl labeling and high-resolution mass spectrometry, more than 5,000 proteins were quantified. From biological triplicate experiments subjected to rigorous statistical...

  5. Biodegradable Polymers and Stem Cells for Bioprinting

    Directory of Open Access Journals (Sweden)

    Meijuan Lei

    2016-04-01

    Full Text Available It is imperative to develop organ manufacturing technologies based on the high organ failure mortality and serious donor shortage problems. As an emerging and promising technology, bioprinting has attracted more and more attention with its super precision, easy reproduction, fast manipulation and advantages in many hot research areas, such as tissue engineering, organ manufacturing, and drug screening. Basically, bioprinting technology consists of inkjet bioprinting, laser-based bioprinting and extrusion-based bioprinting techniques. Biodegradable polymers and stem cells are common printing inks. In the printed constructs, biodegradable polymers are usually used as support scaffolds, while stem cells can be engaged to differentiate into different cell/tissue types. The integration of biodegradable polymers and stem cells with the bioprinting techniques has provided huge opportunities for modern science and technologies, including tissue repair, organ transplantation and energy metabolism.

  6. Biodegradable Polymers and Stem Cells for Bioprinting.

    Science.gov (United States)

    Lei, Meijuan; Wang, Xiaohong

    2016-04-29

    It is imperative to develop organ manufacturing technologies based on the high organ failure mortality and serious donor shortage problems. As an emerging and promising technology, bioprinting has attracted more and more attention with its super precision, easy reproduction, fast manipulation and advantages in many hot research areas, such as tissue engineering, organ manufacturing, and drug screening. Basically, bioprinting technology consists of inkjet bioprinting, laser-based bioprinting and extrusion-based bioprinting techniques. Biodegradable polymers and stem cells are common printing inks. In the printed constructs, biodegradable polymers are usually used as support scaffolds, while stem cells can be engaged to differentiate into different cell/tissue types. The integration of biodegradable polymers and stem cells with the bioprinting techniques has provided huge opportunities for modern science and technologies, including tissue repair, organ transplantation and energy metabolism.

  7. Chromatin in embryonic stem cell neuronal differentiation.

    Science.gov (United States)

    Meshorer, E

    2007-03-01

    Chromatin, the basic regulatory unit of the eukaryotic genetic material, is controlled by epigenetic mechanisms including histone modifications, histone variants, DNA methylation and chromatin remodeling. Cellular differentiation involves large changes in gene expression concomitant with alterations in genome organization and chromatin structure. Such changes are particularly evident in self-renewing pluripotent embryonic stem cells, which begin, in terms of cell fate, as a tabula rasa, and through the process of differentiation, acquire distinct identities. Here I describe the changes in chromatin that accompany neuronal differentiation, particularly of embryonic stem cells, and discuss how chromatin serves as the master regulator of cellular destiny.

  8. Wnt Signalling in Gastrointestinal Epithelial Stem Cells

    Directory of Open Access Journals (Sweden)

    Dustin J. Flanagan

    2018-03-01

    Full Text Available Wnt signalling regulates several cellular functions including proliferation, differentiation, apoptosis and migration, and is critical for embryonic development. Stem cells are defined by their ability for self-renewal and the ability to be able to give rise to differentiated progeny. Consequently, they are essential for the homeostasis of many organs including the gastrointestinal tract. This review will describe the huge advances in our understanding of how stem cell functions in the gastrointestinal tract are regulated by Wnt signalling, including how deregulated Wnt signalling can hijack these functions to transform cells and lead to cancer.

  9. Stem cell extracellular vesicles and kidney injury

    OpenAIRE

    Grange, Cristina; Iampietro, Corinne; Bussolati, Benedetta

    2017-01-01

    Extracellular vesicles (EVs) appear as a new promising cell-free therapy for acute and chronic renal diseases. EVs retain characteristics of the cell of origin and those derived from stem cells may mimic their regenerative properties per se. In fact, EVs contain many active molecules such as proteins and RNA species that act on target cells through different mechanisms, stimulating proliferation and angiogenesis and reducing apoptosis and inflammation. There are several reports that demonstra...

  10. The Use of Embryonic Stem Cells

    OpenAIRE

    Corkery, Padraig

    2002-01-01

    Over the past year there has been great interest, optimism and anxiety in many societies about developments in the use of embryonic stem cells (ES cells). Within the scientific community there has been debate for some time on the merits and ethical implications of using ES cells. The discussion entered the public domain inthe decisive way during the past year when there were significant changes in legislation governing the use of such cells in Britain and the United States. These changes c...

