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Sample records for adult stem cell

  1. Therapeutic potential of adult stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Keith, W. Nicol

    2006-01-01

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

  2. Adult stem cells and tissue repair.

    Science.gov (United States)

    Körbling, M; Estrov, Z; Champlin, R

    2003-08-01

    Recently, adult stem cells originating from bone marrow or peripheral blood have been suggested to contribute to repair and genesis of cells specific for liver, cardiac and skeletal muscle, gut, and brain tissue. The mechanism involved has been termed transdifferentiation, although other explanations including cell fusion have been postulated. Using adult stem cells to generate or repair solid organ tissue obviates the immunologic, ethical, and teratogenic issues that accompany embryonic stem cells. PMID:12931235

  3. Adult Stem Cells and Diabetes Therapy

    OpenAIRE

    Ilgun, Handenur; Kim, Joseph William; Luo, LuGuang

    2015-01-01

    The World Health Organization estimates that diabetes will be the fourth most prevalent disease by 2050. Developing a new therapy for diabetes is a challenge for researchers and clinicians in field. Many medications are being used for treatment of diabetes however with no conclusive and effective results therefore alternative therapies are required. Stem cell therapy is a promising tool for diabetes therapy, and it has involved embryonic stem cells, adult stem cells, and pluripotent stem cell...

  4. 28. Embryonic and adult stem cell therapy.

    Science.gov (United States)

    Henningson, Carl T; Stanislaus, Marisha A; Gewirtz, Alan M

    2003-02-01

    Stem cells are characterized by the ability to remain undifferentiated and to self-renew. Embryonic stem cells derived from blastocysts are pluripotent (able to differentiate into many cell types). Adult stem cells, which were traditionally thought to be monopotent multipotent, or tissue restricted, have recently also been shown to have pluripotent properties. Adult bone marrow stem cells have been shown to be capable of differentiating into skeletal muscle, brain microglia and astroglia, and hepatocytes. Stem cell lines derived from both embryonic stem and embryonic germ cells (from the embryonic gonadal ridge) are pluripotent and capable of self-renewal for long periods. Therefore embryonic stem and germ cells have been widely investigated for their potential to cure diseases by repairing or replacing damaged cells and tissues. Studies in animal models have shown that transplantation of fetal, embryonic stem, or embryonic germ cells may be able to treat some chronic diseases. In this review, we highlight recent developments in the use of stem cells as therapeutic agents for three such diseases: Diabetes, Parkinson disease, and congestive heart failure. We also discuss the potential use of stem cells as gene therapy delivery cells and the scientific and ethical issues that arise with the use of human stem cells. PMID:12592319

  5. 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.

  6. Immunological control of adult neural stem cells

    OpenAIRE

    Gonzalez-Perez, Oscar; Quiñones-Hinojosa, Alfredo; Garcia-Verdugo, Jose Manuel

    2010-01-01

    Adult neurogenesis occurs only in discrete regions of adult central nervous system: the subventricular zone and the subgranular zone. These areas are populated by adult neural stem cells (aNSC) that are regulated by a number of molecules and signaling pathways, which control their cell fate choices, survival and proliferation rates. For a long time, it was believed that the immune system did not exert any control on neural proliferative niches. However, it has been observed that many patholog...

  7. Adult stem-like cells in kidney

    Institute of Scientific and Technical Information of China (English)

    Keiichi Hishikawa; Osamu Takase; Masahiro Yoshikawa; Taro Tsujimura; Masaomi Nangaku; Tsuyoshi Takato

    2015-01-01

    Human pluripotent cells are promising for treatmentfor kidney diseases, but the protocols for derivationof kidney cell types are still controversial. Kidneytissue regeneration is well confirmed in several lowervertebrates such as fish, and the repair of nephronsafter tubular damages is commonly observed after renalinjury. Even in adult mammal kidney, renal progenitorcell or system is reportedly presents suggesting thatadult stem-like cells in kidney can be practical clinicaltargets for kidney diseases. However, it is still unclearif kidney stem cells or stem-like cells exist or not. Ingeneral, stemness is defined by several factors suchas self-renewal capacity, multi-lineage potency andcharacteristic gene expression profiles. The definiteuse of stemness may be obstacle to understand kidneyregeneration, and here we describe the recent broadfindings of kidney regeneration and the cells thatcontribute regeneration.

  8. Translational research of adult stem cell therapy

    Institute of Scientific and Technical Information of China (English)

    Gen; Suzuki

    2015-01-01

    Congestive heart failure(CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell based therapies generating new cardiomyocytes and vessels have emerged as a promising treatment to reverse functional deterioration and prevent the progression to CHF. Functional efficacy of progenitor cells isolated from the bone marrow and the heart have been evaluated in preclinical large animal models. Furthermore, several clinical trials using autologous and allogeneic stem cells and progenitor cells have demonstrated their safety in humans yet their clinical relevance is inconclusive. This review will discuss the clinical therapeutic applications of three specific adult stem cells that have shown particularly promising regenerative effects in preclinical studies, bone marrow derived mesenchymal stem cell, heart derived cardiosphere-derived cell and cardiac stem cell. We will also discuss future therapeutic approaches.

  9. Translational research of adult stem cell therapy.

    Science.gov (United States)

    Suzuki, Gen

    2015-11-26

    Congestive heart failure (CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell based therapies generating new cardiomyocytes and vessels have emerged as a promising treatment to reverse functional deterioration and prevent the progression to CHF. Functional efficacy of progenitor cells isolated from the bone marrow and the heart have been evaluated in preclinical large animal models. Furthermore, several clinical trials using autologous and allogeneic stem cells and progenitor cells have demonstrated their safety in humans yet their clinical relevance is inconclusive. This review will discuss the clinical therapeutic applications of three specific adult stem cells that have shown particularly promising regenerative effects in preclinical studies, bone marrow derived mesenchymal stem cell, heart derived cardiosphere-derived cell and cardiac stem cell. We will also discuss future therapeutic approaches.

  10. Clinical grade adult stem cell banking

    OpenAIRE

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

    2009-01-01

    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 t...

  11. Research progress of adult cardiac stem cells

    OpenAIRE

    Zheng, Nan; Ning-kun ZHANG; Lian-ru GAO

    2013-01-01

    The traditional view is that the heart is a terminal organ. This dogma, however, has been widely questioned with the discovery of adult cardiac stem cells (CSCs). Since CSCs have a highly self-renewal capacity and specific myocardial differentiation potential, nowadays they have been regarded as the most promising type of stem cells used in ischemic heart disease and other replacement therapy of end-stage heart disease. The present paper will focus on current results of scientific research on...

  12. 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...

  13. Adult stem cell coatings for regenerative medicine

    Directory of Open Access Journals (Sweden)

    David W. Green

    2012-01-01

    Full Text Available Stem cells can become potent tools for the treatment of degenerative disorders such as heart failure, eye disease and osteoarthritis. Housing stem cells inside a hydrogel coating, directly deposited around them individually and in groups, may be an important solution to the problem of increasing stem cell viability and protection in cultivation. Such coatings can target regulatory proteins and genes for maintenance, differentiation and development into tissues. Already polymer coatings are being applied directly to protect insulin producing pancreatic islet cells in the hope of treating type I diabetes. Here, we review current emerging developments in adult mesenchymal stem cell nanocoating and microcoating techniques and assess their unique practical engineering, biological and potential clinical advantages.

  14. Neural Crest As the Source of Adult Stem Cells

    Science.gov (United States)

    Pierret, Chris; Spears, Kathleen; Maruniak, Joel A.; Kirk, Mark D.

    2012-01-01

    Recent studies suggest that adult stem cells can cross germ layer boundaries. For example, bone marrow-derived stem cells appear to differentiate into neurons and glial cells, as well as other types of cells. How can stem cells from bone marrow, pancreas, skin, or fat become neurons and glia; in other words, what molecular and cellular events direct mesodermal cells to a neural fate? Transdifferentiation, dediffereniation, and fusion of donor adult stem cells with fully differentiated host cells have been proposed to explain the plasticity of adult stem cells. Here we review the origin of select adult stem cell populations and propose a unifying hypothesis to explain adult stem cell plasticity. In addition, we outline specific experiments to test our hypothesis. We propose that peripheral, tissue-derived, or adult stem cells are all progeny of the neural crest. PMID:16646675

  15. Adult Stem Cell Therapy for Periodontal Disease

    OpenAIRE

    Kim, Su-Hwan; Seo, Byoung-Moo; Choung, Pill-Hoon; Lee, Yong-Moo

    2010-01-01

    Periodontal disease is a major cause of tooth loss and characterized by inflammation of tooth-supporting structures. Recently, the association between periodontal disease and other health problems has been reported, the importance of treating periodontal disease for general health is more emphasized. The ultimate goal of periodontal therapy is regeneration of damaged periodontal tissues. The development of adult stem cell research enables to improve the cell-based tissue engineering for perio...

  16. Stem Cells

    Science.gov (United States)

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

  17. Research progress of adult cardiac stem cells

    Directory of Open Access Journals (Sweden)

    Nan ZHENG

    2013-04-01

    Full Text Available The traditional view is that the heart is a terminal organ. This dogma, however, has been widely questioned with the discovery of adult cardiac stem cells (CSCs. Since CSCs have a highly self-renewal capacity and specific myocardial differentiation potential, nowadays they have been regarded as the most promising type of stem cells used in ischemic heart disease and other replacement therapy of end-stage heart disease. The present paper will focus on current results of scientific research on human adult CSCs and epicardium-derived cell (EPDC, as well as the treatment strategies in the field of cardiac regeneration, and the problems and prospect disclosed in the research.

  18. 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.

  19. Wnt signaling in adult intestinal stem cells and cancer

    OpenAIRE

    Krausová, M. (Michaela); Kořínek, V. (Vladimír)

    2014-01-01

    Signaling initiated by secreted glycoproteins of the Wnt family regulates many aspects of embryonic development and it is involved in homeostasis of adult tissues. In the gastrointestinal (GI) tract the Wnt pathway maintains the self-renewal capacity of epithelial stem cells. The stem cell attributes are conferred by mutual interactions of the stem cell with its local microenvironment, the stem cell niche. The niche ensures that the threshold of Wnt signaling in the stem cell is kept in physi...

  20. [Therapeutic use of stem cells. II. Adult stem cells].

    Science.gov (United States)

    Uzan, Georges

    2004-09-30

    Many degenerative diseases are not curable by means of classical medicine. The long term objective of cell therapy is to treat the patients with their own stem cells that could be either purified from the diseased organ or from "reservoirs" of stem cells such as that constituted by the bone marrow. The existence of stem cells in the organs or reservoirs is now established in vitro and in some cases, in animal models. Numbers of technical problems linked to the scarcity of these cells still delay the clinical use of purified stem cells. However, clinical protocols using heterogeneous cell populations have already started to treat a growing number of diseases. In some case, autologous cells can be used, as it is the case for bone marrow transplantation in blood diseases. Mesenchymal cells, also purified from the bone marrow are currently used in orthopaedic diseases. Because these cells reveal a broad differentiation potential, active research programs explore their possible use for treatment of other diseases. Bone marrow also contains vascular stem cells that could be active in reappearing defective vessels responsible for ischaemic diseases. Indeed, clinical trials in which bone marrow cells are injected in the cardiac muscle of patients with myocardial infarction or in the leg muscle (gastrocnemius) of patients with hind limb ischaemia have already started. Artificial skin prepared from skin biopsies is used for the reconstitution of the derma of severely burned patients. Clinical trials have also started, using allogenic cells. The patients must be treated by immunosuppressive drugs. Neurodegenerative diseases such as Parkinson have been successfully treated by intra-cerebral injection of foetal neurones. Pancreatic islets implanted in the liver have shown to re-establish a normal glycaemia in diabetic patients. However, all these clinical trials use differentiated cells or at least progenitors which display differentiation potential and lifetime much more

  1. A novel view of the adult bone marrow stem cell hierarchy and stem cell trafficking

    OpenAIRE

    Ratajczak, M Z

    2015-01-01

    This review presents a novel view and working hypothesis about the hierarchy within the adult bone marrow stem cell compartment and the still-intriguing question of whether adult bone marrow contains primitive stem cells from early embryonic development, such as cells derived from the epiblast, migrating primordial germ cells or yolk sac-derived hemangioblasts. It also presents a novel view of the mechanisms that govern stem cell mobilization and homing, with special emphasis on the role of t...

  2. Adult Mesenchymal Stem Cells and Radiation Injury.

    Science.gov (United States)

    Kiang, Juliann G

    2016-08-01

    Recent understanding of the cellular and molecular signaling activations in adult mesenchymal stem cells (MSCs) has provided new insights into their potential clinical applications, particularly for tissue repair and regeneration. This review focuses on these advances, specifically in the context of self-renewal for tissue repair and recovery after radiation injury. Thus far, MSCs have been characterized extensively and shown to be useful in mitigation and therapy for acute radiation syndrome and cognitive dysfunction. Use of MSCs for treating radiation injury alone or in combination with additional trauma is foreseeable. PMID:27356065

  3. Intestinal stem cells in the adult Drosophila midgut

    International Nuclear Information System (INIS)

    Drosophila has long been an excellent model organism for studying stem cell biology. Notably, studies of Drosophila's germline stem cells have been instrumental in developing the stem cell niche concept. The recent discovery of somatic stem cells in adult Drosophila, particularly the intestinal stem cells (ISCs) of the midgut, has established Drosophila as an exciting model to study stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the major signaling pathways that regulate the self-renewal, proliferation and differentiation of Drosophila ISCs, discussing how this regulation maintains midgut homeostasis and mediates regeneration of the intestinal epithelium after injury. -- Highlights: ► The homeostasis and regeneration of adult fly midguts are mediated by ISCs. ► Damaged enterocytes induce the proliferation of intestinal stem cells (ISC). ► EGFR and Jak/Stat signalings mediate compensatory ISC proliferation. ► Notch signaling regulates ISC self-renewal and differentiation.

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

    Science.gov (United States)

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-06-21

    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. 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.

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

    Science.gov (United States)

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-01-01

    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. PMID:27338364

  7. DNA damage response in adult stem cells.

    Science.gov (United States)

    Insinga, Alessandra; Cicalese, Angelo; Pelicci, Pier Giuseppe

    2014-04-01

    This review discusses the processes of DNA-damage-response and DNA-damage repair in stem and progenitor cells of several tissues. The long life-span of stem cells suggests that they may respond differently to DNA damage than their downstream progeny and, indeed, studies have begun to elucidate the unique stem cell response mechanisms to DNA damage. Because the DNA damage responses in stem cells and progenitor cells are distinctly different, stem and progenitor cells should be considered as two different entities from this point of view. Hematopoietic and mammary stem cells display a unique DNA-damage response, which involves active inhibition of apoptosis, entry into the cell-cycle, symmetric division, partial DNA repair and maintenance of self-renewal. Each of these biological events depends on the up-regulation of the cell-cycle inhibitor p21. Moreover, inhibition of apoptosis and symmetric stem cell division are the consequence of the down-regulation of the tumor suppressor p53, as a direct result of p21 up-regulation. A deeper understanding of these processes is required before these findings can be translated into human anti-aging and anti-cancer therapies. One needs to clarify and dissect the pathways that control p21 regulation in normal and cancer stem cells and define (a) how p21 blocks p53 functions in stem cells and (b) how p21 promotes DNA repair in stem cells. Is this effect dependent on p21s ability to inhibit p53? Such molecular knowledge may pave the way to methods for maintaining short-term tissue reconstitution while retaining long-term cellular and genomic integrity.

  8. Potential of embryonic and adult stem cells in vitro.

    Science.gov (United States)

    Czyz, Jaroslaw; Wiese, Cornelia; Rolletschek, Alexandra; Blyszczuk, Przemyslaw; Cross, Michael; Wobus, Anna M

    2003-01-01

    Recent developments in the field of stem cell research indicate their enormous potential as a source of tissue for regenerative therapies. The success of such applications will depend on the precise properties and potentials of stem cells isolated either from embryonic, fetal or adult tissues. Embryonic stem cells established from the inner cell mass of early mouse embryos are characterized by nearly unlimited proliferation, and the capacity to differentiate into derivatives of essentially all lineages. The recent isolation and culture of human embryonic stem cell lines presents new opportunities for reconstructive medicine. However, important problems remain; first, the derivation of human embryonic stem cells from in vitro fertilized blastocysts creates ethical problems, and second, the current techniques for the directed differentiation into somatic cell populations yield impure products with tumorigenic potential. Recent studies have also suggested an unexpectedly wide developmental potential of adult tissue-specific stem cells. Here too, many questions remain concerning the nature and status of adult stem cells both in vivo and in vitro and their proliferation and differentiation/transdifferentiation capacity. This review focuses on those issues of embryonic and adult stem cell biology most relevant to their in vitro propagation and differentiation. Questions and problems related to the use of human embryonic and adult stem cells in tissue regeneration and transplantation are discussed.

  9. Therapeutics from Adult Stem Cells and the Hype Curve.

    Science.gov (United States)

    Maguire, Greg

    2016-05-12

    The Gartner curve for regenerative and stem cell therapeutics is currently climbing out of the "trough of disillusionment" and into the "slope of enlightenment". Understanding that the early years of stem cell therapy relied on the model of embryonic stem cells (ESCs), and then moved into a period of the overhype of induced pluripotent stem cells (iPSCs), instead of using the model of 40 years of success, i.e. adult stem cells used in bone marrow transplants, the field of stem cell therapy has languished for years, trying to move beyond the early and poorly understood success of bone marrow transplants. Recent studies in the lab and clinic show that adult stem cells of various types, and the molecules that they release, avoid the issues associated with ESCs and iPSCs and lead to better therapeutic outcomes and into the slope of enlightenment. PMID:27190588

  10. Therapeutics from Adult Stem Cells and the Hype Curve.

    Science.gov (United States)

    Maguire, Greg

    2016-05-12

    The Gartner curve for regenerative and stem cell therapeutics is currently climbing out of the "trough of disillusionment" and into the "slope of enlightenment". Understanding that the early years of stem cell therapy relied on the model of embryonic stem cells (ESCs), and then moved into a period of the overhype of induced pluripotent stem cells (iPSCs), instead of using the model of 40 years of success, i.e. adult stem cells used in bone marrow transplants, the field of stem cell therapy has languished for years, trying to move beyond the early and poorly understood success of bone marrow transplants. Recent studies in the lab and clinic show that adult stem cells of various types, and the molecules that they release, avoid the issues associated with ESCs and iPSCs and lead to better therapeutic outcomes and into the slope of enlightenment.

  11. Adult neural stem cells-Functional potential and therapeutic applications

    Institute of Scientific and Technical Information of China (English)

    YANG Lin; ZHU Jianhong

    2004-01-01

    The adult brain has been thought traditionally as a structure with a very limited regenerative capacity. It is now evident that neurogenesis in adult mammalian brain is a prevailing phenomenon. Neural stem cells with the ability to self-renew, differentiate into neurons, astrocytes and oligodendrocytes reside in some regions of the adult brain. Adult neurogenesis can be stimulated by many physiological factors including pregnancy. More strikingly, newborn neurons in hippocampus integrally function with local neurons, thus neural stem cells might play important roles in memory and learning function. It seems that neural stem cells could transdifferentiate into other tissues, such as blood cells and muscles. Although there are some impediments in this field, some attempts have been made to employ adult neural stem cells in the cell replacement therapy for traumatic and ischemic brain injuries.

  12. Coexistence of Quiescent and Active Adult Stem Cells in Mammals

    NARCIS (Netherlands)

    Li, Linheng; Clevers, Hans

    2010-01-01

    Adult stem cells are crucial for physiological tissue renewal and regeneration after injury. Prevailing models assume the existence of a single quiescent population of stem cells residing in a specialized niche of a given tissue. Emerging evidence indicates that both quiescent (out of cell cycle and

  13. Multipotent adult progenitor cell and stem cell plasticity

    OpenAIRE

    Jahagirdar, Balkrishna N; Verfaillie, Catherine

    2005-01-01

    Stem cells are defined by their biological function. A stem cell is an undifferentiated cell that self-renews to maintain the stem cell pool and at the single-cell level differentiates into more than one mature, functional cell. In addition, when transplanted, a stem cell should be capable of replacing a damaged organ or tissue for the lifetime of the recipient. Some would argue that stem cells should also be capable of functionally integrating into nondamaged tissues. Stem cells are critical...

  14. Embryonic and adult stem cell therapy.

    Science.gov (United States)

    Brignier, Anne C; Gewirtz, Alan M

    2010-02-01

    There are many types of stem cells. All share the characteristics of being able to self-renew and to give rise to differentiated progeny. Over the last decades, great excitement has been generated by the prospect of being able to exploit these properties for the repair, improvement, and/or replacement of damaged organs. However, many hurdles, both scientific and ethical, remain in the path of using human embryonic stem cells for tissue-engineering purposes. In this report we review current strategies for isolating, enriching, and, most recently, inducing the development of human pluripotent stem cells. In so doing, we discuss the scientific and ethical issues associated with this endeavor. Finally, progress in the use of stem cells as therapies for type 1 diabetes mellitus, congestive heart failure, and various neurologic and immunohematologic disorders, and as vehicles for the delivery of gene therapy, is briefly discussed. PMID:20061008

  15. A novel view of the adult bone marrow stem cell hierarchy and stem cell trafficking.

    Science.gov (United States)

    Ratajczak, M Z

    2015-04-01

    This review presents a novel view and working hypothesis about the hierarchy within the adult bone marrow stem cell compartment and the still-intriguing question of whether adult bone marrow contains primitive stem cells from early embryonic development, such as cells derived from the epiblast, migrating primordial germ cells or yolk sac-derived hemangioblasts. It also presents a novel view of the mechanisms that govern stem cell mobilization and homing, with special emphasis on the role of the complement cascade as a trigger for egress of hematopoietic stem cells from bone marrow into blood as well as the emerging role of novel homing factors and priming mechanisms that support stromal-derived factor 1-mediated homing of hematopoietic stem/progenitor cells after transplantation. PMID:25486871

  16. Perivascular ancestors of adult multipotent stem cells

    NARCIS (Netherlands)

    M. Corselli (Mirko); C.W. Chen; M. Crisan (Mihaela); L. Lazzari (Lorenza); B. Péault (Bruno)

    2010-01-01

    textabstractIndependent studies by numerous investigators have shown that it is possible to harvest multipotent progenitor cells from diverse dissociated and cultured fetal, perinatal, and principally adult developed tissues. Despite the increasingly recognized medical value of these progenitor cell

  17. Evolutionary insights into postembryonic development of adult intestinal stem cells

    Directory of Open Access Journals (Sweden)

    Ishizuya-Oka Atsuko

    2011-11-01

    Full Text Available Abstract In the adult vertebrate intestine, multi-potent stem cells continuously generate all of the epithelial cells throughout the adulthood. While it has long been known that the frog intestine is formed via the development of adult intestinal stem cells during thyroid hormone (TH-dependent metamorphosis, the basic structure of the adult intestine is formed by birth in mammals and it is unclear if the subsequent maturation of the intestine involves any changes in the intestinal stem cells. Two recent papers showing that B lymphocyte-induced maturation protein 1 (Blimp1 regulates postnatal epithelial stem cell reprogramming during mouse intestinal maturation support the model that adult intestinal stem cells are developed during postembryonic development in mammals, in a TH-dependent process similar to intestinal remodeling during amphibian metamorphosis. Since the formation of the adult intestine in both mammals and amphibians is closely associated with the adaptation from aquatic to terrestrial life during the peak of endogenous TH levels, the molecular mechanisms by which the adult stem cells are developed are likely evolutionally conserved.

  18. Development of neural stem cell in the adult brain

    OpenAIRE

    Duan, Xin; Kang, Eunchai; Liu, Cindy Y.; Ming, Guo-li; Song, Hongjun

    2008-01-01

    New neurons are continuously generated in the dentate gyrus of the mammalian hippocampus and in the subventricular zone of the lateral ventricles throughout life. The origin of these new neurons is believed to be from multipotent adult neural stem cells. Aided by new methodologies, significant progress has been made in the characterization of neural stem cells and their development in the adult brain. Recent studies have also begun to reveal essential extrinsic and intrinsic molecular mechani...

  19. Engineering of the Embryonic and Adult Stem Cell Niches

    OpenAIRE

    Hosseinkhani, Mohsen; Shirazi, Reza; Rajaei, Farzad; Mahmoudi, Masoud; Mohammadi, Navid; Abbasi, Mahnaz

    2013-01-01

    Context Stem cells have the potential to generate a renewable source of cells for regenerative medicine due to their ability to self-renew and differentiate to various functional cell types of the adult organism. The extracellular microenvironment plays a pivotal role in controlling stem cell fate responses. Therefore, identification of appropriate environmental stimuli that supports cellular proliferation and lineage-specific differentiation is critical for the clinical application of the st...

  20. Adult stem cells for chronic lung diseases.

    Science.gov (United States)

    Mora, Ana L; Rojas, Mauricio

    2013-10-01

    Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are chronic, progressive and lethal lung diseases. The incidence of IPF and COPD increases with age, independent of exposure to common environmental risk factors. At present, there is limited understanding of the relationship between ageing and the development of chronic lung diseases. One hypothesis is that chronic injury drives to exhaustion the local and systemic repair responses in the lung. These changes are accentuated during ageing where there is a progressive accumulation of senescent cells. Recently, stem cells have emerged as a critical reparative mechanism for lung injury. In this review, we discuss the repair response of bone marrow-derived mesenchymal stem cells (B-MSC) after lung injury and how their function is affected by ageing. Our own work has demonstrated a protective role of B-MSC in several animal models of acute and chronic lung injury. We recently demonstrated the association, using animal models, between age and an increase in the susceptibility to develop severe injury and fibrosis. At the same time, we have identified functional differences between B-MSC isolated from young and old animals. Further studies are required to understand the functional impairment of ageing B-MSC, ultimately leading to a rapid stem cell depletion or fatigue, interfering with their ability to play a protective role in lung injury. The elucidation of these events will help in the development of rational and new therapeutic strategies for COPD and IPF. PMID:23648014

  1. Intestinal stem cells in the adult Drosophila midgut

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Huaqi, E-mail: Huaqi.Jiang@UTSouthwestern.edu [Department of Developmental Biology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX, 75235 (United States); Edgar, Bruce A., E-mail: b.edgar@dkfz.de [ZMBH-DKFZ Alliance, Im Neuenheimer Feld 282, D-69120 Heidelberg (Germany); Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109 (United States)

    2011-11-15

    Drosophila has long been an excellent model organism for studying stem cell biology. Notably, studies of Drosophila's germline stem cells have been instrumental in developing the stem cell niche concept. The recent discovery of somatic stem cells in adult Drosophila, particularly the intestinal stem cells (ISCs) of the midgut, has established Drosophila as an exciting model to study stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the major signaling pathways that regulate the self-renewal, proliferation and differentiation of Drosophila ISCs, discussing how this regulation maintains midgut homeostasis and mediates regeneration of the intestinal epithelium after injury. -- Highlights: Black-Right-Pointing-Pointer The homeostasis and regeneration of adult fly midguts are mediated by ISCs. Black-Right-Pointing-Pointer Damaged enterocytes induce the proliferation of intestinal stem cells (ISC). Black-Right-Pointing-Pointer EGFR and Jak/Stat signalings mediate compensatory ISC proliferation. Black-Right-Pointing-Pointer Notch signaling regulates ISC self-renewal and differentiation.

  2. Adult neural stem cells in the mammalian central nervous system

    Institute of Scientific and Technical Information of China (English)

    Dengke K Ma; Michael A Bonaguidi; Guo-li Ming; Hongjun Song

    2009-01-01

    Neural stem cells (NSCs) are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to continuously generate functional neurons in specific brain regions throughout life. The adult neurogenesis process is subject to dynamic regulation by various physiological, pathological and pharmacological stimuli. Multipotent adult NSCs also appear to be intrinsically plastic, amenable to genetic programing during normal differentiation, and to epigenetic reprograming during de-differentiation into pluripotency. Increasing evidence suggests that adult NSCs significantly contribute to specialized neural functions under physiological and pathological conditions. Fully understanding the biology of adult NSCs will provide crucial insights into both the etiology and potential therapeutic interventions of major brain disorders. Here, we review recent progress on adult NSCs of the mammalian central nervous system, in-cluding topics on their identity, niche, function, plasticity, and emerging roles in cancer and regenerative medicine.

  3. Adult stem cells and their ability to differentiate.

    Science.gov (United States)

    Tarnowski, Maciej; Sieron, Aleksander L

    2006-08-01

    This is a review of the current status of knowledge on adult stem cells as well as the criteria and evidence for their potential to transform into different cell types and cell lineages. Reports on stem cell sources, focusing on tissues from adult subjects, were also investigated. Numerous reports have been published on the search for early markers of both stem cells and the precursors of various cell lineages. The question is still open about the characteristics of the primary stem cell. The existing proofs and hypotheses have not yielded final solutions to this problem. From a practical point of view it is also crucial to find a minimal set of markers determining the phenotypes of the precursor cells of a particular cell lineage. Several lines of evidence seem to bring closer the day when we will be able to detect the right stem cell niche and successfully isolate precursor cells that are needed for the treatment of a particular disorder. Recent reports on cases of cancer in patients subjected to stem cell therapy are yet another controversial issue looked into in this review, although the pros and cons emerging from the results of published studies still do not provide satisfying evidence to fully understand this issue. PMID:16865077

  4. Adult stem cells and their ability to differentiate.

    Science.gov (United States)

    Tarnowski, Maciej; Sieron, Aleksander L

    2006-08-01

    This is a review of the current status of knowledge on adult stem cells as well as the criteria and evidence for their potential to transform into different cell types and cell lineages. Reports on stem cell sources, focusing on tissues from adult subjects, were also investigated. Numerous reports have been published on the search for early markers of both stem cells and the precursors of various cell lineages. The question is still open about the characteristics of the primary stem cell. The existing proofs and hypotheses have not yielded final solutions to this problem. From a practical point of view it is also crucial to find a minimal set of markers determining the phenotypes of the precursor cells of a particular cell lineage. Several lines of evidence seem to bring closer the day when we will be able to detect the right stem cell niche and successfully isolate precursor cells that are needed for the treatment of a particular disorder. Recent reports on cases of cancer in patients subjected to stem cell therapy are yet another controversial issue looked into in this review, although the pros and cons emerging from the results of published studies still do not provide satisfying evidence to fully understand this issue.

  5. Adult Stromal (Skeletal, Mesenchymal) Stem Cells: Advances Towards Clinical Applications

    DEFF Research Database (Denmark)

    Kermani, Abbas Jafari; Harkness, Linda; Zaher, Walid;

    2014-01-01

    Mesenchymal Stem Cells (MSC) are non-hematopoietic adult stromal cells that reside in a perivascular niche in close association with pericytes and endothelial cells and possess self-renewal and multi-lineage differentiation capacity. The origin, unique properties, and therapeutic benefits of MSC ...

  6. Application of adult stem cells in neural tissue engineering

    Institute of Scientific and Technical Information of China (English)

    Lihong Piao; Wei Wang

    2006-01-01

    OBJECTTIVE:To investigate the progress in finding,isolation and culture.proliferation and differentiation,and application in neural tissue engineering of adult stem cells(ASCs).DATA SOURCES:Using the terms"adult stem cells,nerve,tissue engineering".we searched the PubMed for adult stem ceils-related studies published in English from January 2001 to August 2006.Meanwhile,we also performed a China National Knowledge Infrastructure(CNKI)search for homochronous correlative literatures on the computer by inputting the terms"adult stem cells,nerve,tissue engineering"in Chinese.texts were searched for.Inclusive criteria:①Literatures about the sources,distribution,culture.proliferation and differentiation.and application in the repair of neural ASCs by tissue engineering.②Articles recommended either by randomized.blind or by other methods were not excluded.Exclusive criteria:①Embryonic stem cells.②Review,repetitive study,case report,Meta analysis. DATA EXTRACTION:Totally 1 278 articles related to ASCs were collected,32 were involved and the other 1 246 were excluded. DATA SYNTHESIS:Adult stem cell has the ability of self-renewal.unceasing proliferation and transdifferentiation.It has wide source,which does not involved in ethical problems.It has advantages over embryonic stem cell.Studies on the isolation and culture,induction and differentiation and application in neural ASCs by tissue engineering contribute to obtaining considerable ASCs,so as to provide experimental and theoretical bases for CONCLUSION:ASCs play a very important role in neural tissue engineering.

  7. Human Intestinal Tissue with Adult Stem Cell Properties Derived from Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Ryan Forster

    2014-06-01

    Full Text Available Genetically engineered human pluripotent stem cells (hPSCs have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the isolation of defined functional tissues. Here, using an endogenous LGR5-GFP reporter, we derived adult stem cells from hPSCs that gave rise to functional human intestinal tissue comprising all major cell types of the intestine. Histological and functional analyses revealed that such human organoid cultures could be derived with high purity and with a composition and morphology similar to those of cultures obtained from human biopsies. Importantly, hPSC-derived organoids responded to the canonical signaling pathways that control self-renewal and differentiation in the adult human intestinal stem cell compartment. This adult stem cell system provides a platform for studying human intestinal disease in vitro using genetically engineered hPSCs.

  8. Embryonic and adult neural stem cell research in China

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Neural stem cells(NSCs) are one specific type of multipotential stem cells that have the ability to proliferate for a long time and to differentiate into neural cells,including neurons,astrocytes and oligodendrocytes.These NSCs exist in both the embryonic and adult central nervous system(CNS) of all mammalian species.Progress has been made in the understanding of the developmental regulation of NSCs and their function in neurogenesis.This review discusses recent progress in this area,with emphasis on work done by investigators in China.

  9. Haploidentical Stem Cell Transplantation in Adult Haematological Malignancies

    Directory of Open Access Journals (Sweden)

    Kevon Parmesar

    2016-01-01

    Full Text Available Haematopoietic stem cell transplantation is a well-established treatment option for both hematological malignancies and nonmalignant conditions such as aplastic anemia and haemoglobinopathies. For those patients lacking a suitable matched sibling or matched unrelated donor, haploidentical donors are an alternative expedient donor pool. Historically, haploidentical transplantation led to high rates of graft rejection and GVHD. Strategies to circumvent these issues include T cell depletion and management of complications thereof or T replete transplants with GVHD prophylaxis. This review is an overview of these strategies and contemporaneous outcomes for hematological malignancies in adult haploidentical stem cell transplant recipients.

  10. Switching roles: the functional plasticity of adult tissue stem cells

    OpenAIRE

    Wabik, A.; Jones, P H

    2015-01-01

    Adult organisms have to adapt to survive, and the same is true for their tissues. Rates and types of cell production must be rapidly and reversibly adjusted to meet tissue demands in response to both local and systemic challenges. Recent work reveals how stem cell (SC) populations meet these requirements by switching between functional states tuned to homoeostasis or regeneration. This plasticity extends to differentiating cells, which are capable of reverting to SCs after injury. The concept...

  11. Isolation and Culture of Adult Epithelial Stem Cells from Human Skin

    OpenAIRE

    Guo, Zhiru; Draheim, Kyle; Lyle, Stephen

    2011-01-01

    The homeostasis of all self-renewing tissues is dependent on adult stem cells. As undifferentiated stem cells undergo asymmetric divisions, they generate daughter cells that retain the stem cell phenotype and transit-amplifying cells (TA cells) that migrate from the stem cell niche, undergo rapid proliferation and terminally differentiate to repopulate the tissue.

  12. Further proof of the plasticity of adult stem cells and their role in tissue repair

    OpenAIRE

    Prockop, Darwin J.

    2003-01-01

    In this issue, De Bari et al. (2003) present elegant data to counter the recent claims that adult stem cells have a limited plasticity. Further, they provide evidence that adult stem cells can seek out damaged tissues and repair them.

  13. Properties of Adult Lung Stem and Progenitor Cells.

    Science.gov (United States)

    Bertoncello, Ivan

    2016-12-01

    The last decade has seen significant progress in understanding the organisation of regenerative cells in the adult lung. Cell-lineage tracing and in vitro clonogenic assays have enabled the identification and characterisation of endogenous lung epithelial stem and progenitor cells. Selective lung injury models, and genetically engineered mice have revealed highly conserved gene networks, factors, signalling pathways, and cellular interactions important in maintaining lung homeostasis and regulating lung regeneration and repair following injury. This review describes the current models of lung epithelial stem and progenitor cell organisation in adult mice, and the impediments encountered in translational studies aiming to identify and characterise their human homologs. J. Cell. Physiol. 231: 2582-2589, 2016. © 2016 Wiley Periodicals, Inc. PMID:27062064

  14. Reprogramming of adult human neural stem cells into induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    XIE Li-qian; SUN Hua-ping; WANG Tian; TANG Hai-liang; WANG Pu; ZHU Jian-hong; YAO Zheng-wei

    2013-01-01

    Background Since an effective method for generating induced pluripotent stem cells (iPSCs) from human neural stem cells (hNSCs) can offer us a promising tool for studying brain diseases,here we reported direct reprogramming of adult hNSCs into iPSCs by retroviral transduction of four defined factors.Methods NSCs were successfully isolated and cultured from the hippocampus tissue of epilepsy patients.When combined with four factors (OCT3/4,SOX2,KLF4,and c-MYC),iPSCs colonies were successfully obtained.Results Morphological characterization and specific genetic expression confirmed that these hNSCs-derived iPSCs showed embryonic stem cells-like properties,which include the ability to differentiate into all three germ layers both in vitro and in vivo.Conclusion Our method would be useful for generating human iPSCs from NSCs and provide an important tool for studying neurological diseases.

  15. Detection of embryonic stem cell markers in adult human adipose tissue-derived stem cells

    Directory of Open Access Journals (Sweden)

    Sarasa Bharati Arumugam

    2011-01-01

    Full Text Available Background: Bone marrow transplantation is already an established therapy, which is now widely used in medicine to treat leukemia, lymphoma, and several inherited blood disorders. The culture of multilineage cells from easily available adipose tissue is another source of multipotent mesenchymal stem cells, and is referred to as adipose tissue-derived stem cells (ADSCs. While ADSCs are being used to treat various conditions, some lacuna exists regarding the specific proteins in these. It was therefore decided to analyze the specific proteins of embryonic cells in ADSCs. Aims: To analyze the specific protein of embryonic stem cells (ESCs in ADSCs. Materials and Methods: Adult human adipose tissue-derived stem cells (ADSCs were harvested from 13 patients after obtaining patients′ consent. The specific markers of ESCs included surface proteins CD10, CD13, CD44, CD59, CD105, and CD166, and further nucleostemin,(NS NANOG, peroxisome proliferator-activated receptor-gγ, collagen type 1 (Coll1, alkaline phosphate, (ALP osteocalcin (OC, and core binding factor 1 (Cbfa1 were analyzed using by reverse transcription-polymerase chain reaction, (RT-PCR immunofluorescence (IF, and western blot. Results: All the proteins were expressed distinctly, except CD13 and OC. CD13 was found individually with different expressions, and OC expression was discernable. Conclusions: Although the ESC with its proven self-renewal capacity and pluripotency seems appropriate for clinical use, the recent work on ADSCs suggests that these adult stem cells would be a valuable source for future biotechnology, especially since there is a relative ease of procurement.

  16. Recent advances in bone regeneration using adult stem cells.

    Science.gov (United States)

    Zigdon-Giladi, Hadar; Rudich, Utai; Michaeli Geller, Gal; Evron, Ayelet

    2015-04-26

    Bone is a highly vascularized tissue reliant on the close spatial and temporal association between blood vessels and bone cells. Therefore, cells that participate in vasculogenesis and osteogenesis play a pivotal role in bone formation during prenatal and postnatal periods. Nevertheless, spontaneous healing of bone fracture is occasionally impaired due to insufficient blood and cellular supply to the site of injury. In these cases, bone regeneration process is interrupted, which might result in delayed union or even nonunion of the fracture. Nonunion fracture is difficult to treat and have a high financial impact. In the last decade, numerous technological advancements in bone tissue engineering and cell-therapy opened new horizon in the field of bone regeneration. This review starts with presentation of the biological processes involved in bone development, bone remodeling, fracture healing process and the microenvironment at bone healing sites. Then, we discuss the rationale for using adult stem cells and listed the characteristics of the available cells for bone regeneration. The mechanism of action and epigenetic regulations for osteogenic differentiation are also described. Finally, we review the literature for translational and clinical trials that investigated the use of adult stem cells (mesenchymal stem cells, endothelial progenitor cells and CD34(+) blood progenitors) for bone regeneration.

  17. Adult human neural stem cell therapeutics: Currentdevelopmental status and prospect

    Institute of Scientific and Technical Information of China (English)

    Hyun Nam; Kee-Hang Lee; Do-Hyun Nam; Kyeung Min Joo

    2015-01-01

    Over the past two decades, regenerative therapies usingstem cell technologies have been developed for variousneurological diseases. Although stem cell therapy is anattractive option to reverse neural tissue damage and torecover neurological deficits, it is still under developmentso as not to show significant treatment effects in clinicalsettings. In this review, we discuss the scientific andclinical basics of adult neural stem cells (aNSCs), andtheir current developmental status as cell therapeuticsfor neurological disease. Compared with other typesof stem cells, aNSCs have clinical advantages, suchas limited proliferation, inborn differentiation potentialinto functional neural cells, and no ethical issues. Inspite of the merits of aNSCs, difficulties in the isolationfrom the normal brain, and in the in vitro expansion,have blocked preclinical and clinical study using aNSCs.However, several groups have recently developed noveltechniques to isolate and expand aNSCs from normaladult brains, and showed successful applications ofaNSCs to neurological diseases. With new technologiesfor aNSCs and their clinical strengths, previous hurdlesin stem cell therapies for neurological diseases could beovercome, to realize clinically efficacious regenerativestem cell therapeutics.

  18. Cuban experience with the therapeutic use of adult stem cells

    International Nuclear Information System (INIS)

    The basic and clinical researches carried out during past years on the stem cells and its therapeutic possibilities are at present times, one of the most interesting subjects of the contemporaneous medicine. There are advances in the study and application of adult stem cells showing remarkable advantages on the embryonic ones, since its handling is more simple, economic and they are obtained from the own subject to be treated. For the introduction in Cuba of the regenerative cellular therapy in the Institute of Hematology and Immunology the cellular sources selected were the adult stem cells derived from bone marrow and the mobilized ones to the peripheral blood. To make easy the expansion of treatment to other hospital centers, authors standardized a technique for the mobilization of the hematopoietic stem cells to peripheral blood using a granulocyte colony-stimulating factor (Filgrastim, of national production) developing a simple, economic and more tolerable method for patients. In this way, the cellular therapy has been expanded to 6 Cuban provinces and until April, 2009 562 cases with autologous adult stem cells transplant have been treated, from which the 81.7% to correspond to patients presenting with Angiology diseases with a significant reduction of major amputations. Also, the results have been very promising in the bone lesions and periodontal processes among other diseases treated. The results obtained until now may be considered as a new achievement of revolutionary science and of our national health systems and of science and technique. The method used is an economic and feasible procedure for the institutions with scarce resources

  19. Angiogenic factors stimulate growth of adult neural stem cells.

    Directory of Open Access Journals (Sweden)

    Andreas Androutsellis-Theotokis

    Full Text Available BACKGROUND: The ability to grow a uniform cell type from the adult central nervous system (CNS is valuable for developing cell therapies and new strategies for drug discovery. The adult mammalian brain is a source of neural stem cells (NSC found in both neurogenic and non-neurogenic zones but difficulties in culturing these hinders their use as research tools. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that NSCs can be efficiently grown in adherent cell cultures when angiogenic signals are included in the medium. These signals include both anti-angiogenic factors (the soluble form of the Notch receptor ligand, Dll4 and pro-angiogenic factors (the Tie-2 receptor ligand, Angiopoietin 2. These treatments support the self renewal state of cultured NSCs and expression of the transcription factor Hes3, which also identifies the cancer stem cell population in human tumors. In an organotypic slice model, angiogenic factors maintain vascular structure and increase the density of dopamine neuron processes. CONCLUSIONS/SIGNIFICANCE: We demonstrate new properties of adult NSCs and a method to generate efficient adult NSC cultures from various central nervous system areas. These findings will help establish cellular models relevant to cancer and regeneration.

  20. Neural stem cells and the regulation of adult neurogenesis

    Directory of Open Access Journals (Sweden)

    Conover Joanne C

    2003-11-01

    Full Text Available Abstract Presumably, the 'hard-wired' neuronal circuitry of the adult brain dissuades addition of new neurons, which could potentially disrupt existing circuits. This is borne out by the fact that, in general, new neurons are not produced in the mature brain. However, recent studies have established that the adult brain does maintain discrete regions of neurogenesis from which new neurons migrate and become incorporated into the functional circuitry of the brain. These neurogenic zones appear to be vestiges of the original developmental program that initiates brain formation. The largest of these germinal regions in the adult brain is the subventricular zone (SVZ, which lines the lateral walls of the lateral ventricles. Neural stem cells produce neuroblasts that migrate from the SVZ along a discrete pathway, the rostral migratory stream, into the olfactory bulb where they form mature neurons involved in the sense of smell. The subgranular layer (SGL of the hippocampal dentate gyrus is another neurogenic region; new SGL neurons migrate only a short distance and differentiate into hippocampal granule cells. Here, we discuss the surprising finding of neural stem cells in the adult brain and the molecular mechanisms that regulate adult neurogenesis.

  1. Adult Stem Cells for Acute Lung Injury: Remaining Questions & Concerns

    OpenAIRE

    Zhu, Ying-Gang; Hao, Qi; Monsel, Antoine; Feng, Xiao-mei; Lee, Jae W.

    2013-01-01

    Acute lung injury (ALI) or acute respiratory distress syndrome remains a major cause of morbidity and mortality in hospitalized patients. The pathophysiology of ALI involves complex interactions between the inciting event, such as pneumonia, sepsis or aspiration, and the host immune response resulting in lung protein permeability, impaired resolution of pulmonary edema, an intense inflammatory response in the injured alveolus and hypoxemia. In multiple pre-clinical studies, adult stem cells h...

  2. Switching roles: the functional plasticity of adult tissue stem cells.

    Science.gov (United States)

    Wabik, Agnieszka; Jones, Philip H

    2015-05-01

    Adult organisms have to adapt to survive, and the same is true for their tissues. Rates and types of cell production must be rapidly and reversibly adjusted to meet tissue demands in response to both local and systemic challenges. Recent work reveals how stem cell (SC) populations meet these requirements by switching between functional states tuned to homoeostasis or regeneration. This plasticity extends to differentiating cells, which are capable of reverting to SCs after injury. The concept of the niche, the micro-environment that sustains and regulates stem cells, is broadening, with a new appreciation of the role of physical factors and hormonal signals. Here, we review different functions of SCs, the cellular mechanisms that underlie them and the signals that bias the fate of SCs as they switch between roles. PMID:25812989

  3. Adult stem cells applied to tissue engineering and regenerative medicine.

    Science.gov (United States)

    Cuenca-López, M D; Zamora-Navas, P; García-Herrera, J M; Godino, M; López-Puertas, J M; Guerado, E; Becerra, J; Andrades, J A

    2008-01-01

    Regeneration takes place in the body at a moment or another throughout life. Bone, cartilage, and tendons (the key components of the structure and articulation in the body) have a limited capacity for self-repair and, after traumatic injury or disease, the regenerative power of adult tissue is often insufficient. When organs or tissues are irreparably damaged, they may be replaced by an artificial device or by a donor organ. However, the number of available donor organs is considerably limited. Generation of tissue-engineered replacement organs by extracting stem cells from the patient, growing them and modifying them in clinical conditions after re-introduction in the body represents an ideal source for corrective treatment. Mesenchymal stem cells (MSCs) are the multipotential progenitors that give rise to skeletal cells, vascular smooth muscle cells, muscle (skeletal and cardiac muscle), adipocytes (fat tissue) and hematopoietic (blood)-supportive stromal cells. MSCs are found in multiple connective tissues, in adult bone marrow, skeletal muscles and fat pads. The wide representation in adult tissues may be related to the existence of a circulating blood pool or that MSCs are associated to the vascular system.

  4. Stirred bioreactors for the expansion of adult pancreatic stem cells.

    Science.gov (United States)

    Serra, Margarida; Brito, Catarina; Leite, Sofia B; Gorjup, Erwin; von Briesen, Hagen; Carrondo, Manuel J T; Alves, Paula M

    2009-01-01

    Adult pluripotent stem cells are a cellular resource representing unprecedented potential for cell therapy and tissue engineering. Complementary to this promise, there is a need for efficient bioprocesses for their large scale expansion and/or differentiation. With this goal in mind, our work focused on the development of three-dimensional (3-D) culture systems for controlled expansion of adult pancreatic stem cells (PSCs). For this purpose, two different culturing strategies were evaluated, using spinner vessels: cell aggregated cultures versus microcarrier technology. The use of microcarrier supports (Cytodex 1 and Cytodex 3) rendered expanded cell populations which retained their self-renewal ability, cell marker, and the potential to differentiate into adipocytes. This strategy surmounted the drawbacks of aggregates in culture which were demonstrably unfeasible as cells clumped together did not proliferate and lost PSC marker expression. Furthermore, the results obtained showed that although both microcarriers tested here were suitable for sustaining cell expansion, Cytodex 3 provided a better substrate for the promotion of cell adherence and growth. For the latter approach, the potential of bioreactor technology was combined with the efficient Cytodex 3 strategy under controlled environmental conditions (pH-7.2, pO2-30% and temperature-37 degrees C); cell growth was more efficient, as shown by faster doubling time, higher growth rate and higher fold increase in cell concentration, when compared to spinner cultures. This study describes a robust bioprocess for the controlled expansion of adult PSC, representing an efficient starting point for the development of novel technologies for cell therapy.

  5. Recent Progress on Tissue-Resident Adult Stem Cell Biology and Their Therapeutic Implications

    OpenAIRE

    Mimeault, Murielle; Batra, Surinder K.

    2008-01-01

    Recent progress in the field of the stem cell research has given new hopes to treat and even cure diverse degenerative disorders and incurable diseases in human. Particularly, the identification of a rare population of adult stem cells in the most tissues/organs in human has emerged as an attractive source of multipotent stem/progenitor cells for cell replacement-based therapies and tissue engineering in regenerative medicine. The tissue-resident adult stem/progenitor cells offer the possibil...

  6. Adult Bone Marrow: Which Stem Cells for Cellular Therapy Protocols in Neurodegenerative Disorders?

    OpenAIRE

    Sabine Wislet-Gendebien; Emerence Laudet; Virginie Neirinckx; Bernard Rogister

    2012-01-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs). In th...

  7. The Drosophila hindgut lacks constitutively active adult stem cells but proliferates in response to tissue damage

    OpenAIRE

    D.T., Fox; Spradling, A.C.

    2009-01-01

    The adult Drosophila hindgut was recently reported to contain active, tissue-replenishing stem cells, like those of the midgut, but located within an anterior ring so as to comprise a single giant crypt. In contrast to this view, we observed no active stem cells and little cell turnover in adult hindgut tissue based on clonal marking and BrdU incorporation studies. Again contradicting the previous proposal, we showed that the adult hindgut is not generated by anterior stem cells during larval...

  8. The proteome of neural stem cells from adult rat hippocampus

    Directory of Open Access Journals (Sweden)

    Fütterer Carsten D

    2003-06-01

    Full Text Available Abstract Background Hippocampal neural stem cells (HNSC play an important role in cerebral plasticity in the adult brain and may contribute to tissue repair in neurological disease. To describe their biological potential with regard to plasticity, proliferation, or differentiation, it is important to know the cellular composition of their proteins, subsumed by the term proteome. Results Here, we present for the first time a proteomic database for HNSC isolated from the brains of adult rats and cultured for 10 weeks. Cytosolic proteins were extracted and subjected to two-dimensional gel electrophoresis followed by protein identification through mass spectrometry, database search, and gel matching. We could map about 1141 ± 209 (N = 5 protein spots for each gel, of which 266 could be identified. We could group the identified proteins into several functional categories including metabolism, protein folding, energy metabolism and cellular respiration, as well as cytoskeleton, Ca2+ signaling pathways, cell cycle regulation, proteasome and protein degradation. We also found proteins belonging to detoxification, neurotransmitter metabolism, intracellular signaling pathways, and regulation of DNA transcription and RNA processing. Conclusions The HNSC proteome database is a useful inventory which will allow to specify changes in the cellular protein expression pattern due to specific activated or suppressed pathways during differentiation or proliferation of neural stem cells. Several proteins could be identified in the HNSC proteome which are related to differentiation and plasticity, indicating activated functional pathways. Moreover, we found a protein for which no expression has been described in brain cells before.

  9. A modified enrichment protocol for adult caprine skeletal muscle stem cell

    OpenAIRE

    Tripathi, Ajai K.; Ramani, Umed V.; Ahir, Viral B.; Rank, Dharamshi N.; Joshi, Chaitanya G.

    2010-01-01

    To establish an adequate model to study the proliferation and differentiation of adult caprine skeletal muscle in response to bioactive compounds, a pool of satellite cells (SC) was derived from the rectus abdominis muscle of adult goat. Skeletal muscle contains a population of adult stem cells, named as satellite cells that reside beneath the basal lamina of skeletal muscle fiber and other populations of cells. These SC are multipotent stem cells, since cells cultured in the presence of spec...

  10. Identification and Characterization of Adult Porcine Muscle Stem Cells

    NARCIS (Netherlands)

    Wilschut, K.J.

    2009-01-01

    In the past decade, tissue-specific stem cell research has been emerging. Stem cells are characterized by a long-term expansion and a broad developmental potential in vitro. Pre-clinical studies appear promising, but still many limitations have to be overcome before broad therapeutic use of stem cel

  11. Thyroid Hormone Regulation of Adult Intestinal Stem Cell Development: Mechanisms and Evolutionary Conservations

    OpenAIRE

    Sun, Guihong; Shi, Yun-Bo

    2012-01-01

    The adult mammalian intestine has long been used as a model to study adult stem cell function and tissue renewal as the intestinal epithelium is constantly undergoing self-renewal throughout adult life. This is accomplished through the proliferation and subsequent differentiation of the adult stem cells located in the crypt. The development of this self-renewal system is, however, poorly understood. A number of studies suggest that the formation/maturation of the adult intestine is conserved ...

  12. Strategies for homeostatic stem cell self-renewal in adult tissues

    NARCIS (Netherlands)

    Simons, B.D.; Clevers, H.

    2011-01-01

    In adult tissues, an exquisite balance exists between stem cell proliferation and the generation of differentiated offspring. Classically, it has been argued that this balance is obtained at the level of a single stem cell, which divides strictly into a new stem cell and a progenitor. However, recen

  13. Phenotypic characterizations and comparison of adult dental stem cells with adipose-derived stem cells

    Directory of Open Access Journals (Sweden)

    Razieh Alipour

    2010-01-01

    Conclusions: Both cell populations derived from adipose tissue and dental pulp showed common phenotypic markers of mesenchymal stem cells. In conclusion, mesenchymal stem cells could be isolated and cultured successfully from dental pulp of human exfo-liated deciduous teeth, they are very good candidates for treatment and prevention of human diseases.

  14. Development and application of human adult stem or progenitor cell organoids

    NARCIS (Netherlands)

    Rookmaaker, Maarten B; Schutgens, Frans; Verhaar, Marianne C; Clevers, Hans

    2015-01-01

    Adult stem or progenitor cell organoids are 3D adult-organ-derived epithelial structures that contain self-renewing and organ-specific stem or progenitor cells as well as differentiated cells. This organoid culture system was first established in murine intestine and subsequently developed for sever

  15. Characterization of TLX Expression in Neural Stem Cells and Progenitor Cells in Adult Brains

    OpenAIRE

    Shengxiu Li; Guoqiang Sun; Kiyohito Murai; Peng Ye; Yanhong Shi

    2012-01-01

    TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then, using a double thymidine analo...

  16. The Molecular Basic for Adult Stem Cell Plasticity

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Embryonic stem cells (ES cells) would be the future for regenerative medicine, but it is so far still difficult to efficiently and specifically differentiate ES cells into certain cell types for treating human diseases. Tissue-specific stem cells, neural progenitor cells (NPCs) for example, appear to have the advantage in this regard. However, they cannot expand efficiently to provide sufficient numbers of cells for clinical use. We therefore tested whether NPCs can be immortalized by ectopic expression of ...

  17. Crypt region localization of intestinal stem cells in adults

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The intestinal epithelial lining plays a central role in the digestion and absorption of nutrients, but exists in a harsh luminal environment that necessitates continual renewal. This renewal process involves epithelial cell proliferation in the crypt base and later cell migration from the crypt base to the luminal surface. This process is dependent on multi-potent progenitor cells, or stem cells, located in each crypt. There are about 4 to 6 stem cells per crypt, and these stem cells are believed to generate distinct end-differentiated epithelial cell types, including absorptive cells, goblet cells, enteroendocrine cells and Paneth cells, while also maintaining their own progenitor cell state. Earlier studies suggested that intestinal stem cells were located either in the crypt base interspersed between the Paneth cells [i.e. Crypt base columnar (CBC) cell model] or at an average position of 4 cells from the crypt base [I.e. Label-retaining cells (LRC +4) model]. Recent studies have employed biomarkers in the in vivo mammalian state to more precisely evaluate the location of these progenitor cells in the intestinal crypt. Most notable of these novel markers are Lgr5, a gene that encodes a G-protein-coupled receptor with expression restricted to CBC cells, and Bmi 1, which encodes a chromatin remodeling protein expressed by LRC. These studies raise the possibility that there may be separate stem cell lines or different states of stem cell activation involved in the renewal of normal mammalian intestinal tract.

  18. Cell competition modifies adult stem cell and tissue population dynamics in a JAKSTAT dependent manner

    OpenAIRE

    Kolahgar, Golnar; Suijkerbuijk, Saskia J. E.; Kucinski, Iwo; Poirier, Enzo Z.; Mansour, Sarah; Simons, Benjamin D.; Piddini, Eugenia

    2015-01-01

    Summary Throughout their lifetime, cells may suffer insults that reduce their fitness and disrupt their function, and it is unclear how these potentially harmful cells are managed in adult tissues. We address this question using the adult Drosophila posterior midgut as a model of homeostatic tissue and ribosomal Minute mutations to reduce fitness in groups of cells. We take a quantitative approach combining lineage tracing and biophysical modeling and address how cell competition affects stem...

  19. Multipotent (adult) and pluripotent stem cells for heart regeneration: what are the pros and cons?

    Science.gov (United States)

    Liao, Song-Yan; Tse, Hung-Fat

    2013-01-01

    Heart failure after myocardial infarction is the leading cause of mortality and morbidity worldwide. Existing medical and interventional therapies can only reduce the loss of cardiomyocytes during myocardial infarction but are unable to replenish the permanent loss of cardiomyocytes after the insult, which contributes to progressive pathological left ventricular remodeling and progressive heart failure. As a result, cell-based therapies using multipotent (adult) stem cells and pluripotent stem cells (embryonic stem cells or induced pluripotent stem cells) have been explored as potential therapeutic approaches to restore cardiac function in heart failure. Nevertheless, the optimal cell type with the best therapeutic efficacy and safety for heart regeneration is still unknown. In this review, the potential pros and cons of different types of multipotent (adult) stem cells and pluripotent stem cells that have been investigated in preclinical and clinical studies are reviewed, and the future perspective of stem cell-based therapy for heart regeneration is discussed. PMID:24476362

  20. Multipotent (adult) and pluripotent stem cells for heart regeneration: what are the pros and cons?

    Science.gov (United States)

    Liao, Song-Yan; Tse, Hung-Fat

    2013-12-24

    Heart failure after myocardial infarction is the leading cause of mortality and morbidity worldwide. Existing medical and interventional therapies can only reduce the loss of cardiomyocytes during myocardial infarction but are unable to replenish the permanent loss of cardiomyocytes after the insult, which contributes to progressive pathological left ventricular remodeling and progressive heart failure. As a result, cell-based therapies using multipotent (adult) stem cells and pluripotent stem cells (embryonic stem cells or induced pluripotent stem cells) have been explored as potential therapeutic approaches to restore cardiac function in heart failure. Nevertheless, the optimal cell type with the best therapeutic efficacy and safety for heart regeneration is still unknown. In this review, the potential pros and cons of different types of multipotent (adult) stem cells and pluripotent stem cells that have been investigated in preclinical and clinical studies are reviewed, and the future perspective of stem cell-based therapy for heart regeneration is discussed.

  1. Adult and Embryonic Stem Cell-�from isolation to differentiation

    OpenAIRE

    Bosnakovski, Darko

    2012-01-01

    In this lecture the new prospective of adult stem isolation from various tissues and generation of human embryonic stem cells will be presented. In addition the generation of induced pluripotent stem cells and their potential use will be discussed. Furthermore differentiation methods toward mesenchymal lineage will be elaborated. The lecture will be base on our own data in the field.

  2. GREAT PROMISE OF TISSUE-RESIDENT ADULT STEM/PROGENITOR CELLS IN TRANSPLANTATION AND CANCER THERAPIES

    OpenAIRE

    Mimeault, Murielle; Batra, Surinder K.

    2012-01-01

    Recent progress in tissue-resident adult stem/progenitor cell research has inspired great interest because these immature cells from your own body can act as potential, easily accessible cell sources for cell transplantation in regenerative medicine and cancer therapies. The use of adult stem/progenitor cells endowed with a high self-renewal ability and multilineage differentiation potential, which are able to regenerate all the mature cells in the tissues from their origin, offers great prom...

  3. Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences.

    Science.gov (United States)

    Wislet-Gendebien, Sabine; Laudet, Emerence; Neirinckx, Virginie; Alix, Philippe; Leprince, Pierre; Glejzer, Aneta; Poulet, Christophe; Hennuy, Benoit; Sommer, Lukas; Shakhova, Olga; Rogister, Bernard

    2012-08-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crest stem cells (NCSC) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSC), including their similarities and differences. In this paper, using transcriptomic as well as proteomic technologies, we compared NCSC to MSC and stromal nestin-positive cells, all of them isolated from adult bone marrow. We demonstrated that the nestin-positive cell population, which was the first to be described as able to differentiate into functional neurons, was a mixed population of NCSC and MSC. More interestingly, we demonstrated that MSC shared with NCSC the same ability to truly differentiate into Tuj1-positive cells when co-cultivated with paraformaldehyde-fixed cerebellar granule neurons. Altogether, those results suggest that both NCSC and MSC can be considered as important tools for cellular therapies in order to replace neurons in various neurological diseases. PMID:22349262

  4. Stemness Evaluation of Mesenchymal Stem Cells from Placentas According to Developmental Stage: Comparison to Those from Adult Bone Marrow

    OpenAIRE

    Sung, Hwa Jung; Hong, Soon Cheol; Yoo, Ji Hyun; Oh, Jee Hyun; Shin, Hye Jin; Choi, In Young; Ahn, Ki Hoon; Kim, Sun Haeng; Park, Yong; Kim, Byung Soo

    2010-01-01

    This study was done to evaluate the stemness of human mesenchymal stem cells (hMSCs) derived from placenta according to the development stage and to compare the results to those from adult bone marrow (BM). Based on the source of hMSCs, three groups were defined: group I included term placentas, group II included first-trimester placentas, and group III included adult BM samples. The stemness was evaluated by the proliferation capacity, immunophenotypic expression, mesoderm differentiation, e...

  5. Adult Bone Marrow: Which Stem Cells for Cellular Therapy Protocols in Neurodegenerative Disorders?

    Directory of Open Access Journals (Sweden)

    Sabine Wislet-Gendebien

    2012-01-01

    Full Text Available The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs. In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy.

  6. Adult bone marrow: which stem cells for cellular therapy protocols in neurodegenerative disorders?

    Science.gov (United States)

    Wislet-Gendebien, Sabine; Laudet, Emerence; Neirinckx, Virginie; Rogister, Bernard

    2012-01-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs). In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy. PMID:22319243

  7. Cerebellar stem cells do not produce neurons and astrocytes in adult mouse

    Energy Technology Data Exchange (ETDEWEB)

    Su, Xin; Guan, Wuqiang; Yu, Yong-Chun; Fu, Yinghui, E-mail: fuyh@fudan.edu.cn

    2014-07-18

    Highlights: • No new neurons and astrocytes are generated in adult mouse cerebellum. • Very few mash1{sup +} or nestin{sup +} stem cells exist, and most of them are quiescent. • Cell proliferation rate is diversified among cerebellar regions and decreases over time. - Abstract: Although previous studies implied that cerebellar stem cells exist in some adult mammals, little is known about whether these stem cells can produce new neurons and astrocytes. In this study by bromodeoxyuridine (BrdU) intraperitoneal (i.p.) injection, we found that there are abundant BrdU{sup +} cells in adult mouse cerebellum, and their quantity and density decreases significantly over time. We also found cell proliferation rate is diversified in different cerebellar regions. Among these BrdU{sup +} cells, very few are mash1{sup +} or nestin{sup +} stem cells, and the vast majority of cerebellar stem cells are quiescent. Data obtained by in vivo retrovirus injection indicate that stem cells do not produce neurons and astrocytes in adult mouse cerebellum. Instead, some cells labeled by retrovirus are Iba1{sup +} microglia. These results indicate that very few stem cells exist in adult mouse cerebellum, and none of these stem cells contribute to neurogenesis and astrogenesis under physiological condition.

  8. Cerebellar stem cells do not produce neurons and astrocytes in adult mouse

    International Nuclear Information System (INIS)

    Highlights: • No new neurons and astrocytes are generated in adult mouse cerebellum. • Very few mash1+ or nestin+ stem cells exist, and most of them are quiescent. • Cell proliferation rate is diversified among cerebellar regions and decreases over time. - Abstract: Although previous studies implied that cerebellar stem cells exist in some adult mammals, little is known about whether these stem cells can produce new neurons and astrocytes. In this study by bromodeoxyuridine (BrdU) intraperitoneal (i.p.) injection, we found that there are abundant BrdU+ cells in adult mouse cerebellum, and their quantity and density decreases significantly over time. We also found cell proliferation rate is diversified in different cerebellar regions. Among these BrdU+ cells, very few are mash1+ or nestin+ stem cells, and the vast majority of cerebellar stem cells are quiescent. Data obtained by in vivo retrovirus injection indicate that stem cells do not produce neurons and astrocytes in adult mouse cerebellum. Instead, some cells labeled by retrovirus are Iba1+ microglia. These results indicate that very few stem cells exist in adult mouse cerebellum, and none of these stem cells contribute to neurogenesis and astrogenesis under physiological condition

  9. Neuro-muscular differentiation of adult porcine skin derived stem cell-like cells.

    Directory of Open Access Journals (Sweden)

    Dominik Lermen

    Full Text Available BACKGROUND: Due to the genetic relationship to humans, porcine stem cells are a very important model system to investigate cell differentiation, associated cell signaling pathways, and cell fate. Porcine skin derived stem cells have been isolated from mid-gestation porcine fetus recently. To our knowledge, stem cells from the skin of the adult porcine organism have not been isolated until now. Hence, to our knowledge, we here describe the isolation, expansion, characterization and differentiation of multipotent porcine skin derived stem cell-like cells (pSSCs from the adult porcine organism for the first time. METHODOLOGY/PRINCIPAL FINDINGS: pSSCs had a spindle shaped morphology similar to mesenchymal stem cells (MSCs. They could be maintained proliferatively active in vitro for more than 120 days and were able to form colonies from single cells. pSSCs expressed Sox2 and Oct3/4, both transcription factors essential to the pluripotent and self-renewing phenotypes of embryonic stem cells, which recently gained attention due to their function in inducing pluripotent stem cells. Furthermore, the expression of the progenitor marker nestin, the somatic stem cell markers Bcrp1/ABCG2, Bmi1, and Stat3 was detected by reverse transcriptase-polymerase chain reaction (RT-PCR in undifferentiated pSSCs. Flow cytometry revealed the expression of the MSC related proteins CD9, CD29, CD44 and CD105, but not CD90. After neuronal differentiation cells with a characteristic morphology of neuronal and smooth muscle-like cells were present in the cultures. Subsequent immunochemistry and flow cytometry revealed the down-regulation of nestin and the up-regulation of the neuron specific protein beta-III-tubulin and the astrocyte marker GFAP. Also, alpha-SMA expressing cells increased during differentiation suggesting the neuro-muscular differentiation of these skin derived cells. pSSCs could also be induced to differentiate into adipocyte-like cells when cultured under

  10. Haploidentical Hematopoietic Stem-Cell Transplantation in Adults

    Directory of Open Access Journals (Sweden)

    Salem Alshemmari

    2011-01-01

    Full Text Available Haploidentical hematopoietic stem-cell transplantation is an alternative transplant strategy for patients without an HLA-matched donor. Still, only half of patients who might benefit from transplantation are able to find an HLA-matched related or unrelated donor. Haploidentical donor is readily available for many patients in need of immediate stem-cell transplantation. Historical experience with haploidentical stem-cell transplantation has been characterised by a high rejection rate, graft-versus-host disease, and transplant-related mortality. Important advances have been made in this field during the last 20 years. Many drawbacks of haploidentical transplants such as graft failure and significant GVHD have been overcome due to the development of new extensive T cell depletion methods with mega dose stem-cell administration. However, prolonged immune deficiency and an increased relapse rate remain unresolved problems of T cell depletion. New approaches such as partial ex vivo or in vivo alloreactive T cell depletion and posttransplant cell therapy will allow to improve immune reconstitution in haploidentical transplants. Results of unmanipulated stem-cell transplantation with using ATG and combined immunosuppression in mismatched/haploidentical transplant setting are promising. This paper focuses on recent advances in haploidentical hematopoietic stem-cell transplantation for hematologic malignancies.

  11. A planarian p53 homolog regulates proliferation and self-renewal in adult stem cell lineages

    OpenAIRE

    Pearson, Bret J.; Alvarado, Alejandro Sánchez

    2010-01-01

    The functions of adult stem cells and tumor suppressor genes are known to intersect. However, when and how tumor suppressors function in the lineages produced by adult stem cells is unknown. With a large population of stem cells that can be manipulated and studied in vivo, the freshwater planarian is an ideal system with which to investigate these questions. Here, we focus on the tumor suppressor p53, homologs of which have no known role in stem cell biology in any invertebrate examined thus ...

  12. Tissue-resident adult stem cell populations of rapidly self-renewing organs

    NARCIS (Netherlands)

    Barker, N.; Bartfeld, S.; Clevers, H.

    2010-01-01

    The epithelial lining of the intestine, stomach, and skin is continuously exposed to environmental assault, imposing a requirement for regular self-renewal. Resident adult stem cell populations drive this renewal, and much effort has been invested in revealing their identity. Reliable adult stem cel

  13. Diversity of epithelial stem cell types in adult lung.

    Science.gov (United States)

    Li, Feng; He, Jinxi; Wei, Jun; Cho, William C; Liu, Xiaoming

    2015-01-01

    Lung is a complex organ lined with epithelial cells. In order to maintain its homeostasis and normal functions following injuries caused by varied extraneous and intraneous insults, such as inhaled environmental pollutants and overwhelming inflammatory responses, the respiratory epithelium normally undergoes regenerations by the proliferation and differentiation of region-specific epithelial stem/progenitor cells that resided in distinct niches along the airway tree. The importance of local epithelial stem cell niches in the specification of lung stem/progenitor cells has been recently identified. Studies using cell differentiating and lineage tracing assays, in vitro and/or ex vivo models, and genetically engineered mice have suggested that these local epithelial stem/progenitor cells within spatially distinct regions along the pulmonary tree contribute to the injury repair of epithelium adjacent to their respective niches. This paper reviews recent findings in the identification and isolation of region-specific epithelial stem/progenitor cells and local niches along the airway tree and the potential link of epithelial stem cells for the development of lung cancer. PMID:25810726

  14. Diversity of Epithelial Stem Cell Types in Adult Lung

    Directory of Open Access Journals (Sweden)

    Feng Li

    2015-01-01

    Full Text Available Lung is a complex organ lined with epithelial cells. In order to maintain its homeostasis and normal functions following injuries caused by varied extraneous and intraneous insults, such as inhaled environmental pollutants and overwhelming inflammatory responses, the respiratory epithelium normally undergoes regenerations by the proliferation and differentiation of region-specific epithelial stem/progenitor cells that resided in distinct niches along the airway tree. The importance of local epithelial stem cell niches in the specification of lung stem/progenitor cells has been recently identified. Studies using cell differentiating and lineage tracing assays, in vitro and/or ex vivo models, and genetically engineered mice have suggested that these local epithelial stem/progenitor cells within spatially distinct regions along the pulmonary tree contribute to the injury repair of epithelium adjacent to their respective niches. This paper reviews recent findings in the identification and isolation of region-specific epithelial stem/progenitor cells and local niches along the airway tree and the potential link of epithelial stem cells for the development of lung cancer.

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

    OpenAIRE

    Bhonde RR

    2008-01-01

    In recent years regenerative biology has reached to greater heights due to its therapeutic potential in treating degenerative diseases; as they are not curable by modern medicine. With the advent of research in stem cells and developmental biology the regenerative potential of adult resident stem cells is becoming clearer. The long term objective of regenerative medicine or cell therapy is to treat patients with their own stem cells. These stem cells could be derived from the diseased organs ...

  16. Evidence for a stem cell hierarchy in the adult human breast

    DEFF Research Database (Denmark)

    Villadsen, René; Fridriksdottir, Agla J; Rønnov-Jessen, Lone;

    2007-01-01

    Cellular pathways that contribute to adult human mammary gland architecture and lineages have not been previously described. In this study, we identify a candidate stem cell niche in ducts and zones containing progenitor cells in lobules. Putative stem cells residing in ducts were essentially...... in laminin-rich extracellular matrix gels. Staining for the lineage markers keratins K14 and K19 further revealed multipotent cells in the stem cell zone and three lineage-restricted cell types outside this zone. Multiparameter cell sorting and functional characterization with reference to anatomical sites...... in situ confirmed this pattern. The proposal that the four cell types are indeed constituents of an as of yet undescribed stem cell hierarchy was assessed in long-term cultures in which senescence was bypassed. These findings identify an adult human breast ductal stem cell activity and its earliest...

  17. Strategies in Haploidentical Stem Cell Transplantation in Adults

    Directory of Open Access Journals (Sweden)

    Ulaş D. Bayraktar

    2013-12-01

    Full Text Available Haploidentical related donors are alternative stem cell sources for patients without human leukocyte antigen (HLA-matched related or unrelated donors. Immediate access to the donor, availability for patients with rare haplotypes, ease of stem cell procurement, and lack of a requirement for a physical cord blood bank or an extensive HLA database render this type of hematopoietic stem cell transplantation particularly attractive despite the high histoincompatibility barrier between the recipient and the haploidentical graft. In this review, we answer the following questions: 1 What are the current transplant strategies used to overcome the histoincompatibility barrier in haploidentical stem cell transplantation and their clinical results? 2 How should we choose the donor when there is more than one available haploidentical donor? 3 How does transplantation from haploidentical donors compare to that from umbilical cord blood?

  18. Ex vivo Expansion of Human Adult Pancreatic Cells with Properties of Distributed Stem Cells by Suppression of Asymmetric Cell Kinetics

    OpenAIRE

    Paré, JF; Sherley, JL

    2013-01-01

    Transplantation therapy for type I diabetes (T1D) might be improved if pancreatic stem cells were readily available for investigation. Unlike macroscopic islets, pancreatic tissue stem cells could more easily access the retroperitoneal pancreatic environment and thereby might achieve more effective pancreatic regeneration. Unfortunately, whether the adult pancreas actually contains renewing stem cells continues as a controversial issue in diabetes research. We evaluated a new method developed...

  19. Differentiation of adult human bone marrow mesenchymal stem cells into Schwann-like cells in vitro

    Institute of Scientific and Technical Information of China (English)

    YANG Li-ye; ZHENG Jia-kun; WANG Chao-yang; LI Wen-yu

    2005-01-01

    Objective: To investigate the differentiative capability of adult human bone marrow mesenchymal stem cells (BMSCs) into Schwann-like cells. Methods: Bone marrows were aspirated from healthy donors and mononuclear cells were separated by Percoll lymphocytes separation liquid (1.073 g/ml) with centrifugation, cells were cultured in DMEM/F12 (1:1) medium containing 10% fetal bovine serum (FBS), 20 ng/ml epidermal growth factor (EGF) and 20 ng/ml basic fibroblast growth factor (bFGF). Cells of passage 1 were identified with immunocytochemistry. Conclusions: Bone marrow contains the stem cells with the ability of differentiating into Schwann-like cells, which may represent an alternative stem cell sources for neural transplantation.

  20. Lin-28 promotes symmetric stem cell division and drives adaptive growth in the adult Drosophila intestine.

    Science.gov (United States)

    Chen, Ching-Huan; Luhur, Arthur; Sokol, Nicholas

    2015-10-15

    Stem cells switch between asymmetric and symmetric division to expand in number as tissues grow during development and in response to environmental changes. The stem cell intrinsic proteins controlling this switch are largely unknown, but one candidate is the Lin-28 pluripotency factor. A conserved RNA-binding protein that is downregulated in most animals as they develop from embryos to adults, Lin-28 persists in populations of adult stem cells. Its function in these cells has not been previously characterized. Here, we report that Lin-28 is highly enriched in adult intestinal stem cells in the Drosophila intestine. lin-28 null mutants are homozygous viable but display defects in this population of cells, which fail to undergo a characteristic food-triggered expansion in number and have reduced rates of symmetric division as well as reduced insulin signaling. Immunoprecipitation of Lin-28-bound mRNAs identified Insulin-like Receptor (InR), forced expression of which completely rescues lin-28-associated defects in intestinal stem cell number and division pattern. Furthermore, this stem cell activity of lin-28 is independent of one well-known lin-28 target, the microRNA let-7, which has limited expression in the intestinal epithelium. These results identify Lin-28 as a stem cell intrinsic factor that boosts insulin signaling in intestinal progenitor cells and promotes their symmetric division in response to nutrients, defining a mechanism through which Lin-28 controls the adult stem cell division patterns that underlie tissue homeostasis and regeneration.

  1. Adult Stem Cells as a Renewable Source of Insulin-Producing Cells

    OpenAIRE

    Jun, Hee-Sook; Park, Eun-Young

    2009-01-01

    Diabetes mellitus is a metabolic disorder resulting from an inadequate mass of insulin-producing pancreatic beta cells. The replacement or restoration of damaged beta cells would be considered the optimal therapeutic options. Islet transplantation seems to be a promising approach for replacement therapy; however, the main obstacle is the shortage of organ donors. As mature beta cells have been shown to be difficult to expand in vitro, regeneration of beta cells from embryonic or adult stem ce...

  2. Intrinsic Ability of Adult Stem Cell in Skeletal Muscle: An Effective and Replenishable Resource to the Establishment of Pluripotent Stem Cells

    OpenAIRE

    Shin Fujimaki; Masanao Machida; Ryo Hidaka; Makoto Asashima; Tohru Takemasa; Tomoko Kuwabara

    2013-01-01

    Adult stem cells play an essential role in mammalian organ maintenance and repair throughout adulthood since they ensure that organs retain their ability to regenerate. The choice of cell fate by adult stem cells for cellular proliferation, self-renewal, and differentiation into multiple lineages is critically important for the homeostasis and biological function of individual organs. Responses of stem cells to stress, injury, or environmental change are precisely regulated by intercellular a...

  3. Stem Cell Information: Glossary

    Science.gov (United States)

    ... Neurons Oligodendrocyte Parthenogenesis Passage Pluripotent Polar body Preimplantation Proliferation Regenerative medicine Reproductive cloning Signals Somatic cell Somatic cell nuclear transfer (SCNT) Somatic (adult) stem cell Stem cells Stromal cells Subculturing Surface markers ...

  4. Adult human neural stem cell therapeutics: Current developmental status and prospect

    OpenAIRE

    Nam, Hyun; Lee, Kee-Hang; Nam, Do-Hyun; Joo, Kyeung Min

    2015-01-01

    Over the past two decades, regenerative therapies using stem cell technologies have been developed for various neurological diseases. Although stem cell therapy is an attractive option to reverse neural tissue damage and to recover neurological deficits, it is still under development so as not to show significant treatment effects in clinical settings. In this review, we discuss the scientific and clinical basics of adult neural stem cells (aNSCs), and their current developmental status as ce...

  5. Pluripotency of adult stem cells derived from human and rat pancreas

    Science.gov (United States)

    Kruse, C.; Birth, M.; Rohwedel, J.; Assmuth, K.; Goepel, A.; Wedel, T.

    Adult stem cells are undifferentiated cells found within fully developed tissues or organs of an adult individuum. Until recently, these cells have been considered to bear less self-renewal ability and differentiation potency compared to embryonic stem cells. In recent studies an undifferentiated cell type was found in primary cultures of isolated acini from exocrine pancreas termed pancreatic stellate cells. Here we show that pancreatic stellate-like cells have the capacity of extended self-renewal and are able to differentiate spontaneously into cell types of all three germ layers expressing markers for smooth muscle cells, neurons, glial cells, epithelial cells, chondrocytes and secretory cells (insulin, amylase). Differentiation and subsequent formation of three-dimensional cellular aggregates (organoid bodies) were induced by merely culturing pancreatic stellate-like cells in hanging drops. These cells were developed into stable, long-term, in vitro cultures of both primary undifferentiated cell lines as well as organoid cultures. Thus, evidence is given that cell lineages of endodermal, mesodermal, and ectodermal origin arise spontaneously from a single adult undifferentiated cell type. Based on the present findings it is assumed that pancreatic stellate-like cells are a new class of lineage uncommitted pluripotent adult stem cells with a remarkable self-renewal ability and differentiation potency. The data emphasize the versatility of adult stem cells and may lead to a reappraisal of their use for the treatment of inherited disorders or acquired degenerative diseases.

  6. Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells

    NARCIS (Netherlands)

    Forster, Ryan; Chiba, Kunitoshi; Schaeffer, Lorian; Regalado, Samuel G; Lai, Christine S; Gao, Qing; Kiani, Samira; Farin, Henner F; Clevers, Hans; Cost, Gregory J; Chan, Andy; Rebar, Edward J; Urnov, Fyodor D; Gregory, Philip D; Pachter, Lior; Jaenisch, Rudolf; Hockemeyer, Dirk

    2014-01-01

    Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the i

  7. Epigenetic regulation of adult neural stem cells: implications for Alzheimer's disease

    NARCIS (Netherlands)

    C.P. Fitzsimons; E. van Bodegraven; M. Schouten; R. Lardenoije; K. Kompotis; G. Kenis; M. van den Hurk; M.P. Boks; C. Biojone; S. Joca; H.W. Steinbusch; K. Lunnon; D.F. Mastroeni; J. Mill; P.J. Lucassen; P.D. Coleman; D.L. Van den Hove; B.P.F. Rutten

    2014-01-01

    Experimental evidence has demonstrated that several aspects of adult neural stem cells (NSCs), including their quiescence, proliferation, fate specification and differentiation, are regulated by epigenetic mechanisms. These control the expression of specific sets of genes, often including those enco

  8. A Sox2 BAC transgenic approach for targeting adult neural stem cells.

    Directory of Open Access Journals (Sweden)

    Wenfei Kang

    Full Text Available The transcription factor gene Sox2 is expressed in embryonic neural stem/progenitor cells and previous evidence suggests that it is also expressed in adult neural stem cells. To target Sox2-expressing neural stem/progenitor cells in a temporal manner, we generated a bacterial artificial chromosome (BAC transgenic mouse line, in which an inducible form of Cre, CreER™, is expressed under Sox2 regulatory elements. Inducible Cre activity in these mice was characterized using floxed reporters. During development, the Sox2-CreER transgenic mice show inducible Cre activity specifically in CNS stem/progenitor cells, making them a useful tool to regulate the expression of floxed genes temporally in embryonic neural stem/progenitor cells. In the adult, we examined the cell-specific expression of Sox2 and performed long-term lineage tracing. Four months after the transient induction of Cre activity, recombined GFAP+ stem-like cells and DCX+ neuroblasts were still abundant in the neurogenic regions including the subventricular zone (SVZ, rostral migratory stream (RMS, and subgranular zone (SGZ of the dentate gyrus. These results provide definitive in vivo evidence that Sox2 is expressed in neural stem cells (NSC in both the SVZ and SGZ that are capable of self-renewal and long-term neurogenesis. Therefore, Sox2-CreER mice should be useful in targeting floxed genes in adult neural stem cells.

  9. Adult lung stem cells and their contribution to lung tumourigenesis

    OpenAIRE

    Asselin-Labat, Marie-Liesse; Filby, Caitlin E

    2012-01-01

    The isolation and characterization of lung stem and progenitor cells represent an important step towards the understanding of lung repair after injury, lung disease pathogenesis and the identification of the target cells of transformation in lung carcinogenesis. Different approaches using prospective isolation of progenitor cells by flow cytometry or lineage-tracing experiments in mouse models of lung injury have led to the identification of distinct progenitor subpopulations in different mor...

  10. Autophagy is required for self-renewal and differentiation of adult human stem cells

    Institute of Scientific and Technical Information of China (English)

    Souzan Salemi; Shida Yousefi; Mihai A Constantinescu; Martin F Fey; Hans-Uwe Simon

    2012-01-01

    Dear Editor,Patients receiving anticancer therapy usually suffer from side effects,such as loss of hair,epithelial barrier defects,and myelosuppression,which,however,are usually reversible when the therapy is discontinued.Although this clinical experience suggests that adult stem cells may survive such therapeutic interventions,the underlying molecular regulatory mechanisms are poorly understood.Such regulatory mechanisms also seem to protect adult stem cells from acquiring mutations,which could lead to additional tumorigenesis.

  11. GABA's Control of Stem and Cancer Cell Proliferation in Adult Neural and Peripheral Niches

    OpenAIRE

    Young, Stephanie Z.; Bordey, Angélique

    2009-01-01

    Aside from traditional neurotransmission and regulation of secretion, γ-amino butyric acid (GABA) through GABAA receptors negatively regulates proliferation of pluripotent and neural stem cells in embryonic and adult tissue. There has also been evidence that GABAergic signaling and its control over proliferation is not only limited to the nervous system, but is widespread through peripheral organs containing adult stem cells. GABA has emerged as a tumor signaling molecule in the periphery tha...

  12. Fetal and adult liver stem cells for liver regeneration and tissue engineering.

    Science.gov (United States)

    Fiegel, H C; Lange, Claudia; Kneser, U; Lambrecht, W; Zander, A R; Rogiers, X; Kluth, D

    2006-01-01

    For the development of innovative cell-based liver directed therapies, e.g. liver tissue engineering, the use of stem cells might be very attractive to overcome the limitation of donor liver tissue. Liver specific differentiation of embryonic, fetal or adult stem cells is currently under investigation. Different types of fetal liver (stem) cells during development were identified, and their advantageous growth potential and bipotential differentiation capacity were shown. However, ethical and legal issues have to be addressed before using fetal cells. Use of adult stem cells is clinically established, e.g. transplantation of hematopoietic stem cells. Other bone marrow derived liver stem cells might be mesenchymal stem cells (MSC). However, the transdifferentiation potential is still in question due to the observation of cellular fusion in several in vivo experiments. In vitro experiments revealed a crucial role of the environment (e.g. growth factors and extracellular matrix) for specific differentiation of stem cells. Co-cultured liver cells also seemed to be important for hepatic gene expression of MSC. For successful liver cell transplantation, a novel approach of tissue engineering by orthotopic transplantation of gel-immobilized cells could be promising, providing optimal environment for the injected cells. Moreover, an orthotopic tissue engineering approach using bipotential stem cells could lead to a repopulation of the recipients liver with healthy liver and biliary cells, thus providing both hepatic functions and biliary excretion. Future studies have to investigate, which stem cell and environmental conditions would be most suitable for the use of stem cells for liver regeneration or tissue engineering approaches. PMID:16989722

  13. Fetal and adult liver stem cells for liver regeneration and tissue engineering.

    Science.gov (United States)

    Fiegel, H C; Lange, Claudia; Kneser, U; Lambrecht, W; Zander, A R; Rogiers, X; Kluth, D

    2006-01-01

    For the development of innovative cell-based liver directed therapies, e.g. liver tissue engineering, the use of stem cells might be very attractive to overcome the limitation of donor liver tissue. Liver specific differentiation of embryonic, fetal or adult stem cells is currently under investigation. Different types of fetal liver (stem) cells during development were identified, and their advantageous growth potential and bipotential differentiation capacity were shown. However, ethical and legal issues have to be addressed before using fetal cells. Use of adult stem cells is clinically established, e.g. transplantation of hematopoietic stem cells. Other bone marrow derived liver stem cells might be mesenchymal stem cells (MSC). However, the transdifferentiation potential is still in question due to the observation of cellular fusion in several in vivo experiments. In vitro experiments revealed a crucial role of the environment (e.g. growth factors and extracellular matrix) for specific differentiation of stem cells. Co-cultured liver cells also seemed to be important for hepatic gene expression of MSC. For successful liver cell transplantation, a novel approach of tissue engineering by orthotopic transplantation of gel-immobilized cells could be promising, providing optimal environment for the injected cells. Moreover, an orthotopic tissue engineering approach using bipotential stem cells could lead to a repopulation of the recipients liver with healthy liver and biliary cells, thus providing both hepatic functions and biliary excretion. Future studies have to investigate, which stem cell and environmental conditions would be most suitable for the use of stem cells for liver regeneration or tissue engineering approaches.

  14. Tumor suppressors Sav/Scrib and oncogene Ras regulate stem cell transformation in adult Drosophila Malpighian Tubules

    OpenAIRE

    Zeng, Xiankun; Singh, Shree Ram; Hou, David; Steven X Hou

    2010-01-01

    An increasing body of evidence suggests that tumors might originate from a few transformed cells that share many properties with normal stem cells. However, it remains unclear how normal stem cells are transformed into cancer stem cells. Here, we demonstrated that mutations causing the loss of tumor suppressor Sav or Scrib or activation of the oncogene Ras transform normal stem cells into cancer stem cells through a multistep process in the adult Drosophila Malpighian Tubules (MTs). In wild-t...

  15. Cell growth characteristics, differentiation frequency, and immunophenotype of adult ear mesenchymal stem cells.

    Science.gov (United States)

    Staszkiewicz, Jaroslaw; Frazier, Trivia P; Rowan, Brian G; Bunnell, Bruce A; Chiu, Ernest S; Gimble, Jeffrey M; Gawronska-Kozak, Barbara

    2010-01-01

    Ear mesenchymal stem cells (EMSCs) represent a readily accessible population of stem-like cells that are adherent, clonogenic, and have the ability to self-renew. Previously, we have demonstrated that they can be induced to differentiate into adipocyte, osteocyte, chondrocyte, and myocyte lineages. The purpose of the current study was to characterize the growth kinetics of the cells and to determine their ability to form colonies of fibroblasts, adipocytes, osteocytes, and chondrocytes. In addition, the immunophenotypes of freshly isolated and culture-expanded cells were evaluated. From 1 g of tissue, we were able to isolate an average of 7.8 x 10(6) cells exhibiting a cell cycle length of approximately 2-3 days. Colony-forming unit (CFU) assays indicated high proliferation potential, and confirmed previously observed multipotentiality of the cells. Fluorescence-activated cell sorting (FACS) showed that EMSCs were negative for hematopoietic markers (CD4, CD45), proving that they did not derive from circulating hematopoietic cells. The FACS analyses also showed high expression of stem cell antigen-1 (Sca-1) with only a minor population of cells expressing CD117, thus identifying Sca-1 as the more robust stem cell biomarker. Additionally, flow cytometry data revealed that the expression patterns of hematopoietic, stromal, and stem cell markers were maintained in the passaged EMSCs, consistent with the persistence of an undifferentiated state. This study indicates that EMSCs provide an alternative model for in vitro analyses of adult mesenchymal stem cells (MSCs). Further studies will be necessary to determine their utility for tissue engineering and regenerative medical applications. PMID:19400629

  16. Potential therapeutic application of adult stem cells in acute respiratory distress syndrome

    Institute of Scientific and Technical Information of China (English)

    JIANG Jian-xin; LI Li

    2009-01-01

    Acute respiratory distress syndrome (ARDS) remains a poor prognosis in spite of the recent development of new therapeutic strategies. Cell-based therapy with stem cells has been considered as a promising way for the treatment of vital organ damage. Putative endogenous stem cells have been shown to be located within the adult lung in the basal layer of the upper airways, within or near pulmonary neu-roendocrine cell rests, at the bronchoalveolar junction, as well as within the alveolar epithelium. These stem cells are hypothesized to be the source of lung regeneration and repair. But this mechanism seems to be insufficient after lung injury. There is increasing excitement over the last few years with the suggestion that exogenous stem cells may offer new treatment options for ARDS. Exogenous stem cells have the abihty to differentiate and function as both airway and lung parenchymal epithelial cells in both in vitro and in-creasingly in vivo experiments. However, there is great con-troversy concerning the repair effect of adult stem cells in lung injury. This review evaluates the advances in endog-enous respiratory stem cells, and assesses the evidence for the use of stem cells in the repair of lung injury.

  17. Cell cycle restriction by histone H2AX limits proliferation of adult neural stem cells

    OpenAIRE

    Fernando, R. N.; Eleuteri, B.; Abdelhady, S.; Nussenzweig, A; Andang, M; Ernfors, P.

    2011-01-01

    Adult neural stem cell proliferation is dynamic and has the potential for massive self-renewal yet undergoes limited cell division in vivo. Here, we report an epigenetic mechanism regulating proliferation and self-renewal. The recruitment of the PI3K-related kinase signaling pathway and histone H2AX phosphorylation following GABAA receptor activation limits subventricular zone proliferation. As a result, NSC self-renewal and niche size is dynamic and can be directly modulated in both directio...

  18. CD133 does not enrich for the stem cell activity in vivo in adult mouse prostates

    Directory of Open Access Journals (Sweden)

    Xing Wei

    2016-05-01

    Full Text Available CD133 is widely used as a marker for stem/progenitor cells in many organ systems. Previous studies using in vitro stem cell assays have suggested that the CD133-expressing prostate basal cells may serve as the putative prostate stem cells. However, the precise localization of the CD133-expressing cells and their contributions to adult murine prostate homeostasis in vivo remain undetermined. We show that loss of function of CD133 does not impair murine prostate morphogenesis, homeostasis and regeneration, implying a dispensable role for CD133 in prostate stem cell function. Using a CD133-CreERT2 model in conjunction with a fluorescent report line, we show that CD133 is not only expressed in a fraction of prostate basal cells, but also in some luminal cells and stromal cells. CD133+ basal cells possess higher in vitro sphere-forming activities than CD133− basal cells. However, the in vivo lineage tracing study reveals that the two cell populations possess the same regenerative capacity and contribute equally to the maintenance of the basal cell lineage. Similarly, CD133+ and CD133− luminal cells are functionally equivalent in maintaining the luminal cell lineage. Collectively, our study demonstrates that CD133 does not enrich for the stem cell activity in vivo in adult murine prostate. This study does not contradict previous reports showing CD133+ cells as prostate stem cells in vitro. Instead, it highlights a substantial impact of biological contexts on cellular behaviors.

  19. Epicardial Origin of Resident Mesenchymal Stem Cells in the Adult Mammalian Heart

    Directory of Open Access Journals (Sweden)

    Naisana S. Asli

    2014-04-01

    Full Text Available The discovery of stem and progenitor cells in the adult mammalian heart has added a vital dimension to the field of cardiac regeneration. Cardiac-resident stem cells are likely sequestered as reserve cells within myocardial niches during the course of embryonic cardiogenesis, although they may also be recruited from external sources, such as bone marrow. As we begin to understand the nature of cardiac-resident stem and progenitor cells using a variety of approaches, it is evident that they possess an identity embedded within their gene regulatory networks that favours cardiovascular lineage potential. In addition to contributing lineage descendants, cardiac stem cells may also be stress sensors, offering trophic cues to other cell types, including cardiomyocytes and vasculature cells, and likely other stem cells and immune cells, during adaptation and repair. This presents numerous possibilities for endogenous cardiac stem and progenitor cells to be used in cell therapies or as targets in heart rejuvenation. In this review, we focus on the epicardium as an endogenous source of multi-potential mesenchymal progenitor cells in development and as a latent source of such progenitors in the adult. We track the origin and plasticity of the epicardium in embryos and adults in both homeostasis and disease. In this context, we ask whether directed activation of epicardium-derived progenitor cells might have therapeutic application.

  20. Mathematical model of adult stem cell regeneration with cross-talk between genetic and epigenetic regulation

    OpenAIRE

    Lei, Jinzhi; Levin, Simon A.; Nie, Qing

    2014-01-01

    This paper examines how adult stem cells maintain their ability to carry out a complex set of tasks, including tissue regeneration and replacement of defective cells. To do so, stem cell populations must coordinate differentiation, proliferation, and cell death (apoptosis) to maintain an appropriate distribution of epigenetic states. Using the tools of applied mathematics, and borrowing from the theory of intergenerational transfer of resources, this paper shows how control strategies during ...

  1. Diversity of Epithelial Stem Cell Types in Adult Lung

    OpenAIRE

    Feng Li; Jinxi He; Jun Wei; Cho, William C.; Xiaoming Liu

    2015-01-01

    Lung is a complex organ lined with epithelial cells. In order to maintain its homeostasis and normal functions following injuries caused by varied extraneous and intraneous insults, such as inhaled environmental pollutants and overwhelming inflammatory responses, the respiratory epithelium normally undergoes regenerations by the proliferation and differentiation of region-specific epithelial stem/progenitor cells that resided in distinct niches along the airway tree. The importance of local e...

  2. Adult stem cells in neural repair: Current options,limitations and perspectives

    Institute of Scientific and Technical Information of China (English)

    Eric Domingos Mariano; Manoel Jacobsen Teixeira; Suely Kazue Nagahashi Marie; Guilherme Lepski

    2015-01-01

    Stem cells represent a promising step for the future ofregenerative medicine. As they are able to differentiateinto any cell type, tissue or organ, these cells are greatcandidates for treatments against the worst diseasesthat defy doctors and researchers around the world.Stem cells can be divided into three main groups (1)embryonic stem cells; (2) fetal stem cells; and (3) adultstem cells. In terms of their capacity for proliferation,stem cells are also classified as totipotent, pluripotentor multipotent. Adult stem cells, also known as somaticcells, are found in various regions of the adult organism,such as bone marrow, skin, eyes, viscera and brain.They can differentiate into unipotent cells of theresiding tissue, generally for the purpose of repair.These cells represent an excellent choice in regenerativemedicine, every patient can be a donor of adult stemcells to provide a more customized and efficient therapyagainst various diseases, in other words, they allow theopportunity of autologous transplantation. But in orderto start clinical trials and achieve great results, we needto understand how these cells interact with the hosttissue, how they can manipulate or be manipulated bythe microenvironment where they will be transplantedand for how long they can maintain their multipotentstate to provide a full regeneration.

  3. Differentiation of embryonic versus adult rat neural stem cells into dopaminergic neurons in vitro

    Institute of Scientific and Technical Information of China (English)

    Chunlong Ke; Baili Chen; Shaolei Guo; Chao Yang

    2008-01-01

    BACKGROUND: It has been reported that the conversion of neural stem cells into dopaminergic neurons in vitro can be increased through specific cytokine combinations. Such neural stem cell-derived dopaminergic neurons could be used for the treatment of Parkinson's disease. However, little is known about the differences in dopaminergic differentiation between neural stem cells derived from adult and embryonic rats.OBJECTIVE: To study the ability of rat adult and embryonic-derived neural stem cells to differentiate into dopaminergic neurons in vitro.DESIGN: Randomized grouping design.SETTING: Department of Neurosurgery in the First Affiliated Hospital of Sun Yat-sen University.MATERIALS: This experiment was performed at the Surgical Laboratory in the First Affiliated Hospital of Sun Yat-scn University (Guangzhou, Guangdong, China) from June to December 2007. Eight, adult, male,Sprague Dawley rats and eight, pregnant, Sprague Dawley rats (embryonic day 14 or 15) were provided by the Experimental Animal Center of Sun Yat-sen University.METHODS: Neural stem cells derived from adult and embryonic rats were respectively cultivated in serum-free culture medium containing epidermal growth factor and basic fibroblast growth factor. After passaging, neural stem cells were differentiated in medium containing interleukin-1 ct, interleukin-11, human leukemia inhibition factor, and glial cell line-derived neurotrophic factor. Six days later, cells were analyzed by immunocytochemistry and flow cytometry.MAIN OUTCOME MEASURES: Alterations in cellular morphology after differentiation of neural stem cells derived from adult and embryonic rats; and percentage of tyrosine hydroxylase-positive neurons in the differentiated cells.RESULTS: Neural stem cells derived from adult and embryonic rats were cultivated in differentiation medium. Six days later, differentiated cells were immunoreactive for tyrosine hydroxylasc. The percentage of tyrosine hydroxylase positive neurons was (5.6 ± 2

  4. Expression profile of microRNAs regulating proliferation and differentiation in mouse adult cardiac stem cells.

    Directory of Open Access Journals (Sweden)

    Luis Brás-Rosário

    Full Text Available The identification of cardiac cells with stem cell properties changed the paradigm of the heart as a post mitotic organ. These cells proliferate and differentiate into cardiomyocytes, endothelial and vascular smooth muscle cells, providing for cardiac cell homeostasis and regeneration. microRNAs are master switches controlling proliferation and differentiation, in particular regulating stem cell biology and cardiac development. Modulation of microRNAs -regulated gene expression networks holds the potential to control cell fate and proliferation, with predictable biotechnologic and therapeutic applications. To obtain insights into the regulatory networks active in cardiac stem cells, we characterized the expression profile of 95 microRNAs with reported functions in stem cell and tissue differentiation in mouse cardiac stem cells, and compared it to that of mouse embryonic heart and mesenchymal stem cells. The most highly expressed microRNAs identified in cardiac stem cells are known to target key genes involved in the control of cell proliferation and adhesion, vascular function and cardiomyocyte differentiation. We report a subset of differentially expressed microRNAs that are proposed to act as regulators of differentiation and proliferation of adult cardiac stem cells, providing novel insights into active gene expression networks regulating their biological properties.

  5. A planarian p53 homolog regulates proliferation and self-renewal in adult stem cell lineages.

    Science.gov (United States)

    Pearson, Bret J; Sánchez Alvarado, Alejandro

    2010-01-01

    The functions of adult stem cells and tumor suppressor genes are known to intersect. However, when and how tumor suppressors function in the lineages produced by adult stem cells is unknown. With a large population of stem cells that can be manipulated and studied in vivo, the freshwater planarian is an ideal system with which to investigate these questions. Here, we focus on the tumor suppressor p53, homologs of which have no known role in stem cell biology in any invertebrate examined thus far. Planaria have a single p53 family member, Smed-p53, which is predominantly expressed in newly made stem cell progeny. When Smed-p53 is targeted by RNAi, the stem cell population increases at the expense of progeny, resulting in hyper-proliferation. However, ultimately the stem cell population fails to self-renew. Our results suggest that prior to the vertebrates, an ancestral p53-like molecule already had functions in stem cell proliferation control and self-renewal. PMID:20040488

  6. The novel steroidal alkaloids dendrogenin A and B promote proliferation of adult neural stem cells.

    OpenAIRE

    Khalifa, Shaden,; de Medina, Philippe; Erlandsson, Anna; El-Seedi, Hesham; Silvente-Poirot, Sandrine; Poirot, Marc

    2014-01-01

    International audience Dendrogenin A (DDA) and dendrogenin B (DDB) are new aminoalkyl oxysterols which display re-differentiation of tumor cells of neuronal origin at nanomolar concentrations. We analyzed the influence of dendrogenins on adult mice neural stem cell proliferation, sphere formation and differentiation. DDA and DDB were found to have potent proliferative effects in neural stem cells. Additionally, they induce neuronal outgrowth from neurospheres during in vitro cultivation. T...

  7. Isolation and Culture of Dental Epithelial Stem Cells from the Adult Mouse Incisor

    OpenAIRE

    Chavez, Miquella G.; Hu, Jimmy; SEIDEL, KERSTIN; Li, Chunying; Jheon, Andrew; Naveau, Adrien; Horst, Orapin; Klein, Ophir D.

    2014-01-01

    Understanding the cellular and molecular mechanisms that underlie tooth regeneration and renewal has become a topic of great interest1-4, and the mouse incisor provides a model for these processes. This remarkable organ grows continuously throughout the animal's life and generates all the necessary cell types from active pools of adult stem cells housed in the labial (toward the lip) and lingual (toward the tongue) cervical loop (CL) regions. Only the dental stem cells from the labial CL give...

  8. Multipotent stem cells isolated from the adult mouse retina are capable of producing functional photoreceptor cells

    Institute of Scientific and Technical Information of China (English)

    Tianqing Li; Michelle Lewallen; Shuyi Chen; Wei Yu; Nian Zhang; Ting Xie

    2013-01-01

    Various stem cell types have been tested for their potential application in treating photoreceptor degenerative diseases,such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD).Only embryonic stem cells (ESCs) have so far been shown to generate functional photoreceptor cells restoring light response of photoreceptordeficient mice,but there is still some concern of tumor formation.In this study,we have successfully cultured Nestin+Sox2+Pax6+ multipotent retinal stem cells (RSCs) from the adult mouse retina,which are capable of producing functional photoreceptor cells that restore the light response of photoreceptor-deficient rd1 mutant mice following transplantation.After they have been expanded for over 35 passages in the presence of FGF and EGF,the cultured RSCs still maintain stable proliferation and differentiation potential.Under proper differentiation conditions,they can differentiate into all the major retinal cell types found in the adult retina.More importantly,they can efficiently differentiate into photoreceptor cells under optimized differentiation conditions.Following transplantation into the subretinal space of slowly degenerating rd7 mutant eyes,RSC-derived photoreceptor cells integrate into the retina,morphologically resembling endogenous photoreceptors and forming synapases with resident retinal neurons.When transplanted into eyes of photoreceptor-deficient rd1 mutant mice,a RP model,RSC-derived photoreceptors can partially restore light response,indicating that those RSC-derived photoreceptors are functional.Finally,there is no evidence for tumor formation in the photoreceptor-transplanted eyes.Therefore,this study has demonstrated that RSCs isolated from the adult retina have the potential of producing functional photoreceptor cells that can potentially restore lost vision caused by loss of photoreceptor cells in RP and AMD.

  9. Regenerating medicine related to the stem-cells and its mechanisms of action from adults cells

    International Nuclear Information System (INIS)

    Regenerating medicine is a branch of Medicine very developed in past years. Advances in this field have been closely linked with the new knowledge achieved on stem-cells and its ability to become in cells of different tissues. This type of medicine is based on the behaviors adopted by organism to substitute those damaged cells by the healthy ones by different processes in specific tissues. Therapeutic measures used may include the stem-cell transplantation, the use of soluble molecules, genic therapy and tissues engineering. Nowadays, the more used method is the adult stem-cells. However, is not well known the mechanisms by which the transplanted cells could to improve or to promote the tissue regeneration. To explain these mechanisms some hypotheses has been proposed including the cellular trans-differentiation, cells fusion, and the effects secondaries to cells release by cells of different soluble molecules with specific actions; in addition to the autocrine and paracrine effects that may have these soluble factors, it is suggested too the existence of a telecrine action. It is probable that more than one of these mechanisms be executed

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

    Science.gov (United States)

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

    2016-09-01

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

  11. Concise Review: Quiescence in Adult Stem Cells: Biological Significance and Relevance to Tissue Regeneration.

    Science.gov (United States)

    Rumman, Mohammad; Dhawan, Jyotsna; Kassem, Moustapha

    2015-10-01

    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 of this review is to provide an update regarding the biological mechanisms of ASC quiescence and their role in tissue regeneration.

  12. Hematopoietic Stem Cell Transplantation in Adult Sickle Cell Disease: Problems and Solutions

    Directory of Open Access Journals (Sweden)

    Hakan Özdoğu

    2015-09-01

    Full Text Available Sickle cell disease-related organ injuries cannot be prevented despite hydroxyurea use, infection prophylaxis, and supportive therapies. As a consequence, disease-related mortality reaches 14% in adolescents and young adults. Hematopoietic stem cell transplantation is a unique curative therapeutic approach for sickle cell disease. Myeloablative allogeneic hematopoietic stem cell transplantation is curative for children with sickle cell disease. Current data indicate that long-term disease-free survival is about 90% and overall survival about 95% after transplantation. However, it is toxic in adults due to organ injuries. In addition, this curative treatment approach has several limitations, such as difficulties to find donors, transplant-related mortality, graft loss, graft-versus-host disease (GVHD, and infertility. Engraftment effectivity and toxicity for transplantations performed with nonmyeloablative reduced-intensity regimens in adults are being investigated in phase 1/2 trials at many centers. Preliminary data indicate that GVHD could be prevented with transplantations performed using reduced-intensity regimens. It is necessary to develop novel regimens to prevent graft loss and reduce the risk of GVHD.

  13. The plasticity of adult stem cells and their application in myocardial regenerative medicine

    Institute of Scientific and Technical Information of China (English)

    Feng CAO; Guoliang JIA; Lili NIU; Yunfang WANG; Xuetao PEI

    2004-01-01

    Current therapies for myocardial infarction and congestive heart failure are limited in efficacy or in applicability. The plasticity of adult stem cells and cellular transplantation offer a novel therapeutic approach to improve cardiac function. This review describes the latest progress in research, summarizes recent studies of adult stem cells and their application in myocardial regenerative medicine in China and abroad, and discusses the future directions of cell transplantation as a new therapy to repair injured hearts. (J Geriatr Cardiol 2004;1(2) :77-82. )

  14. The novel steroidal alkaloids dendrogenin A and B promote proliferation of adult neural stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Khalifa, Shaden A.M., E-mail: shaden.khalifa@ki.se [Department of Neuroscience, Karolinska Institute, Stockholm (Sweden); Medina, Philippe de [Affichem, Toulouse (France); INSERM UMR 1037, Team “Sterol Metabolism and Therapeutic Innovations in Oncology”, Cancer Research Center of Toulouse, F-31052 Toulouse (France); Erlandsson, Anna [Department of Public Health and Caring Sciences, Uppsala University, Uppsala (Sweden); El-Seedi, Hesham R. [Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Uppsala (Sweden); Silvente-Poirot, Sandrine [INSERM UMR 1037, Team “Sterol Metabolism and Therapeutic Innovations in Oncology”, Cancer Research Center of Toulouse, F-31052 Toulouse (France); University of Toulouse III, Toulouse (France); Institut Claudius Regaud, Toulouse (France); Poirot, Marc, E-mail: marc.poirot@inserm.fr [INSERM UMR 1037, Team “Sterol Metabolism and Therapeutic Innovations in Oncology”, Cancer Research Center of Toulouse, F-31052 Toulouse (France); University of Toulouse III, Toulouse (France); Institut Claudius Regaud, Toulouse (France)

    2014-04-11

    Highlights: • Dendrogenin A and B are new aminoalkyl oxysterols. • Dendrogenins stimulated neural stem cells proliferation. • Dendrogenins induce neuronal outgrowth from neurospheres. • Dendrogenins provide new therapeutic options for neurodegenerative disorders. - Abstract: Dendrogenin A (DDA) and dendrogenin B (DDB) are new aminoalkyl oxysterols which display re-differentiation of tumor cells of neuronal origin at nanomolar concentrations. We analyzed the influence of dendrogenins on adult mice neural stem cell proliferation, sphere formation and differentiation. DDA and DDB were found to have potent proliferative effects in neural stem cells. Additionally, they induce neuronal outgrowth from neurospheres during in vitro cultivation. Taken together, our results demonstrate a novel role for dendrogenins A and B in neural stem cell proliferation and differentiation which further increases their likely importance to compensate for neuronal cell loss in the brain.

  15. The novel steroidal alkaloids dendrogenin A and B promote proliferation of adult neural stem cells

    International Nuclear Information System (INIS)

    Highlights: • Dendrogenin A and B are new aminoalkyl oxysterols. • Dendrogenins stimulated neural stem cells proliferation. • Dendrogenins induce neuronal outgrowth from neurospheres. • Dendrogenins provide new therapeutic options for neurodegenerative disorders. - Abstract: Dendrogenin A (DDA) and dendrogenin B (DDB) are new aminoalkyl oxysterols which display re-differentiation of tumor cells of neuronal origin at nanomolar concentrations. We analyzed the influence of dendrogenins on adult mice neural stem cell proliferation, sphere formation and differentiation. DDA and DDB were found to have potent proliferative effects in neural stem cells. Additionally, they induce neuronal outgrowth from neurospheres during in vitro cultivation. Taken together, our results demonstrate a novel role for dendrogenins A and B in neural stem cell proliferation and differentiation which further increases their likely importance to compensate for neuronal cell loss in the brain

  16. How electromagnetic fields can influence adult stem cells: positive and negative impacts.

    Science.gov (United States)

    Maziarz, Aleksandra; Kocan, Beata; Bester, Mariusz; Budzik, Sylwia; Cholewa, Marian; Ochiya, Takahiro; Banas, Agnieszka

    2016-01-01

    The electromagnetic field (EMF) has a great impact on our body. It has been successfully used in physiotherapy for the treatment of bone disorders and osteoarthritis, as well as for cartilage regeneration or pain reduction. Recently, EMFs have also been applied in in vitro experiments on cell/stem cell cultures. Stem cells reside in almost all tissues within the human body, where they exhibit various potential. These cells are of great importance because they control homeostasis, regeneration, and healing. Nevertheless, stem cells when become cancer stem cells, may influence the pathological condition. In this article we review the current knowledge on the effects of EMFs on human adult stem cell biology, such as proliferation, the cell cycle, or differentiation. We present the characteristics of the EMFs used in miscellaneous assays. Most research has so far been performed during osteogenic and chondrogenic differentiation of mesenchymal stem cells. It has been demonstrated that the effects of EMF stimulation depend on the intensity and frequency of the EMF and the time of exposure to it. However, other factors may affect these processes, such as growth factors, reactive oxygen species, and so forth. Exploration of this research area may enhance the development of EMF-based technologies used in medical applications and thereby improve stem cell-based therapy and tissue engineering. PMID:27086866

  17. Notch3 signaling gates cell cycle entry and limits neural stem cell amplification in the adult pallium

    OpenAIRE

    Alunni, A.; Krecsmarik, M.; A Bosco; Galant, S.; Pan, L.; Moens, C.B.; Bally-Cuif, L.

    2013-01-01

    Maintaining the homeostasis of germinal zones in adult organs is a fundamental but mechanistically poorly understood process. In particular, what controls stem cell activation remains unclear. We have previously shown that Notch signaling limits neural stem cell (NSC) proliferation in the adult zebrafish pallium. Combining pharmacological and genetic manipulations, we demonstrate here that long-term Notch invalidation primarily induces NSC amplification through their activation from quiescenc...