  11. Potential Application of Electrical Stimulation in Stem Cell-Based Treatment against Hearing Loss

    Directory of Open Access Journals (Sweden)

    Mingliang Tang

    2018-01-01

    Full Text Available Deafness is a common human disease, which is mainly caused by irreversible damage to hair cells and spiral ganglion neurons (SGNs in the mammalian cochlea. At present, replacement of damaged or missing hair cells and SGNs by stem cell transplantation therapy is an effective treatment. However, the survival rate of stem cell transplantation is low, with uncontrollable differentiation hindering its application. Most researchers have focused on biochemical factors to regulate the growth and differentiation of stem cells, whereas little study has been performed using physical factors. This review intends to illustrate the current problems in stem cell-based treatment against deafness and to introduce electric field stimulation as a physical factor to regulate stem cell behavior and facilitate stem cell therapy to treat hearing loss in the future.

  12. Genetic modification of hematopoietic stem cells: recent advances in the gene therapy of inherited diseases.

    Science.gov (United States)

    Bueren, Juan A; Guenechea, Guillermo; Casado, José A; Lamana, María Luisa; Segovia, José C

    2003-01-01

    Hematopoietic stem cells constitute a rare population of precursor cells with remarkable properties for being used as targets in gene therapy protocols. The last years have been particularly productive both in the fields of gene therapy and stem cell biology. Results from ongoing clinical trials have shown the first unquestionable clinical benefits of immunodeficient patients transplanted with genetically modified autologous stem cells. On the other hand, severe side effects in a few patients treated with gene therapy have also been reported, indicating the usefulness of further improving the vectors currently used in gene therapy clinical trials. In the field of stem cell biology, evidence showing the plastic potential of adult hematopoietic stem cells and data indicating the multipotency of adult mesenchymal precursor cells have been presented. Also, the generation of embryonic stem cells by means of nuclear transfer techniques has appeared as a new methodology with direct implications in gene therapy.

  13. The Potential for Synovium-derived Stem Cells in Cartilage Repair

    DEFF Research Database (Denmark)

    Kubosch, Eva Johanna; Lang, Gernot Michael; Fürst, David

    2018-01-01

    for the treatment of large, isolated, full thickness cartilage defects. Several disadvantages such as the need for two surgical procedures or hypertrophic regenerative cartilage, underline the need for alternative cell sources. OBJECTIVE: Mesenchymal stem cells, particularly synovium-derived mesenchymal stem cells......, represent a promising cell source. Synovium-derived mesenchymal stem cells have attracted considerable attention since they display great chondrogenic potential and less hypertrophic differentiation than mesenchymal stem cells derived from bone marrow. The aim of this review was to summarize the current...... knowledge on the chondrogenic potential for synovial stem cells in regard to cartilage repair purposes. RESULTS: A literature search was carried out identifying 260 articles in the databases up to January 2017. Several in vitro and initial animal in vivo studies of cartilage repair using synovia stem cell...

  14. Endovascular transplantation of stem cells to the injured rat CNS

    International Nuclear Information System (INIS)

    Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan; Le Blanc, Katarina

    2009-01-01

    Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)

  15. Endovascular transplantation of stem cells to the injured rat CNS

    Energy Technology Data Exchange (ETDEWEB)

    Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan [Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Department of Neuroradiology, Stockholm (Sweden); Le Blanc, Katarina [Karolinska University Hospital, Department of Stem Cell Research, Karolinska Institutet, Department of Clinical Immunology, Stockholm (Sweden)

    2009-10-15

    Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)

  16. What's missing? Discussing stem cell translational research in educational information on stem cell "tourism".

    Science.gov (United States)