  18. Characterization of pancreatic stem cells derived from adult human pancreas ducts by fluorescence activated cell sorting

    Institute of Scientific and Technical Information of China (English)

    Han-Tso Lin; Shih-Hwa Chiou; Chung-Lan Kao; Yi-Ming Shyr; Chien-Jen Hsu; Yih-Wen Tarng; Larry L-T Ho; Ching-Fai Kwok; Hung-Hai Ku

    2006-01-01

    AIM: To isolate putative pancreatic stem cells (PSCs)from human adult tissues of pancreas duct using serumfree, conditioned medium. The characterization of surface phenotype of these PSCs was analyzed by flow cytometry. The potential for pancreatic lineage and the capability of β-cell differentiation in these PSCs were evaluated as well.METHODS: By using serum-free medium supplemented with essential growth factors, we attempted to isolate the putative PSCs which has been reported to express nestin and pdx-1. The MatrigelTM was employed to evaluate the differential capacity of isolated cells. Dithizone staining, insulin content/secretion measurement, and immunohistochemistry staining were used to monitor the differentiation. Fluorescence activated cell sorting (FACS)was used to detect the phenotypic markers of putative PSCs.RESULTS: A monolayer of spindle-like cells was cultivated. The putative PSCs expressed pdx-1 and nestin.They were also able to differentiate into insulin-, glucagon-, and somatostatin-positive cells. The spectrum of phenotypic markers in PSCs was investigated; a similarity was revealed when using human bone marrow-derived stem cells as the comparative experiment, such as CD29,CD44, CD49, CD50, CD51, CD62E, PDGFR-α, CD73 (SH2),CD81, CD105(SH3).CONCLUSION: In this study, we successfully isolated PSCs from adult human pancreatic duct by using serumfree medium. These PSCs not only expressed nestin and pdx-1 but also exhibited markers attributable to mesenchymal stem cells. Although work is needed to elucidate the role of these cells, the application of these PSCs might be therapeutic strategies for diabetes mellitus.

  19. Embryonic and adult stem cells as a source for cell therapy in Parkinson's disease.

    Science.gov (United States)

    Levy, Yossef S; Stroomza, Merav; Melamed, Eldad; Offen, Daniel

    2004-01-01

    The rationale behind the use of cells as therapeutic modalities for neurodegenerative diseases in general, and in Parkinson's disease (PD) in particular, is that they will improve patient's functioning by replacing the damaged cell population. It is reasoned that these cells will survive, grow neurites, establish functional synapses, integrate best and durably with the host tissue mainly in the striatum, renew the impaired wiring, and lead to meaningful clinical improvement. To increase the generation of dopamine, researchers have already transplanted non-neuronal cells, without any genetic manipulation or after introduction of genes such as tyrosine hydroxylase, in animal models of PD. Because these cells were not of neuronal origin, they developed without control, did not integrate well into the brain parenchyma, and their survival rates were low. Clinical experiments using cell transplantation as a therapy for PD have been conducted since the 1980s. Most of these experiments used fetal dopaminergic cells originating in the ventral mesencephalic tissue obtained from fetuses. Although it was shown that the transplanted cells survived and some patients benefited from this treatment, others suffered from severe dyskinesia, probably caused by the graft's excessive and uncontrolled production and release of dopamine. It is now recognized that cell-replacement strategy will be effective in PD only if the transplanted cells have the same abilities, such as dopamine synthesis and control release, reuptake, and metabolizing dopamine, as the original dopaminergic neurons. Recent studies on embryonic and adult stem cells have demonstrated that cells are able to both self-renew and produce differentiated tissues, including dopaminergic neurons. These new methods offer real hope for tissue replacement in a wide range of diseases, especially PD. In this review we summarize the evidence of dopaminergic neuron generation from embryonic and adult stem cells, and discuss their

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

    Institute of Scientific and Technical Information of China (English)

    WANG Yunfang; PEI Xuetao

    2003-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sveva Bollini

    2013-12-01

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

  2. Epithelial cells with hepatobiliary phenotype: Is it another stem cell candidate for healthy adult human liver?

    Institute of Scientific and Technical Information of China (English)

    Dung Ngoc Khuu; Mustapha Najimi; Etienne M Sokal

    2007-01-01

    AIM: To investigate the presence and role of liver epithelial cells in the healthy human adult liver.METHODS: Fifteen days after human hepatocyte primary culture, epithelial like cells emerged and started proliferating. Cell colonies were isolated and sub-cultured for more than 160 d under specific culture conditions. Cells were analyzed for each passage using immunofluorescence, flow cytometry and reverse transcriptionpolymerase chain reaction (RT-PCR).RESULTS: Flow cytometry analysis demonstrated that liver epithelial cells expressed common markers for hepatic and stem cells such as CD90, CD44 and CD29 but were negative for CD34 and CD117. Using immunofluorescence we demonstrated that liver epithelial cells expressed not only immature (a-fetoprotein) but also differentiated hepatocyte (albumin and CK-18) and biliary markers (CK-7 and 19), whereas they were negative for OV-6. RT-PCR analysis confirmed immunofluorescence data and revealed that liver epithelial cells did not express mature hepatocyte markers such as CYP2B6, CYP3A4 and tyrosine amino-transferase. Purified liver epithelial cells were transplanted into SCID mice. One month after transplantation, albumin positive cell foci were detected in the recipient mouse parenchyma.CONCLUSION: According to their immature and bipotential phenotype, liver epithelial cells might represent a pool of precursors in the healthy human adult liver other than oval cells.

  3. Stroke increases neural stem cells and angiogenesis in the neurogenic niche of the adult mouse.

    Directory of Open Access Journals (Sweden)

    Rui Lan Zhang

    Full Text Available The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ neurogenic niche plays an important role in regulating neural stem cell function. However, the in vivo identification of neural stem cells and their relationship to blood vessels within this niche in response to stroke remain largely unknown. Using whole-mount preparation of the lateral ventricle wall, we examined the architecture of neural stem cells and blood vessels in the V/SVZ of adult mouse over the course of 3 months after onset of focal cerebral ischemia. Stroke substantially increased the number of glial fibrillary acidic protein (GFAP positive neural stem cells that are in contact with the cerebrospinal fluid (CSF via their apical processes at the center of pinwheel structures formed by ependymal cells residing in the lateral ventricle. Long basal processes of these cells extended to blood vessels beneath the ependymal layer. Moreover, stroke increased V/SVZ endothelial cell proliferation from 2% in non-ischemic mice to 12 and 15% at 7 and 14 days after stroke, respectively. Vascular volume in the V/SVZ was augmented from 3% of the total volume prior to stroke to 6% at 90 days after stroke. Stroke-increased angiogenesis was closely associated with neuroblasts that expanded to nearly encompass the entire lateral ventricular wall in the V/SVZ. These data indicate that stroke induces long-term alterations of the neural stem cell and vascular architecture of the adult V/SVZ neurogenic niche. These post-stroke structural changes may provide insight into neural stem cell mediation of stroke-induced neurogenesis through the interaction of neural stem cells with proteins in the CSF and their sub-ependymal neurovascular interaction.

  4. CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells.

    Science.gov (United States)

    Pfenninger, Cosima V; Roschupkina, Teona; Hertwig, Falk; Kottwitz, Denise; Englund, Elisabet; Bengzon, Johan; Jacobsen, Sten Eirik; Nuber, Ulrike A

    2007-06-15

    Human brain tumor stem cells have been enriched using antibodies against the surface protein CD133. An antibody recognizing CD133 also served to isolate normal neural stem cells from fetal human brain, suggesting a possible lineage relationship between normal neural and brain tumor stem cells. Whether CD133-positive brain tumor stem cells can be derived from CD133-positive neural stem or progenitor cells still requires direct experimental evidence, and an important step toward such investigations is the identification and characterization of normal CD133-presenting cells in neurogenic regions of the embryonic and adult brain. Here, we present evidence that CD133 is a marker for embryonic neural stem cells, an intermediate radial glial/ependymal cell type in the early postnatal stage, and for ependymal cells in the adult brain, but not for neurogenic astrocytes in the adult subventricular zone. Our findings suggest two principal possibilities for the origin of brain tumor stem cells: a derivation from CD133-expressing cells, which are normally not present in the adult brain (embryonic neural stem cells and an early postnatal intermediate radial glial/ependymal cell type), or from CD133-positive ependymal cells in the adult brain, which are, however, generally regarded as postmitotic. Alternatively, brain tumor stem cells could be derived from proliferative but CD133-negative neurogenic astrocytes in the adult brain. In the latter case, brain tumor development would involve the production of CD133. PMID:17575139

  5. Spontaneous transformation of adult mesenchymal stem cells from cynomolgus macaques in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Zhenhua [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China); Department of Anatomy, Anhui Medical University, Hefei, 230032 (China); Wang, Jiayin; Zhu, Wanwan; Guan, Yunqian; Zou, Chunlin [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China); Chen, Zhiguo, E-mail: chenzhiguo@gmail.com [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China); Stanford Institute for Stem Cell Biology and Regenerative Medicine and Department of Neurosurgery, Stanford, CA (United States); Zhang, Y. Alex, E-mail: yaz@bjsap.org [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China)

    2011-12-10

    Mesenchymal stem cells (MSCs) have shown potential clinical utility in cell therapy and tissue engineering, due to their ability to proliferate as well as to differentiate into multiple lineages, including osteogenic, adipogenic, and chondrogenic specifications. Therefore, it is crucial to assess the safety of MSCs while extensive expansion ex vivo is a prerequisite to obtain the cell numbers for cell transplantation. Here we show that MSCs derived from adult cynomolgus monkey can undergo spontaneous transformation following in vitro culture. In comparison with MSCs, the spontaneously transformed mesenchymal cells (TMCs) display significantly different growth pattern and morphology, reminiscent of the characteristics of tumor cells. Importantly, TMCs are highly tumorigenic, causing subcutaneous tumors when injected into NOD/SCID mice. Moreover, no multiple differentiation potential of TMCs is observed in vitro or in vivo, suggesting that spontaneously transformed adult stem cells may not necessarily turn into cancer stem cells. These data indicate a direct transformation of cynomolgus monkey MSCs into tumor cells following long-term expansion in vitro. The spontaneous transformation of the cultured cynomolgus monkey MSCs may have important implications for ongoing clinical trials and for models of oncogenesis, thus warranting a more strict assessment of MSCs prior to cell therapy. -- Highlights: Black-Right-Pointing-Pointer Spontaneous transformation of cynomolgus monkey MSCs in vitro. Black-Right-Pointing-Pointer Transformed mesenchymal cells lack multipotency. Black-Right-Pointing-Pointer Transformed mesenchymal cells are highly tumorigenic. Black-Right-Pointing-Pointer Transformed mesenchymal cells do not have the characteristics of cancer stem cells.

  6. Spontaneous transformation of adult mesenchymal stem cells from cynomolgus macaques in vitro

    International Nuclear Information System (INIS)

    Mesenchymal stem cells (MSCs) have shown potential clinical utility in cell therapy and tissue engineering, due to their ability to proliferate as well as to differentiate into multiple lineages, including osteogenic, adipogenic, and chondrogenic specifications. Therefore, it is crucial to assess the safety of MSCs while extensive expansion ex vivo is a prerequisite to obtain the cell numbers for cell transplantation. Here we show that MSCs derived from adult cynomolgus monkey can undergo spontaneous transformation following in vitro culture. In comparison with MSCs, the spontaneously transformed mesenchymal cells (TMCs) display significantly different growth pattern and morphology, reminiscent of the characteristics of tumor cells. Importantly, TMCs are highly tumorigenic, causing subcutaneous tumors when injected into NOD/SCID mice. Moreover, no multiple differentiation potential of TMCs is observed in vitro or in vivo, suggesting that spontaneously transformed adult stem cells may not necessarily turn into cancer stem cells. These data indicate a direct transformation of cynomolgus monkey MSCs into tumor cells following long-term expansion in vitro. The spontaneous transformation of the cultured cynomolgus monkey MSCs may have important implications for ongoing clinical trials and for models of oncogenesis, thus warranting a more strict assessment of MSCs prior to cell therapy. -- Highlights: ► Spontaneous transformation of cynomolgus monkey MSCs in vitro. ► Transformed mesenchymal cells lack multipotency. ► Transformed mesenchymal cells are highly tumorigenic. ► Transformed mesenchymal cells do not have the characteristics of cancer stem cells.

  7. An opposite effect of the CDK inhibitor, p18(INK4c on embryonic stem cells compared with tumor and adult stem cells.

    Directory of Open Access Journals (Sweden)

    Yanxin Li

    Full Text Available Self-renewal is a feature common to both adult and embryonic stem (ES cells, as well as tumor stem cells (TSCs. The cyclin-dependent kinase inhibitor, p18(INK4c, is a known tumor suppressor that can inhibit self-renewal of tumor cells or adult stem cells. Here, we demonstrate an opposite effect of p18 on ES cells in comparison with teratoma cells. Our results unexpectedly showed that overexpression of p18 accelerated the growth of mouse ES cells and embryonic bodies (EB; on the contrary, inhibited the growth of late stage teratoma. Up-regulation of ES cell markers (i.e., Oct4, Nanog, Sox2, and Rex1 were detected in both ES and EB cells, while concomitant down-regulation of various differentiation markers was observed in EB cells. These results demonstrate that p18 has an opposite effect on ES cells as compared with tumor cells and adult stem cells. Mechanistically, expression of CDK4 was significantly increased with overexpression of p18 in ES cells, likely leading to a release of CDK2 from the inhibition by p21 and p27. As a result, self-renewal of ES cells was enhanced. Our current study suggests that targeting p18 in different cell types may yield different outcomes, thereby having implications for therapeutic manipulations of cell cycle machinery in stem cells.

  8. Human Adult Stem Cells as the Target Cells for the Initiation of Carcinogenesis and for the Generation of “Cancer Stem Cells”

    OpenAIRE

    Trosko, James E.

    2008-01-01

    The inference to stem cells has been found in ancient myths and the concept of stem cells has existed in the fields of plant biology, developmental biology and embryology for decades. In the field of cancer research, the stem cell theory was one of the earliest hypotheses on the origin of a cancer from a single cell. However, an opposing hypothesis had it that an adult differentiated somatic cell could “de-differentiate” to become a cancer cell. Only within the last decade, via the “cloning” ...

  9. EXPERIMENTAL STUDY ON PLASTICITY OF PROLIFERATED NEURAL STEM CELLS IN ADULT RATS AFTER CEREBRAL INFARCTION

    Institute of Scientific and Technical Information of China (English)

    Bo Zhang; Ren-zhi Wang; Zhi-gang Lian; Yang Song; Yong Yao

    2006-01-01

    Objective To investigate whether there is endogenous neural stem cell proliferation and whether these proliferated neural stem cells represent neural plasticity in the adult rats after cerebral infarction.Methods Cerebral infarction models of rats were established and the dynamic expression of bromodeoxyuridine (BrdU), BrdU/polysialylated neural cell adhesion molecule (PSA-NCAM) were determined by immunohistochemistry and immunofluorescence staining. BrdU was used to mark dividing neural stem cells. PSA-NCAM was used to mark the plasticity of neural stem cells.Results Compared with controls, the number of BrdU-positive cells in the subventricular zone (SVZ) and hippocampus increased significantly at 1st day after cerebral infarction (P<0.05), reached maximum at 7th day, decreased markedly at 14th day, but it was still elevated compared with that of the controls (P<0.05). The number of BrdU-labeled with PSA-NCAM-positive cells increased significantly at 7th day (P<0.05 ), reached maximum at 14th day,markedly decreased at 28th day, but it was still elevated compared with that of the controls (P<0.05). It was equal to 60% of the number of BrdU-positive cells in the same period.Conclusion Cerebral infarction may stimulate the proliferation of endogenous neural stem cells in situ and most proliferated neural stem cells represent neural plasticity.

  10. Artificial Stem Cell Niches

    OpenAIRE

    Lutolf, Matthias P.; Blau, Helen M.

    2009-01-01

    Stem cells are characterized by their dual ability to reproduce themselves (self-renew) and specialize (differentiate), yielding a plethora of daughter cells that maintain and regenerate tissues. In contrast to their embryonic counterparts, adult stem cells retain their unique functions only if they are in intimate contact with an instructive microenvironment, termed stem cell niche. In these niches, stem cells integrate a complex array of molecular signals that, in concert with induced cell-...

  11. NGF induces adult stem Leydig cells to proliferate and differentiate during Leydig cell regeneration

    International Nuclear Information System (INIS)

    Highlights: •Nerve growth factor has shown significant changes on mRNA levels during Adult Leydig cells regeneration. •We established the organ culture model of rat seminiferous tubules with ethane dimethyl sulphonate (EDS) treatment. •Nerve growth factor has shown proliferation and differentiation-promoting effects on Adult stem Leydig cells. •Nerve growth factor induces progenitor Leydig cells to proliferate and differentiate and immature Leydig cells to proliferate. -- Abstract: Nerve growth factor (NGF) has been reported to be involved in male reproductive physiology. However, few reports have described the activity of NGF during Leydig cell development. The objective of the present study was to examine the role of NGF during stem-Leydig-cell (SLC) regeneration. We investigated the effects of NGF on Leydig-cell (LC) regeneration by measuring mRNA levels in the adult rat testis after ethane dimethanesulfonate (EDS) treatment. Furthermore, we used the established organ culture model of rat seminiferous tubules to examine the regulation of NGF during SLC proliferation and differentiation using EdU staining, real-time PCR and western blotting. Progenitor Leydig cells (PLCs) and immature Leydig cells (ILCs) were also used to investigate the effects of NGF on LCs at different developmental stages. NGF mRNA levels changed significantly during Leydig-cell regeneration in vivo. In vitro, NGF significantly promoted the proliferation of stem Leydig cells and also induced steroidogenic enzyme gene expression and 3β-HSD protein expression. The data from PLCs and ILCs showed that NGF could increase Cyclin D1 and Hsd 17b3 mRNA levels in PLCs and Cyclin D1 mRNA levels in ILCs. These results indicate that NGF may play an important role during LC regeneration by regulating the proliferation and differentiation of LCs at different developmental stages, from SLCs to PLCs and from PLCs to ILCs. The discovery of this effect of NGF on Leydig cells will provide useful

  12. NGF induces adult stem Leydig cells to proliferate and differentiate during Leydig cell regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Lei [Department of Cell Biology, College of Life Science and Technology, Jinan University, 510632 Guangzhou (China); Wang, Huaxi [Southern Medical University, 510515 Guangzhou (China); Yang, Yan [College of Pharmacy, Jinan University, 510632 Guangzhou (China); Liu, Hui [Department of Cell Biology, College of Life Science and Technology, Jinan University, 510632 Guangzhou (China); Zhang, Qihao; Xiang, Qi [Department of Cell Biology, College of Life Science and Technology, Jinan University, 510632 Guangzhou (China); National Engineering Research Center of Genetic Medicine, 510632 Guangzhou (China); Ge, Renshan [Population Council, Rockefeller University, 10065 New York (United States); Su, Zhijian, E-mail: tjnuszj@jnu.edu.cn [Department of Cell Biology, College of Life Science and Technology, Jinan University, 510632 Guangzhou (China); Huang, Yadong, E-mail: tydhuang@jnu.edu.cn [Department of Cell Biology, College of Life Science and Technology, Jinan University, 510632 Guangzhou (China); National Engineering Research Center of Genetic Medicine, 510632 Guangzhou (China)

    2013-06-28

    Highlights: •Nerve growth factor has shown significant changes on mRNA levels during Adult Leydig cells regeneration. •We established the organ culture model of rat seminiferous tubules with ethane dimethyl sulphonate (EDS) treatment. •Nerve growth factor has shown proliferation and differentiation-promoting effects on Adult stem Leydig cells. •Nerve growth factor induces progenitor Leydig cells to proliferate and differentiate and immature Leydig cells to proliferate. -- Abstract: Nerve growth factor (NGF) has been reported to be involved in male reproductive physiology. However, few reports have described the activity of NGF during Leydig cell development. The objective of the present study was to examine the role of NGF during stem-Leydig-cell (SLC) regeneration. We investigated the effects of NGF on Leydig-cell (LC) regeneration by measuring mRNA levels in the adult rat testis after ethane dimethanesulfonate (EDS) treatment. Furthermore, we used the established organ culture model of rat seminiferous tubules to examine the regulation of NGF during SLC proliferation and differentiation using EdU staining, real-time PCR and western blotting. Progenitor Leydig cells (PLCs) and immature Leydig cells (ILCs) were also used to investigate the effects of NGF on LCs at different developmental stages. NGF mRNA levels changed significantly during Leydig-cell regeneration in vivo. In vitro, NGF significantly promoted the proliferation of stem Leydig cells and also induced steroidogenic enzyme gene expression and 3β-HSD protein expression. The data from PLCs and ILCs showed that NGF could increase Cyclin D1 and Hsd 17b3 mRNA levels in PLCs and Cyclin D1 mRNA levels in ILCs. These results indicate that NGF may play an important role during LC regeneration by regulating the proliferation and differentiation of LCs at different developmental stages, from SLCs to PLCs and from PLCs to ILCs. The discovery of this effect of NGF on Leydig cells will provide useful

  13. PDGFRα demarcates the cardiogenic clonogenic Sca1+ stem/progenitor cell in adult murine myocardium

    Science.gov (United States)

    Noseda, Michela; Harada, Mutsuo; McSweeney, Sara; Leja, Thomas; Belian, Elisa; Stuckey, Daniel J.; Abreu Paiva, Marta S.; Habib, Josef; Macaulay, Iain; de Smith, Adam J.; al-Beidh, Farah; Sampson, Robert; Lumbers, R. Thomas; Rao, Pulivarthi; Harding, Sian E.; Blakemore, Alexandra I. F.; Eirik Jacobsen, Sten; Barahona, Mauricio; Schneider, Michael D.

    2015-01-01

    Cardiac progenitor/stem cells in adult hearts represent an attractive therapeutic target for heart regeneration, though (inter)-relationships among reported cells remain obscure. Using single-cell qRT–PCR and clonal analyses, here we define four subpopulations of cardiac progenitor/stem cells in adult mouse myocardium all sharing stem cell antigen-1 (Sca1), based on side population (SP) phenotype, PECAM-1 (CD31) and platelet-derived growth factor receptor-α (PDGFRα) expression. SP status predicts clonogenicity and cardiogenic gene expression (Gata4/6, Hand2 and Tbx5/20), properties segregating more specifically to PDGFRα+ cells. Clonal progeny of single Sca1+ SP cells show cardiomyocyte, endothelial and smooth muscle lineage potential after cardiac grafting, augmenting cardiac function although durable engraftment is rare. PDGFRα− cells are characterized by Kdr/Flk1, Cdh5, CD31 and lack of clonogenicity. PDGFRα+/CD31− cells derive from cells formerly expressing Mesp1, Nkx2-5, Isl1, Gata5 and Wt1, distinct from PDGFRα−/CD31+ cells (Gata5 low; Flk1 and Tie2 high). Thus, PDGFRα demarcates the clonogenic cardiogenic Sca1+ stem/progenitor cell. PMID:25980517

  14. Stem Cells

    OpenAIRE

    Madhukar Thakur

    2009-01-01

    Objective: The objective of this presentation is to create awareness of stem cell applications in the ISORBE community and to foster a strategy of how the ISORBE community can disseminate information and promote the use of radiolabeled stem cells in biomedical applications. Methods: The continued excitement in Stem Cells, in many branches of basic and applied biomedical science, stems from the remarkable ability of stem cells to divide and develop into different types of cells in ...

  15. Profiling of Sox4-dependent transcriptome in skin links tumour suppression and adult stem cell activation

    Directory of Open Access Journals (Sweden)

    Miguel Foronda

    2015-12-01

    Full Text Available Adult stem cells (ASCs reside in specific niches in a quiescent state in adult mammals. Upon specific cues they become activated and respond by self-renewing and differentiating into newly generated specialised cells that ensure appropriate tissue fitness. ASC quiescence also serves as a tumour suppression mechanism by hampering cellular transformation and expansion (White AC et al., 2014. Some genes restricted to early embryonic development and adult stem cell niches are often potent modulators of stem cell quiescence, and derailed expression of these is commonly associated to cancer (Vervoort SJ et al., 2013. Among them, it has been shown that recommissioned Sox4 expression facilitates proliferation, survival and migration of malignant cells. By generating a conditional Knockout mouse model in stratified epithelia (Sox4cKO mice, we demonstrated a delayed plucking-induced Anagen in the absence of Sox4. Skin global transcriptome analysis revealed a prominent defect in the induction of transcriptional networks that control hair follicle stem cell (HFSC activation such as those regulated by Wnt/Ctnnb1, Shh, Myc or Sox9, cell cycle and DNA damage response-associated pathways. Besides, Sox4cKO mice are resistant to skin carcinogenesis, thus linking Sox4 to both normal and pathological HFSC activation (Foronda M et al., 2014. Here we provide additional details on the analysis of Sox4-regulated transcriptome in Telogen and Anagen skin. The raw and processed microarray data is deposited in GEO under GSE58155.

  16. Recents patents for isolating, delivering and tracking adult stem cells in regenerative medicine.

    Science.gov (United States)

    Fierabracci, Alessandra

    2010-06-01

    The field of regenerative medicine offers nowadays the potential to significantly impact a wide spectrum of healthcare issues, from insulin-dependent diabetes mellitus (Type 1 diabetes, T1D) to cardiovascular disease. In tissue engineering biomaterials, biological factors, regeneration competent cells are used in the process of creating functional tissue. Regarding the type of stem or progenitor cells which represents the best candidate for therapy, embryonic stem cells have been considered the master cells capable of differentiating into every type of cells either in vitro or in vivo, in spite of serious ethical concerns. Nevertheless experimental evidence suggests that adult stem cells and even terminally differentiated somatic cells under appropriate microenvironmental treatments can be reprogrammed and contribute to a much wider spectrum of differentiated progeny than previously anticipated. One of the main goals is to exploit novel technologies aiming to isolate, expand and enrich sources of regeneration competent cells, especially adult somatic stem cells. Researchers are also trying to develop innovative strategies for effectively delivering regenerative cell populations and to implement 'tracking' tools to verify their engraftment and destiny in vivo. Here we review recent patents on the field issued over the past five years.

  17. The transcriptional coactivator Cbp regulates self-renewal and differentiation in adult hematopoietic stem cells.

    NARCIS (Netherlands)

    Chan, W.I.; Hannah, R.L.; Dawson, M.A.; Pridans, C.; Foster, D.; Joshi, A.; Gottgens, B.; Deursen, J.M.A. van; Huntly, B.J.

    2011-01-01

    The transcriptional coactivator Cbp plays an important role in a wide range of cellular processes, including proliferation, differentiation, and apoptosis. Although studies have shown its requirement for hematopoietic stem cell (HSC) development, its role in adult HSC maintenance, as well as the cel

  18. Adult Cardiac-Resident MSC-like Stem Cells with a Proepicardial Origin

    NARCIS (Netherlands)

    Chong, James J. H.; Chandrakanthan, Vashe; Xaymardan, Munira; Asli, Naisana S.; Li, Joan; Ahmed, Ishtiaq; Heffernan, Corey; Menon, Mary K.; Scarlett, Christopher J.; Rashidianfar, Amirsalar; Biben, Christine; Zoellner, Hans; Colvin, Emily K.; Pimanda, John E.; Biankin, Andrew V.; Zhou, Bin; Pu, William T.; Prall, Owen W. J.; Harvey, Richard P.

    2011-01-01

    Colony-forming units fibroblast (CFU-Fs), analogous to those giving rise to bone marrow (BM) mesenchymal stem cells (MSCs), are present in many organs, although the relationship between BM and organ-specific CFU-Fs in homeostasis and tissue repair is unknown. Here we describe a population of adult c

  19. Adult human neural stem cells : Properties in vitro and as xenografts in the spinal cord

    OpenAIRE

    Westerlund, Ulf

    2005-01-01

    Though the presence of stem cells in the adult human brain has been presented earlier, much has yet to be discovered about these cells. However, the mere potential of these cells has had a significant impact of how we today evaluate the regenerative capacity of the central nervous system and, importantly, on the possible means for science to provide insights in neural repair. In this thesis a series of in vitro studies, based on the formation of neurospheres, was used to...

  20. The histone variant His2Av is required for adult stem cell maintenance in the Drosophila testis.

    Directory of Open Access Journals (Sweden)

    Jose Rafael Morillo Prado

    2013-11-01

    Full Text Available Many tissues are sustained by adult stem cells, which replace lost cells by differentiation and maintain their own population through self-renewal. The mechanisms through which adult stem cells maintain their identity are thus important for tissue homeostasis and repair throughout life. Here, we show that a histone variant, His2Av, is required cell autonomously for maintenance of germline and cyst stem cells in the Drosophila testis. The ATP-dependent chromatin-remodeling factor Domino is also required in this tissue for adult stem cell maintenance possibly by regulating the incorporation of His2Av into chromatin. Interestingly, although expression of His2Av was ubiquitous, its function was dispensable for germline and cyst cell differentiation, suggesting a specific role for this non-canonical histone in maintaining the stem cell state in these lineages.

  1. In Vitro and In Vivo Hepatic Differentiation of Adult Somatic Stem Cells and Extraembryonic Stem Cells for Treating End Stage Liver Diseases

    Directory of Open Access Journals (Sweden)

    Chenxia Hu

    2015-01-01

    Full Text Available The shortage of liver donors is a major handicap that prevents most patients from receiving liver transplantation and places them on a waiting list for donated liver tissue. Then, primary hepatocyte transplantation and bioartificial livers have emerged as two alternative treatments for these often fatal diseases. However, another problem has emerged. Functional hepatocytes for liver regeneration are in short supply, and they will dedifferentiate immediately in vitro after they are isolated from liver tissue. Alternative stem-cell-based therapeutic strategies, including hepatic stem cells (HSCs, embryonic stem cells (ESCs, induced pluripotent stem cells (iPSCs, and mesenchymal stem cells (MSCs, are more promising, and more attention has been devoted to these approaches because of the high potency and proliferation ability of the cells. This review will focus on the general characteristics and the progress in hepatic differentiation of adult somatic stem cells and extraembryonic stem cells in vitro and in vivo for the treatment of end stage liver diseases. The hepatic differentiation of stem cells would offer an ideal and promising source for cell therapy and tissue engineering for treating liver diseases.

  2. PROLIFERATION AND DIFFERENTIATION OF NEURAL STEM CELLS IN ADULT RATS AFTER CEREBRAL INFARCTION

    Institute of Scientific and Technical Information of China (English)

    Bo Zhang; Ren-zhi Wang; Yong Yao; Zhi-hai Liu; Zhi-gang Lian; Yu-jie Zou; Yu-kui Wei

    2004-01-01

    Objective To investigate proliferation and differentiation of neural stem cells in adult rats after cerebral infarction.Methods Models of cerebral infarction in rats were made and the time-course expression of bromodeoxyuridine (BrdU), Musashil, glial fibrillary acidic protein (GFAP), and neuronal nuclear antigen (NeuN) were determined by immunohistochemistry and immunofluorescence staining. BrdU and Musashil were used to mark dividing neural stem cells. GFAP and NeuN were used to mark differentiating neural stem cells.Results Compared with controls, the number of BrdU-labeled and BrdU-labeled with Musashil-positive cells increased strikingly 1 day after cerebral infarction; approximately 6 fold with a peak 7 days later; markedly decreased 14 days later, but was still elevated compared with that of controls; decling to the control level 28 days later. The number of BrdU-labeled with GFAP-positive cells nearly remained unchanged in the hippocampus after cerebral infarction. The number of BrdU-labeled with NeuN-positive cells increased strikingly 14 days after cerebral infarction, reached maximum peak in the hippocampus 28 days after cerebral infarction in rats.Conclusion Cerebral infarction stimulate proliferation of inherent neural stem cells and most proliferated neural stem cells differentiate into neurons.

  3. Types of Stem Cells

    Science.gov (United States)

    ... PDF) Download an introduction to stem cells and stem cell research. Stem Cell Glossary Stem cell terms to know. ... stem cells blog from the International Society for Stem Cell Research. Learn About Stem Cells From Lab to You ...

  4. Critical Role of Jak2 in the Maintenance and Function of Adult Hematopoietic Stem Cells

    OpenAIRE

    Akada, Hajime; Akada, Saeko; Hutchison, Robert E.; Sakamoto, Kazuhito; Wagner, Kay-Uwe; Mohi, Golam

    2014-01-01

    Jak2, a member of the Janus kinase family of non-receptor protein tyrosine kinases, is activated in response to a variety of cytokines, and functions in survival and proliferation of cells. An activating JAK2V617F mutation has been found in most patients with myeloproliferative neoplasms, and patients treated with Jak2 inhibitors show significant hematopoietic toxicities. However, the role of Jak2 in adult hematopoietic stem cells (HSCs) has not been clearly elucidated. Using a conditional Ja...

  5. Brain micro-ecologies: neural stem cell niches in the adult mammalian brain

    OpenAIRE

    Riquelme, Patricio A; Drapeau, Elodie; Doetsch, Fiona

    2007-01-01

    Neurogenesis persists in two germinal regions in the adult mammalian brain, the subventricular zone of the lateral ventricles and the subgranular zone in the hippocampal formation. Within these two neurogenic niches, specialized astrocytes are neural stem cells, capable of self-renewing and generating neurons and glia. Cues within the niche, from cell–cell interactions to diffusible factors, are spatially and temporally coordinated to regulate proliferation and neurogenesis, ultimately affect...

  6. Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5⁺ stem cell

    DEFF Research Database (Denmark)

    Yui, Shiro; Nakamura, Tetsuya; Sato, Toshiro;

    2012-01-01

    Adult stem-cell therapy holds promise for the treatment of gastrointestinal diseases. Here we describe methods for long-term expansion of colonic stem cells positive for leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5(+) cells) in culture. To test the transplantability of these ...

  7. Loss of DNA mismatch repair imparts a selective advantage in planarian adult stem cells.

    Directory of Open Access Journals (Sweden)

    Jessica P Hollenbach

    Full Text Available Lynch syndrome (LS leads to an increased risk of early-onset colorectal and other types of cancer and is caused by germline mutations in DNA mismatch repair (MMR genes. Loss of MMR function results in a mutator phenotype that likely underlies its role in tumorigenesis. However, loss of MMR also results in the elimination of a DNA damage-induced checkpoint/apoptosis activation barrier that may allow damaged cells to grow unchecked. A fundamental question is whether loss of MMR provides pre-cancerous stem cells an immediate selective advantage in addition to establishing a mutator phenotype. To test this hypothesis in an in vivo system, we utilized the planarian Schmidtea mediterranea which contains a significant population of identifiable adult stem cells. We identified a planarian homolog of human MSH2, a MMR gene which is mutated in 38% of LS cases. The planarian Smed-msh2 is expressed in stem cells and some progeny. We depleted Smed-msh2 mRNA levels by RNA-interference and found a striking survival advantage in these animals treated with a cytotoxic DNA alkylating agent compared to control animals. We demonstrated that this tolerance to DNA damage is due to the survival of mitotically active, MMR-deficient stem cells. Our results suggest that loss of MMR provides an in vivo survival advantage to the stem cell population in the presence of DNA damage that may have implications for tumorigenesis.

  8. Loss of DNA mismatch repair imparts a selective advantage in planarian adult stem cells.

    Science.gov (United States)

    Hollenbach, Jessica P; Resch, Alissa M; Palakodeti, Dasaradhi; Graveley, Brenton R; Heinen, Christopher D

    2011-01-01

    Lynch syndrome (LS) leads to an increased risk of early-onset colorectal and other types of cancer and is caused by germline mutations in DNA mismatch repair (MMR) genes. Loss of MMR function results in a mutator phenotype that likely underlies its role in tumorigenesis. However, loss of MMR also results in the elimination of a DNA damage-induced checkpoint/apoptosis activation barrier that may allow damaged cells to grow unchecked. A fundamental question is whether loss of MMR provides pre-cancerous stem cells an immediate selective advantage in addition to establishing a mutator phenotype. To test this hypothesis in an in vivo system, we utilized the planarian Schmidtea mediterranea which contains a significant population of identifiable adult stem cells. We identified a planarian homolog of human MSH2, a MMR gene which is mutated in 38% of LS cases. The planarian Smed-msh2 is expressed in stem cells and some progeny. We depleted Smed-msh2 mRNA levels by RNA-interference and found a striking survival advantage in these animals treated with a cytotoxic DNA alkylating agent compared to control animals. We demonstrated that this tolerance to DNA damage is due to the survival of mitotically active, MMR-deficient stem cells. Our results suggest that loss of MMR provides an in vivo survival advantage to the stem cell population in the presence of DNA damage that may have implications for tumorigenesis. PMID:21747960

  9. Sex hormones establish a reserve pool of adult muscle stem cells.

    Science.gov (United States)

    Kim, Ji-Hoon; Han, Gi-Chan; Seo, Ji-Yun; Park, Inkuk; Park, Wookjin; Jeong, Hyun-Woo; Lee, Su Hyeon; Bae, Sung-Hwan; Seong, Jinwoo; Yum, Min-Kyu; Hann, Sang-Hyeon; Kwon, Young-Guen; Seo, Daekwan; Choi, Man Ho; Kong, Young-Yun

    2016-09-01

    Quiescent satellite cells, known as adult muscle stem cells, possess a remarkable ability to regenerate skeletal muscle following injury throughout life. Although they mainly originate from multipotent stem/progenitor cells of the somite, the mechanism underlying the establishment of quiescent satellite cell populations is unknown. Here, we show that sex hormones induce Mind bomb 1 (Mib1) expression in myofibres at puberty, which activates Notch signalling in cycling juvenile satellite cells and causes them to be converted into adult quiescent satellite cells. Myofibres lacking Mib1 fail to send Notch signals to juvenile satellite cells, leading to impaired cell cycle exit and depletion. Our findings reveal that the hypothalamic-pituitary-gonadal axis drives Mib1 expression in the myofibre niche. Moreover, the same axis regulates the re-establishment of quiescent satellite cell populations following injury. Our data show that sex hormones establish adult quiescent satellite cell populations by regulating the myofibre niche at puberty and re-establish them during regeneration. PMID:27548913

  10. Regional and Stage-Specific Effects of Prospectively Purified Vascular Cells on the Adult V-SVZ Neural Stem Cell Lineage

    OpenAIRE

    Crouch, Elizabeth E.; Liu, Chang; Silva-Vargas, Violeta; Doetsch, Fiona

    2015-01-01

    Adult neural stem cells reside in specialized niches. In the ventricular-subventricular zone (V-SVZ), quiescent neural stem cells (qNSCs) become activated (aNSCs), and generate transit amplifying cells (TACs), which give rise to neuroblasts that migrate to the olfactory bulb. The vasculature is an important component of the adult neural stem cell niche, but whether vascular cells in neurogenic areas are intrinsically different from those elsewhere in the brain is unknown. Moreover, the contri...

  11. In vivo tumorigenesis was observed after injection of in vitro expanded neural crest stem cells isolated from adult bone marrow

    OpenAIRE

    Sabine Wislet-Gendebien; Christophe Poulet; Virginie Neirinckx; Benoit Hennuy; Swingland, James T.; Emerence Laudet; Lukas Sommer; Olga Shakova; Vincent Bours; Bernard Rogister

    2012-01-01

    Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells alters the functional and biological properties of those cells, leading to the accumulation of genetic aberrations. Recent studies described bone marrow stromal cells (BMSC) as mixed populations of cells including mesenchymal (MSC) and neural crest stem cells (NCSC). Here, we report the ...

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

    Science.gov (United States)

    Kuwabara, Tomoko; Asashima, Makoto

    2012-06-01

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

  13. Period 2 regulates neural stem/progenitor cell proliferation in the adult hippocampus

    OpenAIRE

    Albrecht Urs; Maquet Pierre; Moonen Gustave; Nguyen Laurent; Vandenbosch Renaud; Beukelaers Pierre; Borgs Laurence; Belachew Shibeshih; Malgrange Brigitte

    2009-01-01

    Abstract Background Newborn granule neurons are generated from proliferating neural stem/progenitor cells and integrated into mature synaptic networks in the adult dentate gyrus of the hippocampus. Since light/dark variations of the mitotic index and DNA synthesis occur in many tissues, we wanted to unravel the role of the clock-controlled Period2 gene (mPer2) in timing cell cycle kinetics and neurogenesis in the adult DG. Results In contrast to the suprachiasmatic nucleus, we observed a non-...

  14. Empowering Adult Stem Cells for Myocardial Regeneration V2.0: Success in Small Steps.

    Science.gov (United States)

    Broughton, Kathleen M; Sussman, Mark A

    2016-03-01

    Much has changed since our survey of the landscape for myocardial regeneration powered by adult stem cells 4 years ago.(1) The intervening years since that first review has witnessed an explosive expansion of studies that advance both understanding and implementation of adult stem cells in promoting myocardial repair. Painstaking research from innumerable laboratories throughout the world is prying open doors that may lead to restoration of myocardial structure and function in the wake of pathological injury. This global effort has produced deeper mechanistic comprehension coupled with an evolving appreciation for the complexity of myocardial regeneration in the adult context. Undaunted by both known and (as yet) unknown challenges, pursuit of myocardial regenerative medicine mediated by adult stem cell therapy has gathered momentum fueled by tantalizing clues and visionary goals. This concise review takes a somewhat different perspective than our initial treatise, taking stock of the business sector that has become an integral part of the field while concurrently updating state of affairs in cutting edge research. Looking retrospectively at advancement over the years as all reviews eventually must, the fundamental lesson to be learned is best explained by Jonatan Mårtensson: "Success will never be a big step in the future. Success is a small step taken just now."

  15. Peripheral Blood Monocytes as Adult Stem Cells: Molecular Characterization and Improvements in Culture Conditions to Enhance Stem Cell Features and Proliferative Potential

    OpenAIRE

    Hendrik Ungefroren; Ayman Hyder; Maren Schulze; Fawzy El-Sayed, Karim M.; Evelin Grage-Griebenow; Nussler, Andreas K.; Fred Fändrich

    2016-01-01

    Adult stem or programmable cells hold great promise in diseases in which damaged or nonfunctional cells need to be replaced. We have recently demonstrated that peripheral blood monocytes can be differentiated in vitro into cells resembling specialized cell types like hepatocytes and pancreatic beta cells. During phenotypic conversion, the monocytes downregulate monocyte/macrophage differentiation markers, being indicative of partial dedifferentiation, and are partially reprogrammed to acquire...

  16. Introduction to Stem Cell Therapy

    OpenAIRE

    Biehl, Jesse K.; Russell, Brenda

    2009-01-01

    Stem cells have the ability to differentiate into specific cell types. The two defining characteristics of a stem cell are perpetual self-renewal and the ability to differentiate into a specialized adult cell type. There are two major classes of stem cells: pluripotent that can become any cell in the adult body, and multipotent that are restricted to becoming a more limited population of cells. Cell sources, characteristics, differentiation and therapeutic applications are discussed. Stem cel...

  17. The Ly-6A (Sca-1) GFP transgene is expressed in all adult mouse hematopoietic stem cells

    NARCIS (Netherlands)

    X. Ma (Xiaoqian); C.I. Robin; K. Ottersbach (Katrin); E.A. Dzierzak (Elaine)

    2002-01-01

    textabstractThe Sca-1 cell surface glycoprotein is used routinely as a marker of adult hematopoietic stem cells (HSCs), allowing a >100-fold enrichment of these rare cells from the bone marrow of the adult mouse. The Sca-1 protein is encoded by the Ly-6A/E gene, a small 4-exon gene

  18. In Vivo Targeted Magnetic Resonance Imaging of Endogenous Neural Stem Cells in the Adult Rodent Brain

    Directory of Open Access Journals (Sweden)

    Xiao-Mei Zhong

    2015-01-01

    Full Text Available Neural stem cells in the adult mammalian brain have a significant level of neurogenesis plasticity. In vivo monitoring of adult endogenous NSCs would be of great benefit to the understanding of the neurogenesis plasticity under normal and pathological conditions. Here we show the feasibility of in vivo targeted MR imaging of endogenous NSCs in adult mouse brain by intraventricular delivery of monoclonal anti-CD15 antibody conjugated superparamagnetic iron oxide nanoparticles. After intraventricular administration of these nanoparticles, the subpopulation of NSCs in the anterior subventricular zone and the beginning of the rostral migratory stream could be in situ labeled and were in vivo visualized with 7.0-T MR imaging during a period from 1 day to 7 days after the injection. Histology confirmed that the injected targeted nanoparticles were specifically bound to CD15 positive cells and their surrounding extracellular matrix. Our results suggest that in vivo targeted MR imaging of endogenous neural stem cells in adult rodent brain could be achieved by using anti-CD15-SPIONs as the molecular probe; and this targeting imaging strategy has the advantage of a rapid in vivo monitoring of the subpopulation of endogenous NSCs in adult brains.

  19. zebraflash transgenic lines for in vivo bioluminescence imaging of stem cells and regeneration in adult zebrafish

    OpenAIRE

    Chen, Chen-Hui; Durand, Ellen; Wang, Jinhu; Zon, Leonard I.; Poss, Kenneth D.

    2013-01-01

    The zebrafish has become a standard model system for stem cell and tissue regeneration research, based on powerful genetics, high tissue regenerative capacity and low maintenance costs. Yet, these studies can be challenged by current limitations of tissue visualization techniques in adult animals. Here we describe new imaging methodology and present several ubiquitous and tissue-specific luciferase-based transgenic lines, which we have termed zebraflash, that facilitate the assessment of rege...

  20. Low Connexin Channel-Dependent Intercellular Communication in Human Adult Hematopoietic Progenitor/Stem Cells: Probing Mechanisms of Autologous Stem Cell Therapy

    OpenAIRE

    Yang, Jian; Darley, Richard L.; Hallett, Maurice; Evans, W. Howard

    2010-01-01

    Human bone marrow is a clinical source of autologous progenitor stem cells showing promise for cardiac repair following ischemic insult. Functional improvements following delivery of adult bone marrow CD34+ cells into heart tissue may require metabolic/electrical communication between participating cells. Since connexin43 (Cx43) channels are implicated in cardiogenesis and provide intercellular connectivity in the heart, the authors analyzed the expression of 20 connexins (Cx) in CD34+ cells ...

  1. Adult neurogenesis, neural stem cells and Alzheimer's disease: developments, limitations, problems and promises.

    Science.gov (United States)

    Taupin, Philippe

    2009-12-01

    Alzheimer's disease (AD) is an irreversible progressive neurodegenerative disease, leading to severe incapacity and death. It is the most common form of dementia among older people. AD is characterized in the brain by amyloid plaques, neurofibrillary tangles, neuronal degeneration, aneuploidy and enhanced neurogenesis and by cognitive, behavioral and physical impairments. Inherited mutations in several genes and genetic, acquired and environmental risk factors have been reported as causes for developing the disease, for which there is currently no cure. Current treatments for AD involve drugs and occupational therapies, and future developments involve early diagnosis and stem cell therapy. In this manuscript, we will review and discuss the recent developments, limitations, problems and promises on AD, particularly related to aneuploidy, adult neurogenesis, neural stem cells (NSCs) and cellular therapy. Though adult neurogenesis may be beneficial for regeneration of the nervous system, it may underly the pathogenesis of AD. Cellular therapy is a promising strategy for AD. Limitations in protocols to establish homogeneous populations of neural progenitor and stem cells and niches for neurogenesis need to be resolved and unlocked, for the full potential of adult NSCs to be realized for therapy.

  2. Stem Cells

    Directory of Open Access Journals (Sweden)

    Madhukar Thakur

    2015-02-01

    Full Text Available Objective: The objective of this presentation is to create awareness of stem cell applications in the ISORBE community and to foster a strategy of how the ISORBE community can disseminate information and promote the use of radiolabeled stem cells in biomedical applications. Methods: The continued excitement in Stem Cells, in many branches of basic and applied biomedical science, stems from the remarkable ability of stem cells to divide and develop into different types of cells in the body. Often called as Magic Seeds, stem cells are produced in bone marrow and circulate in blood, albeit at a relatively low concentration. These virtues together with the ability of stem cells to grow in tissue culture have paved the way for their applications to generate new and healthy tissues and to replace diseased or injured human organs. Although possibilities of stem cell applications are many, much remains yet to be understood of these remarkable magic seeds. Conclusion: This presentation shall briefly cover the origin of stem cells, the pros and cons of their growth and division, their potential application, and shall outline some examples of the contributions of radiolabeled stem cells, in this rapidly growing branch of biomedical science

  3. The adult retinal stem cell is a rare cell in the ciliary epithelium whose progeny can differentiate into photoreceptors

    Directory of Open Access Journals (Sweden)

    Brian G. Ballios

    2012-02-01

    Self-renewing, multipotential retinal stem cells (RSCs reside in the pigmented ciliary epithelium of the peripheral retina in adult mammals. RSCs can give rise to rhodopsin positive-cells, which can integrate into early postnatal retina, and represent a potentially useful option for cellular therapy. The ability to purify a stem cell population and direct the differentiation toward a particular cell lineage is a challenge facing the application of stem cells in regenerative medicine. Here we use cell sorting to prospectively enrich mouse RSCs based on size, granularity and low expression of P-cadherin and demonstrate that only rare cells with defined properties proliferate to form colonies. We show that clonally-derived mouse and human RSC progeny are multipotent and can differentiate into mature rhodopsin-positive cells with high efficiency using combinations of exogenous culture additives known to influence neural retinal development, including taurine and retinoic acid. This directed RSC differentiation follows the temporal sequence of photoreceptor differentiation in vivo, and the cells exhibit morphology, protein and gene expression consistent with primary cultures of rods in vitro. These results demonstrate that the RSC, an adult stem cell, can be enriched and directed to produce photoreceptors as a first step toward a targeted cell replacement strategy to treat retinal degenerative disease.

  4. HDAC3 controls gap 2/mitosis progression in adult neural stem/progenitor cells by regulating CDK1 levels

    OpenAIRE

    Jiang, Yindi; Hsieh, Jenny

    2014-01-01

    Cell cycle regulation is one of the most fundamental mechanisms to control various biological processes, including the proliferation of neural stem/progenitor cells (NSPCs) in adult mouse brain. This study shows that histone deacetylase 3 (HDAC3), a well-studied epigenetic factor, is required for the proliferation of neural stem cells. We also demonstrate that HDAC3 controls gap 2 and mitosis phase of cell cycle through stabilization of cell cycle protein cyclin-dependent kinase 1. These find...

  5. Chromatin-based epigenetics of adult subventricular zone neural stem cells

    Directory of Open Access Journals (Sweden)

    Gabriel eGonzales-Roybal

    2013-10-01

    Full Text Available In specific regions of the adult mammalian brain, neural stem cells (NSCs generate new neurons throughout life. Emerging evidence indicate that chromatin-based transcriptional regulation is a key epigenetic mechanism for the life-long function of adult NSCs. In the adult mouse brain, NSCs in the subventricular zone (SVZ retain the ability to produce both neurons and glia for the life of the animal. In this review, we discuss the origin and function of SVZ NSCs as they relate to key epigenetic concepts of development and potential underlying mechanism of chromatin-based transcriptional regulation. A central point of discussion is how SVZ NSCs – which possess many characteristics of mature, non-neurogenic astrocytes – maintain a youthful ability to produce both neuronal and glial lineages. In addition to reviewing data regarding the function of chromatin-modifying factors in SVZ neurogenesis, we incorporate our growing understanding that long noncoding RNAs (lncRNAs serve as an important element to chromatin-based transcriptional regulation, including that of SVZ NSCs. Discoveries regarding the epigenetic mechanisms of adult SVZ NSCs may provide key insights into fundamental principles of adult stem cell biology as well as the more complex and dynamic developmental environment of the embryonic brain.

  6. Novel Action of FSH on Stem Cells in Adult Mammalian Ovary Induces Postnatal Oogenesis and Primordial Follicle Assembly.

    Science.gov (United States)

    Bhartiya, Deepa; Parte, Seema; Patel, Hiren; Sriraman, Kalpana; Zaveri, Kusum; Hinduja, Indira

    2016-01-01

    Adult mammalian ovary has been under the scanner for more than a decade now since it was proposed to harbor stem cells that undergo postnatal oogenesis during reproductive period like spermatogenesis in testis. Stem cells are located in the ovary surface epithelium and exist in adult and menopausal ovary as well as in ovary with premature failure. Stem cells comprise two distinct populations including spherical, very small embryonic-like stem cells (VSELs which express nuclear OCT-4 and other pluripotent and primordial germ cells specific markers) and slightly bigger ovarian germ stem cells (OGSCs with cytoplasmic OCT-4 which are equivalent to spermatogonial stem cells in the testes). These stem cells have the ability to spontaneously differentiate into oocyte-like structures in vitro and on exposure to a younger healthy niche. Bone marrow may be an alternative source of these stem cells. The stem cells express FSHR and respond to FSH by undergoing self-renewal, clonal expansion, and initiating neo-oogenesis and primordial follicle assembly. VSELs are relatively quiescent and were recently reported to survive chemotherapy and initiate oogenesis in mice when exposed to FSH. This emerging understanding and further research in the field will help evolving novel strategies to manage ovarian pathologies and also towards oncofertility. PMID:26635884

  7. Novel Action of FSH on Stem Cells in Adult Mammalian Ovary Induces Postnatal Oogenesis and Primordial Follicle Assembly

    Directory of Open Access Journals (Sweden)

    Deepa Bhartiya

    2016-01-01

    Full Text Available Adult mammalian ovary has been under the scanner for more than a decade now since it was proposed to harbor stem cells that undergo postnatal oogenesis during reproductive period like spermatogenesis in testis. Stem cells are located in the ovary surface epithelium and exist in adult and menopausal ovary as well as in ovary with premature failure. Stem cells comprise two distinct populations including spherical, very small embryonic-like stem cells (VSELs which express nuclear OCT-4 and other pluripotent and primordial germ cells specific markers and slightly bigger ovarian germ stem cells (OGSCs with cytoplasmic OCT-4 which are equivalent to spermatogonial stem cells in the testes. These stem cells have the ability to spontaneously differentiate into oocyte-like structures in vitro and on exposure to a younger healthy niche. Bone marrow may be an alternative source of these stem cells. The stem cells express FSHR and respond to FSH by undergoing self-renewal, clonal expansion, and initiating neo-oogenesis and primordial follicle assembly. VSELs are relatively quiescent and were recently reported to survive chemotherapy and initiate oogenesis in mice when exposed to FSH. This emerging understanding and further research in the field will help evolving novel strategies to manage ovarian pathologies and also towards oncofertility.

  8. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

    International Nuclear Information System (INIS)

    Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC with epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders

  9. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

    Energy Technology Data Exchange (ETDEWEB)

    Park, Kyoung Ho [Department of Otolaryngology Head and Neck Surgery, College of Medicine, Catholic University, Seoul (Korea, Republic of); Yeo, Sang Won, E-mail: swyeo@catholic.ac.kr [Department of Otolaryngology Head and Neck Surgery, College of Medicine, Catholic University, Seoul (Korea, Republic of); Troy, Frederic A., E-mail: fatroy@ucdavis.edu [Department of Biochemistry and Molecular Medicine, University of California, School of Medicine, Davis, CA 95616 (United States); Xiamen University, School of Medicine, Xiamen City (China)

    2014-10-17

    Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC with epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders.

  10. An essential and evolutionarily conserved role of protein arginine methyltransferase 1 for adult intestinal stem cells during postembryonic development

    OpenAIRE

    Matsuda, Hiroki; Shi, Yun-Bo

    2010-01-01

    Organ-specific adult stem cells are critical for the homeostasis of adult organs and organ repair and regeneration. Unfortunately, it has been difficult to investigate the origins of these stem cells and the mechanisms of their development, especially in mammals. Intestinal remodeling during frog metamorphosis offers a unique opportunity for such studies. During the transition from an herbivorous tadpole to a carnivorous frog, the intestine is completely remodeled with the larval epithelial c...

  11. Adult liver stem cells in hepatic regeneration and cancer

    NARCIS (Netherlands)

    Nantasanti, Sathidpak

    2015-01-01

    An alternative source of livers for transplantation in patients with (genetic) liver diseases and liver failure is needed because liver donors are scarce. HPC-derived hepatocyte-like cells could be one of the options. Because dogs and humans share liver-pathologies and disease-pathways, the dog is c

  12. Toward 'SMART' stem cells.

    Science.gov (United States)

    Cheng, T

    2008-01-01

    Stem cell research is at the heart of regenerative medicine, which holds great promise for the treatment of many devastating disorders. However, in addition to hurdles posed by well-publicized ethical issues, this emerging field presents many biological challenges. What is a stem cell? How are embryonic stem cells different from adult stem cells? What are the physiological bases for therapeutically acceptable stem cells? In this editorial review, I will briefly discuss these superficially simple but actually rather complex issues that surround this fascinating cell type. The goal of this special issue on stem cells in Gene Therapy is to review some fundamental and critical aspects of current stem cell research that have translational potential. PMID:18046429

  13. Pten deletion in adult neural stem/progenitor cells enhances constitutive neurogenesis.

    Science.gov (United States)

    Gregorian, Caroline; Nakashima, Jonathan; Le Belle, Janel; Ohab, John; Kim, Rachel; Liu, Annie; Smith, Kate Barzan; Groszer, Matthias; Garcia, A Denise; Sofroniew, Michael V; Carmichael, S Thomas; Kornblum, Harley I; Liu, Xin; Wu, Hong

    2009-02-11

    Here we show that conditional deletion of Pten in a subpopulation of adult neural stem cells in the subependymal zone (SEZ) leads to persistently enhanced neural stem cell self-renewal without sign of exhaustion. These Pten null SEZ-born neural stem cells and progenies can follow the endogenous migration, differentiation, and integration pathways and contribute to constitutive neurogenesis in the olfactory bulb. As a result, Pten deleted animals have increased olfactory bulb mass and enhanced olfactory function. Pten null cells in the olfactory bulb can establish normal connections with peripheral olfactory epithelium and help olfactory bulb recovery from acute damage. Following a focal stroke, Pten null progenitors give rise to greater numbers of neuroblasts that migrate to peri-infarct cortex. However, in contrast to the olfactory bulb, no significant long-term survival and integration can be observed, indicating that additional factors are necessary for long-term survival of newly born neurons after stroke. These data suggest that manipulating PTEN-controlled signaling pathways may be a useful step in facilitating endogenous neural stem/progenitor expansion for the treatment of disorders or lesions in regions associated with constitutive neurogenesis.