    Master, Zubin; Zarzeczny, Amy; Rachul, Christen; Caulfield, Timothy

    2013-01-01

    Stem cell tourism is a growing industry in which patients pursue unproven stem cell therapies for a wide variety of illnesses and conditions. It is a challenging market to regulate due to a number of factors including its international, online, direct-to-consumer approach. Calls to provide education and information to patients, their families, physicians, and the general public about the risks associated with stem cell tourism are mounting. Initial studies examining the perceptions of patients who have pursued stem cell tourism indicate many are highly critical of the research and regulatory systems in their home countries and believe them to be stagnant and unresponsive to patient needs. We suggest that educational material should include an explanation of the translational research process, in addition to other aspects of stem cell tourism, as one means to help promote greater understanding and, ideally, curb patient demand for unproven stem cell interventions. The material provided must stress that strong scientific research is required in order for therapies to be safe and have a greater chance at being effective. Through an analysis of educational material on stem cell tourism and translational stem cell research from patient groups and scientific societies, we describe essential elements that should be conveyed in educational material provided to patients. Although we support the broad dissemination of educational material on stem cell translational research, we also acknowledge that education may simply not be enough to engender patient and public trust in domestic research and regulatory systems. However, promoting patient autonomy by providing good quality information to patients so they can make better informed decisions is valuable in itself, irrespective of whether it serves as an effective deterrent of stem cell tourism. © 2013 American Society of Law, Medicine & Ethics, Inc.

  17. Lingual Epithelial Stem Cells and Organoid Culture of Them

    Directory of Open Access Journals (Sweden)

    Hiroko Hisha

    2016-01-01

    Full Text Available As tongue cancer is one of the major malignant cancers in the world, understanding the mechanism of maintenance of lingual epithelial tissue, which is known to be the origin of tongue cancer, is unquestionably important. However, the actual stem cells that are responsible for the long-term maintenance of the lingual epithelium have not been identified. Moreover, a simple and convenient culture method for lingual epithelial stem cells has not yet been established. Recently, we have shown that Bmi1-positive cells, residing at the second or third layer of the epithelial cell layer at the base of the interpapillary pit (IPP, were slow-cycling and could supply keratinized epithelial cells for over one year, indicating that Bmi1-positive cells are long-term lingual epithelial stem cells. In addition, we have developed a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Here, we discuss current progress in the identification of lingual stem cells and future applications of the lingual culture system for studying the regulatory mechanisms of the lingual epithelium and for regenerative medicine.

  18. Stem Cell Tracking Technologies for Neurological Regenerative Medicine Purposes

    Directory of Open Access Journals (Sweden)

    Yongtao Zheng

    2017-01-01

    Full Text Available The growing field of stem cell therapy is moving toward clinical trials in a variety of applications, particularly for neurological diseases. However, this translation of cell therapies into humans has prompted a need to create innovative and breakthrough methods for stem cell tracing, to explore the migration routes and its reciprocity with microenvironment targets in the body, to monitor and track the outcome after stem cell transplantation therapy, and to track the distribution and cell viability of transplanted cells noninvasively and longitudinally. Recently, a larger number of cell tracking methods in vivo were developed and applied in animals and humans, including magnetic resonance imaging, nuclear medicine imaging, and optical imaging. This review has been intended to summarize the current use of those imaging tools in tracking stem cells, detailing their main features and drawbacks, including image resolution, tissue penetrating depth, and biosafety aspects. Finally, we address that multimodality imaging method will be a more potential tracking tool in the future clinical application.

  19. Effect of Induced Pluripotent Stem Cell Technology in Blood Banking

    Science.gov (United States)

    Focosi, Daniele

    2016-01-01

    Summary Population aging has imposed cost-effective alternatives to blood donations. Artificial blood is still at the preliminary stages of development, and the need for viable cells seems unsurmountable. Because large numbers of viable cells must be promptly available for clinical use, stem cell technologies, expansion, and banking represent ideal tools to ensure a regular supply. Provided key donors can be identified, induced pluripotent stem cell (iPSC) technology could pave the way to a new era in transfusion medicine, just as it is already doing in many other fields of medicine. The present review summarizes the current state of research on iPSC technology in the field of blood banking, highlighting hurdles, and promises. Significance The aging population in Western countries is causing a progressive reduction of blood donors and a constant increase of blood recipients. Because blood is the main therapeutic option to treat acute hemorrhage, cost-effective alternatives to blood donations are being actively investigated. The enormous replication capability of induced pluripotent stem cells and their promising results in many other fields of medicine could be an apt solution to produce the large numbers of viable cells required in transfusion and usher in a new era in transfusion medicine. The present report describes the potentiality, technological hurdles, and promises of induced pluripotent stem cells to generate red blood cells by redifferentiation. PMID:26819256

  20. Stem Cells Matter in Response to Fasting

    Directory of Open Access Journals (Sweden)

    Badi Sri Sailaja

    2015-12-01

    Full Text Available The molecular processes underlying intestinal adaptation to fasting and re-feeding remain largely uncharacterized. In this issue of Cell Reports, Richmond et al. report that dormant intestinal stem cells are regulated by PTEN and nutritional status.