  14. Pten deletion in adult neural stem/progenitor cells enhances constitutive neurogenesis.

    Science.gov (United States)

    Gregorian, Caroline; Nakashima, Jonathan; Le Belle, Janel; Ohab, John; Kim, Rachel; Liu, Annie; Smith, Kate Barzan; Groszer, Matthias; Garcia, A Denise; Sofroniew, Michael V; Carmichael, S Thomas; Kornblum, Harley I; Liu, Xin; Wu, Hong

    2009-02-11

    Here we show that conditional deletion of Pten in a subpopulation of adult neural stem cells in the subependymal zone (SEZ) leads to persistently enhanced neural stem cell self-renewal without sign of exhaustion. These Pten null SEZ-born neural stem cells and progenies can follow the endogenous migration, differentiation, and integration pathways and contribute to constitutive neurogenesis in the olfactory bulb. As a result, Pten deleted animals have increased olfactory bulb mass and enhanced olfactory function. Pten null cells in the olfactory bulb can establish normal connections with peripheral olfactory epithelium and help olfactory bulb recovery from acute damage. Following a focal stroke, Pten null progenitors give rise to greater numbers of neuroblasts that migrate to peri-infarct cortex. However, in contrast to the olfactory bulb, no significant long-term survival and integration can be observed, indicating that additional factors are necessary for long-term survival of newly born neurons after stroke. These data suggest that manipulating PTEN-controlled signaling pathways may be a useful step in facilitating endogenous neural stem/progenitor expansion for the treatment of disorders or lesions in regions associated with constitutive neurogenesis. PMID:19211894

  15. Stem cells in urology.

    Science.gov (United States)

    Aboushwareb, Tamer; Atala, Anthony

    2008-11-01

    The shortage of donors for organ transplantation has stimulated research on stem cells as a potential resource for cell-based therapy in all human tissues. Stem cells have been used for regenerative medicine applications in many organ systems, including the genitourinary system. The potential applications for stem cell therapy have, however, been restricted by the ethical issues associated with embryonic stem cell research. Instead, scientists have explored other cell sources, including progenitor and stem cells derived from adult tissues and stem cells derived from the amniotic fluid and placenta. In addition, novel techniques for generating stem cells in the laboratory are being developed. These techniques include somatic cell nuclear transfer, in which the nucleus of an adult somatic cell is placed into an oocyte, and reprogramming of adult cells to induce stem-cell-like behavior. Such techniques are now being used in tissue engineering applications, and some of the most successful experiments have been in the field of urology. Techniques to regenerate bladder tissue have reached the clinic, and exciting progress is being made in other areas, such as regeneration of the kidney and urethra. Cell therapy as a treatment for incontinence and infertility might soon become a reality. Physicians should be optimistic that regenerative medicine and tissue engineering will one day provide mainstream treatment options for urologic disorders.

  16. The behaviour of Drosophila adult hindgut stem cells is controlled by Wnt and Hh signalling.

    Science.gov (United States)

    Takashima, Shigeo; Mkrtchyan, Marianna; Younossi-Hartenstein, Amelia; Merriam, John R; Hartenstein, Volker

    2008-07-31

    The intestinal tract maintains proper function by replacing aged cells with freshly produced cells that arise from a population of self-renewing intestinal stem cells (ISCs). In the mammalian intestine, ISC self renewal, amplification and differentiation take place along the crypt-villus axis, and are controlled by the Wnt and hedgehog (Hh) signalling pathways. However, little is known about the mechanisms that specify ISCs within the developing intestinal epithelium, or about the signalling centres that help maintain them in their self-renewing stem cell state. Here we show that in adult Drosophila melanogaster, ISCs of the posterior intestine (hindgut) are confined to an anterior narrow segment, which we name the hindgut proliferation zone (HPZ). Within the HPZ, self renewal of ISCs, as well as subsequent proliferation and differentiation of ISC descendants, are controlled by locally emanating Wingless (Wg, a Drosophila Wnt homologue) and Hh signals. The anteriorly restricted expression of Wg in the HPZ acts as a niche signal that maintains cells in a slow-cycling, self-renewing mode. As cells divide and move posteriorly away from the Wg source, they enter a phase of rapid proliferation. During this phase, Hh signal is required for exiting the cell cycle and the onset of differentiation. The HPZ, with its characteristic proliferation dynamics and signalling properties, is set up during the embryonic phase and becomes active in the larva, where it generates all adult hindgut cells including ISCs. The mechanism and genetic control of cell renewal in the Drosophila HPZ exhibits a large degree of similarity with what is seen in the mammalian intestine. Our analysis of the Drosophila HPZ provides an insight into the specification and control of stem cells, highlighting the way in which the spatial pattern of signals that promote self renewal, growth and differentiation is set up within a genetically tractable model system. PMID:18633350

  17. Clonal analysis of the differentiation potential of human adipose-derived adult stem cells.

    Science.gov (United States)

    Guilak, Farshid; Lott, Kristen E; Awad, Hani A; Cao, Qiongfang; Hicok, Kevin C; Fermor, Beverley; Gimble, Jeffrey M

    2006-01-01

    Pools of human adipose-derived adult stem (hADAS) cells can exhibit multiple differentiated phenotypes under appropriate in vitro culture conditions. Because adipose tissue is abundant and easily accessible, hADAS cells offer a promising source of cells for tissue engineering and other cell-based therapies. However, it is unclear whether individual hADAS cells can give rise to multiple differentiated phenotypes or whether each phenotype arises from a subset of committed progenitor cells that exists within a heterogeneous population. The goal of this study was to test the hypothesis that single hADAS are multipotent at a clonal level. hADAS cells were isolated from liposuction waste, and ring cloning was performed to select cells derived from a single progenitor cell. Forty-five clones were expanded through four passages and then induced for adipogenesis, osteogenesis, chondrogenesis, and neurogenesis using lineage-specific differentiation media. Quantitative differentiation criteria for each lineage were determined using histological and biochemical analyses. Eighty one percent of the hADAS cell clones differentiated into at least one of the lineages. In addition, 52% of the hADAS cell clones differentiated into two or more of the lineages. More clones expressed phenotypes of osteoblasts (48%), chondrocytes (43%), and neuron-like cells (52%) than of adipocytes (12%), possibly due to the loss of adipogenic ability after repeated subcultures. The findings are consistent with the hypothesis that hADAS cells are a type of multipotent adult stem cell and not solely a mixed population of unipotent progenitor cells. However, it is important to exercise caution in interpreting these results until they are validated using functional in vivo assays.

  18. A Sox Transcription Factor Is a Critical Regulator of Adult Stem Cell Proliferation in the Drosophila Intestine

    OpenAIRE

    Fanju W. Meng; Benoît Biteau

    2015-01-01

    Adult organs and their resident stem cells are constantly facing the challenge of adapting cell proliferation to tissue demand, particularly in response to environmental stresses. Whereas most stress-signaling pathways are conserved between progenitors and differentiated cells, stem cells have the specific ability to respond by increasing their proliferative rate, using largely unknown mechanisms. Here, we show that a member of the Sox family of transcription factors in Drosophila, Sox21a, is...

  19. The postnatal origin of adult neural stem cells and the effects of glucocorticoids on their genesis.

    Science.gov (United States)

    Ortega-Martínez, Sylvia; Trejo, José L

    2015-02-15

    The relevance of adult neurogenesis in hippocampal function is well documented, as is the potential impact stress has on the adult neurogenic niche. Adult born neurons are generated from neural precursors in the dentate gyrus (DG), although the point in postnatal development that these cell precursors originate is not known. This is particularly relevant if we consider the effects stress may have on the development of neural precursors, and whether such effects on adult neurogenesis and behavior may persist in the long-term. We have analyzed the proportion of neural precursors in the adult murine hippocampus born on specific days during postnatal development using a dual birth-dating analysis, and we assessed their sensitivity to dexamethasone (DEX) on the peak day of cell generation. We also studied the consequences of postnatal DEX administration on adult hippocampal-dependent behavior. Postnatal day 6 (P6) is a preferred period for proliferating neural stem cells (NSCs) to become the precursors that remain in a proliferative state throughout adulthood. This window is independent of gender, the cell's location in the DG granule cell layer or their rostro-caudal position. DEX administration at P6 reduces the size of the adult NSC pool in the DG, which is correlated with poor learning/memory capacity and increased anxiety-like behavior. These results indicate that aNSCs are generated non-uniformly during postnatal development, with peak generation on day P6, and that stress receptor activation during the key period of postnatal NSC generation has a profound impact on both adult hippocampal neurogenesis and behavior.

  20. PPARs Expression in Adult Mouse Neural Stem Cells: Modulation of PPARs during Astroglial Differentiaton of NSC

    Directory of Open Access Journals (Sweden)

    A. Cimini

    2007-01-01

    Full Text Available PPAR isotypes are involved in the regulation of cell proliferation, death, and differentiation, with different roles and mechanisms depending on the specific isotype and ligand and on the differentiated, undifferentiated, or transformed status of the cell. Differentiation stimuli are integrated by key transcription factors which regulate specific sets of specialized genes to allow proliferative cells to exit the cell cycle and acquire specialized functions. The main differentiation programs known to be controlled by PPARs both during development and in the adult are placental differentiation, adipogenesis, osteoblast differentiation, skin differentiation, and gut differentiation. PPARs may also be involved in the differentiation of macrophages, brain, and breast. However, their functions in this cell type and organs still awaits further elucidation. PPARs may be involved in cell proliferation and differentiation processes of neural stem cells (NSC. To this aim, in this work the expression of the three PPAR isotypes and RXRs in NSC has been investigated.

  1. Lung Stem cell biology

    OpenAIRE

    Ardhanareeswaran, Karthikeyan; Mirotsou, Maria

    2013-01-01

    Over the past few years new insights have been added to the study of stem cells in the adult lung. The exploration of the endogenous lung progenitors as well as the study of exogenously delivered stem cell populations holds promise for advancing our understanding of the biology of lung repair mechanisms. Moreover, it opens new possibilities for the use of stem cell therapy for the development of regenerative medicine approaches for the treatment of lung disease. Here, we discuss the main type...

  2. Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver

    OpenAIRE

    Huch, Meritxell; Gehart, Helmuth; van Boxtel, Ruben; Hamer, Karien; Blokzijl, Francis; Verstegen, Monique M.A.; Ellis, Ewa; van Wenum, Martien; Fuchs, Sabine A.; de Ligt, Joep; van de Wetering, Marc; SASAKI, Nobuo; Boers, Susanne J.; Kemperman, Hans; de Jonge, Jeroen

    2015-01-01

    Summary Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human live...

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

    Institute of Scientific and Technical Information of China (English)

    Tomoko Kuwabara; Makoto Asashima

    2012-01-01

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

  4. Extensive neuronal differentiation of human neural stem cell grafts in adult rat spinal cord.

    Directory of Open Access Journals (Sweden)

    Jun Yan

    2007-02-01

    Full Text Available BACKGROUND: Effective treatments for degenerative and traumatic diseases of the nervous system are not currently available. The support or replacement of injured neurons with neural grafts, already an established approach in experimental therapeutics, has been recently invigorated with the addition of neural and embryonic stem-derived precursors as inexhaustible, self-propagating alternatives to fetal tissues. The adult spinal cord, i.e., the site of common devastating injuries and motor neuron disease, has been an especially challenging target for stem cell therapies. In most cases, neural stem cell (NSC transplants have shown either poor differentiation or a preferential choice of glial lineages. METHODS AND FINDINGS: In the present investigation, we grafted NSCs from human fetal spinal cord grown in monolayer into the lumbar cord of normal or injured adult nude rats and observed large-scale differentiation of these cells into neurons that formed axons and synapses and established extensive contacts with host motor neurons. Spinal cord microenvironment appeared to influence fate choice, with centrally located cells taking on a predominant neuronal path, and cells located under the pia membrane persisting as NSCs or presenting with astrocytic phenotypes. Slightly fewer than one-tenth of grafted neurons differentiated into oligodendrocytes. The presence of lesions increased the frequency of astrocytic phenotypes in the white matter. CONCLUSIONS: NSC grafts can show substantial neuronal differentiation in the normal and injured adult spinal cord with good potential of integration into host neural circuits. In view of recent similar findings from other laboratories, the extent of neuronal differentiation observed here disputes the notion of a spinal cord that is constitutively unfavorable to neuronal repair. Restoration of spinal cord circuitry in traumatic and degenerative diseases may be more realistic than previously thought, although major

  5. Characterization of neural stem cells and their progeny in the sensory circumventricular organs of adult mouse.

    Science.gov (United States)

    Furube, Eriko; Morita, Mitsuhiro; Miyata, Seiji

    2015-11-01

    Although evidence has accumulated that neurogenesis and gliogenesis occur in the subventricular zone (SVZ) and subgranular zone (SGZ) of adult mammalian brains, recent studies indicate the presence of neural stem cells (NSCs) in adult brains, particularly the circumventricular regions. In the present study, we aimed to determine characterization of NSCs and their progenitor cells in the sensory circumventricular organs (CVOs), including organum vasculosum of the lamina terminalis, subfornical organ, and area postrema of adult mouse. There were two types of NSCs: tanycyte-like ependymal cells and astrocyte-like cells. Astrocyte-like NSCs proliferated slowly and oligodendrocyte progenitor cells (OPCs) and neural progenitor cells (NPCs) actively divided. Molecular marker protein expression of NSCs and their progenitor cells were similar to those reported in the SVZ and SGZ, except that astrocyte-like NSCs expressed S100β. These circumventricular NSCs possessed the capacity to give rise to oligodendrocytes and sparse numbers of neurons and astrocytes in the sensory CVOs and adjacent brain regions. The inhibition of vascular endothelial growth factor (VEGF) signaling by using a VEGF receptor-associated tyrosine kinase inhibitor AZD2171 largely suppressed basal proliferation of OPCs. A single systemic administration of lipopolysaccharide attenuated proliferation of OPCs and induced remarkable proliferation of microglia. The present study indicates that sensory circumventricular NSCs provide new neurons and glial cells in the sensory CVOs and adjacent brain regions. PMID:25994374

  6. Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult haematopoietic stem cells.

    Science.gov (United States)

    Souilhol, Céline; Gonneau, Christèle; Lendinez, Javier G; Batsivari, Antoniana; Rybtsov, Stanislav; Wilson, Heather; Morgado-Palacin, Lucia; Hills, David; Taoudi, Samir; Antonchuk, Jennifer; Zhao, Suling; Medvinsky, Alexander

    2016-01-01

    During embryonic development, adult haematopoietic stem cells (HSCs) emerge preferentially in the ventral domain of the aorta in the aorta-gonad-mesonephros (AGM) region. Several signalling pathways such as Notch, Wnt, Shh and RA are implicated in this process, yet how these interact to regulate the emergence of HSCs has not previously been described in mammals. Using a combination of ex vivo and in vivo approaches, we report here that stage-specific reciprocal dorso-ventral inductive interactions and lateral input from the urogenital ridges are required to drive HSC development in the aorta. Our study strongly suggests that these inductive interactions in the AGM region are mediated by the interplay between spatially polarized signalling pathways. Specifically, Shh produced in the dorsal region of the AGM, stem cell factor in the ventral and lateral regions, and BMP inhibitory signals in the ventral tissue are integral parts of the regulatory system involved in the development of HSCs. PMID:26952187

  7. Promotion of Cortical Neurogenesis from the Neural Stem Cells in the Adult Mouse Subcallosal Zone.

    Science.gov (United States)

    Kim, Joo Yeon; Choi, Kyuhyun; Shaker, Mohammed R; Lee, Ju-Hyun; Lee, Boram; Lee, Eunsoo; Park, Jae-Yong; Lim, Mi-Sun; Park, Chang-Hwan; Shin, Ki Soon; Kim, Hyun; Geum, Dongho; Sun, Woong

    2016-04-01

    Neurogenesis occurs spontaneously in the subventricular zone (SVZ) of the lateral ventricle in adult rodent brain, but it has long been debated whether there is sufficient adult neurogenesis in human SVZ. Subcallosal zone (SCZ), a posterior continuum of SVZ closely associated with posterior regions of cortical white matter, has also been reported to contain adult neural stem cells (aNSCs) in both rodents and humans. However, little is known whether SCZ-derived aNSC (SCZ-aNSCs) can produce cortical neurons following brain injury. We found that SCZ-aNSCs exhibited limited neuronal differentiation potential in culture and after transplantation in mice. Neuroblasts derived from SCZ initially migrated toward injured cortex regions following brain injury, but later exhibited apoptosis. Overexpression of anti-apoptotic bcl-xL in the SCZ by retroviral infection rescued neuroblasts from cell death in the injured cortex, but neuronal maturation was still limited, resulting in atrophy. In combination with Bcl-xL, infusion of brain-derived neurotropic factor rescued atrophy, and importantly, a subset of such SCZ-aNSCs differentiated and attained morphological and physiological characteristics of mature, excitatory neurons. These results suggest that the combination of anti-apoptotic and neurotrophic factors might enable the use of aNSCs derived from the SCZ in cortical neurogenesis for neural replacement therapy. Stem Cells 2016;34:888-901. PMID:26701067

  8. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    OpenAIRE

    Kathrin Hemmer; Mingyue Zhang; Thea van Wüllen; Marna Sakalem; Natalia Tapia; Aidos Baumuratov; Christian Kaltschmidt; Barbara Kaltschmidt; Hans R. Schöler; Weiqi Zhang; Jens C. Schwamborn

    2014-01-01

    Summary Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear ...

  9. Insights from a Chimpanzee Adipose Stromal Cell Population: Opportunities for Adult Stem Cells to Expand Primate Functional Genomics

    OpenAIRE

    Pfefferle, Lisa W.; Wray, Gregory A.

    2013-01-01

    Comparisons between humans and chimpanzees are essential for understanding traits unique to each species. However, linking important phenotypic differences to underlying molecular changes is often challenging. The ability to generate, differentiate, and profile adult stem cells provides a powerful but underutilized opportunity to investigate the molecular basis for trait differences between species within specific cell types and in a controlled environment. Here, we characterize adipose strom...

  10. Single-cell in vivo imaging of adult neural stem cells in the zebrafish telencephalon.

    Science.gov (United States)

    Barbosa, Joana S; Di Giaimo, Rossella; Götz, Magdalena; Ninkovic, Jovica

    2016-08-01

    Adult neural stem cells (aNSCs) in zebrafish produce mature neurons throughout their entire life span in both the intact and regenerating brain. An understanding of the behavior of aNSCs in their intact niche and during regeneration in vivo should facilitate the identification of the molecular mechanisms controlling regeneration-specific cellular events. A greater understanding of the process in regeneration-competent species may enable regeneration to be achieved in regeneration-incompetent species, including humans. Here we describe a protocol for labeling and repetitive imaging of aNSCs in vivo. We label single aNSCs, allowing nonambiguous re-identification of single cells in repetitive imaging sessions using electroporation of a red-reporter plasmid in Tg(gfap:GFP)mi2001 transgenic fish expressing GFP in aNSCs. We image using two-photon microscopy through the thinned skull of anesthetized and immobilized fish. Our protocol allows imaging every 2 d for a period of up to 1 month. This methodology allowed the visualization of aNSC behavior in vivo in their natural niche, in contrast to previously available technologies, which rely on the imaging of either dissociated cells or tissue slices. We used this protocol to follow the mode of aNSC division, fate changes and cell death in both the intact and injured zebrafish telencephalon. This experimental setup can be widely used, with minimal prior experience, to assess key factors for processes that modulate aNSC behavior. A typical experiment with data analysis takes up to 1.5 months. PMID:27362338

  11. Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic retinopathy of mice

    Institute of Scientific and Technical Information of China (English)

    TIAN Bei; LI Xiao-xin; SHEN Li; ZHAO Min; YU Wen-zhen

    2010-01-01

    Background Hematopoietic stem cells (HSCs) can be used to deliver functionally active angiostatic molecules to the retinal vasculature by targeting active astrocytes and may be useful in targeting pre-angiogenic retinal lesions. We sought to determine whether HSC mobilization can ameliorate early diabetic retinopathy in mice.Methods Mice were devided into four groups: normal mice control group, normal mice HSC-mobilized group, diabetic mice control group and diabetic mice HSC mobilized group. Murine stem cell growth factor (murine SCF) and recombined human granulocyte colony stimulating factor (rhG-csf) were administered to the mice with diabetes and without diabetes for continuous 5 days to induce autologous HSCs mobilization, and subcutaneous injection of physiological saline was used as control. Immunohistochemical double staining was conducted with anti-mouse rat CD31 monoclonal antibody and anti-BrdU rat antibody.Results Marked HSCs clearly increased after SCF plus G-csf-mobilization. Non-mobilized diabetic mice showed more HSCs than normal mice (P=0.032), and peripheral blood significantly increased in both diabetic and normal mice (P=0.000).Diabetic mice showed more CD31 positive capillary vessels (P=0.000) and accelerated endothelial cell regeneration. Only diabetic HSC-mobilized mice expressed both BrdU and CD31 antigens in the endothelial cells of new capillaries.Conclusion Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic retinopathy of mice.

  12. Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver

    Science.gov (United States)

    Huch, Meritxell; Gehart, Helmuth; van Boxtel, Ruben; Hamer, Karien; Blokzijl, Francis; Verstegen, Monique M.A.; Ellis, Ewa; van Wenum, Martien; Fuchs, Sabine A.; de Ligt, Joep; van de Wetering, Marc; Sasaki, Nobuo; Boers, Susanne J.; Kemperman, Hans; de Jonge, Jeroen; Ijzermans, Jan N.M.; Nieuwenhuis, Edward E.S.; Hoekstra, Ruurdtje; Strom, Stephen; Vries, Robert R.G.; van der Laan, Luc J.W.; Cuppen, Edwin; Clevers, Hans

    2015-01-01

    Summary Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. The cells can readily be converted into functional hepatocytes in vitro and upon transplantation in vivo. Organoids from α1-antitrypsin deficiency and Alagille syndrome patients mirror the in vivo pathology. Clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy. PMID:25533785

  13. Biological character of human adipose-derived adult stem cells and influence of donor age on cell replication in culture.

    Science.gov (United States)

    Lei, Lei; Liao, WeiMing; Sheng, PuYi; Fu, Ming; He, AiShan; Huang, Gang

    2007-06-01

    To investigate the biological character of human adipose-derived adult stem cells (hADAS cells) when cultured in vitro and the relationship between hADAS cell's replication activity and the donor's age factor, and to assess the stem cells as a new source for tissue engineering. hADAS cells are isolated from human adipose tissue of different age groups (from adolescents to olds: 61 years old groups). The protein markers (CD29, CD34, CD44, CD45, CD49d, HLA-DR, CD106) of hADAS cells were detected by flow cytometry (FCM) to identify the stem cell, and the cell cycle was examined for P20 hADAS cells to evaluate the safety of the subculture in vitro. The generative activity of hADAS cells in different age groups was also examined by MTT method. The formula "TD = t x log2/logNt - logN0" was used to get the time doubling (TD) of the cells. The results showed that the cells kept heredity stabilization by chromosome analysis for at least 20 passages. The TD of these cells increased progressively by ageing, and the TD of the 61 years old group (statistical analysis of variance (ANOVA), P=0.002, PhADAS cells replication activity was found in the younger donators, and they represent novel and valuable seed cells for studies of tissue engineering.

  14. Heterochromatin protein 1 promotes self-renewal and triggers regenerative proliferation in adult stem cells.

    Science.gov (United States)

    Zeng, An; Li, Yong-Qin; Wang, Chen; Han, Xiao-Shuai; Li, Ge; Wang, Jian-Yong; Li, Dang-Sheng; Qin, Yong-Wen; Shi, Yufang; Brewer, Gary; Jing, Qing

    2013-04-29

    Adult stem cells (ASCs) capable of self-renewal and differentiation confer the potential of tissues to regenerate damaged parts. Epigenetic regulation is essential for driving cell fate decisions by rapidly and reversibly modulating gene expression programs. However, it remains unclear how epigenetic factors elicit ASC-driven regeneration. In this paper, we report that an RNA interference screen against 205 chromatin regulators identified 12 proteins essential for ASC function and regeneration in planarians. Surprisingly, the HP1-like protein SMED-HP1-1 (HP1-1) specifically marked self-renewing, pluripotent ASCs, and HP1-1 depletion abrogated self-renewal and promoted differentiation. Upon injury, HP1-1 expression increased and elicited increased ASC expression of Mcm5 through functional association with the FACT (facilitates chromatin transcription) complex, which consequently triggered proliferation of ASCs and initiated blastema formation. Our observations uncover an epigenetic network underlying ASC regulation in planarians and reveal that an HP1 protein is a key chromatin factor controlling stem cell function. These results provide important insights into how epigenetic mechanisms orchestrate stem cell responses during tissue regeneration. PMID:23629965

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

    Directory of Open Access Journals (Sweden)

    Bhonde RR

    2008-11-01

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

  16. Xenobiotic effects on intestinal stem cell proliferation in adult honey bee (Apis mellifera L) workers.

    Science.gov (United States)

    Forkpah, Cordelia; Dixon, Luke R; Fahrbach, Susan E; Rueppell, Olav

    2014-01-01

    The causes of the current global decline in honey bee health are unknown. One major group of hypotheses invokes the pesticides and other xenobiotics to which this important pollinator species is often exposed. Most studies have focused on mortality or behavioral deficiencies in exposed honey bees while neglecting other biological functions and target organs. The midgut epithelium of honey bees presents an important interface between the insect and its environment. It is maintained by proliferation of intestinal stem cells throughout the adult life of honey bees. We used caged honey bees to test multiple xenobiotics for effects on the replicative activity of the intestinal stem cells under laboratory conditions. Most of the tested compounds did not alter the replicative activity of intestinal stem cells. However, colchicine, methoxyfenozide, tetracycline, and a combination of coumaphos and tau-fluvalinate significantly affected proliferation rate. All substances except methoxyfenozide decreased proliferation rate. Thus, the results indicate that some xenobiotics frequently used in apiculture and known to accumulate in honey bee hives may have hitherto unknown physiological effects. The nutritional status and the susceptibility to pathogens of honey bees could be compromised by the impacts of xenobiotics on the maintenance of the midgut epithelium. This study contributes to a growing body of evidence that more comprehensive testing of xenobiotics may be required before novel or existing compounds can be considered safe for honey bees and other non-target species. PMID:24608542

  17. Xenobiotic effects on intestinal stem cell proliferation in adult honey bee (Apis mellifera L workers.

    Directory of Open Access Journals (Sweden)

    Cordelia Forkpah

    Full Text Available The causes of the current global decline in honey bee health are unknown. One major group of hypotheses invokes the pesticides and other xenobiotics to which this important pollinator species is often exposed. Most studies have focused on mortality or behavioral deficiencies in exposed honey bees while neglecting other biological functions and target organs. The midgut epithelium of honey bees presents an important interface between the insect and its environment. It is maintained by proliferation of intestinal stem cells throughout the adult life of honey bees. We used caged honey bees to test multiple xenobiotics for effects on the replicative activity of the intestinal stem cells under laboratory conditions. Most of the tested compounds did not alter the replicative activity of intestinal stem cells. However, colchicine, methoxyfenozide, tetracycline, and a combination of coumaphos and tau-fluvalinate significantly affected proliferation rate. All substances except methoxyfenozide decreased proliferation rate. Thus, the results indicate that some xenobiotics frequently used in apiculture and known to accumulate in honey bee hives may have hitherto unknown physiological effects. The nutritional status and the susceptibility to pathogens of honey bees could be compromised by the impacts of xenobiotics on the maintenance of the midgut epithelium. This study contributes to a growing body of evidence that more comprehensive testing of xenobiotics may be required before novel or existing compounds can be considered safe for honey bees and other non-target species.

  18. Xenobiotic effects on intestinal stem cell proliferation in adult honey bee (Apis mellifera L) workers.

    Science.gov (United States)

    Forkpah, Cordelia; Dixon, Luke R; Fahrbach, Susan E; Rueppell, Olav

    2014-01-01

    The causes of the current global decline in honey bee health are unknown. One major group of hypotheses invokes the pesticides and other xenobiotics to which this important pollinator species is often exposed. Most studies have focused on mortality or behavioral deficiencies in exposed honey bees while neglecting other biological functions and target organs. The midgut epithelium of honey bees presents an important interface between the insect and its environment. It is maintained by proliferation of intestinal stem cells throughout the adult life of honey bees. We used caged honey bees to test multiple xenobiotics for effects on the replicative activity of the intestinal stem cells under laboratory conditions. Most of the tested compounds did not alter the replicative activity of intestinal stem cells. However, colchicine, methoxyfenozide, tetracycline, and a combination of coumaphos and tau-fluvalinate significantly affected proliferation rate. All substances except methoxyfenozide decreased proliferation rate. Thus, the results indicate that some xenobiotics frequently used in apiculture and known to accumulate in honey bee hives may have hitherto unknown physiological effects. The nutritional status and the susceptibility to pathogens of honey bees could be compromised by the impacts of xenobiotics on the maintenance of the midgut epithelium. This study contributes to a growing body of evidence that more comprehensive testing of xenobiotics may be required before novel or existing compounds can be considered safe for honey bees and other non-target species.

  19. Learn About Stem Cells

    Science.gov (United States)

    ... PDF) Download an introduction to stem cells and stem cell research. Stem Cell Glossary Stem cell terms to know. ... ISSCR Get Involved Media © 2015 International Society for Stem Cell Research Terms of Use Disclaimer Privacy Policy

  20. Stem Cell Basics

    Science.gov (United States)

    ... Information Stem Cell Basics Stem Cell Basics: Introduction Stem Cell Information General Information Clinical Trials Funding Information Current Research Policy Glossary Site Map Stem Cell Basics Introduction: What are stem cells, and why ...

  1. A Comparison of Culture Characteristics between Human Amniotic Mesenchymal Stem Cells and Dental Stem Cells

    OpenAIRE

    Yusoff, Nurul Hidayat; Alshehadat, Saaid Ayesh; Azlina, Ahmad; Kannan, Thirumulu Ponnuraj; Hamid, Suzina Sheikh Abdul

    2015-01-01

    In the past decade, the field of stem cell biology is of major interest among researchers due to its broad therapeutic potential. Stem cells are a class of undifferentiated cells that are able to differentiate into specialised cell types. Stem cells can be classified into two main types: adult stem cells (adult tissues) and embryonic stem cells (embryos formed during the blastocyst phase of embryological development). This review will discuss two types of adult mesenchymal stem cells, dental ...

  2. Adrenomedullin as a Growth and Cell Fate Regulatory Factor for Adult Neural Stem Cells

    OpenAIRE

    Sonia Martínez-Herrero; Ignacio M Larráyoz; Laura Ochoa-Callejero; Josune García-Sanmartín; Alfredo Martínez

    2012-01-01

    The use of stem cells as a strategy for tissue repair and regeneration is one of the biomedical research areas that has attracted more interest in the past few years. Despite the classic belief that the central nervous system (CNS) was immutable, now it is well known that cell turnover occurs in the mature CNS. Postnatal neurogenesis is subjected to tight regulation by many growth factors, cell signals, and transcription factors. An emerging molecule involved in this process is adrenomedullin...

  3. LIF independent JAK signalling to chromatin in embryonic stem cells uncovered from an adult stem cell disease

    OpenAIRE

    Griffiths, Dean S.; Li, Juan; Dawson, Mark A.; Trotter, Matthew W B; Cheng, Yi-Han; Smith, Aileen M.; Mansfield, William; Liu, Pentao; Kouzarides, Tony; Nichols, Jennifer; Bannister, Andrew J; Green, Anthony R.; Göttgens, Berthold

    2010-01-01

    Activating mutations in the tyrosine kinase JAK2 cause myeloproliferative neoplasms, clonal blood stem cell disorders with a propensity for leukaemic transformation. LIF signalling through JAK-STAT enables ES cell self-renewal. Here we show that mouse ES cells carrying the human JAK2V617F mutation could self-renew in chemically defined conditions without cytokines or small molecule inhibitors independently of JAK signalling through STAT3 or PI3K pathways. Phosphorylation of histone H3Y41 by J...

  4. Prion replication occurs in endogenous adult neural stem cells and alters their neuronal fate: involvement of endogenous neural stem cells in prion diseases.

    Directory of Open Access Journals (Sweden)

    Aroa Relaño-Ginès

    Full Text Available Prion diseases are irreversible progressive neurodegenerative diseases, leading to severe incapacity and death. They are characterized in the brain by prion amyloid deposits, vacuolisation, astrocytosis, neuronal degeneration, and by cognitive, behavioural and physical impairments. There is no treatment for these disorders and stem cell therapy therefore represents an interesting new approach. Gains could not only result from the cell transplantation, but also from the stimulation of endogenous neural stem cells (NSC or by the combination of both approaches. However, the development of such strategies requires a detailed knowledge of the pathology, particularly concerning the status of the adult neurogenesis and endogenous NSC during the development of the disease. During the past decade, several studies have consistently shown that NSC reside in the adult mammalian central nervous system (CNS and that adult neurogenesis occurs throughout the adulthood in the subventricular zone of the lateral ventricle or the Dentate Gyrus of the hippocampus. Adult NSC are believed to constitute a reservoir for neuronal replacement during normal cell turnover or after brain injury. However, the activation of this system does not fully compensate the neuronal loss that occurs during neurodegenerative diseases and could even contribute to the disease progression. We investigated here the status of these cells during the development of prion disorders. We were able to show that NSC accumulate and replicate prions. Importantly, this resulted in the alteration of their neuronal fate which then represents a new pathologic event that might underlie the rapid progression of the disease.

  5. Strategies for Regenerating Striatal Neurons in the Adult Brain by Using Endogenous Neural Stem Cells

    Directory of Open Access Journals (Sweden)

    Kanako Nakaguchi

    2011-01-01

    Full Text Available Currently, there is no effective treatment for the marked neuronal loss caused by neurodegenerative diseases, such as Huntington's disease (HD or ischemic stroke. However, recent studies have shown that new neurons are continuously generated by endogenous neural stem cells in the subventricular zone (SVZ of the adult mammalian brain, including the human brain. Because some of these new neurons migrate to the injured striatum and differentiate into mature neurons, such new neurons may be able to replace degenerated neurons and improve or repair neurological deficits. To establish a neuroregenerative therapy using this endogenous system, endogenous regulatory mechanisms that can be co-opted for efficient regenerative interventions must be understood, along with any potential drawbacks. Here, we review current knowledge on the generation of new neurons in the adult brain and discuss their potential for use in replacing striatal neurons lost to neurodegenerative diseases, including HD, and to ischemic stroke.

  6. A genetic platform to model sarcomagenesis from primary adult mesenchymal stem cells

    Science.gov (United States)

    Guarnerio, Jlenia; Riccardi, Luisa; Taulli, Riccardo; Maeda, Takahiro; Wang, Guocan; Hobbs, Robin M.; Song, Min Sup; Sportoletti, Paolo; Bernardi, Rosa; Bronson, Roderick T.; Castillo-Martin, Mireia; Cordon-Cardo, Carlos; Lunardi, Andrea; Pandolfi, Pier Paolo

    2015-01-01

    The regulatory factors governing adult mesenchymal stem cells (MSCs) physiology and their tumorigenic potential are still largely unknown, which substantially delays the identification of effective therapeutic approaches for the treatment of aggressive and lethal form of MSC-derived mesenchymal tumors, such as undifferentiated sarcomas. Here we have developed a novel platform to screen and quickly identify genes and pathways responsible for adult MSCs transformation, modeled undifferentiated sarcoma in vivo, and, ultimately, tested the efficacy of targeting the identified oncopathways. Importantly, by taking advantage of this new platform, we demonstrate the key role of an aberrant LRF-DLK1-SOX9 pathway in the pathogenesis of undifferentiated sarcoma with important therapeutic implications. PMID:25614485

  7. Comparison of biological characteristics of marrow mesenchymal stem cells in hepatitis B patients and normal adults

    Institute of Scientific and Technical Information of China (English)

    Liang Peng; Hua Li; Lin Gu; Xiao-Mou Peng; Yang-Su Huang; Zhi-Liang Gao

    2007-01-01

    AIM: To establish a culture system of marrow mesenchymal stem cells (MSCs) from hepatitis B patients and normal adults and to compare their biological characteristics.METHODS: MSCs were isolated from bone marrow in 34 male hepatitis B patients and 15 male normal adults and cultivated in vitro. Their biological characteristics including surface markers, shapes and appearances, growth curves, first passage time and passage generations were compared.RESULTS: Cultivation achievement ratio of hepatitis B patients was lower than that of normal adults, no statistical significance (82.35% vs 100%, P >0.05). Compared with MSCs of normal adults, MSCs of hepatitis B patients presented a statistical lower growth curve, longer first passage time (13.0 ± 1.6 d vs 11.4 ± 1.5 d, P < 0.05), fewer passaging generation numbers (10.5 ± 1.4 generations vs 12.3±1.7 generations, P < 0.05), though both shared same appearances, shapes and surface markers. MSCs in hepatitis B patients would expand, spread out and age more easily and there were more refractive particles in the cytoplasm.CONCLUSION: MSCs from hepatitis B patients can be cultured in vitro. Although their appearance, shape and surface marker are similar to those of MSCs from normal adults, there are differences in their biological characteristics.

  8. Fragile x mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Yuping Luo

    2010-04-01

    Full Text Available Fragile X syndrome (FXS, the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP. FMRP is an RNA-binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs. We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3beta. Dysregulation of GSK3beta led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis.

  9. Mediation of autophagic cell death by type 3 ryanodine receptor (RyR3 in adult hippocampal neural stem cells

    Directory of Open Access Journals (Sweden)

    Kyung Min eChung

    2016-05-01

    Full Text Available Cytoplasmic Ca2+ actively engages in diverse intracellular processes from protein synthesis, folding and trafficking to cell survival and death. Dysregulation of intracellular Ca2+ levels is observed in various neuropathological states including Alzheimer’s and Parkinson’s diseases. Ryanodine receptors (RyRs and IP3 receptors (IP3Rs, the main Ca2+ release channels located in endoplasmic reticulum (ER membranes, are known to direct various cellular events such as autophagy and apoptosis. Here we investigated the intracellular Ca2+-mediated regulation of survival and death of adult hippocampal neural stem (HCN cells utilizing an insulin withdrawal model of autophagic cell death. Despite comparable expression levels of RyR and IP3R transcripts in HCN cells at normal state, the expression levels of RyRs — especially RyR3 — were markedly upregulated upon insulin withdrawal. While treatment with the RyR agonist caffeine significantly promoted the autophagic death of insulin-deficient HCN cells, treatment with its inhibitor dantrolene prevented the induction of autophagy following insulin withdrawal. Furthermore, CRISPR/Cas9-mediated knockout of the RyR3 gene abolished autophagic cell death of HCN cells. This study delineates a distinct, RyR3-mediated ER Ca2+ regulation of autophagy and programmed cell death in neural stem cells. Our findings provide novel insights into the critical, yet understudied mechanisms underlying the regulatory function of ER Ca2+ in neural stem cell biology.

  10. Energy metabolism and energy-sensing pathways in mammalian embryonic and adult stem cell fate

    OpenAIRE

    Rafalski, Victoria A.; Mancini, Elena; Brunet, Anne

    2012-01-01

    Metabolism is influenced by age, food intake, and conditions such as diabetes and obesity. How do physiological or pathological metabolic changes influence stem cells, which are crucial for tissue homeostasis? This Commentary reviews recent evidence that stem cells have different metabolic demands than differentiated cells, and that the molecular mechanisms that control stem cell self-renewal and differentiation are functionally connected to the metabolic state of the cell and the surrounding...

  11. Adult neural stem cell behavior underlying constitutive and restorative neurogenesis in zebrafish.

    Science.gov (United States)

    Barbosa, Joana S; Ninkovic, Jovica

    2016-01-01

    Adult Neural Stem Cells (aNSCs) generate new neurons that integrate into the pre-existing networks in specific locations of the Vertebrate brain. Moreover, aNSCs contribute with new neurons to brain regeneration in some non-mammalian Vertebrates. The similarities and the differences in the cellular and molecular processes governing neurogenesis in the intact and regenerating brain are still to be assessed. Toward this end, we recently established a protocol for non-invasive imaging of aNSC behavior in their niche in vivo in the adult intact and regenerating zebrafish telencephalon. We observed different modes of aNSC division in the intact brain and a novel mode of neurogenesis by direct conversion, which contributes to stem cell depletion with age. After injury, the generation of neurons is increased both by the activation of additional aNSCs and a shift in the division mode of aNSCs, thereby contributing to the successful neuronal regeneration. The cellular behavior we observed opens new questions regarding long-term aNSC maintenance in homeostasis and in regeneration. In this commentary we discuss our data and new questions arising in the context of aNSC behavior, not only in zebrafish but also in other species, including mammals. PMID:27606336

  12. Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model.

    Directory of Open Access Journals (Sweden)

    Chinedu C Ude

    Full Text Available OBJECTIVES: In this study, Adipose stem cells (ADSC and bone marrow stem cells (BMSC, multipotent adult cells with the potentials for cartilage regenerations were induced to chondrogenic lineage and used for cartilage regenerations in surgically induced osteoarthritis in sheep model. METHODS: Osteoarthritis was induced at the right knee of sheep by complete resection of the anterior cruciate ligament and medial meniscus following a 3-weeks exercise regimen. Stem cells from experimental sheep were culture expanded and induced to chondrogenic lineage. Test sheep received a single dose of 2 × 10(7 autologous PKH26-labelled, chondrogenically induced ADSCs or BMSCs as 5 mls injection, while controls received 5 mls culture medium. RESULTS: The proliferation rate of ADSCs 34.4 ± 1.6 hr was significantly higher than that of the BMSCs 48.8 ± 5.3 hr (P = 0.008. Chondrogenic induced BMSCs had significantly higher expressions of chondrogenic specific genes (Collagen II, SOX9 and Aggrecan compared to chondrogenic ADSCs (P = 0.031, 0.010 and 0.013. Grossly, the treated knee joints showed regenerated de novo cartilages within 6 weeks post-treatment. On the International Cartilage Repair Society grade scores, chondrogenically induced ADSCs and BMSCs groups had significantly lower scores than controls (P = 0.0001 and 0.0001. Fluorescence of the tracking dye (PKH26 in the injected cells showed that they had populated the damaged area of cartilage. Histological staining revealed loosely packed matrixes of de novo cartilages and immunostaining demonstrated the presence of cartilage specific proteins, Collagen II and SOX9. CONCLUSION: Autologous chondrogenically induced ADSCs and BMSCs could be promising cell sources for cartilage regeneration in osteoarthritis.

  13. Adult stem cells in mice : visualization and characterization using genetic mouse models

    NARCIS (Netherlands)

    Snippert, H.J.G.

    2011-01-01

    The onset of each living organism starts with pluripotent stem cells that have the ability to differentiate into all the different cell types of an organism. However, during the earliest stages of development, the pluripotent stem cells will stepwise lose their developmental potential. The cells tha

  14. From fetus towards adult : maturation and functional analysis of pluripotent stem cell-derived cardiomyocytes

    NARCIS (Netherlands)

    Catarino, Ribeiro M.

    2016-01-01

    This thesis describes research about the differentiation of human stem cells into cardiomyocytes (heart cells). During the differentiation process the stem cells become contractile myocytes that resemble the native heart cells. Nevertheless, the phenotype of these cardiomyocytes is comparable to a s

  15. Isolation and Assessment of Single Long-Term Reconstituting Hematopoietic Stem Cells from Adult Mouse Bone Marrow.

    Science.gov (United States)

    Kent, David G; Dykstra, Brad J; Eaves, Connie J

    2016-01-01

    Hematopoietic stem cells with long-term repopulating activity can now be routinely obtained at purities of 40% to 50% from suspensions of adult mouse bone marrow. Here we describe robust protocols for both their isolation as CD45(+) EPCR(+) CD150(+) CD48(-) (ESLAM) cells using multiparameter cell sorting and for tracking their clonal growth and differentiation activity in irradiated mice transplanted with single ESLAM cells. The simplicity of these procedures makes them attractive for characterizing the molecular and biological properties of individual hematopoietic stem cells with unprecedented power and precision. © 2016 by John Wiley & Sons, Inc. PMID:27532815

  16. Biological character of human adipose-derived adult stem cells and influence of donor age on cell replication in culture

    Institute of Scientific and Technical Information of China (English)

    LEI Lei; LIAO WeiMing; SHENG PuYi; FU Ming; HE AiShan; HUANG Gang

    2007-01-01

    To investigate the biological character of human adipose-derived adult stem cells (hADAS cells) when cultured in vitro and the relationship between hADAS cell's replication activity and the donor's age factor, and to assess the stem cells as a new source for tissue engineering, hADAS cells are isolated from human adipose tissue of different age groups (from adolescents to olds: <20 years old, 21-40years old, 41-60 years old and >61 years old groups). The protein markers (CD29, CD34, CD44, CD45,CD49d, HLA-DR, CD106) of hADAS cells were detected by flow cytometry (FCM) to identify the stem cell,and the cell cycle was examined for P20 hADAS cells to evaluate the safety of the subculture in vitro.The generative activity of hADAS cells in different age groups was also examined by MTT method. The formula "TD = t log2/logNt - logN0 "was used to get the time doubling (TD) of the cells. The results showed that the cells kept heredity stabilization by chromosome analysis for at least 20 passages. The TD of these cells increased progressively by ageing, and the TD of the <20 years old group was lower than that of the >61 years old group (statistical analysis of variance (ANOVA), P=-0.002, P<0.05). These findings suggested that a higher level of hADAS cells replication activity was found in the younger donators, and they represent novel and valuable seed cells for studies of tissue engineering.

  17. Mesenchymal stem cells.

    Science.gov (United States)

    Ding, Dah-Ching; Shyu, Woei-Cherng; Lin, Shinn-Zong

    2011-01-01

    Stem cells have two features: the ability to differentiate along different lineages and the ability of self-renewal. Two major types of stem cells have been described, namely, embryonic stem cells and adult stem cells. Embryonic stem cells (ESC) are obtained from the inner cell mass of the blastocyst and are associated with tumorigenesis, and the use of human ESCs involves ethical and legal considerations. The use of adult mesenchymal stem cells is less problematic with regard to these issues. Mesenchymal stem cells (MSCs) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as umbilical cord, endometrial polyps, menses blood, bone marrow, adipose tissue, etc. This is because the ease of harvest and quantity obtained make these sources most practical for experimental and possible clinical applications. Recently, MSCs have been found in new sources, such as menstrual blood and endometrium. There are likely more sources of MSCs waiting to be discovered, and MSCs may be a good candidate for future experimental or clinical applications. One of the major challenges is to elucidate the mechanisms of differentiation, mobilization, and homing of MSCs, which are highly complex. The multipotent properties of MSCs make them an attractive choice for possible development of clinical applications. Future studies should explore the role of MSCs in differentiation, transplantation, and immune response in various diseases. PMID:21396235

  18. Is there any reason to prefer cord blood instead of adult donors for hematopoietic stem cell transplants?

    Directory of Open Access Journals (Sweden)

    Meral eBeksac

    2016-01-01

    Full Text Available As cord blood (CB enables rapid access and tolerance to HLA mismatches, number of unrelated cord blood transplants have reached 30 000. Such transplant activity has been the result of international accreditation programs maintaining highly qualified CBUs reaching more than 600 000 CBUs stored worldwide. Efforts to increase stem cell content or engraftment rate of the graft by ex vivo expansion, modulation by molecules such as fucose, Prostaglandin E2 derivative, complement, CD26 inhibitors or CXCR4/CXCL12 axis have been able to accelerate engraftment speed and rate. Furthermore introduction of reduced intensity conditioning protocols, better HLA matching and recognition of the importance of HLA-C have improved CBT success by decreasing Transplant Related Mortality (TRM. Cord blood progenitor/stem cell content has been compared with adult stem cells revealing higher long-term repopulating capacity compared to BM-MSC and less oncogenic potential than Induced Progenitor Stem Cells. This chapter summarizes the advantage and disadvantages of CB compared to adult stem cells within the context of stem cell biology and transplantation.

  19. Biological character of human adipose-derived adult stem cells and influence of donor age on cell replication in culture

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To investigate the biological character of human adipose-derived adult stem cells (hADAS cells) when cultured in vitro and the relationship between hADAS cell’s replication activity and the donor’s age factor, and to assess the stem cells as a new source for tissue engineering. hADAS cells are isolated from human adipose tissue of different age groups (from adolescents to olds: <20 years old, 21―40 years old, 41―60 years old and >61 years old groups). The protein markers (CD29, CD34, CD44, CD45, CD49d, HLA-DR, CD106) of hADAS cells were detected by flow cytometry (FCM) to identify the stem cell, and the cell cycle was examined for P20 hADAS cells to evaluate the safety of the subculture in vitro. The generative activity of hADAS cells in different age groups was also examined by MTT method. The formula “ log2T D = t logN t ? logN 0” was used to get the time doubling (TD) of the cells. The results showed that the cells kept heredity stabilization by chromosome analysis for at least 20 passages. The TD of these cells increased progressively by ageing, and the TD of the <20 years old group was lower than that of the >61 years old group (statistical analysis of variance (ANOVA), P=0.002, P<0.05). These find- ings suggested that a higher level of hADAS cells replication activity was found in the younger dona- tors, and they represent novel and valuable seed cells for studies of tissue engineering.

  20. Expression Profile of microRNAs Regulating Proliferation and Differentiation in Mouse Adult Cardiac Stem Cells

    OpenAIRE

    Brás-Rosário, Luis; Matsuda, Alex; Pinheiro, Ana Isabel; Gardner, Rui; Lopes, Telma; Amaral, Andreia; Gama-Carvalho, Margarida

    2013-01-01

    The identification of cardiac cells with stem cell properties changed the paradigm of the heart as a post mitotic organ. These cells proliferate and differentiate into cardiomyocytes, endothelial and vascular smooth muscle cells, providing for cardiac cell homeostasis and regeneration. microRNAs are master switches controlling proliferation and differentiation, in particular regulating stem cell biology and cardiac development. Modulation of microRNAs -regulated gene expression networks holds...

  1. Autonomous isolation, long-term culture and differentiation potential of adult salivary gland-derived stem/progenitor cells.

    Science.gov (United States)

    Baek, Hyunjung; Noh, Yoo Hun; Lee, Joo Hee; Yeon, Soo-In; Jeong, Jaemin; Kwon, Heechung

    2014-09-01

    Salivary gland stem/progenitor cells belong to the endodermal lineage and may serve as good candidates to replace their dysfunctional counterparts. The objective of this study was to isolate large numbers of salivary gland tissue-derived stem cells (SGSCs) from adult rats in order to develop a clinically applicable method that does not involve sorting or stem cell induction by duct ligation. We analysed SGSCs isolated from normal rat salivary glands to determine whether they retained the major characteristics of stem cells, self-renewal and multipotency, especially with respect to the various endodermal cell types. SGSCs expressed high levels of integrin α6β1 and c-kit, which are surface markers of SGSCs. In particular, the integrin α6β1(+) /c-kit(+) salivary gland cells maintained the morphology, proliferation activity and multipotency of stem cells for up to 92 passages in 12 months. Furthermore, we analysed the capacity of SGSCs to differentiate into endoderm lineage cell types, such as acinar-like and insulin-secreting cells. When cultured on growth factor reduced matrigel, the morphology of progenitor cells changed to acinar-like structures and these cells expressed the acinar cell-specific marker, α-amylase, and tight junction markers. Moreover, reverse transcription-polymerase chain reaction (RT-PCR) data showed increased expression of pancreatic cell markers, including insulin, Pdx1, pan polypeptide and neurogenin-3, when these cells formed pancreatic clusters in the presence of activin A, exendin-4 and retinoic acid. These data demonstrate that adult salivary stem/progenitor cells may serve as a potential source for cell therapy in salivary gland hypofunction and diabetes.

  2. 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...

  3. Expression Profiling of Intestinal Tissues Implicates Tissue-Specific Genes and Pathways Essential for Thyroid Hormone-Induced Adult Stem Cell Development

    OpenAIRE

    Sun, Guihong; Heimeier, Rachel A; Fu, Liezhen; Hasebe, Takashi; Das, Biswajit; Ishizuya-Oka, Atsuko; Shi, Yun-Bo

    2013-01-01

    The study of the epithelium during development in the vertebrate intestine touches upon many contemporary aspects of biology: to name a few, the formation of the adult stem cells (ASCs) essential for the life-long self-renewal and the balance of stem cell activity for renewal vs cancer development. Although extensive analyses have been carried out on the property and functions of the adult intestinal stem cells in mammals, little is known about their formation during development due to the di...

  4. Liver Cancer Stem Cells

    OpenAIRE

    Sameh Mikhail; Aiwu Ruth He

    2011-01-01

    Hepatocellular carcinoma is the most common primary malignancy of the liver in adults. It is also the fifth most common solid cancer worldwide and the third leading cause of cancer-related death. Recent research supports that liver cancer is a disease of adult stem cells. From the models of experimental hepatocarcinogenesis, there may be at least three distinct cell lineages with progenitor properties susceptible to neoplastic transformation. Identification of specific cell surface markers fo...

  5. Impact of electromagnetic fields on stem cells: common mechanisms at the crossroad between adult neurogenesis and osteogenesis

    Directory of Open Access Journals (Sweden)

    Lucia eLeone

    2015-06-01

    Full Text Available In the recent years adult neural and mesenchymal stem cells have been intensively investigated as effective resources for repair therapies.In vivo and in vitro studies have provided insights on the molecular mechanisms underlying the neurogenic and osteogenic processes in adulthood. This knowledge appears fundamental for the development of targeted strategies to manipulate stem cells.Here we review recent literature dealing with the effects of electromagnetic fields on stem cell biology that lends support to their use as promising tool to positively influence the different steps of neurogenic and osteogenic processes.We will focus on recent studies revealing that extremely-low frequency electromagnetic fields enhance adult hippocampal neurogenesis by inducing epigenetic modifications on the regulatory sequences of genes responsible for neural stem cell proliferation and neuronal differentiation.In light of the emerging critical role played by chromatin modifications in maintaining the stemness as well as in regulating stem cell differentiation, we will also attempt to exploit epigenetic changes that can represent common targets for electromagnetic field effects on neurogenic and osteogenic processes.

  6. Clinical trial perspective for adult and juvenile Huntington's disease using genetically-engineered mesenchymal stem cells.

    Science.gov (United States)

    Deng, Peter; Torrest, Audrey; Pollock, Kari; Dahlenburg, Heather; Annett, Geralyn; Nolta, Jan A; Fink, Kyle D

    2016-05-01

    Progress to date from our group and others indicate that using genetically-engineered mesenchymal stem cells (MSC) to secrete brain-derived neurotrophic factor (BDNF) supports our plan to submit an Investigational New Drug application to the Food and Drug Administration for the future planned Phase 1 safety and tolerability trial of MSC/BDNF in patients with Huntington's disease (HD). There are also potential applications of this approach beyond HD. Our biological delivery system for BDNF sets the precedent for adult stem cell therapy in the brain and could potentially be modified for other neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), Alzheimer's disease, and some forms of Parkinson's disease. The MSC/BDNF product could also be considered for studies of regeneration in traumatic brain injury, spinal cord and peripheral nerve injury. This work also provides a platform for our future gene editing studies, since we will again use MSCs to deliver the needed molecules into the central nervous system.

  7. Clinical trial perspective for adult and juvenile Huntington's disease using genetically-engineered mesenchymal stem cells.

    Science.gov (United States)

    Deng, Peter; Torrest, Audrey; Pollock, Kari; Dahlenburg, Heather; Annett, Geralyn; Nolta, Jan A; Fink, Kyle D

    2016-05-01

    Progress to date from our group and others indicate that using genetically-engineered mesenchymal stem cells (MSC) to secrete brain-derived neurotrophic factor (BDNF) supports our plan to submit an Investigational New Drug application to the Food and Drug Administration for the future planned Phase 1 safety and tolerability trial of MSC/BDNF in patients with Huntington's disease (HD). There are also potential applications of this approach beyond HD. Our biological delivery system for BDNF sets the precedent for adult stem cell therapy in the brain and could potentially be modified for other neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), Alzheimer's disease, and some forms of Parkinson's disease. The MSC/BDNF product could also be considered for studies of regeneration in traumatic brain injury, spinal cord and peripheral nerve injury. This work also provides a platform for our future gene editing studies, since we will again use MSCs to deliver the needed molecules into the central nervous system. PMID:27335539

  8. 3D culture of adult mouse neural stem cells within functionalized self-assembling peptide scaffolds

    Directory of Open Access Journals (Sweden)

    Cunha C

    2011-05-01

    Full Text Available Carla Cunha1,2, Silvia Panseri3,4, Omar Villa1,2, Diego Silva1,2, Fabrizio Gelain1,21Department of Biotechnology and Biosciences, University of Milano-Bicocca; 2Center for Nanomedicine and Tissue Engineering, CNTE – A.O. Ospedale Niguarda Ca' Granda, Milan; 3Laboratory of Biomechanics and Technology Innovation, Rizzoli Orthopaedic Institute, Bologna; 4Laboratory of Nano-Biomagnetism, Institute of Science and Technology for Ceramics, National Research Council, Faenza, ItalyAbstract: Three-dimensional (3D in vitro models of cell culture aim to fill the gap between the standard two-dimensional cell studies and the in vivo environment. Especially for neural tissue regeneration approaches where there is little regenerative capacity, these models are important for mimicking the extracellular matrix in providing support, allowing the natural flow of oxygen, nutrients, and growth factors, and possibly favoring neural cell regrowth. We have previously demonstrated that a new self-assembling nanostructured biomaterial, based on matrigel, was able to support adult neural stem cell (NSC culture. In this study, we developed a new 3D cell culture system that takes advantage of the nano- and microfiber assembling process, under physiologic conditions, of these biomaterials. The assembled scaffold forms an intricate and biologically active matrix that displays specifically designed functional motifs: RGD (Arg-Gly-Asp, BMHP1 (bone marrow homing peptide 1, and BMHP2, for the culture of adult NSCs. These scaffolds were prepared at different concentrations, and microscopic examination of the cell-embedded scaffolds showed that NSCs are viable and they proliferate and differentiate within the nanostructured environment of the scaffold. Such a model has the potential to be tailored to develop ad hoc designed peptides for specific cell lines.Keywords: biomaterials, tissue engineering, 3D in vitro model

  9. The transcriptional coactivator Cbp regulates self-renewal and differentiation in adult hematopoietic stem cells.

    Science.gov (United States)

    Chan, Wai-In; Hannah, Rebecca L; Dawson, Mark A; Pridans, Clare; Foster, Donna; Joshi, Anagha; Göttgens, Berthold; Van Deursen, Jan M; Huntly, Brian J P

    2011-12-01

    The transcriptional coactivator Cbp plays an important role in a wide range of cellular processes, including proliferation, differentiation, and apoptosis. Although studies have shown its requirement for hematopoietic stem cell (HSC) development, its role in adult HSC maintenance, as well as the cellular and molecular mechanisms underlying Cbp function, is not clear. Here, we demonstrate a gradual loss of phenotypic HSCs and differentiation defects following conditional ablation of Cbp during adult homeostasis. In addition, Cbp-deficient HSCs reconstituted hematopoiesis with lower efficiency than their wild-type counterparts, and this response was readily exhausted under replicative stress. This phenotype relates to an alteration in cellular fate decisions for HSCs, with Cbp loss leading to an increase in differentiation, quiescence, and apoptosis. Genome-wide analyses of Cbp occupancy and differential gene expression upon Cbp deletion identified HSC-specific genes regulated by Cbp, providing a molecular basis for the phenotype. Finally, Cbp binding significantly overlapped at genes combinatorially bound by 7 major hematopoietic transcriptional regulators, linking Cbp to a critical HSC transcriptional regulatory network. Our data demonstrate that Cbp plays a role in adult HSC homeostasis by maintaining the balance between different HSC fate decisions, and our findings identify a putative HSC-specific transcriptional network coordinated by Cbp.

  10. Laser biomodulation on stem cells

    Science.gov (United States)

    Liu, Timon C.; Duan, Rui; Li, Yan; Li, Xue-Feng; Tan, Li-Ling; Liu, Songhao

    2001-08-01

    Stem cells are views from the perspectives of their function, evolution, development, and cause. Counterintuitively, most stem cells may arise late in development, to act principally in tissue renewal, thus ensuring an organisms long-term survival. Surprisingly, recent reports suggest that tissue-specific adult stem cells have the potential to contribute to replenishment of multiple adult tissues. Stem cells are currently in the news for two reasons: the successful cultivation of human embryonic stem cell lines and reports that adult stem cells can differentiate into developmentally unrelated cell types, such as nerve cells into blood cells. The spotlight on stem cells has revealed gaps in our knowledge that must be filled if we are to take advantage of their full potential for treating devastating degenerative diseases such as Parkinsons's disease and muscular dystrophy. We need to know more about the intrinsic controls that keep stem cells as stem cells or direct them along particular differentiation pathways. Such intrinsic regulators are, in turn, sensitive to the influences of the microenvironment, or niche, where stem cells normally reside. Both intrinsic and extrinsic signals regular stem cell fate and some of these signals have now been identified. Vacek et al and Wang et al have studied the effect of low intensity laser on the haemopoietic stem cells in vitro. There experiments show there is indeed the effect of low intensity laser on the haemopoietic stem cells in vitro, and the present effect is the promotion of haemopoietic stem cells proliferation. In other words, low intensity laser irradiation can act as an extrinsic signal regulating stem cell fate. In this paper, we study how low intensity laser can be used to regulate stem cell fate from the viewpoint of collective phototransduction.

  11. Lineage tracing in the adult mouse corneal epithelium supports the limbal epithelial stem cell hypothesis with intermittent periods of stem cell quiescence

    Directory of Open Access Journals (Sweden)

    Natalie J. Dorà

    2015-11-01

    Full Text Available The limbal epithelial stem cell (LESC hypothesis proposes that LESCs in the corneal limbus maintain the corneal epithelium both during normal homeostasis and wound repair. The alternative corneal epithelial stem cell (CESC hypothesis proposes that LESCs are only involved in wound repair and CESCs in the corneal epithelium itself maintain the corneal epithelium during normal homeostasis. We used tamoxifen-inducible, CreER-loxP lineage tracing to distinguish between these hypotheses. Clones of labelled cells were induced in adult CAGG-CreER;R26R-LacZ reporter mice and their distributions analysed after different chase periods. Short-lived clones, derived from labelled transient amplifying cells, were shed during the chase period and long-lived clones, derived from stem cells, expanded. At 6 weeks, labelled clones appeared at the periphery, extended centripetally as radial stripes and a few reached the centre by 14 weeks. Stripe numbers depended on the age of tamoxifen treatment. Stripes varied in length, some were discontinuous, few reached the centre and almost half had one end at the limbus. Similar stripes extended across the cornea in CAGG-CreER;R26R-mT/mG reporter mice. The distributions of labelled clones are inconsistent with the CESC hypothesis and support the LESC hypothesis if LESCs cycle between phases of activity and quiescence, each lasting several weeks.

  12. Cell Therapy for Diabetic Neuropathy Using Adult Stem or Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Ji Woong Han

    2013-04-01

    Full Text Available Diabetic neuropathy (DN is the most common and disabling complication of diabetes that may lead to foot ulcers and limb amputations. Despite widespread awareness of DN, the only effective treatments are glucose control and pain management. A growing body of evidence suggests that DN is characterized by reduction of vascularity in peripheral nerves and deficiency in neurotrophic and angiogenic factors. Previous studies have tried to introduce neurotrophic or angiogenic factors in the form of protein or gene for therapy, but the effect was not significant. Recent studies have shown that bone marrow (BM-derived stem or progenitor cells have favorable effects on the repair of cardiovascular diseases. Since these BM-derived stem or progenitor cells contain various angiogenic and neurotrophic factors, these cells have been attempted for treating experimental DN, and turned out to be effective for reversing various manifestations of experimental DN. These evidences suggest that cell therapy, affecting both vascular and neural components, can represent a novel therapeutic option for treatment of clinical DN.

  13. Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma

    NARCIS (Netherlands)

    G. van Imhoff (Gustaaf); B. van der Holt (Bronno); M.A. MacKenzie (Marius); G.J. Ossenkoppele (Gert); P.W. Wijermans (Pierre); M.H.H. Kramer (Mark); M.B. van 't Veer (Mars); H. Schouten (Harry); M. van Marwijk Kooy (Marinus); M.H.J. van Oers (Marinus); J. Raemaekers; P. Sonneveld (Pieter); L.A.M.H. Meulendijks (L. A M H); P.M. Kluin; H.C. Kluin-Nelemans (H.); L.F. Verdonck (Leo)

    2005-01-01

    textabstractThe feasibility and efficacy of up-front high-dose sequential chemotherapy followed by autologous stem cell transplantation (ASCT) in previously untreated adults (median age 33 years; range 15-64) with Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL) or lymphoblastic lymphoma (LyLy), b

  14. Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma

    NARCIS (Netherlands)

    van Imhoff, GW; van der Holt, B; MacKenzie, MA; Ossenkoppele, GJ; Wijermans, PW; Kramer, MHH; van't Veer, MB; Schouten, HC; Kooy, MV; van Oers, MHJ; Raemaekers, JMM; Sonneveld, P; Meulendijks, LAMH; Kluin, PM; Kluin-Nelemans, HC; Verdonck, LF

    2005-01-01

    The feasibility and efficacy of up- front high- dose sequential chemotherapy followed by autologous stem cell transplantation ( ASCT) in previously untreated adults ( median age 33 years; range 15 - 64) with Burkitt lymphoma ( BL), Burkitt- like lymphoma ( BLL) or lymphoblastic lymphoma ( LyLy), bot

  15. Chondrogenic potential of human adult mesenchymal stem cells is independent of age or osteoarthritis etiology

    NARCIS (Netherlands)

    Scharstuhl, A.; Schewe, B.; Benz, K.; Gaissmaier, C.; Bühring, H.J.; Stoop, R.

    2007-01-01

    Osteoarthritis (OA) is a multifactorial disease strongly correlated with history of joint trauma, joint dysplasia, and advanced age. Mesenchymal stem cells (MSCs) are promising cells for biological cartilage regeneration. Conflicting data have been published concerning the availability of MSCs from

  16. The Therapeutic Effect of Human Adult Stem Cells Derived from Adipose Tissue in Endotoxemic Rat Model

    OpenAIRE

    Soyoung Shin, Yonggoo Kim, Sikyoung Jeong, Sungyoup Hong, Insoo Kim, Woonjeong Lee, Seungphil Choi

    2013-01-01

    Excessive systemic inflammation following sepsis, trauma or burn could lead to multi-organ damage and death. Bone marrow stromal cells (BMSCs), commonly referred to as mesenchymal stem cells (MSCs), has been studied in several immune-associated diseases in human and animal by modulating the inflammatory response. Adipose tissue derived mesenchymal stem cells (ATSCs), which can be obtained more easily, compared with BMSCs, has emerged as an attractive alternative MSCs source for cell therapy. ...

  17. The Therapeutic Effect of Human Adult Stem Cells Derived from Adipose Tissue in Endotoxemic Rat Model

    OpenAIRE

    Shin, Soyoung; Kim, Yonggoo; Jeong, Sikyoung; Hong, Sungyoup; Kim, Insoo; Lee, Woonjeong; Choi, Seungphil

    2012-01-01

    Excessive systemic inflammation following sepsis, trauma or burn could lead to multi-organ damage and death. Bone marrow stromal cells (BMSCs), commonly referred to as mesenchymal stem cells (MSCs), has been studied in several immune-associated diseases in human and animal by modulating the inflammatory response. Adipose tissue derived mesenchymal stem cells (ATSCs), which can be obtained more easily, compared with BMSCs, has emerged as an attractive alternative MSCs source for cell therapy. ...

  18. Therapeutic Strategies for Oxidative Stress-Related Cardiovascular Diseases: Removal of Excess Reactive Oxygen Species in Adult Stem Cells

    Directory of Open Access Journals (Sweden)

    Hyunyun Kim

    2016-01-01

    Full Text Available Accumulating evidence indicates that acute and chronic uncontrolled overproduction of oxidative stress-related factors including reactive oxygen species (ROS causes cardiovascular diseases (CVDs, atherosclerosis, and diabetes. Moreover ROS mediate various signaling pathways underlying vascular inflammation in ischemic tissues. With respect to stem cell-based therapy, several studies clearly indicate that modulating antioxidant production at cellular levels enhances stem/progenitor cell functionalities, including proliferation, long-term survival in ischemic tissues, and complete differentiation of transplanted cells into mature vascular cells. Recently emerging therapeutic strategies involving adult stem cells, including endothelial progenitor cells (EPCs, for treating ischemic CVDs have highlighted the need to control intracellular ROS production, because it critically affects the replicative senescence of ex vivo expanded therapeutic cells. Better understanding of the complexity of cellular ROS in stem cell biology might improve cell survival in ischemic tissues and enhance the regenerative potentials of transplanted stem/progenitor cells. In this review, we will discuss the nature and sources of ROS, drug-based therapeutic strategies for scavenging ROS, and EPC based therapeutic strategies for treating oxidative stress-related CVDs. Furthermore, we will discuss whether primed EPCs pretreated with natural ROS-scavenging compounds are crucial and promising therapeutic strategies for vascular repair.

  19. Adult Stem Cell as New Advanced Therapy for Experimental Neuropathic Pain Treatment

    Directory of Open Access Journals (Sweden)

    Silvia Franchi

    2014-01-01

    Full Text Available Neuropathic pain (NP is a highly invalidating disease resulting as consequence of a lesion or disease affecting the somatosensory system. All the pharmacological treatments today in use give a long lasting pain relief only in a limited percentage of patients before pain reappears making NP an incurable disease. New approaches are therefore needed and research is testing stem cell usage. Several papers have been written on experimental neuropathic pain treatment using stem cells of different origin and species to treat experimental NP. The original idea was based on the capacity of stem cell to offer a totipotent cellular source for replacing injured neural cells and for delivering trophic factors to lesion site; soon the researchers agreed that the capacity of stem cells to contrast NP was not dependent upon their regenerative effect but was mostly linked to a bidirectional interaction between the stem cell and damaged microenvironment resident cells. In this paper we review the preclinical studies produced in the last years assessing the effects induced by several stem cells in different models of neuropathic pain. The overall positive results obtained on pain remission by using stem cells that are safe, of easy isolation, and which may allow an autologous transplant in patients may be encouraging for moving from bench to bedside, although there are several issues that still need to be solved.

  20. Aberrant neural stem cell proliferation and increased adult neurogenesis in mice lacking chromatin protein HMGB2.

    Directory of Open Access Journals (Sweden)

    Ariel B Abraham

    Full Text Available Neural stem and progenitor cells (NSCs/NPCs are distinct groups of cells found in the mammalian central nervous system (CNS. Previously we determined that members of the High Mobility Group (HMG B family of chromatin structural proteins modulate NSC proliferation and self-renewal. Among them HMGB2 was found to be dynamically expressed in proliferating and differentiating NSCs, suggesting that it may regulate NSC maintenance. We report now that Hmgb2(-/- mice exhibit SVZ hyperproliferation, increased numbers of SVZ NSCs, and a trend towards aberrant increases in newly born neurons in the olfactory bulb (OB granule cell layer. Increases in the levels of the transcription factor p21 and the Neural cell adhesion molecule (NCAM, along with down-regulation of the transcription/pluripotency factor Oct4 in the Hmgb2-/- SVZ point to a possible pathway for this increased proliferation/differentiation. Our findings suggest that HMGB2 functions as a modulator of neurogenesis in young adult mice through regulation of NSC proliferation, and identify a potential target via which CNS repair could be amplified following trauma or disease-based neuronal degeneration.

  1. The intestinal stem cell

    OpenAIRE

    Barker, Nick; van de Wetering, Marc; Clevers, Hans

    2008-01-01

    The epithelium of the adult mammalian intestine is in a constant dialog with its underlying mesenchyme to direct progenitor proliferation, lineage commitment, terminal differentiation, and, ultimately, cell death. The epithelium is shaped into spatially distinct compartments that are dedicated to each of these events. While the intestinal epithelium represents the most vigorously renewing adult tissue in mammals, the stem cells that fuel this self-renewal process have been identified only rec...

  2. Detection, characterization, and spontaneous differentiation in vitro of very small embryonic-like putative stem cells in adult mammalian ovary.

    Science.gov (United States)

    Parte, Seema; Bhartiya, Deepa; Telang, Jyoti; Daithankar, Vinita; Salvi, Vinita; Zaveri, Kusum; Hinduja, Indira

    2011-08-01

    The present study was undertaken to detect, characterize, and study differentiation potential of stem cells in adult rabbit, sheep, monkey, and menopausal human ovarian surface epithelium (OSE). Two distinct populations of putative stem cells (PSCs) of variable size were detected in scraped OSE, one being smaller and other similar in size to the surrounding red blood cells in the scraped OSE. The smaller 1-3 μm very small embryonic-like PSCs were pluripotent in nature with nuclear Oct-4 and cell surface SSEA-4, whereas the bigger 4-7 μm cells with cytoplasmic localization of Oct-4 and minimal expression of SSEA-4 were possibly the tissue committed progenitor stem cells. Pluripotent gene transcripts of Oct-4, Oct-4A, Nanog, Sox-2, TERT, and Stat-3 in human and sheep OSE were detected by reverse transcriptase-polymerase chain reaction. The PSCs underwent spontaneous differentiation into oocyte-like structures, parthenote-like structures, embryoid body-like structures, cells with neuronal-like phenotype, and embryonic stem cell-like colonies, whereas the epithelial cells transformed into mesenchymal phenotype by epithelial-mesenchymal transition in 3 weeks of OSE culture. Germ cell markers like c-Kit, DAZL, GDF-9, VASA, and ZP4 were immuno-localized in oocyte-like structures. In conclusion, as opposed to the existing view of OSE being a bipotent source of oocytes and granulosa cells, mammalian ovaries harbor distinct very small embryonic-like PSCs and tissue committed progenitor stem cells population that have the potential to develop into oocyte-like structures in vitro, whereas mesenchymal fibroblasts appear to form supporting granulosa-like somatic cells. Research at the single-cell level, including complete gene expression profiling, is required to further confirm whether postnatal oogenesis is a conserved phenomenon in adult mammals.

  3. Advances in stem cell research

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@In 1998, biologists Thomson and Gearhart successfully derived stem cells from human embryos. One year later, several researchers discovered that adult stem cells still retain the ability to be differentiated into unrelated types of cells. Advances in stem cell research open a promising direction for applied medical science. Moreover, it may also force scientists to reconsider the fundamental theory about how cells grow up. Stem cell research was considered by Science as the top of the ten breakthroughs of science of the year[1]. This paper gives a survey of recent advances in stem cell research. 1 Overview In the 1980s, embryonic stem cell and/or embryonic germ cell line (ES cell line, EG cell line) of multifarious mammalian animals, especially those of non-human pri-mates, had been established. In 1998, Thomson and Shamblott obtained ES, EG cell lines from human blasto-cysts and gonad ridges of early human embryos, respec-tively. Their research brought up an ethical debate about whether human embryos can be used as experimental materials. It was not appeased until 1999 when research-ers discovered that stem cells from adults still retain the ability to become different kinds of tissue cells. For in-stance, brain cells can become blood cells[2], and cells from bone marrow can become cells in liver. Scientists believe, for a long time, that cells can only be developed from early pluripotent embryo cells; the differentiation potential of stem cells from mature tissues is restricted to only one of the cell types of the tissue where stem cells are obtained. Recent stem cell researches, however, sub-verted the traditional view of stem cells. These discoveries made scientists speed ahead with the work on adult stem cells, hoping to discover whether their promise will rival that of ES cells.

  4. Differentiations of transplanted mouse spermatogonial stem cells in the adult mouse renal parenchyma in vivo

    Institute of Scientific and Technical Information of China (English)

    Da-peng WU; Da-lin HE; Xiang LI; Zhao-hui LIU

    2008-01-01

    Aim:Spermatogonial stem cells can initiate the process of cellular differentia-tion to generate mature spermatozoa, but whether it possess the characteristic of pluripotency and plasticity, similar to embryonic stem cells, has not been elucidated. This study was designed to evaluate the differentiation potential of spermatogonial stem cells into renal cells in vivo. Methods: Neonatal mouse spermatogonial stem cells were transplanted into mature male mice lacking en-dogenous spermatogenesis. The restoration of fertility in recipient males was observed. Spermatogonial stem cells were then injected into renal parenchyma of mature female mice to make a new extracellular environment for differentia-tion. Fluorescence in situ hybridization technology (FISH) was used to detect the expression of chromosome Y in recipient renal tissues. To determine the type of cells differentiated from spermatogonial stem cells, the expression of ricinus communis agglutinin, vimentin, CD45, and F4/80 proteins were examined in the renal tissues by immunohistochemistry. Results: The proliferation of seminiferous epithelial cells was distinctly observed in seminiferous tubules of transplanted testes, whereas no regeneration of spermatogenesis was observed in non-transplanted control testes. In transplanted female renal tissues, FISH showed a much stronger immuno-fluorescence signal of chromosome Y in the nucleolus of epithelial cells of the renal tubule and podocytes of the glomerulus. Conclusion: The spermatogonial stem cells were successfully purified from mouse testicles. This finding demonstrated that spermatogonial stem cells could not only restore damaged spermatogenesis, but were also capable of differentiat-ing into mature renal parenchyma cells in vivo.

  5. What are Stem Cells?

    Directory of Open Access Journals (Sweden)

    Ahmadshah Farhat

    2014-05-01

    Full Text Available   Stem cells are undifferentiated self regenerating multi potential cells. There are three types of stem cells categories by the ability to form after cells and correlated with the body’s development process. Totipotent: these stem cells can form an entire organism such as fertilized egg. Ploripotent: ploripotent cells are those that can form any cell in the body but cannot form an entire organism such as developing embryo’s totipotent cells become ploripotent  Multipotent: Multi potent stem cells are those that can only form specific cells in the body such as blood cells based. Based on the sources of stem cells we have three types of these cells: Autologous: Sources of the patient own cells are (Autologous either the cells from patient own body or his or her cord blood. For this type of transplant the physician now usually collects the periphery rather than morrow because the procedure is easier on like a bane morrow harvest it take place outside of an operating room, and the patient does not to be under general unsetting . Allogenic: Sources of stem cells from another donore are primarily relatives (familial allogenic or completely unrelated donors. Xenogenic: In these stem cells from different species are transplanted e .g striatal porcine fetal mesan cephalic (FVM xenotransplants for Parkinson’s disease. On sites of isolation such as embryo, umbilical cord and other body tissues stem cells are named embnyonic, cord blood, and adult stem cells. The scope of results and clinical application of stem cells are such as: Neurodegenerative conditions (MS,ALS, Parkinson’s, Stroke, Ocular disorders- Glaucoma, retinitis Pigmentosa (RP, Auto Immune Conditions (Lupus, MS,R. arthritis, Diabetes, etc, Viral Conditions (Hepatitis C and AIDS, Heart Disease, Adrenal Disorders, Injury(Nerve, Brain, etc, Anti aging (hair, skin, weight control, overall well being/preventive, Emotional disorders, Organ / Tissue Cancers, Blood cancers, Blood diseases

  6. Cited2 is required for the maintenance of glycolytic metabolism in adult hematopoietic stem cells.

    Science.gov (United States)

    Du, Jinwei; Li, Qiang; Tang, Fangqiang; Puchowitz, Michelle A; Fujioka, Hisashi; Dunwoodie, Sally L; Danielpour, David; Yang, Yu-Chung

    2014-01-15

    Mammalian adult hematopoietic stem cells (HSCs) reside in the hypoxic bone marrow microenvironment and display a distinct metabolic phenotype compared with their progenitors. It has been proposed that HSCs generate energy mainly through anaerobic glycolysis in a pyruvate dehydrogenase kinase (Pdk)-dependent manner. Cited2 is an essential regulator for HSC quiescence, apoptosis, and function. Herein, we show that conditional deletion of Cited2 in murine HSCs results in elevated levels of reactive oxygen species, decreased cellular glutathione content, increased mitochondrial activity, and decreased glycolysis. At the molecular level, Cited2 deficiency significantly reduced the expression of genes involved in metabolism, such as Pdk2, Pdk4, and lactate dehydrogenases B and D (LDHB and LDHD). Cited2-deficient HSCs also exhibited increased Akt signaling, concomitant with elevated mTORC1 activity and phosphorylation of FoxOs. Further, inhibition of PI3/Akt, but not mTORC1, partially rescued the repression of Pdk4 caused by deletion of Cited2. Altogether, our results suggest that Cited2 is required for the maintenance of adult HSC glycolytic metabolism likely through regulating Pdk2, Pdk4, LDHB, LDHD, and Akt activity. PMID:24083546

  7. Expression of Genes Related to Germ Cell Lineage and Pluripotency in Single Cells and Colonies of Human Adult Germ Stem Cells

    OpenAIRE

    Sabine Conrad; Hossein Azizi; Maryam Hatami; Mikael Kubista; Michael Bonin; Jörg Hennenlotter; Karl-Dietrich Sievert; Thomas Skutella

    2016-01-01

    The aim of this study was to elucidate the molecular status of single human adult germ stem cells (haGSCs) and haGSC colonies, which spontaneously developed from the CD49f MACS and matrix- (collagen−/laminin+ binding-) selected fraction of enriched spermatogonia. Single-cell transcriptional profiling by Fluidigm BioMark system of a long-term cultured haGSCs cluster in comparison to human embryonic stem cells (hESCs) and human fibroblasts (hFibs) revealed that haGSCs showed a characteristic ge...

  8. Stem cells - biological update and cell therapy progress

    OpenAIRE

    GIRLOVANU, MIHAI; Susman, Sergiu; Soritau, Olga; RUS-CIUCA, DAN; MELINCOVICI, CARMEN; CONSTANTIN, ANNE-MARIE; Carmen Mihaela MIHU

    2015-01-01

    In recent years, the advances in stem cell research have suggested that the human body may have a higher plasticity than it was originally expected. Until now, four categories of stem cells were isolated and cultured in vivo: embryonic stem cells, fetal stem cells, adult stem cells and induced pluripotent stem cells (hiPSCs). Although multiple studies were published, several issues concerning the stem cells are still debated, such as: the molecular mechanisms of differentiation, the methods t...

  9. In vivo tumorigenesis was observed after injection of in vitro expanded neural crest stem cells isolated from adult bone marrow.

    Directory of Open Access Journals (Sweden)

    Sabine Wislet-Gendebien

    Full Text Available Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells alters the functional and biological properties of those cells, leading to the accumulation of genetic aberrations. Recent studies described bone marrow stromal cells (BMSC as mixed populations of cells including mesenchymal (MSC and neural crest stem cells (NCSC. Here, we report the transformation of NCSC into tumorigenic cells, after in vitro long-term passaging. Indeed, the characterization of 6 neural crest-derived clones revealed the presence of one tumorigenic clone. Transcriptomic analyses of this clone highlighted, among others, numerous cell cycle checkpoint modifications and chromosome 11q down-regulation (suggesting a deletion of chromosome 11q compared with the other clones. Moreover, unsupervised analysis such as a dendrogram generated after agglomerative hierarchical clustering comparing several transcriptomic data showed important similarities between the tumorigenic neural crest-derived clone and mammary tumor cell lines. Altogether, it appeared that NCSC isolated from adult bone marrow represents a potential danger for cellular therapy, and consequently, we recommend that phenotypic, functional and genetic assays should be performed on bone marrow mesenchymal and neural crest stem cells before in vivo use, to demonstrate whether their biological properties, after ex vivo expansion, remain suitable for clinical application.

  10. In vivo tumorigenesis was observed after injection of in vitro expanded neural crest stem cells isolated from adult bone marrow.

    Science.gov (United States)

    Wislet-Gendebien, Sabine; Poulet, Christophe; Neirinckx, Virginie; Hennuy, Benoit; Swingland, James T; Laudet, Emerence; Sommer, Lukas; Shakova, Olga; Bours, Vincent; Rogister, Bernard

    2012-01-01

    Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells alters the functional and biological properties of those cells, leading to the accumulation of genetic aberrations. Recent studies described bone marrow stromal cells (BMSC) as mixed populations of cells including mesenchymal (MSC) and neural crest stem cells (NCSC). Here, we report the transformation of NCSC into tumorigenic cells, after in vitro long-term passaging. Indeed, the characterization of 6 neural crest-derived clones revealed the presence of one tumorigenic clone. Transcriptomic analyses of this clone highlighted, among others, numerous cell cycle checkpoint modifications and chromosome 11q down-regulation (suggesting a deletion of chromosome 11q) compared with the other clones. Moreover, unsupervised analysis such as a dendrogram generated after agglomerative hierarchical clustering comparing several transcriptomic data showed important similarities between the tumorigenic neural crest-derived clone and mammary tumor cell lines. Altogether, it appeared that NCSC isolated from adult bone marrow represents a potential danger for cellular therapy, and consequently, we recommend that phenotypic, functional and genetic assays should be performed on bone marrow mesenchymal and neural crest stem cells before in vivo use, to demonstrate whether their biological properties, after ex vivo expansion, remain suitable for clinical application. PMID:23071568

  11. Gastrointestinal stem cell up-to-date.

    Science.gov (United States)

    Pirvulet, V

    2015-01-01

    Cellular and tissue regeneration in the gastrointestinal tract depends on stem cells with properties of self-renewal, clonogenicity, and multipotency. Progress in stem cell research and the identification of potential gastric, intestinal, colonic stem cells new markers and the signaling pathways provide hope for the use of stem cells in regenerative medicine and treatments for disease. This review provides an overview of the different types of stem cells, focusing on tissue-restricted adult stem cells.

  12. Adult stem cells from the hyaluronic acid-rich node and duct system differentiate into neuronal cells and repair brain injury.

    Science.gov (United States)

    Lee, Seung J; Park, Sang H; Kim, Yu I; Hwang, Sunhee; Kwon, Patrick M; Han, In S; Kwon, Byoung S

    2014-12-01

    The existence of a hyaluronic acid-rich node and duct system (HAR-NDS) within the lymphatic and blood vessels was demonstrated previously. The HAR-NDS was enriched with small (3.0-5.0 μm in diameter), adult stem cells with properties similar to those of the very small embryonic-like stem cells (VSELs). Sca-1(+)Lin(-)CD45(-) cells were enriched approximately 100-fold in the intravascular HAR-NDS compared with the bone marrow. We named these adult stem cells "node and duct stem cells (NDSCs)." NDSCs formed colonies on C2C12 feeder layers, were positive for fetal alkaline phosphatase, and could be subcultured on the feeder layers. NDSCs were Oct4(+)Nanog(+)SSEA-1(+)Sox2(+), while VSELs were Oct4(+)Nanog(+)SSEA-1(+)Sox2(-). NDSCs had higher sphere-forming efficiency and proliferative potential than VSELs, and they were found to differentiate into neuronal cells in vitro. Injection of NDSCs into mice partially repaired ischemic brain damage. Thus, we report the discovery of potential adult stem cells that may be involved in tissue regeneration. The intravascular HAR-NDS may serve as a route that delivers these stem cells to their target tissues. PMID:25027245

  13. Mechanisms Underlying the Antiproliferative and Prodifferentiative Effects of Psoralen on Adult Neural Stem Cells via DNA Microarray

    OpenAIRE

    Zi-Yin Shen; Jing-Cheng Dong; Xin-Min Zhang; Yang Chen; Qin Bian; Shi-Jin Xia; Jian-Hua Huang; You Ning

    2013-01-01

    Adult neural stem cells (NSCs) persist throughout life to replace mature cells that are lost during turnover, disease, or injury. The investigation of NSC creates novel treatments for central nervous system (CNS) injuries and neurodegenerative disorders. The plasticity and reparative potential of NSC are regulated by different factors, which are critical for neurological regenerative medicine research. We investigated the effects of Psoralen, which is the mature fruit of Psoralea corylifolia ...

  14. Expression of Genes Related to Germ Cell Lineage and Pluripotency in Single Cells and Colonies of Human Adult Germ Stem Cells.

    Science.gov (United States)

    Conrad, Sabine; Azizi, Hossein; Hatami, Maryam; Kubista, Mikael; Bonin, Michael; Hennenlotter, Jörg; Sievert, Karl-Dietrich; Skutella, Thomas

    2016-01-01

    The aim of this study was to elucidate the molecular status of single human adult germ stem cells (haGSCs) and haGSC colonies, which spontaneously developed from the CD49f MACS and matrix- (collagen-/laminin+ binding-) selected fraction of enriched spermatogonia. Single-cell transcriptional profiling by Fluidigm BioMark system of a long-term cultured haGSCs cluster in comparison to human embryonic stem cells (hESCs) and human fibroblasts (hFibs) revealed that haGSCs showed a characteristic germ- and pluripotency-associated gene expression profile with some similarities to hESCs and with a significant distinction from somatic hFibs. Genome-wide comparisons with microarray analysis confirmed that different haGSC colonies exhibited gene expression heterogeneity with more or less pluripotency. The results of this study confirm that haGSCs are adult stem cells with a specific molecular gene expression profile in vitro, related but not identical to true pluripotent stem cells. Under ES-cell conditions haGSC colonies could be selected and maintained in a partial pluripotent state at the molecular level, which may be related to their cell plasticity and potential to differentiate into cells of all germ layers. PMID:26649052

  15. Expression of Genes Related to Germ Cell Lineage and Pluripotency in Single Cells and Colonies of Human Adult Germ Stem Cells

    Directory of Open Access Journals (Sweden)

    Sabine Conrad

    2016-01-01

    Full Text Available The aim of this study was to elucidate the molecular status of single human adult germ stem cells (haGSCs and haGSC colonies, which spontaneously developed from the CD49f MACS and matrix- (collagen−/laminin+ binding- selected fraction of enriched spermatogonia. Single-cell transcriptional profiling by Fluidigm BioMark system of a long-term cultured haGSCs cluster in comparison to human embryonic stem cells (hESCs and human fibroblasts (hFibs revealed that haGSCs showed a characteristic germ- and pluripotency-associated gene expression profile with some similarities to hESCs and with a significant distinction from somatic hFibs. Genome-wide comparisons with microarray analysis confirmed that different haGSC colonies exhibited gene expression heterogeneity with more or less pluripotency. The results of this study confirm that haGSCs are adult stem cells with a specific molecular gene expression profile in vitro, related but not identical to true pluripotent stem cells. Under ES-cell conditions haGSC colonies could be selected and maintained in a partial pluripotent state at the molecular level, which may be related to their cell plasticity and potential to differentiate into cells of all germ layers.

  16. Pluripotent stem cell lines

    OpenAIRE

    Yu, Junying; Thomson, James A.

    2008-01-01

    The derivation of human embryonic stem cells 10 years ago ignited an explosion of public interest in stem cells, yet this achievement depended on prior decades of research on mouse embryonic carcinoma cells and embryonic stem cells. In turn, the recent derivation of mouse and human induced pluripotent stem cells depended on the prior studies on mouse and human embryonic stem cells. Both human embryonic stem cells and induced pluripotent stem cells can self-renew indefinitely in vitro while ma...

  17. Long-term survival of exogenous embryonic stem cells in adult bone marrow

    Institute of Scientific and Technical Information of China (English)

    Yueying Li; Jing Xu; Weiping Yuan; Shaorong Gao; Tao Cheng; Yanfeng Liu; Jing He; Fengchao Wang; Sheng Liu; Yu Zhang; Zhaohui Kou; Zhenyu Ju; Guoguang Zheng

    2011-01-01

    @@ Dear Editor, Embryonic stem cell (ESC) is an attractive and promising source in regenerative medicine.However, current technologies for ESC differentiation do not ensure complete or synchronized conversion of ESCs into a specific functional tissue type for therapeutic purposes.

  18. The ADP-ribose polymerase Tankyrase regulates adult intestinal stem cell proliferation during homeostasis in Drosophila.

    Science.gov (United States)

    Wang, Zhenghan; Tian, Ai; Benchabane, Hassina; Tacchelly-Benites, Ofelia; Yang, Eungi; Nojima, Hisashi; Ahmed, Yashi

    2016-05-15

    Wnt/β-catenin signaling controls intestinal stem cell (ISC) proliferation, and is aberrantly activated in colorectal cancer. Inhibitors of the ADP-ribose polymerase Tankyrase (Tnks) have become lead therapeutic candidates for Wnt-driven cancers, following the recent discovery that Tnks targets Axin, a negative regulator of Wnt signaling, for proteolysis. Initial reports indicated that Tnks is important for Wnt pathway activation in cultured human cell lines. However, the requirement for Tnks in physiological settings has been less clear, as subsequent studies in mice, fish and flies suggested that Tnks was either entirely dispensable for Wnt-dependent processes in vivo, or alternatively, had tissue-specific roles. Here, using null alleles, we demonstrate that the regulation of Axin by the highly conserved Drosophila Tnks homolog is essential for the control of ISC proliferation. Furthermore, in the adult intestine, where activity of the Wingless pathway is graded and peaks at each compartmental boundary, Tnks is dispensable for signaling in regions where pathway activity is high, but essential where pathway activity is relatively low. Finally, as observed previously for Wingless pathway components, Tnks activity in absorptive enterocytes controls the proliferation of neighboring ISCs non-autonomously by regulating JAK/STAT signaling. These findings reveal the requirement for Tnks in the control of ISC proliferation and suggest an essential role in the amplification of Wnt signaling, with relevance for development, homeostasis and cancer. PMID:27190037

  19. Argonaute-2 regulates the proliferation of adult stem cells in planarian

    Institute of Scientific and Technical Information of China (English)

    Yong-Qin Li; An Zeng; Xiao-Shuai Han; Chen Wang; Ge Li; Zhen-Chao Zhang; Jian-Yong Wang; Yong-Wen Qin; Qing Jing

    2011-01-01

    Dear Editor,Planarian Schmidtea mediterranea has extraordinary regeneration capabilities due to the abundance of adult stem cells (ASCs) known as neoblasts,which make planarian a powerful in vivo system to study ASC biology [ 1 ].The Argonaute (AGO) family proteins are defined by the presence of Piwi-Argonaute-Zwille (PAZ)) and PIWI domains [2],and mediate silencing via cleavage of mRNAs [3] or inhibition of translation [4].The AGO family proteins fall into two subfamilies,one named after Arabidopsis Argonaute and the other after Drosophila PIWI [5].In most organisms investigated so far,PIWI proteins bind Piwi-interacting RNAs (piRNAs) and are functionally involved in the regulation of germ cells [6,7].By contrast,AGO proteins have distinct roles in the smallRNA-mediated gene silencing pathway.In Drosophila,AGO1 has been illustrated to be engaged in the miRNA pathway,while AGO2 plays an important role in the siRNA-mediated gene regulation [4].

  20. Tissue-specific mutation accumulation in human adult stem cells during life

    Science.gov (United States)

    Blokzijl, Francis; de Ligt, Joep; Jager, Myrthe; Sasselli, Valentina; Roerink, Sophie; Sasaki, Nobuo; Huch, Meritxell; Boymans, Sander; Kuijk, Ewart; Prins, Pjotr; Nijman, Isaac J.; Martincorena, Inigo; Mokry, Michal; Wiegerinck, Caroline L.; Middendorp, Sabine; Sato, Toshiro; Schwank, Gerald; Nieuwenhuis, Edward E. S.; Verstegen, Monique M. A.; van der Laan, Luc J. W.; de Jonge, Jeroen; Ijzermans, Jan N. M.; Vries, Robert G.; van de Wetering, Marc; Stratton, Michael R.; Clevers, Hans; Cuppen, Edwin; van Boxtel, Ruben

    2016-10-01

    The gradual accumulation of genetic mutations in human adult stem cells (ASCs) during life is associated with various age-related diseases, including cancer. Extreme variation in cancer risk across tissues was recently proposed to depend on the lifetime number of ASC divisions, owing to unavoidable random mutations that arise during DNA replication. However, the rates and patterns of mutations in normal ASCs remain unknown. Here we determine genome-wide mutation patterns in ASCs of the small intestine, colon and liver of human donors with ages ranging from 3 to 87 years by sequencing clonal organoid cultures derived from primary multipotent cells. Our results show that mutations accumulate steadily over time in all of the assessed tissue types, at a rate of approximately 40 novel mutations per year, despite the large variation in cancer incidence among these tissues. Liver ASCs, however, have different mutation spectra compared to those of the colon and small intestine. Mutational signature analysis reveals that this difference can be attributed to spontaneous deamination of methylated cytosine residues in the colon and small intestine, probably reflecting their high ASC division rate. In liver, a signature with an as-yet-unknown underlying mechanism is predominant. Mutation spectra of driver genes in cancer show high similarity to the tissue-specific ASC mutation spectra, suggesting that intrinsic mutational processes in ASCs can initiate tumorigenesis. Notably, the inter-individual variation in mutation rate and spectra are low, suggesting tissue-specific activity of common mutational processes throughout life.

  1. Current Understanding of the Pathways Involved in Adult Stem and Progenitor Cell Migration for Tissue Homeostasis and Repair.

    Science.gov (United States)

    Goichberg, Polina

    2016-08-01

    With the advancements in the field of adult stem and progenitor cells grows the recognition that the motility of primitive cells is a pivotal aspect of their functionality. There is accumulating evidence that the recruitment of tissue-resident and circulating cells is critical for organ homeostasis and effective injury responses, whereas the pathobiology of degenerative diseases, neoplasm and aging, might be rooted in the altered ability of immature cells to migrate. Furthermore, understanding the biological machinery determining the translocation patterns of tissue progenitors is of great relevance for the emerging methodologies for cell-based therapies and regenerative medicine. The present article provides an overview of studies addressing the physiological significance and diverse modes of stem and progenitor cell trafficking in adult mammalian organs, discusses the major microenvironmental cues regulating cell migration, and describes the implementation of live imaging approaches for the exploration of stem cell movement in tissues and the factors dictating the motility of endogenous and transplanted cells with regenerative potential. PMID:27209167

  2. Expression of the Argonaute protein PiwiL2 and piRNAs in adult mouse mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Qiuling; Ma, Qi; Shehadeh, Lina A.; Wilson, Amber; Xia, Linghui; Yu, Hong [Department of Molecular and Cellular Pharmacology, Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Webster, Keith A., E-mail: kwebster@med.miami.edu [Department of Molecular and Cellular Pharmacology, Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, FL 33136 (United States)

    2010-06-11

    Piwi (P-element-induced wimpy testis) first discovered in Drosophila is a member of the Argonaute family of micro-RNA binding proteins with essential roles in germ-cell development. The murine homologue of PiwiL2, also known as Mili is selectively expressed in the testes, and mice bearing targeted mutations of the PiwiL2 gene are male-sterile. PiwiL2 proteins are thought to protect the germ line genome by suppressing retrotransposons, stabilizing heterochromatin structure, and regulating target genes during meiosis and mitosis. Here, we report that PiwiL2 and associated piRNAs (piRs) may play similar roles in adult mouse mesenchymal stem cells. We found that PiwiL2 is expressed in the cytoplasm of metaphase mesenchymal stem cells from the bone marrow of adult and aged mice. Knockdown of PiwiL2 with a specific siRNA enhanced cell proliferation, significantly increased the number of cells in G1/S and G2/M cell cycle phases and was associated with increased expression of cell cycle genes CCND1, CDK8, microtubule regulation genes, and decreased expression of tumor suppressors Cables 1, LATS, and Cxxc4. The results suggest broader roles for Piwi in genome surveillance beyond the germ line and a possible role in regulating the cell cycle of mesenchymal stem cells.

  3. Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells.

    Science.gov (United States)

    Butovsky, Oleg; Ziv, Yaniv; Schwartz, Adi; Landa, Gennady; Talpalar, Adolfo E; Pluchino, Stefano; Martino, Gianvito; Schwartz, Michal

    2006-01-01

    Cell renewal in the adult central nervous system (CNS) is limited, and is blocked in inflammatory brain conditions. We show that both neurogenesis and oligodendrogenesis of adult neural progenitor cells in mice are blocked by inflammation-associated (endotoxin-activated) microglia, but induced by microglia activated by cytokines (IL-4 or low level of IFN-gamma) associated with T-helper cells. Blockage was correlated with up-regulation of microglial production of tumor necrosis factor-alpha. The effect induced by IL-4-activated microglia was mediated, at least in part, by insulin-like growth factor-I. The IL-4-activated microglia showed a bias towards oligodendrogenesis whereas the IFN-gamma-activated microglia showed a bias towards neurogenesis. It thus appears that microglial phenotype critically affects their ability to support or impair cell renewal from adult stem cell.

  4. LncRNAs in Stem Cells

    OpenAIRE

    Shanshan Hu; Ge Shan

    2016-01-01

    Noncoding RNAs are critical regulatory factors in essentially all forms of life. Stem cells occupy a special position in cell biology and Biomedicine, and emerging results show that multiple ncRNAs play essential roles in stem cells. We discuss some of the known ncRNAs in stem cells such as embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, adult stem cells, and cancer stem cells with a focus on long ncRNAs. Roles and functional mechanisms of these lncRNAs are summa...

  5. Adult stem cells in the small intestine are intrinsically programmed with their location-specific function

    NARCIS (Netherlands)

    Middendorp, Sabine; Schneeberger, Kerstin; Wiegerinck, Caroline L; Mokry, Michal; Akkerman, Ronald D L; van Wijngaarden, Simone; Clevers, Hans; Nieuwenhuis, Edward E S

    2014-01-01

    Differentiation and specialization of epithelial cells in the small intestine are regulated in two ways. First, there is differentiation along the crypt-villus axis of the intestinal stem cells into absorptive enterocytes, Paneth, goblet, tuft, enteroendocrine, or M cells, which is mainly regulated

  6. Cdx2 is essential for embryonic axial growth and identity of the adult intestinal stem cells

    NARCIS (Netherlands)

    Simmini, Salvatore

    2015-01-01

    During mouse development, progenitor cells, allocated along the primitive streak and in the tailbud, lay down descendants that contribute to the generation of all primordia of the trunk and tail tissues of the embryo. Evidence suggested that a pool of these progenitor cells, with stem cell-like pote

  7. Purification of fetal liver stem/progenitor cells containing all the repopulation potential for normal adult rat liver

    DEFF Research Database (Denmark)

    Oertel, Michael; Menthena, Anuradha; Chen, Yuan-Qing;

    2008-01-01

    BACKGROUND & AIMS: Previously, we showed high-level, long-term liver replacement after transplantation of unfractionated embryonic day (ED) 14 fetal liver stem/progenitor cells (FLSPC). However, for clinical applications, it will be essential to transplant highly enriched cells, while maintaining...... high repopulation potential. METHODS: Dlk-1, a member of the delta-like family of cell surface transmembrane proteins, is highly expressed in human and rodent fetal liver. Dlk-1(+) cells, isolated from ED14 fetal liver using immunomagnetic beads, were examined for their hepatic gene expression profile...... and characteristic properties in vitro and their proliferative and differentiation potential in vivo after transplantation into normal adult rat liver. RESULTS: Rat ED14 FLSPC were purified to 95% homogeneity and exhibited cell culture and gene expression characteristics expected for hepatic stem/progenitor cells...

  8. Cell adhesion in regulation of asymmetric stem cell division

    OpenAIRE

    Yamashita, Yukiko M

    2010-01-01

    Adult stem cells inevitably communicate with their cellular neighbors within the tissues they sustain. Indeed, such communication, particularly with components of the stem cell niche, is essential for many aspects of stem cell behavior, including the maintenance of stem cell identity and asymmetric cell division. Cell adhesion mediates this communication by placing stem cells in close proximity to the signaling source and by providing a polarity cue that orients stem cells. Here, I review the...

  9. Limbal Stem Cell Therapy

    OpenAIRE

    Kringlegarden, Hilde Grane

    2013-01-01

    It is widely accepted today that stem cells in the adult corneal epithelium is located to the limbus. No specific marker of limbal epithelial cells (LESCs) has been identified, yet many have been suggested, including ΔNp63α, ABCG2, vimentin and notch 1. Negative markers include amongst others the differentiation markers Ck3 and Ck12. The lack of an identified specific marker elucidates the need for establishment of more exact molecular markers of LESCs. Limbal stem cell deficiency (LSCD) may ...

  10. Adult bone marrow mesenchymal and neural crest stem cells are chemoattractive and accelerate motor recovery in a mouse model of spinal cord injury

    OpenAIRE

    Neirinckx, Virginie; Agirman, Gulistan; Coste, Cécile; Marquet, Alice; Dion, Valérie; Rogister, Bernard; Franzen, Rachelle; Wislet, Sabine

    2015-01-01

    Introduction Stem cells from adult tissues were considered for a long time as promising tools for regenerative therapy of neurological diseases, including spinal cord injuries (SCI). Indeed, mesenchymal (MSCs) and neural crest stem cells (NCSCs) together constitute the bone marrow stromal stem cells (BMSCs) that were used as therapeutic options in various models of experimental SCI. However, as clinical approaches remained disappointing, we thought that reducing BMSC heterogeneity should be a...

  11. T-cell-replete haploidentical transplantation versus autologous stem cell transplantation in adult acute leukemia: a matched pair analysis.

    Science.gov (United States)

    Gorin, Norbert-Claude; Labopin, Myriam; Piemontese, Simona; Arcese, William; Santarone, Stella; Huang, He; Meloni, Giovanna; Ferrara, Felicetto; Beelen, Dietrich; Sanz, Miguel; Bacigalupo, Andrea; Ciceri, Fabio; Mailhol, Audrey; Nagler, Arnon; Mohty, Mohamad

    2015-04-01

    Adult patients with acute leukemia in need of a transplant but without a genoidentical donor are usually considered upfront for transplantation with stem cells from any other allogeneic source, rather than autologous stem cell transplantation. We used data from the European Society for Blood and Marrow Transplantation and performed a matched pair analysis on 188 T-cell-replete haploidentical and 356 autologous transplants done from January 2007 to December 2012, using age, diagnosis, disease status, cytogenetics, and interval from diagnosis to transplant as matching factors. "Haploidentical expert" centers were defined as having reported more than five haploidentical transplants for acute leukemia (median value for the study period). The median follow-up was 28 months. Multivariate analyses, including type of transplant categorized into three classes ("haploidentical regular", "haploidentical expert" and autologous), conditioning intensity (reduced intensity versus myeloablative conditioning) and the random effect taking into account associations related to matching, showed that non-relapse mortality was higher following haploidentical transplants in expert (HR: 4.7; P=0.00004) and regular (HR: 8.98; Ptransplants was lower in expert centers (HR:0.39; P=0.0003) but in regular centers was similar to that for autologous transplants. Leukemia-free survival and overall survival rates were higher following autologous transplantation than haploidentical transplants in regular centers (HR: 1.63; P=0.008 and HR: 2.31; P=0.0002 respectively) but similar to those following haploidentical transplants in expert centers. We conclude that autologous stem cell transplantation should presently be considered as a possible alternative to haploidentical transplantation in regular centers that have not developed a specific expert program.

  12. Induction of Stem Cell Gene Expression in Adult Human Fibroblasts without Transgenes

    OpenAIRE

    Page, Raymond L.; Ambady, Sakthikumar; Holmes, William F.; Vilner, Lucy; Kole, Denis; Kashpur, Olga; Huntress, Victoria; Vojtic, Ina; Whitton, Holly; Dominko, Tanja

    2009-01-01

    Reprogramming of differentiated somatic cells into induced pluripotent stem (iPS) cells has potential for derivation of patient-specific cells for therapy as well as for development of models with which to study disease progression. Derivation of iPS cells from human somatic cells has been achieved by viral transduction of human fibroblasts with early developmental genes. Because forced expression of these genes by viral transduction results in transgene integration with unknown and unpredict...

  13. Tax unleashed: fulminant Tax-positive Adult T-cell Leukemia/Lymphoma after failed allogeneic stem cell transplantation.

    Science.gov (United States)

    Ghez, David; Renand, Amédée; Lepelletier, Yves; Sibon, David; Suarez, Felipe; Rubio, Marie-Thérèse; Delarue, Richard; Buzyn, Agnès; Beljord, Kheira; Tanaka, Yuetsu; Varet, Bruno; Hermine, Olivier

    2009-12-01

    The human retrovirus HTLV-1 causes Adult T-cell Leukemia/Lymphoma (ATLL), a malignant lymphoproliferative disease of CD4+ T cells of dismal prognosis, in 3-5% of the 20 million infected individuals (Proietti et al.(1) and Bazarbachi et al.(2)). Infection with HTLV-1 represents a prototypical model of virus-mediated oncogenesis by virtue of the viral transactivator Tax, a potent oncogenic protein that exerts pleiotropic effects through its ability to deregulate the transcription of various cellular genes and signal transduction pathways and inhibit DNA repair enzymes, which are critical for T-cell homeostasis and genetic stability (Matsuoka and Jeang(3)) (et Boxus Retrovirology 2009). However, the oncogenic potential of Tax remains a conundrum. Tax protein expression is undetectable using conventional methods in freshly harvested ATLL cells and in non-malignant infected CD4+ T cells (Furukawa et al.(4)) but is up regulated after only a few hours of culture in vitro (Hanon et al.(5)). These observations strongly suggest that a host-derived mechanism is able to either actively repress the transcription of viral proteins in vivo or refrain the emergence of Tax-expressing cells, which would have a growth advantage. We report herein a unique case of CD4+ T-cell leukemia highly expressing Tax following rejection of an allogenic peripheral blood stem cell graft for an HTLV-1 associated lymphoma. PMID:19836302

  14. Evaluation of Methylcellulose and Dimethyl Sulfoxide as the Cryoprotectants in a Serum-Free Freezing Media for Cryopreservation of Adipose-Derived Adult Stem Cells

    OpenAIRE

    Thirumala, Sreedhar; Gimble, Jeffrey M.; Devireddy, Ram V.

    2010-01-01

    Developing effective techniques for the cryopreservation of human adipose-derived adult stem cells (ASCs) could increase the usefulness of these cells in tissue engineering and regenerative medicine. To this end, we investigated the post-freeze/thaw viability and apoptotic behavior of Passage 1 (P1) adult stem cells (ASCs) in 11 different media: (i) the traditional media containing Dulbecco’s modified Eagle’s medium (DMEM) with 80% fetal calf serum (FCS) and 10% dimethyl sulfoxide (DMSO), (ii...

  15. Cell-permeable p38 MAP kinase promotes migration of adult neural stem/progenitor cells

    Science.gov (United States)

    Hamanoue, Makoto; Morioka, Kazuhito; Ohsawa, Ikuroh; Ohsawa, Keiko; Kobayashi, Masaaki; Tsuburaya, Kayo; Akasaka, Yoshikiyo; Mikami, Tetsuo; Ogata, Toru; Takamatsu, Ken

    2016-01-01

    Endogenous neural stem/progenitor cells (NPCs) can migrate toward sites of injury, but the migration activity of NPCs is insufficient to regenerate damaged brain tissue. In this study, we showed that p38 MAP kinase (p38) is expressed in doublecortin-positive adult NPCs. Experiments using the p38 inhibitor SB203580 revealed that endogenous p38 participates in NPC migration. To enhance NPC migration, we generated a cell-permeable wild-type p38 protein (PTD-p38WT) in which the HIV protein transduction domain (PTD) was fused to the N-terminus of p38. Treatment with PTD-p38WT significantly promoted the random migration of adult NPCs without affecting cell survival or differentiation; this effect depended on the cell permeability and kinase activity of the fusion protein. These findings indicate that PTD-p38WT is a novel and useful tool for unraveling the roles of p38, and that this protein provides a reasonable approach for regenerating the injured brain by enhancing NPC migration. PMID:27067799

  16. 肺成体干细胞的研究进展%Research advances on lung adult stem cells

    Institute of Scientific and Technical Information of China (English)

    陈蒙蒙; 黑飞龙

    2013-01-01

    Lung injury and chronic lung diseases,including chronic obstructive pulmonary disease,interstitial lung disease,pulmonary arterial hypertension and lung cancer,and so on,have become the main causes of death around the world.Most treatments are based on alleviating the symptoms except lung transplantation.For limit of the donor source and surgical technique,the concerns of treating lung diseases have transferred to researches of adult and embryonic stem cells related to lung regenerative medicine.Compared with the embryonic stem cells,adult stem cells can avoid the problems of ethics,drawing materials,and immune rejection.In this review,we summarizes the progress of the lung adult stem cells in the aspect of endogenous adult stem cells of lung and exogenous adult stem cells of lung.%肺损伤以及慢性肺部疾病,包括慢性阻塞性肺疾病、间质性肺病、肺动脉高压以及肺癌等,已经成为世界范围内疾病发生和死亡的主要原因.除肺移植外,目前大多数治疗方法只能缓解患者的症状,却不能达到治愈的效果.由于供体来源和外科技术的限制,肺部疾病治疗的关注点已经转移到与肺再生医学相关的成体和胚胎干细胞的研究.成体干细胞由于可以避免胚胎干细胞面临的伦理、取材以及免疫排斥等问题而日益受到关注.本文将从肺内源性成体干细胞和肺外源性成体干细胞两方面就肺成体干细胞的研究进展作一综述.

  17. Meis1 Is Required for Adult Mouse Erythropoiesis, Megakaryopoiesis and Hematopoietic Stem Cell Expansion.

    Science.gov (United States)

    Miller, Michelle Erin; Rosten, Patty; Lemieux, Madeleine E; Lai, Courteney; Humphries, R Keith

    2016-01-01

    Meis1 is recognized as an important transcriptional regulator in hematopoietic development and is strongly implicated in the pathogenesis of leukemia, both as a Hox transcription factor co-factor and independently. Despite the emerging recognition of Meis1's importance in the context of both normal and leukemic hematopoiesis, there is not yet a full understanding of Meis1's functions and the relevant pathways and genes mediating its functions. Recently, several conditional mouse models for Meis1 have been established. These models highlight a critical role for Meis1 in adult mouse hematopoietic stem cells (HSCs) and implicate reactive oxygen species (ROS) as a mediator of Meis1 function in this compartment. There are, however, several reported differences between these studies in terms of downstream progenitor populations impacted and effectors of function. In this study, we describe further characterization of a conditional knockout model based on mice carrying a loxP-flanked exon 8 of Meis1 which we crossed onto the inducible Cre localization/expression strains, B6;129-Gt(ROSA)26Sor(tm1(Cre/ERT)Nat)/J or B6.Cg-Tg(Mx1-Cre)1Cgn/J. Findings obtained from these two inducible Meis1 knockout models confirm and extend previous reports of the essential role of Meis1 in adult HSC maintenance and expansion and provide new evidence that highlights key roles of Meis1 in both megakaryopoiesis and erythropoiesis. Gene expression analyses point to a number of candidate genes involved in Meis1's role in hematopoiesis. Our data additionally support recent evidence of a role of Meis1 in ROS regulation. PMID:26986211

  18. Impact of conditioning with TBI in adult patients with T-cell ALL who receive a myeloablative allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Cahu, X; Labopin, M; Giebel, S;

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a therapeutic option for adult patients with T-cell ALL (T-ALL). Meanwhile, few allo-SCT data specific to adult T-ALL have been described thus far. Specifically, the optimal myeloablative conditioning regimen is unknown. In this ret...... patients with T-ALL entitled to receive a myeloablative allo-SCT may benefit from TBI-based regimens.Bone Marrow Transplantation advance online publication, 30 November 2015; doi:10.1038/bmt.2015.278.......Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a therapeutic option for adult patients with T-cell ALL (T-ALL). Meanwhile, few allo-SCT data specific to adult T-ALL have been described thus far. Specifically, the optimal myeloablative conditioning regimen is unknown...

  19. Adult mouse subventricular zone stem and progenitor cells are sessile and epidermal growth factor receptor negatively regulates neuroblast migration.

    Directory of Open Access Journals (Sweden)

    Yongsoo Kim

    Full Text Available BACKGROUND: The adult subventricular zone (SVZ contains stem and progenitor cells that generate neuroblasts throughout life. Although it is well accepted that SVZ neuroblasts are migratory, recent evidence suggests their progenitor cells may also exhibit motility. Since stem and progenitor cells are proliferative and multipotential, if they were also able to move would have important implications for SVZ neurogenesis and its potential for repair. METHODOLOGY/PRINCIPAL FINDINGS: We studied whether SVZ stem and/or progenitor cells are motile in transgenic GFP+ slices with two photon time lapse microscopy and post hoc immunohistochemistry. We found that stem and progenitor cells; mGFAP-GFP+ cells, bright nestin-GFP+ cells and Mash1+ cells were stationary in the SVZ and rostral migratory stream (RMS. In our search for motile progenitor cells, we uncovered a population of motile betaIII-tubulin+ neuroblasts that expressed low levels of epidermal growth factor receptor (EGFr. This was intriguing since EGFr drives proliferation in the SVZ and affects migration in other systems. Thus we examined the potential role of EGFr in modulating SVZ migration. Interestingly, EGFr(low neuroblasts moved slower and in more tortuous patterns than EGFr-negative neuroblasts. We next questioned whether EGFr stimulation affects SVZ cell migration by imaging Gad65-GFP+ neuroblasts in the presence of transforming growth factor alpha (TGF-alpha, an EGFr-selective agonist. Indeed, acute exposure to TGF-alpha decreased the percentage of motile cells by approximately 40%. CONCLUSIONS/SIGNIFICANCE: In summary, the present study directly shows that SVZ stem and progenitor cells are static, that EGFr is retained on some neuroblasts, and that EGFr stimulation negatively regulates migration. This result suggests an additional role for EGFr signaling in the SVZ.

  20. Over-expression of hNGF in adult human olfactory bulb neural stem cells promotes cell growth and oligodendrocytic differentiation

    NARCIS (Netherlands)

    H.E.S. Marei (Hany); A. Althani (Asmaa); N. Afifi (Nahla); A. Abd-Elmaksoud (Ahmed); C. Bernardini (Camilla); F. Michetti (Fabrizio); M. Barba (Marta); M. Pescatori (Mario); G. Maira (Giulio); E. Paldino (Emanuela); L. Manni (Luigi); P. Casalbore (Patrizia); C. Cenciarelli (Carlo)

    2013-01-01

    textabstractThe adult human olfactory bulb neural stem/progenitor cells (OBNC/PC) are promising candidate for cell-based therapy for traumatic and neurodegenerative insults. Exogenous application of NGF was suggested as a promising therapeutic strategy for traumatic and neurodegenerative diseases, h

  1. Clonal proliferation of multipotent stem/progenitor cells in the neonatal and adult salivary glands

    International Nuclear Information System (INIS)

    Salivary gland stem/progenitor cells are thought to be present in intercalated ductal cells, but the fact is unclear. In this study, we sought to clarify if stem/progenitor cells are present in submandibular glands using colony assay, which is one of the stem cell assay methods. Using a low-density culture of submandibular gland cells of neonatal rats, we developed a novel culture system that promotes single cell colony formation. Average doubling time for the colony-forming cells was 24.7 (SD = ±7.02) h, indicating high proliferative potency. When epidermal growth factor (EGF) and hepatocyte growth factor (HGF) were added to the medium, the number of clonal colonies increased greater than those cultured without growth factors (13.2 ± 4.18 vs. 4.5 ± 1.73). The RT-PCR and immunostaining demonstrated expressing acinar, ductal, and myoepithelial cell lineage markers. This study demonstrated the presence of the salivary gland stem/progenitor cells that are highly proliferative and multipotent in salivary glands

  2. The CUL4-DDB1 ubiquitin ligase complex controls adult and embryonic stem cell differentiation and homeostasis.

    Science.gov (United States)

    Gao, Jie; Buckley, Shannon M; Cimmino, Luisa; Guillamot, Maria; Strikoudis, Alexandros; Cang, Yong; Goff, Stephen P; Aifantis, Iannis

    2015-11-27

    Little is known on post-transcriptional regulation of adult and embryonic stem cell maintenance and differentiation. Here we characterize the role of Ddb1, a component of the CUL4-DDB1 ubiquitin ligase complex. Ddb1 is highly expressed in multipotent hematopoietic progenitors and its deletion leads to abrogation of both adult and fetal hematopoiesis, targeting specifically transiently amplifying progenitor subsets. However, Ddb1 deletion in non-dividing lymphocytes has no discernible phenotypes. Ddb1 silencing activates Trp53 pathway and leads to significant effects on cell cycle progression and rapid apoptosis. The abrogation of hematopoietic progenitor cells can be partially rescued by simultaneous deletion of Trp53. Conversely, depletion of DDB1 in embryonic stem cell (ESC) leads to differentiation albeit negative effects on cell cycle and apoptosis. Mass spectrometry reveals differing protein interactions between DDB1 and distinct DCAFs, the substrate recognizing components of the E3 complex, between cell types. Our studies identify CUL4-DDB1 complex as a novel post-translational regulator of stem and progenitor maintenance and differentiation.

  3. In vivo sensitivity of the embryonic and adult neural stem cell compartments to low-dose radiation.

    Science.gov (United States)

    Barazzuol, Lara; Jeggo, Penny A

    2016-08-01

    The embryonic brain is radiation-sensitive, with cognitive deficits being observed after exposure to low radiation doses. Exposure of neonates to radiation can cause intracranial carcinogenesis. To gain insight into the basis underlying these outcomes, we examined the response of the embryonic, neonatal and adult brain to low-dose radiation, focusing on the neural stem cell compartments. This review summarizes our recent findings. At E13.5-14.5 the embryonic neocortex encompasses rapidly proliferating stem and progenitor cells. Exploiting mice with a hypomorphic mutation in DNA ligase IV (Lig4(Y288C) ), we found a high level of DNA double-strand breaks (DSBs) at E14.5, which we attribute to the rapid proliferation. We observed endogenous apoptosis in Lig4(Y288C) embryos and in WT embryos following exposure to low radiation doses. An examination of DSB levels and apoptosis in adult neural stem cell compartments, the subventricular zone (SVZ) and the subgranular zone (SGZ) revealed low DSB levels in Lig4(Y288C) mice, comparable with the levels in differentiated neuronal tissues. We conclude that the adult SVZ does not incur high levels of DNA breakage, but sensitively activates apoptosis; apoptosis was less sensitively activated in the SGZ, and differentiated neuronal tissues did not activate apoptosis. P5/P15 mice showed intermediate DSB levels, suggesting that DSBs generated in the embryo can be transmitted to neonates and undergo slow repair. Interestingly, this analysis revealed a stage of high endogenous apoptosis in the neonatal SVZ. Collectively, these studies reveal that the adult neural stem cell compartment, like the embryonic counterpart, can sensitively activate apoptosis. PMID:27125639

  4. Human embryonic and fetal mesenchymal stem cells differentiate toward three different cardiac lineages in contrast to their adult counterparts.

    Science.gov (United States)

    Ramkisoensing, Arti A; Pijnappels, Daniël A; Askar, Saïd F A; Passier, Robert; Swildens, Jim; Goumans, Marie José; Schutte, Cindy I; de Vries, Antoine A F; Scherjon, Sicco; Mummery, Christine L; Schalij, Martin J; Atsma, Douwe E

    2011-01-01

    Mesenchymal stem cells (MSCs) show unexplained differences in differentiation potential. In this study, differentiation of human (h) MSCs derived from embryonic, fetal and adult sources toward cardiomyocytes, endothelial and smooth muscle cells was investigated. Labeled hMSCs derived from embryonic stem cells (hESC-MSCs), fetal umbilical cord, bone marrow, amniotic membrane and adult bone marrow and adipose tissue were co-cultured with neonatal rat cardiomyocytes (nrCMCs) or cardiac fibroblasts (nrCFBs) for 10 days, and also cultured under angiogenic conditions. Cardiomyogenesis was assessed by human-specific immunocytological analysis, whole-cell current-clamp recordings, human-specific qRT-PCR and optical mapping. After co-culture with nrCMCs, significantly more hESC-MSCs than fetal hMSCs stained positive for α-actinin, whereas adult hMSCs stained negative. Furthermore, functional cardiomyogenic differentiation, based on action potential recordings, was shown to occur, but not in adult hMSCs. Of all sources, hESC-MSCs expressed most cardiac-specific genes. hESC-MSCs and fetal hMSCs contained significantly higher basal levels of connexin43 than adult hMSCs and co-culture with nrCMCs increased expression. After co-culture with nrCFBs, hESC-MSCs and fetal hMSCs did not express α-actinin and connexin43 expression was decreased. Conduction velocity (CV) in co-cultures of nrCMCs and hESC-MSCs was significantly higher than in co-cultures with fetal or adult hMSCs. In angiogenesis bioassays, only hESC-MSCs and fetal hMSCs were able to form capillary-like structures, which stained for smooth muscle and endothelial cell markers.Human embryonic and fetal MSCs differentiate toward three different cardiac lineages, in contrast to adult MSCs. Cardiomyogenesis is determined by stimuli from the cellular microenvironment, where connexin43 may play an important role.

  5. Inhibition of ref-1 stimulates the production of reactive oxygen species and induces differentiation in adult cardiac stem cells.

    Science.gov (United States)

    Gurusamy, Narasimman; Mukherjee, Subhendu; Lekli, Istvan; Bearzi, Claudia; Bardelli, Silvana; Das, Dipak K

    2009-03-01

    Redox effector protein-1 (Ref-1) plays an essential role in DNA repair and redox regulation of several transcription factors. In the present study, we examined the role of Ref-1 in maintaining the redox status and survivability of adult cardiac stem cells challenged with a subtoxic level of H2O2 under inhibition of Ref-1 by RNA interference. Treatment of cardiac stem cells with a low concentration of H2O2 induced Ref-1-mediated survival signaling through phosphorylation of Akt. However, Ref-1 inhibition followed by H2O2 treatment extensively induced the level of intracellular reactive oxygen species (ROS) through activation of the components of NADPH oxidase, like p22( phox ), p47( phox ), and Nox4. Cardiac differentiation markers (Nkx2.5, MEF2C, and GATA4), and cell death by apoptosis were significantly elevated in Ref-1 siRNA followed by H2O2-treated stem cells. Further, inhibition of Ref-1 increased the level of p53 but decreased the phosphorylation of Akt, a molecule involved in survival signaling. Treatment with ROS scavenger N-acetyl-L-cysteine attenuated Ref-1 siRNA-mediated activation of NADPH oxidase and cardiac differentiation. Taken together, these results indicate that Ref-1 plays an important role in maintaining the redox status of cardiac stem cells and protects them from oxidative injury-mediated cell death and differentiation.

  6. Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats.

    Science.gov (United States)

    Müller, Janine; Ossig, Christiana; Greiner, Johannes F W; Hauser, Stefan; Fauser, Mareike; Widera, Darius; Kaltschmidt, Christian; Storch, Alexander; Kaltschmidt, Barbara

    2015-01-01

    Parkinson's disease (PD) is considered the second most frequent and one of the most severe neurodegenerative diseases, with dysfunctions of the motor system and with nonmotor symptoms such as depression and dementia. Compensation for the progressive loss of dopaminergic (DA) neurons during PD using current pharmacological treatment strategies is limited and remains challenging. Pluripotent stem cell-based regenerative medicine may offer a promising therapeutic alternative, although the medical application of human embryonic tissue and pluripotent stem cells is still a matter of ethical and practical debate. Addressing these challenges, the present study investigated the potential of adult human neural crest-derived stem cells derived from the inferior turbinate (ITSCs) transplanted into a parkinsonian rat model. Emphasizing their capability to give rise to nervous tissue, ITSCs isolated from the adult human nose efficiently differentiated into functional mature neurons in vitro. Additional successful dopaminergic differentiation of ITSCs was subsequently followed by their transplantation into a unilaterally lesioned 6-hydroxydopamine rat PD model. Transplantation of predifferentiated or undifferentiated ITSCs led to robust restoration of rotational behavior, accompanied by significant recovery of DA neurons within the substantia nigra. ITSCs were further shown to migrate extensively in loose streams primarily toward the posterior direction as far as to the midbrain region, at which point they were able to differentiate into DA neurons within the locus ceruleus. We demonstrate, for the first time, that adult human ITSCs are capable of functionally recovering a PD rat model.

  7. STEM CELLS: Differentiated cells in a back-up role

    OpenAIRE

    Desai, Tushar J.; Krasnow, Mark A.

    2013-01-01

    Two independent studies show that, if push comes to shove, differentiated cells of the stomach and lung can act as adult stem cells generating various cell types of the tissue, including a pool of stem cells.

  8. Subcellular distribution of N-methyl-D-aspartic acid receptor subunit 1 in neural stem cells within subventricular zone of adult rats

    Institute of Scientific and Technical Information of China (English)

    Zhining Li; Wenlong Lü; Hongyan Dong; Hongbin Fan; Ruiguo Dong; Tiejun Xu

    2011-01-01

    The subcellular localization of N-methyl-D-aspartic acid receptor subunit 1 in neural stem cells of the subventricular zone of adult rats was detected using electron microscopy, following immunohistochemistry and immunogold-silver double staining. Results confirmed the presence of neural stem cells in the subventricular zone, which is a key neurogenic region in the central nervous system of adult mammals. The expression of N-methyl-D-aspartic acid receptor subunit 1 was higher than that of nestin and mainly distributed in the cell membrane, cytoplasm, rough endoplasmic reticulum and Golgi complex of neural stem cells.

  9. Stem cell migration after irradiation

    International Nuclear Information System (INIS)

    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.)

  10. In Vivo Tracking of Murine Adipose Tissue-Derived Multipotent Adult Stem Cells and Ex Vivo Cross-Validation

    Directory of Open Access Journals (Sweden)

    Chiara Garrovo

    2013-01-01

    Full Text Available Stem cells are characterized by the ability to renew themselves and to differentiate into specialized cell types, while stem cell therapy is believed to treat a number of different human diseases through either cell regeneration or paracrine effects. Herein, an in vivo and ex vivo near infrared time domain (NIR TD optical imaging study was undertaken to evaluate the migratory ability of murine adipose tissue-derived multipotent adult stem cells [mAT-MASC] after intramuscular injection in mice. In vivo NIR TD optical imaging data analysis showed a migration of DiD-labelled mAT-MASC in the leg opposite the injection site, which was confirmed by a fibered confocal microendoscopy system. Ex vivo NIR TD optical imaging results showed a systemic distribution of labelled cells. Considering a potential microenvironmental contamination, a cross-validation study by multimodality approaches was followed: mAT-MASC were isolated from male mice expressing constitutively eGFP, which was detectable using techniques of immunofluorescence and qPCR. Y-chromosome positive cells, injected into wild-type female recipients, were detected by FISH. Cross-validation confirmed the data obtained by in vivo/ex vivo TD optical imaging analysis. In summary, our data demonstrates the usefulness of NIR TD optical imaging in tracking delivered cells, giving insights into the migratory properties of the injected cells.

  11. Stimulation of adult neural stem cells with a novel glycolipid biosurfactant

    OpenAIRE

    Stipcevic, Tamara; Knight, Christopher P.; Kippin, Tod E.

    2013-01-01

    Glycolipids are amphipatic molecules which are highly expressed on cell membranes in skin and brain where they mediate several key cellular processes. Neural stem cells are defined as undifferentiated, proliferative, multipotential cells with extensive self-renewal and are responsive to brain injury. Di-rhamnolipid: α-L-rhamnopyranosyl-(1-2)α-L-rhamnopyranosyl-3-hydroxydecanoyl-3-hydroxydecanoic acid, also referred to as di-rhamnolipid BAC-3, is a glycolipid isolated from bacteria Pseudomonas...

  12. Intertwining extracellular nucleotides and their receptors with Ca2+ in determining adult neural stem cell survival, proliferation and final fate.

    Science.gov (United States)

    Lecca, Davide; Fumagalli, Marta; Ceruti, Stefania; Abbracchio, Maria P

    2016-08-01

    In the central nervous system (CNS), during both brain and spinal cord development, purinergic and pyrimidinergic signalling molecules (ATP, UTP and adenosine) act synergistically with peptidic growth factors in regulating the synchronized proliferation and final specification of multipotent neural stem cells (NSCs) to neurons, astrocytes or oligodendrocytes, the myelin-forming cells. Some NSCs still persist throughout adulthood in both specific 'neurogenic' areas and in brain and spinal cord parenchyma, retaining the potentiality to generate all the three main types of adult CNS cells. Once CNS anatomical structures are defined, purinergic molecules participate in calcium-dependent neuron-to-glia communication and also control the behaviour of adult NSCs. After development, some purinergic mechanisms are silenced, but can be resumed after injury, suggesting a role for purinergic signalling in regeneration and self-repair also via the reactivation of adult NSCs. In this respect, at least three different types of adult NSCs participate in the response of the adult brain and spinal cord to insults: stem-like cells residing in classical neurogenic niches, in particular, in the ventricular-subventricular zone (V-SVZ), parenchymal oligodendrocyte precursor cells (OPCs, also known as NG2-glia) and parenchymal injury-activated astrocytes (reactive astrocytes). Here, we shall review and discuss the purinergic regulation of these three main adult NSCs, with particular focus on how and to what extent modulation of intracellular calcium levels by purinoceptors is mandatory to determine their survival, proliferation and final fate.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377726

  13. The circadian clock in skin: implications for adult stem cells, tissue regeneration, cancer, aging, and immunity.

    Science.gov (United States)

    Plikus, Maksim V; Van Spyk, Elyse N; Pham, Kim; Geyfman, Mikhail; Kumar, Vivek; Takahashi, Joseph S; Andersen, Bogi

    2015-06-01

    Historically, work on peripheral circadian clocks has been focused on organs and tissues that have prominent metabolic functions, such as the liver, fat, and muscle. In recent years, skin has emerged as a model for studying circadian clock regulation of cell proliferation, stem cell functions, tissue regeneration, aging, and carcinogenesis. Morphologically, skin is complex, containing multiple cell types and structures, and there is evidence for a functional circadian clock in most, if not all, of its cell types. Despite the complexity, skin stem cell populations are well defined, experimentally tractable, and exhibit prominent daily cell proliferation cycles. Hair follicle stem cells also participate in recurrent, long-lasting cycles of regeneration: the hair growth cycles. Among other advantages of skin is a broad repertoire of available genetic tools enabling the creation of cell type-specific circadian mutants. Also, due to the accessibility of skin, in vivo imaging techniques can be readily applied to study the circadian clock and its outputs in real time, even at the single-cell level. Skin provides the first line of defense against many environmental and stress factors that exhibit dramatic diurnal variations such as solar ultraviolet (UV) radiation and temperature. Studies have already linked the circadian clock to the control of UVB-induced DNA damage and skin cancers. Due to the important role that skin plays in the defense against microorganisms, it also represents a promising model system to further explore the role of the clock in the regulation of the body's immune functions. To that end, recent studies have already linked the circadian clock to psoriasis, one of the most common immune-mediated skin disorders. Skin also provides opportunities to interrogate the clock regulation of tissue metabolism in the context of stem cells and regeneration. Furthermore, many animal species feature prominent seasonal hair molt cycles, offering an attractive model

  14. Transplantation of adult monkey neural stem cells into a contusion spinal cord injury model in rhesus macaque monkeys

    DEFF Research Database (Denmark)

    Nemati, Shiva Nemati; Jabbari, Reza; Hajinasrollah, Mostafa;

    2014-01-01

    OBJECTIVE: Currently, cellular transplantation for spinal cord injuries (SCI) is the subject of numerous preclinical studies. Among the many cell types in the adult brain, there is a unique subpopulation of neural stem cells (NSC) that can self-renew and differentiate into neurons. The study aims......, therefore, to explore the efficacy of adult monkey NSC (mNSC) in a primate SCI model. MATERIALS AND METHODS: In this experimental study, isolated mNSCs were analyzed by flow cytometry, immunocytochemistry, and RT-PCR. Next, BrdU-labeled cells were transplanted into a SCI model. The SCI animal model...... was confirmed by magnetic resonance imaging (MRI) and histological analysis. Animals were clinically observed for 6 months. RESULTS: Analysis confirmed homing of mNSCs into the injury site. Transplanted cells expressed neuronal markers (TubIII). Hind limb performance improved in trans- planted animals based...

  15. Pituitary Adenlylate Cyclase Activating Peptide Protects Adult Neural Stem Cells from a Hypoglycaemic milieu.

    Science.gov (United States)

    Mansouri, Shiva; Lietzau, Grazyna; Lundberg, Mathias; Nathanson, David; Nyström, Thomas; Patrone, Cesare

    2016-01-01

    Hypoglycaemia is a common side-effect of glucose-lowering therapies for type-2 diabetic patients, which may cause cognitive/neurological impairment. Although the effects of hypoglycaemia in the brain have been extensively studied in neurons, how hypoglycaemia impacts the viability of adult neural stem cells (NSCs) has been poorly investigated. In addition, the cellular and molecular mechanisms of how hypoglycaemia regulates NSCs survival have not been characterized. Recent work others and us have shown that the pituitary adenylate cyclase-activating polypeptide (PACAP) and the glucagon-like peptide-1 receptor (GLP-1R) agonist Exendin-4 stimulate NSCs survival against glucolipoapoptosis. The aim of this study was to establish an in vitro system where to study the effects of hypoglycaemia on NSC survival. Furthermore, we determine the potential role of PACAP and Exendin-4 in counteracting the effect of hypoglycaemia. A hypoglycaemic in vitro milieu was mimicked by exposing subventricular zone-derived NSC to low levels of glucose. Moreover, we studied the potential involvement of apoptosis and endoplasmic reticulum stress by quantifying protein levels of Bcl-2, cleaved caspase-3 and mRNA levels of CHOP. We show that PACAP via PAC-1 receptor and PKA activation counteracts impaired NSC viability induced by hypoglycaemia. The protective effect induced by PACAP correlated with endoplasmic reticulum stress, Exendin-4 was ineffective. The results show that hypoglycaemia decreases NSC viability and that this effect can be substantially counteracted by PACAP via PAC-1 receptor activation. The data supports a potential therapeutic role of PAC-1 receptor agonists for the treatment of neurological complications, based on neurogenesis impairment by hypoglycaemia. PMID:27305000

  16. Long-term culture of genome-stable bipotent stem cells from adult human liver

    NARCIS (Netherlands)

    Huch, Meritxell; Gehart, Helmuth; van Boxtel, Ruben; Hamer, Karien; Blokzijl, Francis; Verstegen, Monique M A; Ellis, Ewa; van Wenum, Martien; Fuchs, Sabine A; de Ligt, Joep; van de Wetering, Marc; Sasaki, Nobuo; Boers, Susanne J; Kemperman, Hans; de Jonge, Jeroen; Ijzermans, Jan N M; Nieuwenhuis, Edward E S; Hoekstra, Ruurdtje; Strom, Stephen; Vries, Robert R G; van der Laan, Luc J W; Cuppen, Edwin; Clevers, Hans

    2015-01-01

    Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be

  17. Sonic hedgehog controls stem cell behavior in the postnatal and adult brain

    OpenAIRE

    Palma, Veronica; Lim, D A; Dahmane, Nadia; Sanchez, Pilar; Brionne, T. C.; Herzberg, C. D.; Gitton, Yorick; Carleton, Alan; Alvarez-Buylla, Arturo; Ruiz Altaba, Ariel

    2005-01-01

    Sonic hedgehog (Shh) signaling controls many aspects of ontogeny, orchestrating congruent growth and patterning. During brain development, Shh regulates early ventral patterning while later on it is critical for the regulation of precursor proliferation in the dorsal brain, namely in the neocortex, tectum and cerebellum. We have recently shown that Shh also controls the behavior of cells with stem cell properties in the mouse embryonic neocortex, and additional studies have implicated it in t...

  18. Aberrant Neural Stem Cell Proliferation and Increased Adult Neurogenesis in Mice Lacking Chromatin Protein HMGB2

    OpenAIRE

    Abraham, Ariel B; Robert Bronstein; Avanish S Reddy; Mirjana Maletic-Savatic; Adan Aguirre; Tsirka, Stella E.

    2013-01-01

    Neural stem and progenitor cells (NSCs/NPCs) are distinct groups of cells found in the mammalian central nervous system (CNS). Previously we determined that members of the High Mobility Group (HMG) B family of chromatin structural proteins modulate NSC proliferation and self-renewal. Among them HMGB2 was found to be dynamically expressed in proliferating and differentiating NSCs, suggesting that it may regulate NSC maintenance. We report now that Hmgb2(-/-) mice exhibit SVZ hyperproliferation...

  19. Clinical application of stem cells: An update 2015

    OpenAIRE

    Van, Phuc Pham

    2016-01-01

    Stem cell transplantation has the long history of more than 50 years from the first bone marrow transplantation in 1957. From the 2000s, clinical applications of stem cells significantly increased with more diseases and more patients treated with stem cells. Both autologous stem cells and allogenic stem cells as well as adult stem cells and induced pluripotent stem cells (iPSCs), and both in vitro non-expanded stem cells and in vitro expanded stem cells were clinically applied. For adult stem...

  20. Polarity in Stem Cell Division: Asymmetric Stem Cell Division in Tissue Homeostasis

    OpenAIRE

    Yamashita, Yukiko M; Yuan, Hebao; Cheng, Jun; Hunt, Alan J.

    2010-01-01

    Many adult stem cells divide asymmetrically to balance self-renewal and differentiation, thereby maintaining tissue homeostasis. Asymmetric stem cell divisions depend on asymmetric cell architecture (i.e., cell polarity) within the cell and/or the cellular environment. In particular, as residents of the tissues they sustain, stem cells are inevitably placed in the context of the tissue architecture. Indeed, many stem cells are polarized within their microenvironment, or the stem cell niche, a...

  1. Urothelial Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Irena Dimov

    2010-01-01

    Full Text Available There is mounting evidence supporting the idea that tumors, similar to normal adult tissues, arise from a specific stem-like cell population, the cancer stem cells (CSCs, which are considered as the real driving force behind tumor growth, the ability to metastasize, as well as resistance to conventional antitumor therapy. The concept that cancer growth recapitulates normal proliferative and/or regenerative processes, even though in very dysfunctional ways, has tremendous implications for cancer therapy. The rapid development of the CSC field, shoulder to shoulder with powerful genome-wide screening techniques, has provided cause for optimism for the development of more reliable therapies in the future. However, several important issues still lie ahead. Recent identification of a highly tumorigenic stem-like compartment and existence of urothelial differentiation programs in urothelial cell carcinomas (UCCs raised important questions about UCC initiation and development. This review examines the present knowledge on CSCs in UCCs regarding the similarities between CSCs and the adult urothelial stem cells, potential origin of urothelial CSCs, main regulatory pathways, surface markers expression, and the current state of CSC-targeting therapeutic strategies.

  2. Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain.

    Science.gov (United States)

    Hemmer, Kathrin; Zhang, Mingyue; van Wüllen, Thea; Sakalem, Marna; Tapia, Natalia; Baumuratov, Aidos; Kaltschmidt, Christian; Kaltschmidt, Barbara; Schöler, Hans R; Zhang, Weiqi; Schwamborn, Jens C

    2014-09-01

    Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications. PMID:25241741

  3. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Kathrin Hemmer

    2014-09-01

    Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  4. Rapid and Efficient Direct Conversion of Human Adult Somatic Cells into Neural Stem Cells by HMGA2/let-7b

    Directory of Open Access Journals (Sweden)

    Kyung-Rok Yu

    2015-01-01

    Full Text Available A recent study has suggested that fibroblasts can be converted into mouse-induced neural stem cells (miNSCs through the expression of defined factors. However, successful generation of human iNSCs (hiNSCs has proven challenging to achieve. Here, using microRNA (miRNA expression profile analyses, we showed that let-7 microRNA has critical roles for the formation of PAX6/NESTIN-positive colonies from human adult fibroblasts and the proliferation and self-renewal of hiNSCs. HMGA2, a let-7-targeting gene, enables induction of hiNSCs that displayed morphological/molecular features and in vitro/in vivo differentiation potential similar to H9-derived NSCs. Interestingly, HMGA2 facilitated the efficient conversion of senescent somatic cells or blood CD34+ cells into hiNSCs through an interaction with SOX2, whereas other combinations or SOX2 alone showed a limited conversion ability. Taken together, these findings suggest that HMGA2/let-7 facilitates direct reprogramming toward hiNSCs in minimal conditions and maintains hiNSC self-renewal, providing a strategy for the clinical treatment of neurological diseases.

  5. Multipotential stem cells from the adult mouse brain proliferate and self-renew in response to basic fibroblast growth factor.

    Science.gov (United States)

    Gritti, A; Parati, E A; Cova, L; Frolichsthal, P; Galli, R; Wanke, E; Faravelli, L; Morassutti, D J; Roisen, F; Nickel, D D; Vescovi, A L

    1996-02-01

    It has been established that the adult mouse forebrain contains multipotential (neuronal/glial) progenitor cells that can be induced to proliferate in vitro when epidermal growth factor is provided. These cells are found within the subventricular zone of the lateral ventricles, together with other progenitor cell populations, whose requirements for proliferation remain undefined. Using basic fibroblast growth factor (bFGF), we have isolated multipotential progenitors from adult mouse striatum. These progenitors proliferate and can differentiate into cells displaying the antigenic properties of astrocytes, oligodendrocytes, and neurons. The neuron-like cells possess neuronal features, exhibit neuronal electrophysiological properties, and are immunoreactive for GABA, substance P, choline acetyl-transferase, and glutamate. Clonal analysis confirmed the multipotency of these bFGF-dependent cells. Most significantly, subcloning experiments demonstrated that they were capable of self-renewal, which led to a progressive increase in population size over serial passaging. These results demonstrate that bFGF is mitogenic for multipotential cells from adult mammalian forebrain that possess stem cell properties. PMID:8558238

  6. Hindsight/RREB-1 functions in both the specification and differentiation of stem cells in the adult midgut of Drosophila.

    Science.gov (United States)

    Baechler, Brittany L; McKnight, Cameron; Pruchnicki, Porsha C; Biro, Nicole A; Reed, Bruce H

    2015-01-01

    The adult Drosophila midgut is established during the larval/pupal transition from undifferentiated cells known as adult midgut precursors (AMPs). Four fundamental cell types are found in the adult midgut epithelium: undifferentiated intestinal stem cells (ISCs) and their committed daughter cells, enteroblasts (EBs), plus enterocytes (ECs) and enteroendocrine cells (EEs). Using the Drosophila posterior midgut as a model, we have studied the function of the transcription factor Hindsight (Hnt)/RREB-1 and its relationship to the Notch and Egfr signaling pathways. We show that hnt is required for EC differentiation in the context of ISC-to-EC differentiation, but not in the context of AMP-to-EC differentiation. In addition, we show that hnt is required for the establishment of viable or functional ISCs. Overall, our studies introduce hnt as a key factor in the regulation of both the developing and the mature adult midgut. We suggest that the nature of these contextual differences can be explained through the interaction of hnt with multiple signaling pathways. PMID:26658272

  7. Hindsight/RREB-1 functions in both the specification and differentiation of stem cells in the adult midgut of Drosophila

    Directory of Open Access Journals (Sweden)

    Brittany L. Baechler

    2016-01-01

    Full Text Available The adult Drosophila midgut is established during the larval/pupal transition from undifferentiated cells known as adult midgut precursors (AMPs. Four fundamental cell types are found in the adult midgut epithelium: undifferentiated intestinal stem cells (ISCs and their committed daughter cells, enteroblasts (EBs, plus enterocytes (ECs and enteroendocrine cells (EEs. Using the Drosophila posterior midgut as a model, we have studied the function of the transcription factor Hindsight (Hnt/RREB-1 and its relationship to the Notch and Egfr signaling pathways. We show that hnt is required for EC differentiation in the context of ISC-to-EC differentiation, but not in the context of AMP-to-EC differentiation. In addition, we show that hnt is required for the establishment of viable or functional ISCs. Overall, our studies introduce hnt as a key factor in the regulation of both the developing and the mature adult midgut. We suggest that the nature of these contextual differences can be explained through the interaction of hnt with multiple signaling pathways.

  8. Neural stem cell derived tumourigenesis

    OpenAIRE

    Francesca Froldi; Milán Szuperák; Cheng, Louise Y.

    2015-01-01

    In the developing Drosophila CNS, two pools of neural stem cells, the symmetrically dividing progenitors in the neuroepithelium (NE) and the asymmetrically dividing neuroblasts (NBs) generate the majority of the neurons that make up the adult central nervous system (CNS). The generation of a correct sized brain depends on maintaining the fine balance between neural stem cell self-renewal and differentiation, which are regulated by cell-intrinsic and cell-extrinsic cues. In this review, we wil...

  9. Enhanced Fitness of Adult Spermatogonial Stem Cells Bearing a Paternal Age-Associated FGFR2 Mutation

    Directory of Open Access Journals (Sweden)

    Laura A. Martin

    2014-08-01

    Full Text Available Pathogenic de novo mutations increase with fathers’ age and could be amplified through competition between genetically distinct subpopulations of spermatogonial stem cells (SSCs. Here, we tested the fitness of SSCs bearing wild-type human FGFR2 or an Apert syndrome mutant, FGFR2 (S252W, to provide experimental evidence for SSC competition. The S252W allele conferred enhanced FGFR2-mediated signaling, particularly at very low concentrations of ligand, and also subtle changes in gene expression. Mutant SSCs exhibited improved competitiveness in vitro and increased stem cell activity in vivo upon transplantation. The fitness advantage in vitro only occurred in low concentrations of fibroblast growth factor (FGF, was independent of FGF-driven proliferation, and was accompanied by increased response to glial cell line-derived neurotrophic factor (GDNF. Our studies provide experimental evidence of enhanced stem cell fitness in SSCs bearing a paternal age-associated mutation. Our model will be useful for interrogating other candidate mutations in the future to reveal mechanisms of disease risk.

  10. Fish Stem Cell Cultures

    OpenAIRE

    Ni Hong, Zhendong Li, Yunhan Hong

    2011-01-01

    Stem cells have the potential for self-renewal and differentiation. First stem cell cultures were derived 30 years ago from early developing mouse embryos. These are pluripotent embryonic stem (ES) cells. Efforts towards ES cell derivation have been attempted in other mammalian and non-mammalian species. Work with stem cell culture in fish started 20 years ago. Laboratory fish species, in particular zebrafish and medaka, have been the focus of research towards stem cell cultures. Medaka is th...

  11. Stem Cell Separation Technologies

    OpenAIRE

    Zhu, Beili; Murthy, Shashi K

    2013-01-01

    Stem cell therapy and translational stem cell research require large-scale supply of stem cells at high purity and viability, thus leading to the development of stem cell separation technologies. This review covers key technologies being applied to stem cell separation, and also highlights exciting new approaches in this field. First, we will cover conventional separation methods that are commercially available and have been widely adapted. These methods include Fluorescence-activated cell so...

  12. Three-dimensional approach to stem cell therapy.

    OpenAIRE

    Oh, Il-Hoan; Kim, Dong-Wook

    2002-01-01

    Recent progress in stem cell research is opening a new hope for cell therapy in regenerative medicine. Two breakthroughs were made in the stem cell era, one, new discoveries in multi-potentiality of adult stem cells beyond the traditionally appreciated extent, and the other, establishment of pluripotent stem cell from human embryo. In addition to the newly identified multi-potentiality of adult stem cells, their ability to be trans-differentiated toward other tissue types (stem cell plasticit...

  13. Cell Sorting of Neural Stem and Progenitor Cells from the Adult Mouse Subventricular Zone and Live-imaging of their Cell Cycle Dynamics.

    Science.gov (United States)

    Daynac, Mathieu; Morizur, Lise; Kortulewski, Thierry; Gauthier, Laurent R; Ruat, Martial; Mouthon, Marc-André; Boussin, François D

    2015-01-01

    Neural stem cells (NSCs) in the subventricular zone of the lateral ventricles (SVZ) sustain olfactory neurogenesis throughout life in the mammalian brain. They successively generate transit amplifying cells (TACs) and neuroblasts that differentiate into neurons once they integrate the olfactory bulbs. Emerging fluorescent activated cell sorting (FACS) techniques have allowed the isolation of NSCs as well as their progeny and have started to shed light on gene regulatory networks in adult neurogenic niches. We report here a cell sorting technique that allows to follow and distinguish the cell cycle dynamics of the above-mentioned cell populations from the adult SVZ with a LeX/EGFR/CD24 triple staining. Isolated cells are then plated as adherent cells to explore in details their cell cycle progression by time-lapse video microscopy. To this end, we use transgenic Fluorescence Ubiquitination Cell Cycle Indicator (FUCCI) mice in which cells are red-fluorescent during G1 phase due to a G1 specific red-Cdt1 reporter. This method has recently revealed that proliferating NSCs progressively lengthen their G1 phase during aging, leading to neurogenesis impairment. This method is easily transposable to other systems and could be of great interest for the study of the cell cycle dynamics of brain cells in the context of brain pathologies. PMID:26436641

  14. Cytoarchitecture and Ultrastructure of Neural Stem Cell Niches and Neurogenic Complexes Maintaining Adult Neurogenesis in the Olfactory Midbrain of Spiny Lobsters, Panulirus argus

    OpenAIRE

    Schmidt, Manfred; Derby, Charles D.

    2011-01-01

    New interneurons are continuously generated in small proliferation zones within neuronal somata clusters in the olfactory deutocerebrum of adult decapod crustaceans. Each proliferation zone is connected to a clump of cells containing one neural stem cell (i.e., adult neuroblast), thus forming a “neurogenic complex.” Here we provide a detailed analysis of the cytoarchitecture of neurogenic complexes in adult spiny lobsters, Panulirus argus, based on transmission electron microscopy and labelin...

  15. Dominant-Negative Effects of Adult-Onset Huntingtin Mutations Alter the Division of Human Embryonic Stem Cells-Derived Neural Cells

    Science.gov (United States)

    Lopes, Carla; Aubert, Sophie; Bourgois-Rocha, Fany; Barnat, Monia; Rego, Ana Cristina; Déglon, Nicole

    2016-01-01

    Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington’s disease (HD). HTT modulates mitotic spindle orientation and cell fate in mouse cortical progenitors from the ventricular zone. Using human embryonic stem cells (hESC) characterized as carrying mutations associated with adult-onset disease during pre-implantation genetic diagnosis, we investigated the influence of human HTT and of an adult-onset HD mutation on mitotic spindle orientation in human neural stem cells (NSCs) derived from hESCs. The RNAi-mediated silencing of both HTT alleles in neural stem cells derived from hESCs disrupted spindle orientation and led to the mislocalization of dynein, the p150Glued subunit of dynactin and the large nuclear mitotic apparatus (NuMA) protein. We also investigated the effect of the adult-onset HD mutation on the role of HTT during spindle orientation in NSCs derived from HD-hESCs. By combining SNP-targeting allele-specific silencing and gain-of-function approaches, we showed that a 46-glutamine expansion in human HTT was sufficient for a dominant-negative effect on spindle orientation and changes in the distribution within the spindle pole and the cell cortex of dynein, p150Glued and NuMA in neural cells. Thus, neural derivatives of disease-specific human pluripotent stem cells constitute a relevant biological resource for exploring the impact of adult-onset HD mutations of the HTT gene on the division of neural progenitors, with potential applications in HD drug discovery targeting HTT-dynein-p150Glued complex interactions. PMID:26863614

  16. Dominant-Negative Effects of Adult-Onset Huntingtin Mutations Alter the Division of Human Embryonic Stem Cells-Derived Neural Cells.

    Science.gov (United States)

    Lopes, Carla; Aubert, Sophie; Bourgois-Rocha, Fany; Barnat, Monia; Rego, Ana Cristina; Déglon, Nicole; Perrier, Anselme L; Humbert, Sandrine

    2016-01-01

    Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington's disease (HD). HTT modulates mitotic spindle orientation and cell fate in mouse cortical progenitors from the ventricular zone. Using human embryonic stem cells (hESC) characterized as carrying mutations associated with adult-onset disease during pre-implantation genetic diagnosis, we investigated the influence of human HTT and of an adult-onset HD mutation on mitotic spindle orientation in human neural stem cells (NSCs) derived from hESCs. The RNAi-mediated silencing of both HTT alleles in neural stem cells derived from hESCs disrupted spindle orientation and led to the mislocalization of dynein, the p150Glued subunit of dynactin and the large nuclear mitotic apparatus (NuMA) protein. We also investigated the effect of the adult-onset HD mutation on the role of HTT during spindle orientation in NSCs derived from HD-hESCs. By combining SNP-targeting allele-specific silencing and gain-of-function approaches, we showed that a 46-glutamine expansion in human HTT was sufficient for a dominant-negative effect on spindle orientation and changes in the distribution within the spindle pole and the cell cortex of dynein, p150Glued and NuMA in neural cells. Thus, neural derivatives of disease-specific human pluripotent stem cells constitute a relevant biological resource for exploring the impact of adult-onset HD mutations of the HTT gene on the division of neural progenitors, with potential applications in HD drug discovery targeting HTT-dynein-p150Glued complex interactions.

  17. Evaluation of a novel non-destructive catch and release technology for harvesting autologous adult stem cells.

    Directory of Open Access Journals (Sweden)

    Nicholas Bryan

    Full Text Available BACKGROUND: Cell based therapies are required now to meet the critical care needs of paediatrics and healthy ageing in an increasingly long-lived human population. Repair of compromised tissue by supporting autologous regeneration is a life changing objective uniting the fields of medical science and engineering. Adipose stem cells (adSCs are a compelling candidate for use in cell based medicine due to their plasticity and residence in numerous tissues. Adipose found in all animals contains a relatively high concentration of stem cells and is easily isolated by a minimally invasive clinical intervention; such as liposuction. METHODS: This study utilised primary rat adipose to validate a novel strategy for selecting adult stem cells. Experiments explored the use of large, very dense cell-specific antibody loaded isolation beads (diameter 5x-10x greater than target cells which overcome the problem of endocytosis and have proved to be very effective in cell isolation from minimally processed primary tissue. The technique also benefited from pH mediated release, which enabled elution of captured cells using a simple pH shift. RESULTS: Large beads successfully captured and released adSCs from rat adipose, which were characterised using a combination of microscopy, flow cytometry and PCR. The resultant purified cell population retains minimal capture artefact facilitating autologous reperfusion or application in in vitro models. CONCLUSION: Although evidenced here for adSCs, this approach provides a technological advance at a platform level; whereby it can be applied to isolate any cell population for which there is a characterised surface antigen.

  18. Mesenchymal Stem Cells and Tooth Engineering

    Institute of Scientific and Technical Information of China (English)

    Li Peng; Ling Ye; Xue-dong Zhou

    2009-01-01

    Tooth loss compromises human oral health. Although several prosthetic methods, such as artificial denture and dental implants, are clinical therapies to tooth loss problems, they are thought to have safety and usage time issues. Recently, tooth tissue engineering has attracted more and more attention. Stem cell based tissue engineering is thought to be a promising way to replace the missing tooth. Mesenchymal stem cells (MSCs) are multipotent stem cells which can differentiate into a variety of cell types. The potential MSCs for tooth regeneration mainly include stem cells from human exfoliated deciduous teeth (SHEDs), adult dental pulp stem cells (DPSCs), stem cells from the apical part of the papilla (SCAPs), stem cells from the dental follicle (DFSCs), periodontal ligament stem cells (PDLSCs) and bone marrow derived mesenchymal stem cells (BMSCs). This review outlines the recent progress in the mesenchymal stem cells used in tooth regeneration.

  19. Differences between the neurogenic and proliferative abilities of Müller glia with stem cell characteristics and the ciliary epithelium from the adult human eye

    OpenAIRE

    Bhatia, Bhairavi; Jayaram, Hari; Singhal, Shweta; Jones, Megan F; Limb, G. Astrid

    2011-01-01

    Much controversy has arisen on the nature and sources of stem cells in the adult human retina. Whilst ciliary epithelium has been thought to constitute a source of neural stem cells, a population of Müller glia in the neural retina has also been shown to exhibit neurogenic characteristics. This study aimed to compare the neurogenic and proliferative abilities between these two major cell populations. It also examined whether differences exist between the pigmented and non-pigmented ciliary ep...

  20. Adult Stem Cell Therapies for Wound Healing: Biomaterials and Computational Models

    OpenAIRE

    Tartarini, Daniele; Mele, Elisa

    2016-01-01

    The increased incidence of diabetes and tumors, associated with global demographic issues (aging and life styles), has pointed out the importance to develop new strategies for the effective management of skin wounds. Individuals affected by these diseases are in fact highly exposed to the risk of delayed healing of the injured tissue that typically leads to a pathological inflammatory state and consequently to chronic wounds. Therapies based on stem cells (SCs) have been proposed for the trea...

  1. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    Science.gov (United States)

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL). PMID:27000734

  2. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    Science.gov (United States)

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL).

  3. Stem Cell Networks

    OpenAIRE

    Werner, Eric

    2016-01-01

    We present a general computational theory of stem cell networks and their developmental dynamics. Stem cell networks are special cases of developmental control networks. Our theory generates a natural classification of all possible stem cell networks based on their network architecture. Each stem cell network has a unique topology and semantics and developmental dynamics that result in distinct phenotypes. We show that the ideal growth dynamics of multicellular systems generated by stem cell ...

  4. Limbal stem cell transplantation

    OpenAIRE

    Fernandes Merle; Sangwan Virender; Rao Srinivas; Basti Surendra; Sridhar Mittanamalli; Bansal Aashish; Dua Harminder

    2004-01-01

    The past two decades have witnessed remarkable progress in limbal stem cell transplantation. In addition to harvesting stem cells from a cadaver or a live related donor, it is now possible to cultivate limbal stem cells in vitro and then transplant them onto the recipient bed. A clear understanding of the basic disease pathology and a correct assessment of the extent of stem cell deficiency are essential. A holistic approach towards management of limbal stem cell deficiency is needed. This ...

  5. Stem cell research in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chengyi SUN; Shi ZUO

    2008-01-01

    The traditional view that adult human liver tumors, mainly hepatocellular carcinoma (HCC), arise from mature cell types has been challenged in recent dec-ades. The results of several studies suggest that HCC can be derived from liver stem cells. There are four levels of cells in the liver stem cell lineage: hepatocytes, hepatic stem cells/oval cells, bone marrow stem cells and hepato-pancreas stem cells. However, whether HCC is resulted from the differentiation block of stem cells and, moreover, which liver stem cell lineage is the source cell of hepatocarcinogenesis remain controversial. In this review, we focus on the current status of liver stem cell research and their roles in carcinogenesis of HCC, in order to explore new approaches for stem cell therapy of HCC.

  6. What are Stem Cells?

    OpenAIRE

    Ahmadshah Farhat; Ashraf Mohammadzadeh; M. Rezaie

    2014-01-01

      Stem cells are undifferentiated self regenerating multi potential cells. There are three types of stem cells categories by the ability to form after cells and correlated with the body’s development process. Totipotent: these stem cells can form an entire organism such as fertilized egg. Ploripotent: ploripotent cells are those that can form any cell in the body but cannot form an entire organism such as developing embryo’s totipotent cells become ploripotent  Multipotent: Multi potent stem ...

  7. Multipotent adult germ-line stem cells, like other pluripotent stem cells, can be killed by cytotoxic T lymphocytes despite low expression of major histocompatibility complex class I molecules

    Directory of Open Access Journals (Sweden)

    Nayernia Karim

    2009-08-01

    Full Text Available Abstract Background Multipotent adult germ-line stem cells (maGSCs represent a new pluripotent cell type that can be derived without genetic manipulation from spermatogonial stem cells (SSCs present in adult testis. Similarly to induced pluripotent stem cells (iPSCs, they could provide a source of cellular grafts for new transplantation therapies of a broad variety of diseases. To test whether these stem cells can be rejected by the recipients, we have analyzed whether maGSCs and iPSCs can become targets for cytotoxic T lymphocytes (CTL or whether they are protected, as previously proposed for embryonic stem cells (ESCs. Results We have observed that maGSCs can be maintained in prolonged culture with or without leukemia inhibitory factor and/or feeder cells and still retain the capacity to form teratomas in immunodeficient recipients. They were, however, rejected in immunocompetent allogeneic recipients, and the immune response controlled teratoma growth. We analyzed the susceptibility of three maGSC lines to CTL in comparison to ESCs, iPSCs, and F9 teratocarcinoma cells. Major histocompatibility complex (MHC class I molecules were not detectable by flow cytometry on these stem cell lines, apart from low levels on one maGSC line (maGSC Stra8 SSC5. However, using a quantitative real time PCR analysis H2K and B2m transcripts were detected in all pluripotent stem cell lines. All pluripotent stem cell lines were killed in a peptide-dependent manner by activated CTLs derived from T cell receptor transgenic OT-I mice after pulsing of the targets with the SIINFEKL peptide. Conclusion Pluripotent stem cells, including maGSCs, ESCs, and iPSCs can become targets for CTLs, even if the expression level of MHC class I molecules is below the detection limit of flow cytometry. Thus they are not protected against CTL-mediated cytotoxicity. Therefore, pluripotent cells might be rejected after transplantation by this mechanism if specific antigens are presented

  8. The Therapeutic Effect of Human Adult Stem Cells Derived from Adipose Tissue in Endotoxemic Rat Model

    Directory of Open Access Journals (Sweden)

    Soyoung Shin, Yonggoo Kim, Sikyoung Jeong, Sungyoup Hong, Insoo Kim, Woonjeong Lee, Seungphil Choi

    2013-01-01

    Full Text Available Excessive systemic inflammation following sepsis, trauma or burn could lead to multi-organ damage and death. Bone marrow stromal cells (BMSCs, commonly referred to as mesenchymal stem cells (MSCs, has been studied in several immune-associated diseases in human and animal by modulating the inflammatory response. Adipose tissue derived mesenchymal stem cells (ATSCs, which can be obtained more easily, compared with BMSCs, has emerged as an attractive alternative MSCs source for cell therapy. We investigated the therapeutic effects of human ATSCs (hATSCs in endotoxemic rat model and their capacity to modulate the inflammatory response. Endotoxemia was induced with Lipopolysaccaride intravenously injection (LPS, 10mg/kg. Animals were divided into the following three groups: (1 saline + saline (n=5, (2 LPS + saline (n=5 and (3 LPS + hATSCs (2x106 (n=5. The administration of LPS caused a consistent systemic inflammatory responses, increased concentrations of the pro-inflammatory cytokines that have an important role in sepsis. Treatment of endotoxemia with hATSCs decreased the level of inflammatory cytokines both in serum and in the lung, reduced inflammatory changes in the lung, prevented apoptosis in the kidney and improved multi-organ injury. In conclusion, our data demonstrates that hATSCs regulate the immue/inflammatory responses and improve multi-organ injury and they could be attractive candidates for cell therapy to treat endotoxemia.

  9. Adult hair follicle stem cells do not retain the older DNA strands in vivo during normal tissue homeostasis.

    Science.gov (United States)

    Waghmare, Sanjeev K; Tumbar, Tudorita

    2013-05-01

    Tissue stem cells have been proposed to segregate the chromosomes asymmetrically (in a non-random manner), thereby retaining preferentially the older "immortal" DNA strands bearing the stemness characteristics into one daughter cell, whereas the newly synthesized strands are segregated to the other daughter cell that will commit to differentiation. Moreover, this non-random segregation would protect the stem cell genome from accumulating multiple mutations during repeated DNA replication. This long-standing hypothesis remains an active subject of study due to conflicting results for some systems and lack of consistency among different tissue stem cell populations. In this review, we will focus on work done in the hair follicle, which is one of the best-understood vertebrate tissue stem cell system to date. In cell culture analysis of paired cultured keratinocytes derived from hair follicle, stem cells suggested a non-random segregation of chromosome with respect to the older DNA strand. In vivo, the hair follicle stem cells appear to self-renew and differentiate at different phases of their homeostatic cycle. The fate decisions occur in quiescence when some stem cells migrate out of their niche and commit to differentiation without self-renewal. The stem cells left behind in the niche self-renew symmetrically and randomly segregate the chromosomes at each division, making more stem cells. This model seems to apply to at least a few other vertebrate tissue stem cells in vivo. PMID:23681654

  10. Defects in ErbB-dependent establishment of adult melanocyte stem cells reveal independent origins for embryonic and regeneration melanocytes.

    Directory of Open Access Journals (Sweden)

    Keith A Hultman

    2009-07-01

    Full Text Available Adult stem cells are responsible for maintaining and repairing tissues during the life of an organism. Tissue repair in humans, however, is limited compared to the regenerative capabilities of other vertebrates, such as the zebrafish (Danio rerio. An understanding of stem cell mechanisms, such as how they are established, their self-renewal properties, and their recruitment to produce new cells is therefore important for the application of regenerative medicine. We use larval melanocyte regeneration following treatment with the melanocytotoxic drug MoTP to investigate these mechanisms in Melanocyte Stem Cell (MSC regulation. In this paper, we show that the receptor tyrosine kinase, erbb3b, is required for establishing the adult MSC responsible for regenerating the larval melanocyte population. Both the erbb3b mutant and wild-type fish treated with the ErbB inhibitor, AG1478, develop normal embryonic melanocytes but fail to regenerate melanocytes after MoTP-induced melanocyte ablation. By administering AG1478 at different time points, we show that ErbB signaling is only required for regeneration prior to MoTP treatment and before 48 hours of development, consistent with a role in establishing MSCs. We then show that overexpression of kitla, the Kit ligand, in transgenic larvae leads to recruitment of MSCs, resulting in overproliferation of melanocytes. Furthermore, kitla overexpression can rescue AG1478-blocked regeneration, suggesting that ErbB signaling is required to promote the progression and specification of the MSC from a pre-MSC state. This study provides evidence that ErbB signaling is required for the establishment of adult MSCs during embryonic development. That this requirement is not shared with the embryonic melanocytes suggests that embryonic melanocytes develop directly, without proceeding through the ErbB-dependent MSC. Moreover, the shared requirement of larval melanocyte regeneration and metamorphic melanocytes that develops at

  11. Stem cells for spine surgery.

    Science.gov (United States)

    Schroeder, Joshua; Kueper, Janina; Leon, Kaplan; Liebergall, Meir

    2015-01-26

    In the past few years, stem cells have become the focus of research by regenerative medicine professionals and tissue engineers. Embryonic stem cells, although capable of differentiating into cell lineages of all three germ layers, are limited in their utilization due to ethical issues. In contrast, the autologous harvest and subsequent transplantation of adult stem cells from bone marrow, adipose tissue or blood have been experimentally utilized in the treatment of a wide variety of diseases ranging from myocardial infarction to Alzheimer's disease. The physiologic consequences of stem cell transplantation and its impact on functional recovery have been studied in countless animal models and select clinical trials. Unfortunately, the bench to bedside translation of this research has been slow. Nonetheless, stem cell therapy has received the attention of spinal surgeons due to its potential benefits in the treatment of neural damage, muscle trauma, disk degeneration and its potential contribution to bone fusion. PMID:25621119

  12. Stem cells for spine surgery

    Institute of Scientific and Technical Information of China (English)

    Joshua Schroeder; Janina Kueper; Kaplan Leon; Meir Liebergall

    2015-01-01

    In the past few years, stem cells have become the focusof research by regenerative medicine professionals andtissue engineers. Embryonic stem cells, although capableof differentiating into cell lineages of all three germlayers, are limited in their utilization due to ethical issues.In contrast, the autologous harvest and subsequenttransplantation of adult stem cells from bone marrow,adipose tissue or blood have been experimentally utilizedin the treatment of a wide variety of diseases rangingfrom myocardial infarction to Alzheimer's disease. Thephysiologic consequences of stem cell transplantationand its impact on functional recovery have been studiedin countless animal models and select clinical trials.Unfortunately, the bench to bedside translation of thisresearch has been slow. Nonetheless, stem cell therapyhas received the attention of spinal surgeons due to itspotential benefits in the treatment of neural damage,muscle trauma, disk degeneration and its potentialcontribution to bone fusion.

  13. Lgr proteins in epithelial stem cell biology

    NARCIS (Netherlands)

    Barker, N.; Tan, S.; Clevers, H.

    2013-01-01

    The ultimate success of global efforts to exploit adult stem cells for regenerative medicine will depend heavily on the availability of robust, highly selective stem cell surface markers that facilitate the isolation of stem cells from human tissues. Any subsequent expansion or manipulation of isola

  14. 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...

  15. Sphingosine-1-phosphate mediates proliferation maintaining the multipotency of human adult bone marrow and adipose tissue-derived stem cells.

    Science.gov (United States)

    He, Xiaoli; H'ng, Shiau-Chen; Leong, David T; Hutmacher, Dietmar W; Melendez, Alirio J

    2010-08-01

    High renewal and maintenance of multipotency of human adult stem cells (hSCs), are a prerequisite for experimental analysis as well as for potential clinical usages. The most widely used strategy for hSC culture and proliferation is using serum. However, serum is poorly defined and has a considerable degree of inter-batch variation, which makes it difficult for large-scale mesenchymal stem cells (MSCs) expansion in homogeneous culture conditions. Moreover, it is often observed that cells grown in serum-containing media spontaneously differentiate into unknown and/or undesired phenotypes. Another way of maintaining hSC development is using cytokines and/or tissue-specific growth factors; this is a very expensive approach and can lead to early unwanted differentiation. In order to circumvent these issues, we investigated the role of sphingosine-1-phosphate (S1P), in the growth and multipotency maintenance of human bone marrow and adipose tissue-derived MSCs. We show that S1P induces growth, and in combination with reduced serum, or with the growth factors FGF and platelet-derived growth factor-AB, S1P has an enhancing effect on growth. We also show that the MSCs cultured in S1P-supplemented media are able to maintain their differentiation potential for at least as long as that for cells grown in the usual serum-containing media. This is shown by the ability of cells grown in S1P-containing media to be able to undergo osteogenic as well as adipogenic differentiation. This is of interest, since S1P is a relatively inexpensive natural product, which can be obtained in homogeneous high-purity batches: this will minimize costs and potentially reduce the unwanted side effects observed with serum. Taken together, S1P is able to induce proliferation while maintaining the multipotency of different human stem cells, suggesting a potential for S1P in developing serum-free or serum-reduced defined medium for adult stem cell cultures.

  16. Development and application of stem cells

    Institute of Scientific and Technical Information of China (English)

    HUI Guo-zhen; SHAN Li-dong

    2005-01-01

    @@ Stem cells are defined by two important characteristics: the ability to proliferate by a process of self-renewal and the potential to form at least one specialized cell type. Transient population of pluripotent or multipotent stem cells first appear during the development at the first days post coitum. The cells of the inner cell mass (ICM) of the blastocyst, of which embryonic stem cells (ES) are the in vitro counterpart, can give rise to any differentiated cell type in the three primary germ layers of the embryo (endoderm, mesoderm and ectoderm).1-3 These cells gradually mature into committed, organ- and tissue-specific stem cells or adult stem cells, such as neural stem cells, mesenchymal stem cells, hematopoietic stem cells, etc. Over the past years, studies have focused on two aspects: molecular level and application, and some new methods and technology have been used.

  17. Effects of FGF-2 on human adipose tissue derived adult stem cells morphology and chondrogenesis enhancement in Transwell culture

    International Nuclear Information System (INIS)

    Highlights: ► We investigated effects of FGF-2 on hADSCs. ► We examine changes in the level of gene expressions of SOX-9, aggrecan and collagen type II and type X. ► FGF-2 induces chondrogenesis in hADSCs, which •Increasing information will decrease quality if hospital costs are very different. ► The result of this study may be beneficial in cartilage tissue engineering. -- Abstract: Injured cartilage is difficult to repair due to its poor vascularisation. Cell based therapies may serve as tools to more effectively regenerate defective cartilage. Both adult mesenchymal stem cells (MSCs) and human adipose derived stem cells (hADSCs) are regarded as potential stem cell sources able to generate functional cartilage for cell transplantation. Growth factors, in particular the TGF-b superfamily, influence many processes during cartilage formation, including cell proliferation, extracellular matrix synthesis, maintenance of the differentiated phenotype, and induction of MSCs towards chondrogenesis. In the current study, we investigated the effects of FGF-2 on hADSC morphology and chondrogenesis in Transwell culture. hADSCs were obtained from patients undergoing elective surgery, and then cultured in expansion medium alone or in the presence of FGF-2 (10 ng/ml). mRNA expression levels of SOX-9, aggrecan and collagen type II and type X were quantified by real-time polymerase chain reaction. The morphology, doubling time, trypsinization time and chondrogenesis of hADSCs were also studied. Expression levels of SOX-9, collagen type II, and aggrecan were all significantly increased in hADSCs expanded in presence of FGF-2. Furthermore FGF-2 induced a slender morphology, whereas doubling time and trypsinization time decreased. Our results suggest that FGF-2 induces hADSCs chondrogenesis in Transwell culture, which may be beneficial in cartilage tissue engineering.

  18. Effects of FGF-2 on human adipose tissue derived adult stem cells morphology and chondrogenesis enhancement in Transwell culture

    Energy Technology Data Exchange (ETDEWEB)

    Kabiri, Azadeh, E-mail: z_kabiri@resident.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Esfandiari, Ebrahim, E-mail: esfandiari@med.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Hashemibeni, Batool, E-mail: hashemibeni@med.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Kazemi, Mohammad, E-mail: m_kazemi@med.mui.ac.i [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Mardani, Mohammad, E-mail: mardani@med.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Esmaeili, Abolghasem, E-mail: abesmaeili@yahoo.com [Cell, Molecular and Developmental Biology Division, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan (Iran, Islamic Republic of)

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer We investigated effects of FGF-2 on hADSCs. Black-Right-Pointing-Pointer We examine changes in the level of gene expressions of SOX-9, aggrecan and collagen type II and type X. Black-Right-Pointing-Pointer FGF-2 induces chondrogenesis in hADSCs, which Bullet Increasing information will decrease quality if hospital costs are very different. Black-Right-Pointing-Pointer The result of this study may be beneficial in cartilage tissue engineering. -- Abstract: Injured cartilage is difficult to repair due to its poor vascularisation. Cell based therapies may serve as tools to more effectively regenerate defective cartilage. Both adult mesenchymal stem cells (MSCs) and human adipose derived stem cells (hADSCs) are regarded as potential stem cell sources able to generate functional cartilage for cell transplantation. Growth factors, in particular the TGF-b superfamily, influence many processes during cartilage formation, including cell proliferation, extracellular matrix synthesis, maintenance of the differentiated phenotype, and induction of MSCs towards chondrogenesis. In the current study, we investigated the effects of FGF-2 on hADSC morphology and chondrogenesis in Transwell culture. hADSCs were obtained from patients undergoing elective surgery, and then cultured in expansion medium alone or in the presence of FGF-2 (10 ng/ml). mRNA expression levels of SOX-9, aggrecan and collagen type II and type X were quantified by real-time polymerase chain reaction. The morphology, doubling time, trypsinization time and chondrogenesis of hADSCs were also studied. Expression levels of SOX-9, collagen type II, and aggrecan were all significantly increased in hADSCs expanded in presence of FGF-2. Furthermore FGF-2 induced a slender morphology, whereas doubling time and trypsinization time decreased. Our results suggest that FGF-2 induces hADSCs chondrogenesis in Transwell culture, which may be beneficial in cartilage tissue engineering.

  19. [Stem cells and cardiac regeneration].

    Science.gov (United States)

    Perez Millan, Maria Ines; Lorenti, Alicia

    2006-01-01

    Stem cells are defined by virtue of their functional attributes: absence of tissue specific differentitated markers, capable of proliferation, able to self-maintain the population, able to produce a large number of differentiated, functional progeny, able to regenerate the tissue after injury. Cell therapy is an alternative for the treatment of several diseases, like cardiac diseases (cell cardiomyoplasty). A variety of stem cells could be used for cardiac repair: from cardiac and extracardiac sources. Each cell type has its own profile of advantages, limitations, and practicability issues in specific clinical settings. Differentiation of bone marrow stem cells to cardiomyocyte-like cells have been observed under different culture conditions. The presence of resident cardiac stem cell population capable of differentiation into cardiomyocyte or vascular lineage suggests that these cells could be used for cardiac tissue repair, and represent a great promise for clinical application. Stem cells mobilization by cytokines may also offer a strategy for cardiac regeneration. The use of stem cells (embryonic and adult) may hold the key to replacing cells lost in many devastating diseases. This potential benefit is a major focus for stem cell research.

  20. Hepatic stem cell niches

    OpenAIRE

    Kordes, Claus; Häussinger, Dieter

    2013-01-01

    Stem cell niches are special microenvironments that maintain stem cells and control their behavior to ensure tissue homeostasis and regeneration throughout life. The liver has a high regenerative capacity that involves stem/progenitor cells when the proliferation of hepatocytes is impaired. In recent years progress has been made in the identification of potential hepatic stem cell niches. There is evidence that hepatic progenitor cells can originate from niches in the canals...

  1. Intraoperative Stem Cell Therapy

    OpenAIRE

    Coelho, Mónica Beato; Cabral, Joaquim M. S.; Karp, Jeffrey M.

    2012-01-01

    Stem cells hold significant promise for regeneration of tissue defects and disease-modifying therapies. Although numerous promising stem cell approaches are advancing in clinical trials, intraoperative stem cell therapies offer more immediate hope by integrating an autologous cell source with a well-established surgical intervention in a single procedure. Herein, the major developments in intraoperative stem cell approaches, from in vivo models to clinical studies, are reviewed, and the poten...

  2. Medaka fish stem cells and their applications

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Stem cells are present in developing embryos and adult tissues of multicellular organisms. Owing to their unique features, stem cells provide excellent opportunities for experimental analyses of basic developmental processes such as pluripotency control and cell fate decision and for regenerative medicine by stem cell-based therapy. Stem cell cultures have been best studied in 3 vertebrate organisms. These are the mouse, human and a small laboratory fish called medaka. Specifically, medaka has given rise to the first embryonic stem (ES) cells besides the mouse, the first adult testis-derived male stem cells spermatogonia capable of test-tube sperm production, and most recently, even haploid ES cells capable of producing Holly, a semi-cloned fertile female medaka from a mosaic oocyte created by microinjecting a haploid ES cell nucleus directly into a normal oocyte. These breakthroughs make medaka a favoring vertebrate model for stem cell research, the topic of this review.

  3. Adult hair follicle stem cells do not retain the older DNA strands in vivo during normal tissue homeostasis

    OpenAIRE

    Waghmare, Sanjeev K; Tumbar, Tudorita

    2013-01-01

    Tissue stem cells have been proposed to segregate the chromosomes asymmetrically (in a non-random manner) thereby retaining preferentially the older ‘immortal’ DNA strand bearing the stemness characteristics into one daughter cell, whereas the newly synthesized strands are segregated to the other daughter cells that will commit to differentiation. Moreover, this non-random segregation would protect the stem cell genome from accumulating multiple mutations during repeated DNA replication. This...

  4. Hyaluronan and Fibrin Biomaterial as Scaffolds for Neuronal Differentiation of Adult Stem Cells Derived from Adipose Tissue and Skin

    Directory of Open Access Journals (Sweden)

    Chiara Gardin

    2011-10-01

    Full Text Available Recently, we have described a simple protocol to obtain an enriched culture of adult stem cells organized in neurospheres from two post-natal tissues: skin and adipose tissue. Due to their possible application in neuronal tissue regeneration, here we tested two kinds of scaffold well known in tissue engineering application: hyaluronan based membranes and fibrin-glue meshes. Neurospheres from skin and adipose tissue were seeded onto two scaffold types: hyaluronan based membrane and fibrin-glue meshes. Neurospheres were then induced to acquire a glial and neuronal-like phenotype. Gene expression, morphological feature and chromosomal imbalance (kariotype were analyzed and compared. Adipose and skin derived neurospheres are able to grow well and to differentiate into glial/neuron cells without any chromosomal imbalance in both scaffolds. Adult cells are able to express typical cell surface markers such as S100; GFAP; nestin; βIII tubulin; CNPase. In summary, we have demonstrated that neurospheres isolated from skin and adipose tissues are able to differentiate in glial/neuron-like cells, without any chromosomal imbalance in two scaffold types, useful for tissue engineering application: hyaluronan based membrane and fibrin-glue meshes.

  5. In Vivo Targeting of Adult Neural Stem Cells in the Dentate Gyrus by a Split-Cre Approach

    OpenAIRE

    Ruth Beckervordersandforth; Aditi Deshpande; Iris Schäffner; Hagen B. Huttner; Alexandra Lepier; Dieter Chichung Lie; Magdalena Götz

    2014-01-01

    Summary We describe the labeling of adult neural stem cells (aNSCs) in the mouse and human dentate gyrus (DG) by the combinatorial expression of glial fibrillary acidic protein (GFAP) and Prominin1, as revealed by immunohistochemistry. Split-Cre-based genetic fate mapping of these double-positive cells in the adult murine DG reveals their NSC identity, as they are self-renewing and contribute to neurogenesis over several months. Their progeny reacts to stimuli such as voluntary exercise with ...

  6. Preliminary Study on Biological Properties of Adult Human Bone Marrow-derived Mesenchymal Stem Cells

    Institute of Scientific and Technical Information of China (English)

    WU Tao; BAI Hai; WANG Jingchang; SHI Jingyun; WANG Cunbang; LU Jihong; OU Jianfeng; WANG Qian

    2006-01-01

    Objective: To establish a method of culture and expansion of adult human bone marrow-derived MSCs in vitro and to explore their biological properties. Methods: Mononuclear cells were obtained from 5 mL adult human bone marrow by density gradient centrifugation with Percoll solution. Adult human MSCs were cultured in Dulbecco's Modified Eagle's Medium with low glucose (LG-DMEM) containing 10% fetal calf serum at a density of 2× 105 cell/cm2. The morphocytology was observed under phase-contrast microscope. The cell growth was measured by MTT method. The flow cytometer was performed to examine the expression of cell surface molecules and cell cycle. The ultrastructure of MSCs was observed under transmission electron microscope. The immunomodulatory functions of MSCs were measured by MTT method. The effects of MSCs on the growth of K562 cells and the dynamic change of HA, Ⅳ-C, LN concentration in the culture supernatant of MSCs was also observed. Results: The MSCs harvested in this study were homogenous population and exhibited a spindle-shaped fibroblastic morphology. The cell growth curve showed that MSCs had a strong ability of proliferation. The cells were positive for CD44,while negative for hematopoietic cell surface marker such as CD3, CD4, CD7, CD13, CD14, CD15, CD19,CD22, CD33, CD34, CD45 and HLA-DR, which was closely related to graft versus host disease. Above 90% cells of MSCs were found at G0/G1 phase. The ultrastructure of MSCs indicated that there were plenty of cytoplasmic organelles. Allogeneic peripheral blood lymphocytes proliferation was suppressed by MSCs and the inhibition ratio was 60.68% (P<0.01). The suppressive effect was also existed in the culture supernatant of MSCs and the inhibition ratio was 9.00% (P<0.05). When lymphocytes were stimulated by PHA, the suppression effects of the culture supernatant were even stronger and the inhibition ratio was 20.91%(P<0.01). Compared with the cell growth curve of the K562 cells alone, the K562

  7. Optimizing stem cell culture.

    OpenAIRE

    van der Sanden, Boudewijn; Dhobb, Mehdi; Berger, François; Wion, Didier

    2010-01-01

    International audience Stem cells always balance between self-renewal and differentiation. Hence, stem cell culture parameters are critical and need to be continuously refined according to progress in our stem cell biology understanding and the latest technological developments. In the past few years, major efforts have been made to define more precisely the medium composition in which stem cells grow or differentiate. This led to the progressive replacement of ill-defined additives such a...

  8. Genetic inactivation of Cdk7 leads to cell cycle arrest and induces premature aging due to adult stem cell exhaustion

    OpenAIRE

    Ganuza, Miguel; Sáiz-Ladera, Cristina; Cañamero, Marta; Gómez, Gonzalo; Schneider, Ralph; Blasco, María A.; Pisano, David; Paramio, Jesús M.; Santamaría, David; Barbacid, Mariano

    2012-01-01

    Employing a conditionally inactive gene trap allele, Cdk7's function in regulating cellular proliferation by Cdk1/2-phosphorylation is convincingly dissected from alternative notions on CTD-phosphorylation of RNA Pol II. Premature aging phenotypes caused by stem cell depletion lend the necessary functional support.

  9. Information on Stem Cell Research

    Science.gov (United States)

    ... Enhancing Diversity Find People About NINDS Information on Stem Cell Research Research @ NINDS Stem Cell Highlights Submit a hESC ... found here: Human Induced Pluripotent Stem Cells NINDS Stem Cell Research on Campus The Intramural Research Program of NINDS ...

  10. Strategies to control human cytomegalovirus infection in adult hematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Lilleri, Daniele; Gerna, Giuseppe

    2016-09-01

    Human cytomegalovirus (HCMV) represents the major viral complication after hematopoietic stem cell transplantation. HCMV infection may be controlled by the reconstituting immune system and remain subclinical or can lead to severe systemic and/or organ disease (mainly pneumonia and gastroenteritis) when immune reconstitution is delayed or impaired. In order to prevent the occurrence of HCMV disease, a prompt diagnosis of HCMV infection is mandatory. The adoption of pre-emptive therapy strategies guided by virological monitoring dramatically reduced the occurrence of HCMV disease. However, late-onset end-organ disease may occur in some patients with apparent immune reconstitution. In the near future, introduction of immunological monitoring and immunotherapies could markedly improve management of HCMV infection. PMID:27485084

  11. The effects of viscoelastic polymer substrates on adult stem cell differentiation

    Science.gov (United States)

    Chang, Chungchueh; Fields, Adam; Ramek, Alex; Jurukovski, Vladimir; Simon, Marcia; Rafailovich, Miriam

    2009-03-01

    Dental Pulp Stem Cells (DPSCs) are known to differentiate in either bone, dentine, or nerve tissue by different environment signals. In this study, we have determined whether differentiation could only through modification of the substrate mechanics. Atomic Force Microscopy (AFM) on Shear Modulation Force Microscopy (SMFM) mode indicated that the spun-cast polybutadiene (PB) thin films could be used to provide different stiffness substrates by changing the thicknesses of thin films. DPSCs were then plated on these substrates and cultured in standard media. After 28 days incubation, Lasar Scanning Confocal Microscopy (LSCM) with mercury lamp indicated that the crystals were observed only on hard surfaces. The Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray analysis (EDX analysis) indicated that the crystals are calcium phosphates. The Glancing Incidence Diffraction (GID) was also used to determine the structure of crystals. These results indicate that DPSCs could be differentiated into osteoblasts by mechanical stimuli from substrate mechanics.

  12. 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.

  13. Lung Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Sharon R. Pine

    2008-01-01

    Full Text Available Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapies. Recent data indicates that stem cells situated throughout the airways may initiate cancer formation. These putative stem cells maintain protumorigenic characteristics including high proliferative capacity, multipotent differentiation, drug resistance and long lifespan relative to other cells. Stem cell signaling and differentiation pathways are maintained within distinct cancer types, and destabilization of this machinery may participate in maintenance of cancer stem cells. Characterization of lung cancer stem cells is an area of active research and is critical for developing novel therapies. This review summarizes the current knowledge on stem cell signaling pathways and cell markers used to identify the lung cancer stem cells.

  14. Adult Stem Cell Therapies for Wound Healing: Biomaterials and Computational Models.

    Science.gov (United States)

    Tartarini, Daniele; Mele, Elisa

    2015-01-01

    The increased incidence of diabetes and tumors, associated with global demographic issues (aging and life styles), has pointed out the importance to develop new strategies for the effective management of skin wounds. Individuals affected by these diseases are in fact highly exposed to the risk of delayed healing of the injured tissue that typically leads to a pathological inflammatory state and consequently to chronic wounds. Therapies based on stem cells (SCs) have been proposed for the treatment of these wounds, thanks to the ability of SCs to self-renew and specifically differentiate in response to the target bimolecular environment. Here, we discuss how advanced biomedical devices can be developed by combining SCs with properly engineered biomaterials and computational models. Examples include composite skin substitutes and bioactive dressings with controlled porosity and surface topography for controlling the infiltration and differentiation of the cells. In this scenario, mathematical frameworks for the simulation of cell population growth can provide support for the design of bioconstructs, reducing the need of expensive, time-consuming, and ethically controversial animal experimentation. PMID:26793702

  15. Regulatory networks define phenotypic classes of human stem cell lines

    OpenAIRE

    Müller, Franz-Josef; Louise C. Laurent; Kostka, Dennis; Ulitsky, Igor; Williams, Roy; Lu, Christina; Park, In-Hyun; Rao, Mahendra S.; Shamir, Ron; Philip H. Schwartz; Schmidt, Nils O.; Loring, Jeanne F.

    2008-01-01

    Stem cells are defined as self-renewing cell populations that can differentiate into multiple distinct cell types. However, hundreds of different human cell lines from embryonic, fetal, and adult sources have been called stem cells, even though they range from pluripotent cells, typified by embryonic stem cells, which are capable of virtually unlimited proliferation and differentiation, to adult stem cell lines, which can generate a far more limited repertory of differentiated cell types. The...

  16. p53 in stem cells

    Institute of Scientific and Technical Information of China (English)

    Valeriya; Solozobova; Christine; Blattner

    2011-01-01

    p53 is well known as a "guardian of the genome" for differentiated cells,in which it induces cell cycle arrest and cell death after DNA damage and thus contributes to the maintenance of genomic stability.In addition to this tumor suppressor function for differentiated cells,p53 also plays an important role in stem cells.In this cell type,p53 not only ensures genomic integrity after genotoxic insults but also controls their proliferation and differentiation.Additionally,p53 provides an effective barrier for the generation of pluripotent stem celllike cells from terminally differentiated cells.In this review,we summarize our current knowledge about p53 activities in embryonic,adult and induced pluripotent stem cells.

  17. Research progress of adult cardiac stem cells%成体心肌干细胞的研究进展

    Institute of Scientific and Technical Information of China (English)

    郑楠; 张宁坤; 高连如

    2013-01-01

    传统观点认为心脏是一个终末分化器官,然而随着成体心肌干细胞(CSCs)的发现,这种观点已受到广泛质疑.由于CSCs具有高度的自我更新能力和特异性心肌分化潜能,目前被认为是最有希望应用于缺血性心脏病及其他终末期心脏病替代治疗的干细胞类型.本文综述了目前关于人源CSCs、心外膜源细胞(EPDC)的研究概况,及其应用于心脏再生领域的治疗策略和研究中存在的问题.%The traditional view is that the heart is a terminal organ. This dogma, however, has been widely questioned with the discovery of adult cardiac stem cells (CSCs). Since CSCs have a highly self-renewal capacity and specific myocardial differentiation potential, nowadays they have been regarded as the most promising type of stem cells used in ischemic heart disease and other replacement therapy of end-stage heart disease. The present paper will focus on current results of scientific research on human adult CSCs and epicardium-derived cell (EPDC), as well as the treatment strategies in the field of cardiac regeneration, and the problems and prospect disclosed in the research.

  18. Advances in haplo-identical stem cell transplantation in adults with high-risk hematological malignancies

    Institute of Scientific and Technical Information of China (English)

    Michael; J; Ricci; Jeffrey; A; Medin; Ronan; S; Foley

    2014-01-01

    Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of donor hematopoietic cell grafts have significantly improved overall rates of success. Yet, the outcomes for patients for whom suitable donors cannot be found remain a significant limitation. These patients may benefit from a hematopoietic cell transplant wherein a relative donor is fully haplotype mismatched. Previously this procedure was limited by graft rejection, lethal graft-versus-host disease, and increased treatmentrelated toxicity. Recent approaches in haplo-identical transplantation have demonstrated significantly improved outcomes. Based on years of incremental preclinical research into this unique form of bone marrow transplant, a range of approaches have now been studied in patients in relatively large phase Ⅱ trials that will be summarized in this review.

  19. Present status and prospect in the clinical use of adult stem cells in tissue repair and regeneration%成体干细胞在组织修复及再生中的治疗现状与展望

    Institute of Scientific and Technical Information of China (English)

    付小兵

    2009-01-01

    Ever since the use of adult stem cells in the field of tissue repair and regeneration, their clinical effects, pos-sible mechanisms and side effects have been questioned. In this article, I review the clinical application of adult stem cells, es-pecially mesenchymal stem cells in functional recovery of skin, acute myocardial infarction and vascular diseases, etc. Mean-whiie, I express my personal opinion on their use in the future.

  20. Pediatric and Adult High-Grade Glioma Stem Cell Culture Models Are Permissive to Lytic Infection with Parvovirus H-1.

    Science.gov (United States)

    Josupeit, Rafael; Bender, Sebastian; Kern, Sonja; Leuchs, Barbara; Hielscher, Thomas; Herold-Mende, Christel; Schlehofer, Jörg R; Dinsart, Christiane; Witt, Olaf; Rommelaere, Jean; Lacroix, Jeannine

    2016-05-19

    Combining virus-induced cytotoxic and immunotherapeutic effects, oncolytic virotherapy represents a promising therapeutic approach for high-grade glioma (HGG). A clinical trial has recently provided evidence for the clinical safety of the oncolytic parvovirus H-1 (H-1PV) in adult glioblastoma relapse patients. The present study assesses the efficacy of H-1PV in eliminating HGG initiating cells. H-1PV was able to enter and to transduce all HGG neurosphere culture models (n = 6), including cultures derived from adult glioblastoma, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Cytotoxic effects induced by the virus have been observed in all HGG neurospheres at half maximal inhibitory concentration (IC50) doses of input virus between 1 and 10 plaque forming units per cell. H-1PV infection at this dose range was able to prevent tumorigenicity of NCH421k glioblastoma multiforme (GBM) "stem-like" cells in NOD/SCID mice. Interestingly NCH421R, an isogenic subclone with equal capacity of xenograft formation, but resistant to H-1PV infection could be isolated from the parental NCH421k culture. To reveal changes in gene expression associated with H-1PV resistance we performed a comparative gene expression analysis in these subclones. Several dysregulated genes encoding receptor proteins, endocytosis factors or regulators innate antiviral responses were identified and represent intriguing candidates for to further study molecular mechanisms of H-1PV resistance.

  1. Clinical trial perspective for adult and juvenile Huntington′s disease using genetically-engineered mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Peter Deng

    2016-01-01

    Full Text Available Progress to date from our group and others indicate that using genetically-engineered mesenchymal stem cells (MSC to secrete brain-derived neurotrophic factor (BDNF supports our plan to submit an Investigational New Drug application to the Food and Drug Administration for the future planned Phase 1 safety and tolerability trial of MSC/BDNF in patients with Huntington′s disease (HD. There are also potential applications of this approach beyond HD. Our biological delivery system for BDNF sets the precedent for adult stem cell therapy in the brain and could potentially be modified for other neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS, spinocerebellar ataxia (SCA, Alzheimer′s disease, and some forms of Parkinson′s disease. The MSC/BDNF product could also be considered for studies of regeneration in traumatic brain injury, spinal cord and peripheral nerve injury. This work also provides a platform for our future gene editing studies, since we will again use MSCs to deliver the needed molecules into the central nervous system.

  2. Clinical trial perspective for adult and juvenile Huntington’s disease using genetically-engineered mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Peter Deng; Audrey Torrest; Kari Pollock; Heather Dahlenburg; Geralyn Annett; Jan A. Nolta; Kyle D. Fink

    2016-01-01

    Progress to date from our group and others indicate that using genetically-engineered mesenchymal stem cells (MSC) to secrete brain-derived neurotrophic factor (BDNF) supports our plan to submit an Investigational New Drug application to the Food and Drug Administration for the future planned Phase 1 safety and tolera-bility trial of MSC/BDNF in patients with Huntington’s disease (HD). There are also potential applications of this approach beyond HD. Our biological delivery system for BDNF sets the precedent for adult stem cell ther-apy in the brain and could potentially be modiifed for other neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), Alzheimer’s disease, and some forms of Parkinson’s dis-ease. The MSC/BDNF product could also be considered for studies of regeneration in traumatic brain injury, spinal cord and peripheral nerve injury. This work also provides a platform for our future gene editing studies, since we will again use MSCs to deliver the needed molecules into the central nervous system.

  3. Allogeneic hematopoietic stem cell transplantation in adult acute lymphoblastic leukemia: potential benefit of medium-dose etoposide conditioning.

    Science.gov (United States)

    Imamura, Masahiro; Shigematsu, Akio

    2015-01-01

    The outcomes of adult acute lymphoblastic leukemia (ALL) patients with chemotherapy or autologous hematopoietic stem cell transplantation (HSCT) are unsatisfactory. Therefore, allogeneic (allo) HSCT has been applied to those patients in first complete remission (CR1), and has shown a long-term survival rate of approximately 50 %. In terms of myeloablative conditioning (MAC) regimen, higher dose of cyclophosphamide (CY) and total body irradiation (TBI) (the standard CY + TBI) has been generally applied to allo HSCT. Other MAC regimens such as busulfan-based or etoposide-based regimens have also been used. Among those, medium-dose etoposide (ETP) in addition to the standard CY + TBI conditioning regimen appears to be promising for allo HSCT in adult ALL when transplanted in ALL patients aged under 50 years in CR1 and also in CR2, showing an excellent outcome without increasing relapse or transplant-related mortality (TRM) rates. By contrast, reduced-intensity conditioning (RIC) regimens have also been applied to adult ALL patients and favorable outcomes have been obtained; however, relapse and TRM rates remain high. Therefore, an allo HSCT conditioning regimen which deserves further study for adult ALL patients aged under 50 years in CR1 and CR2 appears to be medium-dose ETP + CY + TBI and RIC is suitable for patients aged over 50 years or for younger patients with comorbid conditions. On the contrary, new therapeutic strategies for adult ALL patients are increasingly utilized with better outcomes; namely, various tyrosine kinase inhibitors for Philadelphia chromosome (Ph)-positive ALL, human leukocyte antigen-haploidentical HSCT, and pediatric-inspired regimens for Ph-negative ALL. Therefore, the optimal treatment modality should be selected considering patient's age, Ph-positivity, donor availability, risk classification, efficacy, and safety. PMID:26322249

  4. The leukemic stem cell

    OpenAIRE

    Jordan, Craig T.

    2007-01-01

    Malignant stem cells have recently been described as the source of several types of human cancer. These unique cell types are typically rare and possess properties that are distinct from most other tumor cells. The properties of leukemic stem cells indicate that current chemotherapy drugs will not be effective. The use of current cytotoxic agents is not effective in leukemia because the agents target both the leukemic and normal stem cell populations. Consequently, new strategies are required...

  5. Cancer Stem Cells

    OpenAIRE

    Katarzyna Wieczorek; Jolanta Niewiarowska

    2008-01-01

    Cancer stem cell theory gains increasingly greater significance in the world of medicine. Numerous findings of scientific research in vivo and in vitro indicate that it is the population of undifferentiated, self-renewing cells which is responsible for recurrence of cancer and metastasis. Similarly to normal stem cells, cancer stem cells (CSC) function in the environment of the other cells of the organism, called the niche, where they receive signals for differentiation and proliferation proc...

  6. Intrahepatic transplantation of CD34+ cord blood stem cells into newborn and adult NOD/SCID mice induce differential organ engraftment.

    Science.gov (United States)

    Wulf-Goldenberg, Annika; Keil, Marlen; Fichtner, Iduna; Eckert, Klaus

    2012-04-01

    In vivo studies concerning the function of human hematopoietic stem cells (HSC) are limited by relatively low levels of engraftment and the failure of the engrafted HSC preparations to differentiate into functional immune cells after systemic application. In the present paper we describe the effect of intrahepatically transplanted CD34(+) cells from cord blood into the liver of newborn or adult NOD/SCID mice on organ engraftment and differentiation. Analyzing the short and long term time dependency of human cell recruitment into mouse organs after cell transplantation in the liver of newborn and adult NOD/SCID mice by RT-PCR and FACS analysis, a significantly high engraftment was found after transplantation into liver of newborn NOD/SCID mice compared to adult mice, with the highest level of 35% human cells in bone marrow and 4.9% human cells in spleen at day 70. These human cells showed CD19 B-cell, CD34 and CD38 hematopoietic and CD33 myeloid cell differentiation, but lacked any T-cell differentiation. HSC transplantation into liver of adult NOD/SCID mice resulted in minor recruitment of human cells from mouse liver to other mouse organs. The results indicate the usefulness of the intrahepatic application route into the liver of newborn NOD/SCID mice for the investigation of hematopoietic differentiation potential of CD34(+) cord blood stem cell preparations.

  7. Optimizing stem cell culture.

    Science.gov (United States)

    van der Sanden, Boudewijn; Dhobb, Mehdi; Berger, François; Wion, Didier

    2010-11-01

    Stem cells always balance between self-renewal and differentiation. Hence, stem cell culture parameters are critical and need to be continuously refined according to progress in our stem cell biology understanding and the latest technological developments. In the past few years, major efforts have been made to define more precisely the medium composition in which stem cells grow or differentiate. This led to the progressive replacement of ill-defined additives such as serum or feeder cell layers by recombinant cytokines or growth factors. Another example is the control of the oxygen pressure. For many years cell cultures have been done under atmospheric oxygen pressure which is much higher than the one experienced by stem cells in vivo. A consequence of cell metabolism is that cell culture conditions are constantly changing. Therefore, the development of high sensitive monitoring processes and control algorithms is required for ensuring cell culture medium homeostasis. Stem cells also sense the physical constraints of their microenvironment. Rigidity, stiffness, and geometry of the culture substrate influence stem cell fate. Hence, nanotopography is probably as important as medium formulation in the optimization of stem cell culture conditions. Recent advances include the development of synthetic bioinformative substrates designed at the micro- and nanoscale level. On going research in many different fields including stem cell biology, nanotechnology, and bioengineering suggest that our current way to culture cells in Petri dish or flasks will soon be outdated as flying across the Atlantic Ocean in the Lindbergh's plane. PMID:20803548

  8. Stem cells sources for intervertebral disc regeneration.

    Science.gov (United States)

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-05-26

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration. PMID:27247704

  9. Stem cells sources for intervertebral disc regeneration.

    Science.gov (United States)

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-05-26

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration.

  10. Stem cells versus plasticity in liver and pancreas regeneration.

    Science.gov (United States)

    Kopp, Janel L; Grompe, Markus; Sander, Maike

    2016-03-01

    Cell replacement in adult organs can be achieved through stem cell differentiation or the replication or transdifferentiation of existing cells. In the adult liver and pancreas, stem cells have been proposed to replace tissue cells, particularly following injury. Here we review how specialized cell types are produced in the adult liver and pancreas. Based on current evidence, we propose that the plasticity of differentiated cells, rather than stem cells, accounts for tissue repair in both organs. PMID:26911907

  11. Frequent detection of respiratory viruses in adult recipients of stem cell transplants with the use of real-time polymerase chain reaction, compared with viral culture.

    NARCIS (Netherlands)

    Kraaij, M.G.J. van; Elden, L.J. van; Loon, A.M. van; Hendriksen, K.A.; Laterveer, L.; Dekker, A.W.; Nijhuis, M.

    2005-01-01

    BACKGROUND: Respiratory virus infections have been recognized as important causes of severe pneumonia in patients who have undergone stem cell transplantation (SCT). Reported incidences of respiratory virus infection in adult SCT recipients vary in the literature from 3.5% to 36% when determined by

  12. Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: A prospective sibling donor versus no-donor comparison

    NARCIS (Netherlands)

    J.J. Cornelissen (Jan); B. van der Holt (Bronno); G.E.G. Verhoef (Gregor); M.B. van 't Veer (Mars); M.H.J. van Oers (Marinus); G.J. Ossenkoppele (Gert); P. Sonneveld (Pieter); J. Maertens (Johan); M. van Marwijk Kooy (Marinus); M.R. Schaafsma (Martijn); P.W. Wijermans (Pierre); D.H. Biesma (Douwe); S. Wittebol (Shulamit); P.J. Voogt (Paul); J.W. Baars (Joke); P. Zachée (Pierre); L.F. Verdonck (Leo); B. Löwenberg (Bob); A.W. Dekker (Adriaan)

    2009-01-01

    textabstractWhile commonly accepted in poor-risk acute lymphoblastic leukemia (ALL), the role of allogeneic hematopoietic stem cell transplantation (allo-SCT) is still disputed in adult patients with standard-risk ALL. We evaluated outcome of patients with ALL in first complete remission (CR1), acco

  13. 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.

  14. Advances in conditioning regimens for older adults undergoing allogeneic stem cell transplantation to treat hematologic malignancies.

    Science.gov (United States)

    William, Basem M; de Lima, Marcos

    2013-06-01

    Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for patients with hematological malignancies. These diseases, however, have their peak incidence in the sixth to eighth decades of life. Historically, elderly patients have been considered unsuitable candidates for SCT because of high treatment-related mortality (TRM). Over the past 15 years, the use of reduced-intensity conditioning (RIC) regimens before SCT has allowed patients in the sixth and seventh decades of life to be routinely transplanted. Despite major differences among transplant centers in the intensity and composition of the conditioning regimen and immunosuppression, choice of graft source, postgraft immunomodulation, and supportive care, there has been a dramatic decrease in TRM, allowing safer delivery of SCT. Major obstacles to SCT in elderly patients include donor availability, graft-versus-host disease, delayed immune recovery, multiple comorbidities, and chemo refractoriness. Here we review the current results of SCT in elderly patients, focusing on the role of RIC, and using myeloid diseases as the model for discussion.

  15. Oligodendrocyte differentiation from adult multipotent stem cells is modulated by glutamate.

    Science.gov (United States)

    Cavaliere, F; Urra, O; Alberdi, E; Matute, C

    2012-02-02

    We used multipotent stem cells (MSCs) derived from the young rat subventricular zone (SVZ) to study the effects of glutamate in oligodendrocyte maturation. Glutamate stimulated oligodendrocyte differentiation from SVZ-derived MSCs through the activation of specific N-methyl-D-aspartate (NMDA) receptor subunits. The effect of glutamate and NMDA on oligodendrocyte differentiation was evident in both the number of newly generated oligodendrocytes and their morphology. In addition, the levels of NMDAR1 and NMDAR2A protein increased during differentiation, whereas NMDAR2B and NMDAR3 protein levels decreased, suggesting differential expression of NMDA receptor subunits during maturation. Microfluorimetry showed that the activation of NMDA receptors during oligodendrocyte differentiation elevated cytosolic calcium levels and promoted myelination in cocultures with neurons. Moreover, we observed that stimulation of MSCs by NMDA receptors induced the generation of reactive oxygen species (ROS), which were negatively modulated by the NADPH inhibitor apocynin, and that the levels of ROS correlated with the degree of differentiation. Taken together, these findings suggest that ROS generated by NADPH oxidase by the activation of NMDA receptors promotes the maturation of oligodendrocytes and favors myelination.

  16. STEM CELLS AND PROTEOMICS

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yong-ming; GUO Tian-nan; HUANG Shi-ang

    2006-01-01

    The distinctive features of proteomics are large-scale and high throughput. The key techniques of proteomics are two-dimensional gel electrophoresis, mass spectrometry and bioinformatics. Stem cell can differentiate into all kinds of cells, tissues and organs. There are many proteins and cytokines involved in the process of differentiation. Applying proteomics techniques to the research of the complex process of stem cell differentiation is of great importance to study the mechanism and applications of stem cell differentiation.

  17. Prostate cancer stem cells

    OpenAIRE

    Tu, Shi-Ming; Lin, Sue-Hwa

    2011-01-01

    Stem cells have long been implicated in prostate glandular formation. The prostate undergoes regression after androgen deprivation and regeneration after testosterone replacement. Regenerative studies suggest that these cells are found in the proximal ducts and basal layer of the prostate. Many characteristics of prostate cancer indicate that it originates from stem cells. For example, the putative AR− status of prostate stem cells renders them inherently insensitive to androgen blockade ther...

  18. Lung Cancer Stem Cells

    OpenAIRE

    Pine, Sharon R.; Blair Marshall; Lyuba Varticovski

    2008-01-01

    Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapies. Recent data indicates that stem cells situated throughout the airways may initiate cancer formation. These putative stem cells maintain protumorigenic characteristics including high proliferative capacity, multipotent differentiation, drug resistance and long lifespan relative to other cells. Stem cell signaling and differentiation p...

  19. Cyclin-dependent kinase inhibitor p21 controls adult neural stem cell expansion by regulating Sox2 gene expression.

    Science.gov (United States)

    Marqués-Torrejón, M Ángeles; Porlan, Eva; Banito, Ana; Gómez-Ibarlucea, Esther; Lopez-Contreras, Andrés J; Fernández-Capetillo, Oscar; Vidal, Anxo; Gil, Jesús; Torres, Josema; Fariñas, Isabel

    2013-01-01

    In the adult brain, continual neurogenesis of olfactory neurons is sustained by the existence of neural stem cells (NSCs) in the subependymal niche. Elimination of the cyclin-dependent kinase inhibitor 1A (p21) leads to premature exhaustion of the subependymal NSC pool, suggesting a relationship between cell cycle control and long-term self-renewal, but the molecular mechanisms underlying NSC maintenance by p21 remain unexplored. Here we identify a function of p21 in the direct regulation of the expression of pluripotency factor Sox2, a key regulator of the specification and maintenance of neural progenitors. We observe that p21 directly binds a Sox2 enhancer and negatively regulates Sox2 expression in NSCs. Augmented levels of Sox2 in p21 null cells induce replicative stress and a DNA damage response that leads to cell growth arrest mediated by increased levels of p19(Arf) and p53. Our results show a regulation of NSC expansion driven by a p21/Sox2/p53 axis.

  20. Human stem cells and articular cartilage regeneration.

    Science.gov (United States)

    Inui, Atsuyuki; Iwakura, Takashi; Reddi, A Hari

    2012-11-05

    The regeneration of articular cartilage damaged due to trauma and posttraumatic osteoarthritis is an unmet medical need. Current approaches to regeneration and tissue engineering of articular cartilage include the use of chondrocytes, stem cells, scaffolds and signals, including morphogens and growth factors. Stem cells, as a source of cells for articular cartilage regeneration, are a critical factor for articular cartilage regeneration. This is because articular cartilage tissue has a low cell turnover and does not heal spontaneously. Adult stem cells have been isolated from various tissues, such as bone marrow, adipose, synovial tissue, muscle and periosteum. Signals of the transforming growth factor beta superfamily play critical roles in chondrogenesis. However, adult stem cells derived from various tissues tend to differ in their chondrogenic potential. Pluripotent stem cells have unlimited proliferative capacity compared to adult stem cells. Chondrogenesis from embryonic stem (ES) cells has been studied for more than a decade. However, establishment of ES cells requires embryos and leads to ethical issues for clinical applications. Induced pluripotent stem (iPS) cells are generated by cellular reprogramming of adult cells by transcription factors. Although iPS cells have chondrogenic potential, optimization, generation and differentiation toward articular chondrocytes are currently under intense investigation.

  1. Human Stem Cells and Articular Cartilage Regeneration

    Directory of Open Access Journals (Sweden)

    A. Hari Reddi

    2012-11-01

    Full Text Available  The regeneration of articular cartilage damaged due to trauma and posttraumatic osteoarthritis is an unmet medical need. Current approaches to regeneration and tissue engineering of articular cartilage include the use of chondrocytes, stem cells, scaffolds and signals, including morphogens and growth factors. Stem cells, as a source of cells for articular cartilage regeneration, are a critical factor for articular cartilage regeneration. This is because articular cartilage tissue has a low cell turnover and does not heal spontaneously. Adult stem cells have been isolated from various tissues, such as bone marrow, adipose, synovial tissue, muscle and periosteum. Signals of the transforming growth factor beta superfamily play critical roles in chondrogenesis. However, adult stem cells derived from various tissues tend to differ in their chondrogenic potential. Pluripotent stem cells have unlimited proliferative capacity compared to adult stem cells. Chondrogenesis from embryonic stem (ES cells has been studied for more than a decade. However, establishment of ES cells requires embryos and leads to ethical issues for clinical applications. Induced pluripotent stem (iPS cells are generated by cellular reprogramming of adult cells by transcription factors. Although iPS cells have chondrogenic potential, optimization, generation and differentiation toward articular chondrocytes are currently under intense investigation.

  2. Stem cells in dentistry, sources, and applications

    OpenAIRE

    Mozafar Khazaei; Azam Bozorgi; Saber Khazaei; Abbasali Khademi

    2016-01-01

    Introduction: Stem cells (SCs), known as cells with characteristics such as self-renewal and multilineage differentiation, are generally obtained from two sources: Embryonic stem cells (ESCs) and adult stem cells (ASCs). SC research is expected to play a pivotal role in future medicine. The aim of the present review was to introduce dental and nondental SCs, examining the general characteristics, in vivo and in vitro differentiation capacities, immunosuppressive properties as well as the appl...

  3. Adult zebrafish intestine resection: a novel model of short bowel syndrome, adaptation, and intestinal stem cell regeneration

    Science.gov (United States)

    Schall, K. A.; Holoyda, K. A.; Grant, C. N.; Levin, D. E.; Torres, E. R.; Maxwell, A.; Pollack, H. A.; Moats, R. A.; Frey, M. R.; Darehzereshki, A.; Al Alam, D.; Lien, C.

    2015-01-01

    Loss of significant intestinal length from congenital anomaly or disease may lead to short bowel syndrome (SBS); intestinal failure may be partially offset by a gain in epithelial surface area, termed adaptation. Current in vivo models of SBS are costly and technically challenging. Operative times and survival rates have slowed extension to transgenic models. We created a new reproducible in vivo model of SBS in zebrafish, a tractable vertebrate model, to facilitate investigation of the mechanisms of intestinal adaptation. Proximal intestinal diversion at segment 1 (S1, equivalent to jejunum) was performed in adult male zebrafish. SBS fish emptied distal intestinal contents via stoma as in the human disease. After 2 wk, S1 was dilated compared with controls and villus ridges had increased complexity, contributing to greater villus epithelial perimeter. The number of intervillus pockets, the intestinal stem cell zone of the zebrafish increased and contained a higher number of bromodeoxyuridine (BrdU)-labeled cells after 2 wk of SBS. Egf receptor and a subset of its ligands, also drivers of adaptation, were upregulated in SBS fish. Igf has been reported as a driver of intestinal adaptation in other animal models, and SBS fish exposed to a pharmacological inhibitor of the Igf receptor failed to demonstrate signs of intestinal adaptation, such as increased inner epithelial perimeter and BrdU incorporation. We describe a technically feasible model of human SBS in the zebrafish, a faster and less expensive tool to investigate intestinal stem cell plasticity as well as the mechanisms that drive intestinal adaptation. PMID:26089336

  4. Glial cell line-derived neurotrophic factor alters the growth characteristics and genomic imprinting of mouse multipotent adult germline stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Yoon Hee [Department of Bioscience and Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of); Gupta, Mukesh Kumar, E-mail: goops@konkuk.ac.kr [Department of Animal Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of); Oh, Shin Hye [Department of Bioscience and Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of); Uhm, Sang Jun [Department of Animal Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of); Lee, Hoon Taek, E-mail: htl3675@konkuk.ac.kr [Department of Bioscience and Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of); Department of Animal Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of)

    2010-03-10

    This study evaluated the essentiality of glial cell line-derived neurotrophic factor (GDNF) for in vitro culture of established mouse multipotent adult germline stem (maGS) cell lines by culturing them in the presence of GDNF, leukemia inhibitory factor (LIF) or both. We show that, in the absence of LIF, GDNF slows the proliferation of maGS cells and result in smaller sized colonies without any change in distribution of cells to different cell-cycle stages, expression of pluripotency genes and in vitro differentiation potential. Furthermore, in the absence of LIF, GDNF increased the expression of male germ-line genes and repopulated the empty seminiferous tubule of W/W{sup v} mutant mouse without the formation of teratoma. GDNF also altered the genomic imprinting of Igf2, Peg1, and H19 genes but had no effect on DNA methylation of Oct4, Nanog and Stra8 genes. However, these effects of GDNF were masked in the presence of LIF. GDNF also did not interfere with the multipotency of maGS cells if they are cultured in the presence of LIF. In conclusion, our results suggest that, in the absence of LIF, GDNF alters the growth characteristics of maGS cells and partially impart them some of the germline stem (GS) cell-like characteristics.

  5. A population-based cohort study of late mortality in adult autologous hematopoietic stem cell transplant recipients in Australia.

    Science.gov (United States)

    Ashton, Lesley J; Le Marsney, Renate E; Dodds, Anthony J; Nivison-Smith, Ian; Wilcox, Leonie; O'Brien, Tracey A; Vajdic, Claire M

    2014-07-01

    We assessed overall and cause-specific mortality and risk factors for late mortality in a nation-wide population-based cohort of 4547 adult cancer patients who survived 2 or more years after receiving an autologous hematopoietic stem cell transplantation (HSCT) in Australia between 1992 and 2005. Deaths after HSCT were identified from the Australasian Bone Marrow Transplant Recipient Registry and through data linkage with the National Death Index. Overall, the survival probability was 56% at 10 years from HSCT, ranging from 34% for patients with multiple myeloma to 90% for patients with testicular cancer. Mortality rates moved closer to rates observed in the age- and sex-matched Australian general population over time but remained significantly increased 11 or more years from HSCT (standardized mortality ratio, 5.9). Although the proportion of deaths from nonrelapse causes increased over time, relapse remained the most frequent cause of death for all diagnoses, 10 or more years after autologous HSCT. Our findings show that prevention of disease recurrence remains 1 of the greatest challenges for autologous HSCT recipients, while the increasing rates of nonrelapse deaths due to the emergence of second cancers, circulatory diseases, and respiratory diseases highlight the long-term health issues faced by adult survivors of autologous HSCT. PMID:24631736

  6. Epidermal Stem Cells

    OpenAIRE

    Osman Köse

    2015-01-01

    The epidermis is the outermost layer of the human skin and comprises a multilayered epithelium, the interfollicular epidermis, with associated hair follicles, sebaceous glands, and eccrine sweat glands. There are many origins of stem cells in the skin and skin appendages. These stem cells are localized in different part of the pilosebaseous units and also express many different genes. Epidermal stem cells in the pilosebaseous units not only ensure the maintenance of epidermal homeostasis and ...

  7. Chiaroscuro hematopoietic stem cell.

    OpenAIRE

    Quesenberry, P.; Habibian, M. (PhD); Dooner, M; Zhong, S.; Reilly, J; Peters, S.; De Becker, P; Grimaldi, C.; Carlson, J; REDDY, P; Nilsson, S.; Stewart, F. M.

    1998-01-01

    These observations suggest several immediate clinical strategies. In gene therapy, approaches could be targeted to obtain cycling of hematopoietic stem cells and gene-carrying retrovirus vector integration followed by engraftment at an appropriate time interval which favors engraftment. The same type of approach can be utilized for stem cell expansion approaches. Alternatively marrow or peripheral stem cell engraftment can be obtained with minimal to no toxicity in allochimeric strategies in ...

  8. Cancer stem cell metabolism

    OpenAIRE

    Peiris-Pagès, Maria; Martinez-Outschoorn, Ubaldo E.; Pestell, Richard G.; Sotgia, Federica; Lisanti, Michael P

    2016-01-01

    Cancer is now viewed as a stem cell disease. There is still no consensus on the metabolic characteristics of cancer stem cells, with several studies indicating that they are mainly glycolytic and others pointing instead to mitochondrial metabolism as their principal source of energy. Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes. Deter...

  9. Gastric Cancer Stem Cells

    OpenAIRE

    Takaishi, Shigeo; Okumura, Tomoyuki; Timothy C Wang

    2008-01-01

    Cancer stem cells are defined as the unique subpopulation in the tumors that possess the ability to initiate tumor growth and sustain self-renewal as well as metastatic potential. Accumulating evidence in recent years strongly indicate the existence of cancer stem cells in solid tumors of a wide variety of organs. In this review, we will discuss the possible existence of a gastric cancer stem cell. Our recent data suggest that a subpopulation with a defined marker shows spheroid colony format...

  10. Phase I/II Clinical Trials Using Gene-Modified Adult Hematopoietic Stem Cells for HIV: Lessons Learnt

    Directory of Open Access Journals (Sweden)

    Ronald T. Mitsuyasu

    2011-01-01

    Full Text Available Gene therapy for individuals infected with HIV has the potential to provide a once-only treatment that will act to reduce viral load, preserve the immune system, and mitigate cumulative toxicities associated with highly active antiretroviral therapy (HAART. The authors have been involved in two clinical trials (phase I and phase II using gene-modified adult hematopoietic stem cells (HSCs, and these are discussed as prototypic trials within the general field of HSC gene therapy trials for HIV. Taken as a group these trials have shown (i the safety of both the procedure and the anti-HIV agents themselves and (ii the feasibility of the approach. They point to the requirement for (i the ability to transduce and infuse as many as possible gene-containing HSC and/or (ii high engraftment and in vivo expansion of these cells, (iii potentially increased efficacy of the anti-HIV agent(s and (iv automation of the cell processing procedure.

  11. In Vivo Targeting of Adult Neural Stem Cells in the Dentate Gyrus by a Split-Cre Approach

    Directory of Open Access Journals (Sweden)

    Ruth Beckervordersandforth

    2014-02-01

    Full Text Available We describe the labeling of adult neural stem cells (aNSCs in the mouse and human dentate gyrus (DG by the combinatorial expression of glial fibrillary acidic protein (GFAP and Prominin1, as revealed by immunohistochemistry. Split-Cre-based genetic fate mapping of these double-positive cells in the adult murine DG reveals their NSC identity, as they are self-renewing and contribute to neurogenesis over several months. Their progeny reacts to stimuli such as voluntary exercise with increased neurogenesis. Prominin1+/GFAP+ cells also exist in the adult human DG, the only region in the human brain for which adult neurogenesis has been consistently reported. Our data, together with previous evidence of such double-positive NSCs in the developing murine brain and in neurogenic regions of vertebrates with widespread neurogenesis, suggest that Prominin1- and GFAP-expressing cells are NSCs in a wide range of species in development and adulthood.

  12. Human mesenchymal stem cells reprogram adult cardiomyocytes toward a progenitor-like state through partial cell fusion and mitochondria transfer : Cell fusion-mediated cardiomyocyte reprogramming.

    OpenAIRE

    Acquistapace, Adrien; Bru, Thierry; Lesault, Pierre-François; Figeac, Florence; Coudert, Amélie,; Le Coz, Olivier; Christov, Christo; Baudin, Xavier; Auber, Fréderic; Yiou, René; Dubois-Randé, Jean-Luc; Rodriguez, Anne-Marie

    2011-01-01

    International audience Because stem cells are often found to improve repair tissue including heart without evidence of engraftment or differentiation, mechanisms underlying wound healing are still elusive. Several studies have reported that stem cells can fuse with cardiomyocytes either by permanent or partial cell fusion processes. However, the respective physiological impact of these two processes remains unknown in part because of the lack of knowledge of the resulting hybrid cells. To ...

  13. Inhibition of the histone demethylase Kdm5b promotes neurogenesis and derepresses Reln (reelin) in neural stem cells from the adult subventricular zone of mice.

    Science.gov (United States)

    Zhou, Qiong; Obana, Edwin A; Radomski, Kryslaine L; Sukumar, Gauthaman; Wynder, Christopher; Dalgard, Clifton L; Doughty, Martin L

    2016-02-15

    The role of epigenetic regulators in the control of adult neurogenesis is largely undefined. We show that the histone demethylase enzyme Kdm5b (Jarid1b) negatively regulates neurogenesis from adult subventricular zone (SVZ) neural stem cells (NSCs) in culture. shRNA-mediated depletion of Kdm5b in proliferating adult NSCs decreased proliferation rates and reduced neurosphere formation in culture. When transferred to differentiation culture conditions, Kdm5b-depleted adult NSCs migrated from neurospheres with increased velocity. Whole-genome expression screening revealed widespread transcriptional changes with Kdm5b depletion, notably the up-regulation of reelin (Reln), the inhibition of steroid biosynthetic pathway component genes and the activation of genes with intracellular transport functions in cultured adult NSCs. Kdm5b depletion increased extracellular reelin concentration in the culture medium and increased phosphorylation of the downstream reelin signaling target Disabled-1 (Dab1). Sequestration of extracellular reelin with CR-50 reelin-blocking antibodies suppressed the increase in migratory velocity of Kdm5b-depleted adult NSCs. Chromatin immunoprecipitation revealed that Kdm5b is present at the proximal promoter of Reln, and H3K4me3 methylation was increased at this locus with Kdm5b depletion in differentiating adult NSCs. Combined the data suggest Kdm5b negatively regulates neurogenesis and represses Reln in neural stem cells from the adult SVZ. PMID:26739753

  14. The retinoblastoma tumor suppressor and stem cell biology

    OpenAIRE

    Sage, Julien

    2012-01-01

    Stem cells play a critical role during embryonic development and in the maintenance of homeostasis in adult individuals. The retinoblastoma tumor suppressor RB controls the proliferation, differentiation, and survival of cells, and accumulating evidence points to a central role for RB activity in the biology of stem and progenitor cells. In this review by Sage, recent studies investigating the role of RB in embryonic stem cells, adult stem cells, and progenitor cells in plants and mammals is ...

  15. 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 real

  16. 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 embryo

  17. Biased DNA Segregation during Stem Cell Division

    OpenAIRE

    Anversa, Piero; Leri, Annarosa; Kajstura, Jan

    2012-01-01

    Adult skeletal muscle stem cells are a heterogeneous cell population characterized by a small subset of undifferentiated cells that express at high level the paired/homeodomain gene Pax7. This category of satellite cells divides predominantly by asymmetric chromatid segregation generating a daughter cell that carries the mother DNA and retains stem cell property, and a daughter cell that inherits the newly-synthesized DNA and acquires the myocyte lineage.1

  18. Stem cells: sources and therapies.

    Science.gov (United States)

    Monti, Manuela; Perotti, Cesare; Del Fante, Claudia; Cervio, Marila; Redi, Carlo Alberto

    2012-01-01

    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. PMID:23283430

  19. Pancreatic stem cells remain unresolved.

    Science.gov (United States)

    Jiang, Fang-Xu; Morahan, Grant

    2014-12-01

    Diabetes mellitus is caused by absolute (type 1) or relative (type 2) deficiency of insulin-secreting islet β cells. An ideal treatment of diabetes would, therefore, be to replace the lost or deficient β cells, by transplantation of donated islets or differentiated endocrine cells or by regeneration of endogenous islet cells. Due to their ability of unlimited proliferation and differentiation into all functional lineages in our body, including β cells, embryonic stem cells and induced pluripotent stem cells are ideally placed as cell sources for a diabetic transplantation therapy. Unfortunately, the inability to generate functional differentiated islet cells from pluripotent stem cells and the poor availability of donor islets have severely restricted the broad clinical use of the replacement therapy. Therefore, endogenous sources that can be directed to becoming insulin-secreting cells are actively sought after. In particular, any cell types in the developing or adult pancreas that may act as pancreatic stem cells (PSC) would provide an alternative renewable source for endogenous regeneration. In this review, we will summarize the latest progress and knowledge of such PSC, and discuss ways that facilitate the future development of this often controversial, but crucial research.

  20. Many facets of stem cells

    Institute of Scientific and Technical Information of China (English)

    Jiarui Wu

    2011-01-01

    @@ Research area on stem cells is one of frontiers in biology.The collection of five research articles in this issue aims to cover timely developments in stem cell biology, ranging from generating and identifying stem cell line to manipulating stem cells, and from basic mechanism analysis to applied medical potential.These papers reflect the various research tasks in stem cell biology.

  1. 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...

  2. 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.

  3. Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia

    DEFF Research Database (Denmark)

    Ruggeri, A; Labopin, M; Sanz, G;

    2015-01-01

    Outcomes after unmanipulated haploidentical stem cell transplantation (Haplo) and after unrelated cord blood transplantation (UCBT) are encouraging and have become alternative options to treat patients with high-risk acute leukemia without human leukocyte antigen (HLA) matched donor. We compared ...

  4. Epidermal Stem Cells

    Directory of Open Access Journals (Sweden)

    Osman Köse

    2015-03-01

    Full Text Available The epidermis is the outermost layer of the human skin and comprises a multilayered epithelium, the interfollicular epidermis, with associated hair follicles, sebaceous glands, and eccrine sweat glands. There are many origins of stem cells in the skin and skin appendages. These stem cells are localized in different part of the pilosebaseous units and also express many different genes. Epidermal stem cells in the pilosebaseous units not only ensure the maintenance of epidermal homeostasis and hair regeneration, but also contribute to repair of the epidermis after injury. In recent years, human induced pluripotent skin stem cells are produced from the epidermal cells such as keratinocytes, fibroblasts and melanocytes. These cells can be transdifferentiated to embriyonic stem cells. Human induced pluripotent stem cells have potential applications in cell replacement therapy and regenerative medicine. These cells provide a means to create valuable tools for basic research and may also produce a source of patient-matched cells for regenerative therapies. In this review, we aimed an overview of epidermal stem cells for better understanding their functions in the skin. Skin will be main organ for using the epidermal cells for regenerative medicine in near future.

  5. Thyroid stem cells – danger or resource?

    OpenAIRE

    GIBELLI, B.; El-Fattah, AMA; Giugliano, G; PROH, M.; GROSSO, E.

    2009-01-01

    The thyroid gland has long since been known for its self-renewal ability, mainly in cases of hyperplastic disease such as goitre. Recently the amazing improvement in knowledge about stem cells has explained this potentiality. Some stem cell features and their clinical usefulness are summarized here, reviewing data from the literature: the proven presence of adult stem cells in thyroid tissue, either normal, goitrous or neoplastic, bring with it important implications regarding tissue regenera...

  6. Neural Ganglioside GD2+ Cells Define a Subpopulation of Mesenchymal Stem Cells in Adult Murine Bone Marrow

    Directory of Open Access Journals (Sweden)

    Jie Xu

    2013-09-01

    Full Text Available Background/Aims: Due to the lack of specific markers, the isolation of pure mesenchymal stem cells (MSCs from murine bone marrow remains an unsolved problem. The present study explored whether the neural ganglioside GD2 could serve as a single surface marker to uniquely distinguish murine bone marrow MSCs (mBM-MSCs from other marrow elements. Methods: Immunocytochemistry and flow cytometry, in combination with quantitative RT-PCR, were used to identify the expression of GD2 on culture-expanded mBM-MSCs. GD2+ and GD2- fractions from mBM-MSCs cultures were sorted by immunosorting. Flow cytometry was performed to further analyze the biomarkers of GD2-sorted and unsorted cells. Employing CFU-F assay and CCK-8 assay, we examined the clonogenic and proliferative capabilities of GD2-sorted and unsorted cells. Using oil red O and von Kossa staining assay, we also assessed the multi-lineage potential of GD2-sortedand unsorted cells. Results: We found that mBM-MSCs expressed a novel surface marker the neural ganglioside GD2. Importantly, mBM-MSCs were the only cells within bone marrow that expressed this marker. Further studies demonstrated that a homogenous population of MSCs could be obtained from bone marrow cultures in early passages by GD2 immunosorting. Compared to parental cells, GD2+-sorted cells not only possessed much higher clonogenic and proliferative capabilities but also had significantly stronger differentiation potential to adipocytes and osteoblasts. Furthermore, GD2+-sorted cells displayed enhanced expression of ES markers SSEA-1 and Nanog. Conclusion: Our observations provide the first demonstration that GD2 may serve as a maker for identification and purification of mBM-MSCs. Meanwhile, our study indicates that the cells selected by GD2 are a subpopulation of MSCs with features of primitive precursor cells.

  7. Stem cells - biological update and cell therapy progress.

    Science.gov (United States)

    Girlovanu, Mihai; Susman, Sergiu; Soritau, Olga; Rus-Ciuca, Dan; Melincovici, Carmen; Constantin, Anne-Marie; Mihu, Carmen Mihaela

    2015-01-01

    In recent years, the advances in stem cell research have suggested that the human body may have a higher plasticity than it was originally expected. Until now, four categories of stem cells were isolated and cultured in vivo: embryonic stem cells, fetal stem cells, adult stem cells and induced pluripotent stem cells (hiPSCs). Although multiple studies were published, several issues concerning the stem cells are still debated, such as: the molecular mechanisms of differentiation, the methods to prevent teratoma formation or the ethical and religious issues regarding especially the embryonic stem cell research. The direct differentiation of stem cells into specialized cells: cardiac myocytes, neural cells, pancreatic islets cells, may represent an option in treating incurable diseases such as: neurodegenerative diseases, type I diabetes, hematologic or cardiac diseases. Nevertheless, stem cell-based therapies, based on stem cell transplantation, remain mainly at the experimental stages and their major limitation is the development of teratoma and cancer after transplantation. The induced pluripotent stem cells (hiPSCs) represent a prime candidate for future cell therapy research because of their significant self-renewal and differentiation potential and the lack of ethical issues. This article presents an overview of the biological advances in the study of stem cells and the current progress made in the field of regenerative medicine.

  8. Paracrine Molecules of Mesenchymal Stem Cells for Hematopoietic Stem Cell Niche

    OpenAIRE

    Tian Li; Yaojiong Wu

    2011-01-01

    Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are both adult stem cells residing in the bone marrow. MSCs interact with HSCs, they stimulate and enhance the proliferation of HSCs by secreting regulatory molecules and cytokines, providing a specialized microenvironment for controlling the process of hematopoiesis. In this paper we discuss how MSCs contribute to HSC niche, maintain the stemness and proliferation of HSCs, and support HSC transplantation.

  9. c-Kit-mediated functional positioning of stem cells to their niches is essential for maintenance and regeneration of adult hematopoiesis.

    Directory of Open Access Journals (Sweden)

    Yuki Kimura

    Full Text Available The mechanism by which hematopoietic stem and progenitor cells (HSPCs through interaction with their niches maintain and reconstitute adult hematopoietic cells is unknown. To functionally and genetically track localization of HSPCs with their niches, we employed novel mutant loxPs, lox66 and lox71 and Cre-recombinase technology to conditionally delete c-Kit in adult mice, while simultaneously enabling GFP expression in the c-Kit-deficient cells. Conditional deletion of c-Kit resulted in hematopoietic failure and splenic atrophy both at steady state and after marrow ablation leading to the demise of the treated adult mice. Within the marrow, the c-Kit-expressing GFP(+ cells were positioned to Kit ligand (KL-expressing niche cells. This c-Kit-mediated cellular adhesion was essential for long-term maintenance and expansion of HSPCs. These results lay the foundation for delivering KL within specific niches to maintain and restore hematopoiesis.

  10. Stem cell mechanobiology

    OpenAIRE

    David A. Lee; Knight, Martin M.; Jonathan J Campbell; Bader, Dan L.

    2010-01-01

    Stem cells are undifferentiated cells that are capable of proliferation, self-maintenance and differentiation towards specific cell phenotypes. These processes are controlled by a variety of cues including physicochemical factors associated with the specific mechanical environment in which the cells reside. The control of stem cell biology through mechanical factors remains poorly understood and is the focus of the developing field of mechanobiology. This review provides an insight into the c...

  11. Fish Stem Cell Cultures

    Directory of Open Access Journals (Sweden)

    Ni Hong, Zhendong Li, Yunhan Hong

    2011-01-01

    Full Text Available Stem cells have the potential for self-renewal and differentiation. First stem cell cultures were derived 30 years ago from early developing mouse embryos. These are pluripotent embryonic stem (ES cells. Efforts towards ES cell derivation have been attempted in other mammalian and non-mammalian species. Work with stem cell culture in fish started 20 years ago. Laboratory fish species, in particular zebrafish and medaka, have been the focus of research towards stem cell cultures. Medaka is the second organism that generated ES cells and the first that gave rise to a spermatogonial stem cell line capable of test-tube sperm production. Most recently, the first haploid stem cells capable of producing whole animals have also been generated from medaka. ES-like cells have been reported also in zebrafish and several marine species. Attempts for germline transmission of ES cell cultures and gene targeting have been reported in zebrafish. Recent years have witnessed the progress in markers and procedures for ES cell characterization. These include the identification of fish homologs/paralogs of mammalian pluripotency genes and parameters for optimal chimera formation. In addition, fish germ cell cultures and transplantation have attracted considerable interest for germline transmission and surrogate production. Haploid ES cell nuclear transfer has proven in medaka the feasibility of semi-cloning as a novel assisted reproductive technology. In this special issue on “Fish Stem Cells and Nuclear Transfer”, we will focus our review on medaka to illustrate the current status and perspective of fish stem cells in research and application. We will also mention semi-cloning as a new development to conventional nuclear transfer.

  12. Fish stem cell cultures.

    Science.gov (United States)

    Hong, Ni; Li, Zhendong; Hong, Yunhan

    2011-04-13

    Stem cells have the potential for self-renewal and differentiation. First stem cell cultures were derived 30 years ago from early developing mouse embryos. These are pluripotent embryonic stem (ES) cells. Efforts towards ES cell derivation have been attempted in other mammalian and non-mammalian species. Work with stem cell culture in fish started 20 years ago. Laboratory fish species, in particular zebrafish and medaka, have been the focus of research towards stem cell cultures. Medaka is the second organism that generated ES cells and the first that gave rise to a spermatogonial stem cell line capable of test-tube sperm production. Most recently, the first haploid stem cells capable of producing whole animals have also been generated from medaka. ES-like cells have been reported also in zebrafish and several marine species. Attempts for germline transmission of ES cell cultures and gene targeting have been reported in zebrafish. Recent years have witnessed the progress in markers and procedures for ES cell characterization. These include the identification of fish homologs/paralogs of mammalian pluripotency genes and parameters for optimal chimera formation. In addition, fish germ cell cultures and transplantation have attracted considerable interest for germline transmission and surrogate production. Haploid ES cell nuclear transfer has proven in medaka the feasibility of semi-cloning as a novel assisted reproductive technology. In this special issue on "Fish Stem Cells and Nuclear Transfer", we will focus our review on medaka to illustrate the current status and perspective of fish stem cells in research and application. We will also mention semi-cloning as a new development to conventional nuclear transfer.

  13. Recruitment of Mediator Complex by Cell Type and Stage-Specific Factors Required for Tissue-Specific TAF Dependent Gene Activation in an Adult Stem Cell Lineage.

    Science.gov (United States)

    Lu, Chenggang; Fuller, Margaret T

    2015-12-01

    Onset of terminal differentiation in adult stem cell lineages is commonly marked by robust activation of new transcriptional programs required to make the appropriate differentiated cell type(s). In the Drosophila male germ line stem cell lineage, the switch from proliferating spermatogonia to spermatocyte is accompanied by one of the most dramatic transcriptional changes in the fly, as over 1000 new transcripts turn on in preparation for meiosis and spermatid differentiation. Here we show that function of the coactivator complex Mediator is required for activation of hundreds of new transcripts in the spermatocyte program. Mediator appears to act in a sequential hierarchy, with the testis activating Complex (tMAC), a cell type specific form of the Mip/dREAM general repressor, required to recruit Mediator subunits to the chromatin, and Mediator function required to recruit the testis TAFs (tTAFs), spermatocyte specific homologs of subunits of TFIID. Mediator, tMAC and the tTAFs co-regulate expression of a major set of spermatid differentiation genes. The Mediator subunit Med22 binds the tMAC component Topi when the two are coexpressed in S2 cells, suggesting direct recruitment. Loss of Med22 function in spermatocytes causes meiosis I maturation arrest male infertility, similar to loss of function of the tMAC subunits or the tTAFs. Our results illuminate how cell type specific versions of the Mip/dREAM complex and the general transcription machinery cooperate to drive selective gene activation during differentiation in stem cell lineages. PMID:26624996

  14. 成体干细胞向血管内皮细胞定向分化的研究现状%Oriented differentiation of adult stem cells into vascular endothelial cells

    Institute of Scientific and Technical Information of China (English)

    宋秀军; 江其生

    2009-01-01

    Adult stem cells identified in tissue organs possess obviously plasticity. They can differentiate into the cells in other systems and germ layers, which are known to support the continuous repair and regeneration of tissues. In the vascular tissue engineering, the research was more and more widespread and deep on adult stem cells as seed cells~ Research indicated that there are many kinds of adult stem cells which can differentiate into vascular endothelial cells, such as bone marrow mesenchymal stem cells, hematopoietic stem cells, human adipose derived stem cells, and amnion derived stem calls. Thus, this study reviewed the current situation of adult stem cells as seed cells in vascular tissue engineering.%成体干细胞存在于已分化的组织器官中,具有明显的可塑性,能跨系统、跨胚层分化,在组织工程和损伤修复领域具有重要的应用价值.在血管组织工程研究领域中,成体干细胞作为种子细胞得到越来越广泛而深入的研究.目前研究表明,具有向血管内皮细胞分化的成体干细胞主要有骨髓间充质干细胞、造血干细胞、脂肪来源的干细胞以及羊膜来源的干细胞等基于此,就成体干细胞作为种子细胞在血管组织工程领域研究现状进行综述.

  15. Morphological, molecular and functional differences of adult bone marrow- and adipose-derived stem cells isolated from rats of different ages

    International Nuclear Information System (INIS)

    Adult mesenchymal stem cells have self-renewal and multiple differentiation potentials, and play important roles in regenerative medicine. However, their use may be limited by senescence or age of the donor, leading to changes in stem cell functionality. We investigated morphological, molecular and functional differences between bone marrow-derived (MSC) and adipose-derived (ASC) stem cells isolated from neonatal, young and old rats compared to Schwann cells from the same animals. Immunocytochemistry, RT-PCR, proliferation assays, western blotting and transmission electron microscopy were used to investigate expression of senescence markers. Undifferentiated and differentiated ASC and MSC from animals of different ages expressed Notch-2 at similar levels; protein-38 and protein-53 were present in all groups of cells with a trend towards increased levels in cells from older animals compared to those from neonatal and young rats. Following co-culture with adult neuronal cells, dMSC and dASC from animals of all ages elicited robust neurite outgrowth. Mitotracker® staining was consistent with ultrastructural changes seen in the mitochondria of cells from old rats, indicative of senescence. In conclusion, this study showed that although the cells from aged animals expressed markers of senescence, aged MSC and ASC differentiated into SC-like cells still retain potential to support axon regeneration. -- Highlights: ► Aged MSC and ASC differentiated into Schwann-like cells support axon regeneration. ► p53 expression does not appreciably influence the biology of Schwann or stem cells. ► Notch 2 expression was similar in cells derived from animals of different ages. ► Proliferation rates of dMSC varied little over time or with animal age.

  16. Morphological, molecular and functional differences of adult bone marrow- and adipose-derived stem cells isolated from rats of different ages

    Energy Technology Data Exchange (ETDEWEB)

    Mantovani, Cristina [Blond McIndoe Laboratories, School of Biomedicine, The University of Manchester, Room 3,106 Stopford Building, Oxford Road, Manchester M13 9PT, Academic Health Science Centre, Faculty of Medicine and Human Sciences (United Kingdom); Department of Integrative Medical Biology and Surgical and Perioperative Science, Umea University, Umea (Sweden); Department of Surgical and Perioperative Science, Umea University, Umea (Sweden); Raimondo, Stefania [Dipartimento di Scienze Cliniche e Biologiche, University of Turin (Italy); Haneef, Maryam S. [Blond McIndoe Laboratories, School of Biomedicine, The University of Manchester, Room 3,106 Stopford Building, Oxford Road, Manchester M13 9PT, Academic Health Science Centre, Faculty of Medicine and Human Sciences (United Kingdom); Geuna, Stefano [Dipartimento di Scienze Cliniche e Biologiche, University of Turin (Italy); Terenghi, Giorgio [Blond McIndoe Laboratories, School of Biomedicine, The University of Manchester, Room 3,106 Stopford Building, Oxford Road, Manchester M13 9PT, Academic Health Science Centre, Faculty of Medicine and Human Sciences (United Kingdom); Shawcross, Susan G., E-mail: sue.shawcross@manchester.ac.uk [Blond McIndoe Laboratories, School of Biomedicine, The University of Manchester, Room 3,106 Stopford Building, Oxford Road, Manchester M13 9PT, Academic Health Science Centre, Faculty of Medicine and Human Sciences (United Kingdom); Wiberg, Mikael [Department of Integrative Medical Biology and Surgical and Perioperative Science, Umea University, Umea (Sweden); Department of Surgical and Perioperative Science, Umea University, Umea (Sweden)

    2012-10-01

    Adult mesenchymal stem cells have self-renewal and multiple differentiation potentials, and play important roles in regenerative medicine. However, their use may be limited by senescence or age of the donor, leading to changes in stem cell functionality. We investigated morphological, molecular and functional differences between bone marrow-derived (MSC) and adipose-derived (ASC) stem cells isolated from neonatal, young and old rats compared to Schwann cells from the same animals. Immunocytochemistry, RT-PCR, proliferation assays, western blotting and transmission electron microscopy were used to investigate expression of senescence markers. Undifferentiated and differentiated ASC and MSC from animals of different ages expressed Notch-2 at similar levels; protein-38 and protein-53 were present in all groups of cells with a trend towards increased levels in cells from older animals compared to those from neonatal and young rats. Following co-culture with adult neuronal cells, dMSC and dASC from animals of all ages elicited robust neurite outgrowth. Mitotracker{sup Registered-Sign} staining was consistent with ultrastructural changes seen in the mitochondria of cells from old rats, indicative of senescence. In conclusion, this study showed that although the cells from aged animals expressed markers of senescence, aged MSC and ASC differentiated into SC-like cells still retain potential to support axon regeneration. -- Highlights: Black-Right-Pointing-Pointer Aged MSC and ASC differentiated into Schwann-like cells support axon regeneration. Black-Right-Pointing-Pointer p53 expression does not appreciably influence the biology of Schwann or stem cells. Black-Right-Pointing-Pointer Notch 2 expression was similar in cells derived from animals of different ages. Black-Right-Pointing-Pointer Proliferation rates of dMSC varied little over time or with animal age.

  17. Stem cells in dermatology.

    Science.gov (United States)

    Ogliari, Karolyn Sassi; Marinowic, Daniel; Brum, Dario Eduardo; Loth, Fabrizio

    2014-01-01

    Preclinical and clinical research have shown that stem cell therapy could be a promising therapeutic option for many diseases in which current medical treatments do not achieve satisfying results or cure. This article describes stem cells sources and their therapeutic applications in dermatology today.

  18. Stem Cell Transplants (For Teens)

    Science.gov (United States)

    ... Can I Help a Friend Who Cuts? Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants Print ... it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  19. Stem cell applications in diabetes.

    Science.gov (United States)

    Noguchi, Hirofumi

    2012-01-01

    Diabetes mellitus is a devastating disease and the World Health Organization (WHO) expects that the number of diabetic patients will increase to 300 million by the year 2025. Patients with diabetes experience decreased insulin secretion that is linked to a significant reduction in the number of islet cells. Type 1 diabetes is characterized by the selective destruction of pancreatic β cells caused by an autoimmune attack. Type 2 diabetes is a more complex pathology that, in addition to β cell loss caused by apoptotic programs, includes β cell de-differentiation and peripheric insulin resistance. The success achieved over the last few years with islet transplantation suggests that diabetes can be cured by the replenishment of deficient β cells. These observations are proof of the concept and have intensified interest in treating diabetes or other diseases not only by cell transplantation but also by stem cells. An increasing body of evidence indicates that, in addition to embryonic stem cells, several potential adult stem/progenitor cells derived from the pancreas, liver, spleen, and bone marrow could differentiate into insulin-producing cells in vitro or in vivo. However, significant controversy currently exists in this field. Pharmacological approaches aimed at stimulating the in vivo/ex vivo regeneration of β cells have been proposed as a way of augmenting islet cell mass. Overexpression of embryonic transcription factors in stem cells could efficiently induce their differentiation into insulin-expressing cells. A new technology, known as protein transduction, facilitates the differentiation of stem cells into insulin-producing cells. Recent progress in the search for new sources of β cells has opened up several possibilities for the development of new treatments for diabetes.

  20. Dental pulp stem cells

    DEFF Research Database (Denmark)

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

    2015-01-01

    Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of intensive research. Periodontal tissue engineering implies the use of appropriate regenerative cells, delivered through a suitable...... 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....

  1. 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...

  2. Immunology of Stem Cells and Cancer Stem Cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Yang

    2007-01-01

    The capacity of pluri-potent stem cells to repair the tissues in which stem cells reside holds great promise in development of novel cell replacement therapeutics for treating chronic and degenerative diseases. However,numerous reports show that stem cell therapy, even in an autologous setting, triggers lymphocyte infiltration and inflammation. Therefore, an important question to be answered is how the host immune system responds to engrafted autologous stem cells or allogeneous stem cells. In this brief review, we summarize the progress in several related areas in this field, including some of our data, in four sections: (1) immunogenicity of stem cells; (2)strategies to inhibit immune rejection to allograft stem cells; (3) immune responses to cancer stem cells; and (4)mesenchymal stem cells in immune regulation. Improvement of our understanding on these and other aspects of immune system-stem cell interplay would greatly facilitate the development of stem cell-based therapeutics for regenerative purposes.

  3. 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....

  4. Aneuploidy in stem cells

    OpenAIRE

    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 reality. However, as somatic cells might have accumulated various chromosomal abnormalities, including aneuploidies throughout their lives, the resulting IPSCs might no longer carry the perfect bluepri...

  5. Stem Cells May Offer New Hope to Stroke Survivors

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159163.html Stem Cells May Offer New Hope to Stroke Survivors Experimental ... HealthDay News) -- Preliminary research suggests that injecting adult stems cells directly into the brain may give stroke patients ...

  6. Hematopoietic Stem Cell Transplantation: Need for Research & Potential Applications. It’s status in India

    OpenAIRE

    Banavali, Shripad D

    2009-01-01

    Stem cells are undifferentiated cells that through replications have the capabilities of both self-renewal and differentiation into mature specialized cells. Broadly, there are two types of stem cells, embryonic stem cells and adult stem cells. Embryonic stem cell biology has been associated with ethical controversy and also their growth is difficult to control. Adult stem cells are located in tissues throughout the body and function as a reservoir to replace damaged or aging cells. Embryonic...

  7. Alzheimer’s disease and adult neurogenesis—Are endogenous stem cells part of the solution?

    NARCIS (Netherlands)

    M.W. Marlatt; J.J.M. Hoozemans; R. Veerhuis; P.J. Lucassen

    2009-01-01

    The human brain produces new neurons that mediate hippocampal plasticity but also have a potential role in hippocampal-related disorders, such as Alzheimer’s disease and dementia. Factors such as stress and aging that reduce adult neurogenesis also serve as independent risk factors for Alzheimer’s d

  8. Autologous stem cell transplantation for adult acute leukemia in 2015: time to rethink? Present status and future prospects.

    Science.gov (United States)

    Gorin, N-C; Giebel, S; Labopin, M; Savani, B N; Mohty, M; Nagler, A

    2015-12-01

    The use of autologous stem cell transplantation (ASCT) as consolidation therapy for adult patients with acute leukemia has declined over time. However, multiple randomized studies in the past have reported lower relapse rates after autologous transplantation compared with chemotherapy and lower non-relapse mortality rates compared with allogeneic transplantation. In addition, quality of life of long-term survivors is better after autologous transplantation than after allogeneic transplantation. Further, recent developments may improve outcomes of autograft recipients. These include the use of IV busulfan and the busulfan+melphalan combination, better detection of minimal residual disease (MRD) with molecular biology techniques, the introduction of targeted therapies and post-transplant maintenance therapy. Therefore, ASCT may nowadays be reconsidered for consolidation in the following patients if and when they reach a MRD-negative status: good- and at least intermediate-1 risk acute myelocytic leukemia in first CR, acute promyelocytic leukemia in second CR, Ph-positive acute lymphocytic leukemia. Conversely, patients with MRD-positive status or high-risk leukemia should not be considered for consolidation with ASCT. PMID:26281031

  9. Role of Heat Shock Proteins in Stem Cell Behavior

    OpenAIRE

    Fan, Guo-Chang

    2012-01-01

    Stress response is well appreciated to induce the expression of heat shock proteins (Hsps) in the cell. Numerous studies have demonstrated that Hsps function as molecular chaperones in the stabilization of intracellular proteins, repairing damaged proteins, and assisting in protein translocation. Various kinds of stem cells (embryonic stem cells, adult stem cells, or induced pluripotent stem cells) have to maintain their stemness and, under certain circumstances, undergo stress. Therefore, Hs...

  10. Adipose-derived mesenchymal stem cell transplantation promotes adult neurogenesis in the brains of Alzheimer’s disease mice

    Institute of Scientific and Technical Information of China (English)

    Yufang Yan; Tuo Ma; Kai Gong; Qiang Ao; Xiufang Zhang; Yandao Gong

    2014-01-01

    In the present study, we transplanted adipose-derived mesenchymal stem cells into the hippo-campi of APP/PS1 transgenic Alzheimer’s disease model mice. Immunofluorescence staining revealed that the number of newly generated (BrdU+) cells in the subgranular zone of the dentate gyrus in the hippocampus was signiifcantly higher in Alzheimer’s disease mice after adipose-de-rived mesenchymal stem cell transplantation, and there was also a significant increase in the number of BrdU+/DCX+neuroblasts in these animals. Adipose-derived mesenchymal stem cell transplantation enhanced neurogenic activity in the subventricular zone as well. Furthermore, adipose-derived mesenchymal stem cell transplantation reduced oxidative stress and alleviated cognitive impairment in the mice. Based on these ifndings, we propose that adipose-derived mes-enchymal stem cell transplantation enhances endogenous neurogenesis in both the subgranular and subventricular zones in APP/PS1 transgenic Alzheimer’s disease mice, thereby facilitating functional recovery.

  11. Mesenchymal Stem Cell-Based Therapy

    OpenAIRE

    Mundra, Vaibhav; Gerling, Ivan C.; Mahato, Ram I.

    2012-01-01

    Mesenchymal stem cells (MSCs) are multipotent adult stem cells which have self-renewal capacity and differentiation potential into several mesenchymal lineages including bones, cartilages, adipose tissues and tendons. MSCs may repair tissue injuries and prevent immune cell activation and proliferation. Immunomodulation and secretion of growth factors by MSCs have led to realizing the true potential of MSC-based cell therapy. The use of MSCs as immunomdulators has been explored in cell/organ t...

  12. Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland

    OpenAIRE

    Joanna Pyczek; Rolf Buslei; David Schult; Annett Hölsken; Michael Buchfelder; Ina Heß; Heidi Hahn; Anja Uhmann

    2016-01-01

    Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2+ and Sox...

  13. Application of Nanoscaffolds in Mesenchymal Stem Cell-Based Therapy

    OpenAIRE

    Ghoraishizadeh, Saman; Ghorishizadeh, Afsoon; Ghoraishizadeh, Peyman; Daneshvar, Nasibeh; Boroojerdi, Mohadese Hashem

    2014-01-01

    Regenerative medicine is an alternative solution for organ transplantation. Stem cells and nanoscaffolds are two essential components in regenerative medicine. Mesenchymal stem cells (MSCs) are considered as primary adult stem cells with high proliferation capacity, wide differentiation potential, and immunosuppression properties which make them unique for regenerative medicine and cell therapy. Scaffolds are engineered nanofibers that provide suitable microenvironment for cell signalling whi...

  14. Induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    Siddhartha Bhowmik; LI Yong

    2011-01-01

    Induced pluripotent stem (iPS) cells are a recent development which has brought a promise of great therapeutic values. The previous technique of somatic cell nuclear transfer (SCNT) has been ineffective in humans. Recent discoveries show that human fibroblasts can be reprogrammed by a transient over expression of a small number of genes; they can undergo induced pluripotency. iPS were first produced in 2006. By 2008, work was underway to remove the potential oncogenes from their structure. In 2009, protein iPS (piPS) cells were discovered. Surface markers and reporter genes play an important role in stem cell research. Clinical applications include generation of self renewing stem cells, tissue replacement and many more. Stem cell therapy has the ability to dramatically change the treatment of human diseases.

  15. Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: A prospective sibling donor versus no-donor comparison

    OpenAIRE

    Cornelissen, Jan; Holt, Bronno; Verhoef, Gregor; Veer, Mars; Oers, Marinus; Ossenkoppele, Gert; Sonneveld, Pieter; Maertens, Johan; Marwijk Kooy, Marinus; Schaafsma, Martijn; Wijermans, Pierre; Biesma, Douwe; Wittebol, Shulamit; Voogt, Paul; Baars, Joke

    2009-01-01

    textabstractWhile commonly accepted in poor-risk acute lymphoblastic leukemia (ALL), the role of allogeneic hematopoietic stem cell transplantation (allo-SCT) is still disputed in adult patients with standard-risk ALL. We evaluated outcome of patients with ALL in first complete remission (CR1), according to a sibling donor versus no-donor comparison. Eligible patients (433) were entered in 2 consecutive, prospective studies, of whom 288 (67%) were younger than 55 years, in CR1, and eligible t...

  16. Therapeutic potential of amniotic fluid stem cells.

    Science.gov (United States)

    Abdulrazzak, Hassan; De Coppi, Paolo; Guillot, Pascale V

    2013-03-01

    Human amniotic fluid cells have been used traditionally as a diagnostic tool for genetic anomalies. More recently it has been recognized that amniotic fluid contains populations of stem cells. Mesenchymal stem cells (AFMSC) were first to be described. These cells are able to differentiate towards mesodermal lineages. More recently cells with broader potential, defined as amniotic fluid stem cells (AFSC), were also isolated. They have intermediate characteristics between embryonic and adult stem cells and are able to differentiate into lineages representative of all three germ layers but unlike ES cells they do not form tumours in vivo. Furthermore, AFSC have been reverted to functional pluripotency in a transgene-free approach using an epigenetics modifier. These characteristics, together with absence of ethical issues concerning their employment, have made stem cells from amniotic fluid a promising candidate for cell therapy and tissue engineering.

  17. Stem cell myths

    OpenAIRE

    Magnus, Tim; Liu, Ying; Parker, Graham C.; Rao, Mahendra S.

    2007-01-01

    Stem cells, although difficult to define, hold great promise as tools for understanding development and as therapeutic agents. However, as with any new field, uncritical enthusiasm can outstrip reality. In this review, we have listed nine common myths that we believe affect our approach to evaluating stem cells for therapy. We suggest that careful consideration needs to be given to each of these issues when evaluating a particular cell for its use in therapy. Data need to be collected and rep...

  18. The significance of the host inflammatory response on the therapeutic efficacy of cell therapies utilising human adult stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Navarro, Melba, E-mail: mnavarro@ibecbarcelona.eu [UKCTE, The Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L69 3GA (United Kingdom); Biomaterials for Regenerative Therapies Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona, 08028 (Spain); Pu, Fanrong; Hunt, John A. [UKCTE, The Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L69 3GA (United Kingdom)

    2012-02-15

    Controlling the fate of implanted hMSCs is one of the major drawbacks to be overcome to realize tissue engineering strategies. In particular, the effect of the inflammatory environment on hMSCs behaviour is poorly understood. Studying and mimicking the inflammatory process in vitro is a very complex and challenging task that involves multiple variables. This research addressed the questions using in vitro co-cultures of primary derived hMSCs together with human peripheral blood mononucleated cells (PBMCs); the latter are key agents in the inflammatory process. This work explored the in vitro phenotypic changes of hMSCs in co-culture direct contact with monocytes and lymphocytes isolated from blood using both basal and osteogenic medium. Our findings indicated that hMSCs maintained their undifferentiated phenotype and pluripotency despite the contact with PBMCs. Moreover, hMSCs demonstrated increased proliferation and were able to differentiate specifically down the osteogenic lineage pathway. Providing significant crucial evidence to support the hypothesis that inflammation and host defence mechanisms could be utilised rather than avoided and combated to provide for the successful therapeutic application of stem cell therapies.

  19. Perspectives and controversies in the field of stem cell research.

    Science.gov (United States)

    Romano, Gaetano

    2006-09-01

    The fourth annual meeting of the International Society for Stem Cell Research focused on a number of pressing issues, including: (I) the need to better characterize the biology of stem cells; (II) the need to exploit and optimize the great therapeutic potential of stem cells in tissue regeneration; (III) ethical and safety considerations related to the use of human embryonic stem cells; (IV) the contribution of adult stem cells to carcinogenesis; (V) the need to investigate the biology of cancer stem cells. The purpose of this report is to summarize the current status of stem cell research, as surmised by the proceedings of this meeting.

  20. Over-expression of hNGF in adult human olfactory bulb neural stem cells promotes cell growth and oligodendrocytic differentiation.

    Directory of Open Access Journals (Sweden)

    Hany E S Marei

    Full Text Available The adult human olfactory bulb neural stem/progenitor cells (OBNC/PC are promising candidate for cell-based therapy for traumatic and neurodegenerative insults. Exogenous application of NGF was suggested as a promising therapeutic strategy for traumatic and neurodegenerative diseases, however effective delivery of NGF into the CNS parenchyma is still challenging due mainly to its limited ability to cross the blood-brain barrier, and intolerable side effects if administered into the brain ventricular system. An effective method to ensure delivery of NGF into the parenchyma of CNS is the genetic modification of NSC to overexpress NGF gene. Overexpression of NGF in adult human OBNSC is expected to alter their proliferation and differentiation nature, and thus might enhance their therapeutic potential. In this study, we genetically modified adult human OBNS/PC to overexpress human NGF (hNGF and green fluorescent protein (GFP genes to provide insight about the effects of hNGF and GFP genes overexpression in adult human OBNS/PC on their in vitro multipotentiality using DNA microarray, immunophenotyping, and Western blot (WB protocols. Our analysis revealed that OBNS/PC-GFP and OBNS/PC-GFP-hNGF differentiation is a multifaceted process involving changes in major biological processes as reflected in alteration of the gene expression levels of crucial markers such as cell cycle and survival markers, stemness markers, and differentiation markers. The differentiation of both cell classes was also associated with modulations of key signaling pathways such MAPK signaling pathway, ErbB signaling pathway, and neuroactive ligand-receptor interaction pathway for OBNS/PC-GFP, and axon guidance, calcium channel, voltage-dependent, gamma subunit 7 for OBNS/PC-GFP-hNGF as revealed by GO and KEGG. Differentiated OBNS/PC-GFP-hNGF displayed extensively branched cytoplasmic processes, a significant faster growth rate and up modulated the expression of oligodendroglia

  1. Stem Cells and Cancer

    International Nuclear Information System (INIS)

    Stem cell research has thrived over the last years due to their therapeutic and regenerative potential. Scientific breakthroughs in the field are immediately translated from the scientific journals to the mass media, which is not surprising as the characterisation of the molecular mechanisms that regulate the biology of stem cells is crucial for the treatment of degenerative and cardiovascular diseases, as well as cancer. In the Molecular Oncology Unit at Ciemat we work to unravel the role of cancer stem cells in tumour development, and to find new antitumor therapies. (Author)

  2. Prolonged remission state of refractory adult onset Still's disease following CD34-selected autologous peripheral blood stem cell transplantation.

    Science.gov (United States)

    Lanza, F; Dominici, M; Govoni, M; Moretti, S; Campioni, D; Corte, R L; Latorraca, A; Tieghi, A; Castagnari, B; Trotta, F; Castoldi, G

    2000-06-01

    We report a 38-year-old patient affected by refractory adult onset Still's disease who achieved a prolonged remission following CD34-selected ABMT. The conditioning regimen was based on the use of CY and anti-thymocyte globulin. A 3.0 and 2.0 log reduction of T (CD3+) and B (CD19+) lymphocytes, respectively, was obtained using a Ceprate device to select CD34+ cells from PBSC. In the pre-transplant period (1994-1998) the patient had a chronic persistent disease course with frequent and recurrent systemic articular flares and loss of some functional abilities, despite daily prednisone, pulses of CY and immunosuppressive therapy (CYA or MTX). At the time of ABMT the patient had become non-ambulatory. Within 3 weeks of ABMT the patient showed a marked decrease in joint swelling, and morning stiffness. Joint pain and systemic symptoms disappeared, the patient was able to walk and run and gained general well being. ESR, C-reactive protein and WBC count were significantly decreased, while Hb level increased. This partial remission persisted for at least 1 year after ABMT, although at 15 months of follow-up a reappearance of moderate synovitis in the knees and wrists was noted. Our data further showed that both patient BM microenvironment and stem-progenitor cell function (as assessed by LTC-IC assay) were damaged even 1 year after CD34-selected ABMT, suggesting that the persistence of these alterations could have facilitated the favorable outcome of the disease following ABMT. Bone Marrow Transplantation (2000) 25, 1307-1310. PMID:10871738

  3. Stem cells in the nervous system.

    Science.gov (United States)

    Maldonado-Soto, Angel R; Oakley, Derek H; Wichterle, Hynek; Stein, Joel; Doetsch, Fiona K; Henderson, Christopher E

    2014-11-01

    Given their capacity to regenerate cells lost through injury or disease, stem cells offer new vistas into possible treatments for degenerative diseases and their underlying causes. As such, stem cell biology is emerging as a driving force behind many studies in regenerative medicine. This review focuses on the current understanding of the applications of stem cells in treating ailments of the human brain, with an emphasis on neurodegenerative diseases. Two types of neural stem cells are discussed: endogenous neural stem cells residing within the adult brain and pluripotent stem cells capable of forming neural cells in culture. Endogenous neural stem cells give rise to neurons throughout life, but they are restricted to specialized regions in the brain. Elucidating the molecular mechanisms regulating these cells is key in determining their therapeutic potential as well as finding mechanisms to activate dormant stem cells outside these specialized microdomains. In parallel, patient-derived stem cells can be used to generate neural cells in culture, providing new tools for disease modeling, drug testing, and cell-based therapies. Turning these technologies into viable treatments will require the integration of basic science with clinical skills in rehabilitation.

  4. The possibilities of stem cell application in regenerative medicine

    OpenAIRE

    Galiniak Sabina; Krawczyk-Merć Izabela; Pedrycz Agnieszka

    2016-01-01

    Stem cells are characterized by their ability to self-renew and differentiate into various cell types. They offer great potential for a wide range of applications, however, medical studies on the use of embryonal stem cells are largely limited to bioethical issues searching for alternative sources of stem cells, which include isolating cells from adult organisms or inducing pluripotentiality of somatic cells by administration of transcription factors. Nowadays, stem cells are used to study th...

  5. Hippocampal stem cells: so they are multipotent!

    Institute of Scientific and Technical Information of China (English)

    Verdon Taylor

    2011-01-01

    Although neurogenesis continues throughout life in the mammalian brain, the issue of whether the stem cells that drive the process in vivo are self-renewing and multipotent remains unclear. In a recent landmark paper by Bonaguidi et al. (2011) published in Cell, the authors provide clonal evidence that neural stem cells in the dentate gyrus of the adult hippocampus are indeed multipotent and undergo symmetric cell divisions.%Although neurogenesis continues throughout life in the mammalian brain,the issue of whether the stem cells that drive the process in vivo are self-renewing and multipotent remains unclear.In a recent landmark paper by Bonaguidi et al.(2011) pubiished in Cell,the authors provide cional evidence that neural stem cells in the dentate gyrus of the adult hippocampus are indeed multipotent and undergo symmetric cell divisions.

  6. Rapid and efficient reprogramming of human fetal and adult blood CD34+ cells into mesenchymal stem cells with a single factor

    Institute of Scientific and Technical Information of China (English)

    Xianmei Meng; Rui-Jun Su; David J Baylink; Amanda Neises; Jason B Kiroyan; Wayne Yuk-Wai Lee; Kimberly J Payne

    2013-01-01

    The direct conversion of skin cells into somatic stem cells has opened new therapeutic possibilities in regenerative medicine.Here,we show that human induced mesenchymal stem cells (iMSCs) can be efficiently generated from cord blood (CB)-or adult peripheral blood (PB)-CD34+ cells by direct reprogramming with a single factor,OCT4.In the presence of a GSK3 inhibitor,16% of the OCT4-transduced CD34+ cells are converted into iMSCs within 2 weeks.Efficient direct reprogramming is achieved with both episomal vector-mediated transient OCT4 expression and lentiviral vector-mediated OCT4 transduction.The iMSCs express MSC markers,resemble bone marrow (BM)-MSCs in morphology,and possess in vitro multilineage differentiation capacity,yet have a greater proliferative capacity compared with BM-MSCs.Similar to BM-MSCs,the implanted iMSCs form bone and connective tissues,and are non-tumorigenic in mice.However,BM-MSCs do not,whereas iMSCs do form muscle fibers,indicating a potential functional advantage of iMSCs.In addition,we observed that a high level of OCT4 expression is required for the initial reprogramming and the optimal iMSC self-renewal,while a reduction of OCT4 expression is required for multilineage differentiation.Our method will contribute to the generation of patient-specific iMSCs,which could have applications in regenerative medicine.This discovery may also facilitate the development of strategies for direct conversion of blood cells into other types of cells of clinical importance.

  7. SMOOTH MUSCLE STEM CELLS

    Science.gov (United States)

    Vascular smooth muscle cells (SMCs) originate from multiple types of progenitor cells. In the embryo, the most well-studied SMC progenitor is the cardiac neural crest stem cell. Smooth muscle differentiation in the neural crest lineage is controlled by a combination of cell intrinsic factors, includ...

  8. Two-photon imaging of stem cells

    Science.gov (United States)

    Uchugonova, A.; Gorjup, E.; Riemann, I.; Sauer, D.; König, K.

    2008-02-01

    A variety of human and animal stem cells (rat and human adult pancreatic stem cells, salivary gland stem cells, dental pulpa stem cells) have been investigated by femtosecond laser 5D two-photon microscopy. Autofluorescence and second harmonic generation have been imaged with submicron spatial resolution, 270 ps temporal resolution, and 10 nm spectral resolution. In particular, NADH and flavoprotein fluorescence was detected in stem cells. Major emission peaks at 460nm and 530nm with typical mean fluorescence lifetimes of 1.8 ns and 2.0 ns, respectively, were measured using time-correlated single photon counting and spectral imaging. Differentiated stem cells produced the extracellular matrix protein collagen which was detected by SHG signals at 435 nm.

  9. 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.

  10. 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.

  11. Stem cell therapy independent of stemness.

    Science.gov (United States)

    Lee, Techung

    2012-12-26

    Mesenchymal stem cell (MSC) therapy is entering a new era shifting the focus from initial feasibility study to optimization of therapeutic efficacy. However, how MSC therapy facilitates tissue regeneration remains incompletely characterized. Consistent with the emerging notion that secretion of multiple growth factors/cytokines (trophic factors) by MSC provides the underlying tissue regenerative mechanism, the recent study by Bai et al demonstrated a critical therapeutic role of MSC-derived hepatocyte growth factor (HGF) in two animal models of multiple sclerosis (MS), which is a progressive autoimmune disorder caused by damage to the myelin sheath and loss of oligodendrocytes. Although current MS therapies are directed toward attenuation of the immune response, robust repair of myelin sheath likely requires a regenerative approach focusing on long-term replacement of the lost oligodendrocytes. This approach appears feasible because adult organs contain various populations of multipotent resident stem/progenitor cells that may be activated by MSC trophic factors as demonstrated by Bai et al This commentary highlights and discusses the major findings of their studies, emphasizing the anti-inflammatory function and trophic cross-talk mechanisms mediated by HGF and other MSC-derived trophic factors in sustaining the treatment benefits. Identification of multiple functionally synergistic trophic factors, such as HGF and vascular endothelial growth factor, can eventually lead to the development of efficacious cell-free therapeutic regimens targeting a broad spectrum of degenerative conditions. PMID:23516128

  12. In Vitro Study of the Effect of Vitamin E on Viability, Morphological Changes and Induction of Osteogenic Differentiation in Adult Rat Bone Marrow Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    M Soleimani Mehranjani

    2014-10-01

    Full Text Available Introduction: Vitamin E as a strong antioxidant plays an important role in inhibiting free radicals. Therefore, this study aimed to investigate the effect of vitamin E on the viability, morphology and osteogenic differentiation in bone marrow mesenchymal stem cells of an adult rat. Methods: The bone marrow mesenchymal stem cells were extracted using the flashing-out method. At the end of the third passage, cells were divided into groups of control and experimental. Experimental cells were treated withVitamin E (5,10,15,25,50,100,150μM for a period of 21 days in the osteogenic media containing 10% of fetal bovine serum. The cell viability, bone matrix mineralization, intercellular and extracellular calcium deposition, alkaline phosphatase activity, expression of genes and synthesis of proteins of osteopontin and osteocalcin as well as morphological changes of the cells were investigated. The study data was analyzed using one-way ANOVA and T-Test setting the significant P value at P<0.05. Results: Within vitamin- E treated cells, the mean viability, mean bone matrix mineralization, calcium deposition, alkaline phosphatase activity, expression and synthesis of osteopontin and osteocalcin of the mesenchymal stem cells treated with vitamin E significantly increased in a dose dependent manner. Also cytoplasm extensions were observed in the cells treated with vitamin E. Conclusion: Since vitamin E caused a significant increase in cell viability and osteogenic differentiation in the mesenchymal stem cells, therefore it can be utilized in order to increase cell differentiation and cell survival.

  13. Fetal and adult hematopoietic stem cells require beta1 integrin function for colonizing fetal liver, spleen, and bone marrow

    DEFF Research Database (Denmark)

    Potocnik, A J; Brakebusch, C; Fässler, R

    2000-01-01

    Homing of hematopoietic stem cells (HSCs) into hematopoietic organs is a prerequisite for the establishment of hematopoiesis during embryogenesis and after bone marrow transplantation. We show that beta1 integrin-deficient HSCs from the para-aortic splanchnopleura and the fetal blood had hematoly......Homing of hematopoietic stem cells (HSCs) into hematopoietic organs is a prerequisite for the establishment of hematopoiesis during embryogenesis and after bone marrow transplantation. We show that beta1 integrin-deficient HSCs from the para-aortic splanchnopleura and the fetal blood had...

  14. c-kitpos GATA-4 high rat cardiac stem cells foster adult cardiomyocyte survival through IGF-1 paracrine signalling.

    Directory of Open Access Journals (Sweden)

    Nanako Kawaguchi

    Full Text Available BACKGROUND: Resident c-kit positive (c-kitpos cardiac stem cells (CSCs could be considered the most appropriate cell type for myocardial regeneration therapies. However, much is still unknown regarding their biological properties and potential. METHODOLOGY/PRINCIPAL FINDINGS: We produced clones of high and low expressing GATA-4 CSCs from long-term bulk-cultured c-kitpos CSCs isolated from adult rat hearts. When c-kitpos GATA-4 high expressing clonal CSCs (cCSCs were co-cultured with adult rat ventricular cardiomyocytes, we observed increased survival and contractility of the cardiomyocytes, compared to cardiomyocytes cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low expressing cCSCs. When analysed by ELISA, the concentration of IGF-1 was significantly increased in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-cultures and there was a significant correlation between IGF-1 concentration and cardiomyocyte survival. We showed the activation of the IGF-1 receptor and its downstream molecular targets in cardiomyocytes co-cultured with c-kitpos GATA-4 high cCSCs but not in cardiomyocytes that were cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low cCSCs. Addition of a blocking antibody specific to the IGF-1 receptor inhibited the survival of cardiomyocytes and prevented the activation of its signalling in cardiomyocytes in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-culture system. IGF-1 supplementation or IGF-1 high conditioned medium taken from the co-culture of c-kitpos GATA-4 high cCSCs plus cardiomyocytes did extend the survival and contractility of cardiomyocytes cultured alone and cardiomyocytes co-cultured with c-kitpos GATA-4 low cCSCs. CONCLUSION/SIGNIFICANCE: c-kitpos GATA-4 high cCSCs exert a paracrine survival effect on cardiomyocytes through induction of the IGF-1R and signalling pathway.

  15. Stem cell strategies for Alzheimer's disease therapy.

    Science.gov (United States)

    Sugaya, K; Alvarez, A; Marutle, A; Kwak, Y D; Choumkina, E

    2006-06-01

    We have found much evidence that the brain is capable of regenerating neurons after maturation. In our previous study, human neural stem cells (HNSCs) transplanted into aged rat brains differentiated into neural cells and significantly improved the cognitive functions of the animals, indicating that HNSCs may be a promising candidate for cell-replacement therapies for neurodegenerative diseases including Alzheimer's disease (AD). However, ethical and practical issues associated with HNSCs compel us to explore alternative strategies. Here, we report novel technologies to differentiate adult human mesenchymal stem cells, a subset of stromal cells in the bone marrow, into neural cells by modifying DNA methylation or over expression of nanog, a homeobox gene expressed in embryonic stem cells. We also report peripheral administrations of a pyrimidine derivative that increases endogenous stem cell proliferation improves cognitive function of the aged animal. Although these results may promise a bright future for clinical applications used towards stem cell strategies in AD therapy, we must acknowledge the complexity of AD. We found that glial differentiation takes place in stem cells transplanted into amyloid-( precursor protein (APP) transgenic mice. We also found that over expression of APP gene or recombinant APP treatment causes glial differentiation of stem cells. Although further detailed mechanistic studies may be required, RNA interference of APP or reduction of APP levels in the brain can significantly reduced glial differentiation of stem cells and may be useful in promoting neurogenesis after stem cell transplantation. PMID:16953146

  16. Stem cell signatures in glioma

    OpenAIRE

    He, Xiaobing

    2012-01-01

    Gliomas are the most common tumors of the central nervous system in adults. Glioblastoma, the most aggressive form, has a median survival of 15 months regardless of the standard treatment with surgery and temozolomide-based radiochemotherapy. Therefore, it is imperative to improve treatment options for patients with glioblastoma. It has been suggested that the putative tumor stem cells in brain tumors are responsible for glioma initiation, development and resistance to ...

  17. Neural Stem Cells and Glioblastoma

    OpenAIRE

    Rispoli, Rossella; Conti, Carlo; Celli, Paolo; Caroli, Emanuela; Carletti, Sandro

    2014-01-01

    Glioblastoma multiforme represents one of the most common brain cancers with a rather heterogeneous cellular composition, as indicated by the term “multiforme". Recent reports have described the isolation and identification of cancer neural stem cells from human adult glioblastoma multiforme, which possess the capacity to establish, sustain, and expand these tumours, even under the challenging settings posed by serial transplantation experiments. Our study focused on the distribution of neura...

  18. 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

  19. Stem cells: A new paradigm in periodontal regeneration

    Directory of Open Access Journals (Sweden)

    Marawar Pramod P, Shinde Sagar K, Mani Ameet M, Patil Ishwardas D

    2013-04-01

    Full Text Available Stem cells are a unique type of cell that forms the basis of the development, growth and survival of a living organism. Though the term is often used to describe controversial embryonic stem cells, there are many different types of stem cells, classified by their original location and/or method of formation. Stem cells are undifferentiated cells that go on developing into any of more than 200 type of cells that adult Human body hold. Now a days stem cells have significant use in regenerative periodontal therapy. Recently, reports have begun to emerge demonstrating that populations of adult stem cells reside in the periodontal ligament of humans and other animals. This opens the way for new cell-based therapies for periodontal regeneration.This review provides an overview of adult human stem cells and their potential use in periodontal regeneration.

  20. A multistep procedure to prepare pre-vascularized cardiac tissue constructs using adult stem sells, dynamic cell cultures, and porous scaffolds.

    Science.gov (United States)

    Pagliari, Stefania; Tirella, Annalisa; Ahluwalia, Arti; Duim, Sjoerd; Goumans, Marie-Josè; Aoyagi, Takao; Forte, Giancarlo

    2014-01-01

    The vascularization of tissue engineered products represents a key issue in regenerative medicine which needs to be addressed before the translation of these protocols to the bedside can be foreseen. Here we propose a multistep procedure to prepare pre-vascularized three-dimensional (3D) cardiac bio-substitutes using dynamic cell cultures and highly porous biocompatible gelatin scaffolds. The strategy adopted exploits the peculiar differentiation potential of two distinct subsets of adult stem cells to obtain human vascularized 3D cardiac tissues. In the first step of the procedure, human mesenchymal stem cells (hMSCs) are seeded onto gelatin scaffolds to provide interconnected vessel-like structures, while human cardiomyocyte progenitor cells (hCMPCs) are stimulated in vitro to obtain their commitment toward the cardiac phenotype. The use of a modular bioreactor allows the perfusion of the whole scaffold, providing superior performance in terms of cardiac tissue maturation and cell survival. Both the cell culture on natural-derived polymers and the continuous medium perfusion of the scaffold led to the formation of a densely packaged proto-tissue composed of vascular-like and cardiac-like cells, which might complete maturation process and interconnect with native tissue upon in vivo implantation. In conclusion, the data obtained through the approach here proposed highlight the importance to provide stem cells with complementary signals in vitro able to resemble the complexity of cardiac microenvironment.

  1. A Multistep Procedure To Prepare Pre-Vascularized Cardiac Tissue Constructs Using Adult Stem Sells, Dynamic Cell Cultures And Porous Scaffolds

    Directory of Open Access Journals (Sweden)

    Stefania ePagliari

    2014-06-01

    Full Text Available The vascularization of tissue engineered products represents a key issue in regenerative medicine which needs to be addressed before the translation of these protocols to the bedside can be foreseen. Here we propose a multistep procedure to prepare pre-vascularized three-dimensional (3D cardiac bio-substitutes using dynamic cell cultures and highly porous biocompatible gelatin scaffolds. The strategy adopted exploits the peculiar differentiation potential of two distinct subsets of adult stem cells to obtain human vascularized 3D cardiac tissues. In the first step of the procedure, human mesenchymal stem cells (hMSCs are seeded onto gelatin scaffolds to provide interconnected vessel-like structures, while human cardiomyocyte progenitor cells (hCMPCs are stimulated in vitro to obtain their commitment towards the cardiac phenotype. The use of a modular bioreactor allows the perfusion of the whole scaffold, providing superior performance in terms of cardiac tissue maturation and cell survival. Both the cell culture on natural-derived polymers and the continuous medium perfusion of the scaffold led to the formation of a densely packaged proto-tissue composed of vascular-like and cardiac-like cells, which might complete maturation process and interconnect with native tissue upon in vivo implantation. In conclusion, the data obtained through the approach here proposed highlight the importance to provide stem cells with complementary signals in vitro able to resemble the complexity of cardiac microenvironment.

  2. Efficient animal-serum free 3D cultivation method for adult human neural crest-derived stem cell therapeutics

    Directory of Open Access Journals (Sweden)

    JFW Greiner

    2011-12-01

    Full Text Available Due to their broad differentiation potential and their persistence into adulthood, human neural crest-derived stem cells (NCSCs harbour great potential for autologous cellular therapies, which include the treatment of neurodegenerative diseases and replacement of complex tissues containing various cell types, as in the case of musculoskeletal injuries. The use of serum-free approaches often results in insufficient proliferation of stem cells and foetal calf serum implicates the use of xenogenic medium components. Thus, there is much need for alternative cultivation strategies. In this study we describe for the first time a novel, human blood plasma based semi-solid medium for cultivation of human NCSCs. We cultivated human neural crest-derived inferior turbinate stem cells (ITSCs within a blood plasma matrix, where they revealed higher proliferation rates compared to a standard serum-free approach. Three-dimensionality of the matrix was investigated using helium ion microscopy. ITSCs grew within the matrix as revealed by laser scanning microscopy. Genetic stability and maintenance of stemness characteristics were assured in 3D cultivated ITSCs, as demonstrated by unchanged expression profile and the capability for self-renewal. ITSCs pre-cultivated in the 3D matrix differentiated efficiently into ectodermal and mesodermal cell types, particularly including osteogenic cell types. Furthermore, ITSCs cultivated as described here could be easily infected with lentiviruses directly in substrate for potential tracing or gene therapeutic approaches. Taken together, the use of human blood plasma as an additive for a completely defined medium points towards a personalisable and autologous cultivation of human neural crest-derived stem cells under clinical grade conditions.

  3. Facts about Stem Cells and Importance of Them

    Directory of Open Access Journals (Sweden)

    Masumeh Saeidi

    2014-05-01

    Full Text Available Stem cells are undifferentiated biological cells that can differentiate into specialized cells and can divide (through mitosis to produce more stem cells. They are found in multicellular organisms. In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the specialized cells—ectoderm, endoderm and mesoderm (see induced pluripotent stem cells—but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues. There are three accessible sources of autologous adult stem cells in humans: Bone marrow, which requires extraction by harvesting, that is, drilling into bone (typically the femur or iliac crest, Adipose tissue (lipid cells, which requires extraction by liposuction, and Blood, which requires extraction through apheresis, wherein blood is drawn from the donor (similar to a blood donation, and passed through a machine that extracts the stem cells and returns other portions of the blood to the donor. Stem cells can also be taken from umbilical cord blood just after birth. Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may bank his or her own blood for elective surgical procedures. Adult stem cells are frequently used in medical therapies, for example in bone marrow transplantation. Stem cells can now be artificially grown and transformed (differentiated into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves. Embryonic cell lines and autologous embryonic stem cells generated through Somatic-cell nuclear transfer or dedifferentiation

  4. Cellular Modulation of Polymeric Device Surfaces: Promise of Adult Stem Cells for Neuro-Prosthetics

    OpenAIRE

    Richter, Anja; Kruse, Charli; Moser, Andreas; Hofmann, Ulrich G.; Danner, Sandra

    2011-01-01

    Minimizing the foreign body response is seen as one critical research strategy for implants especially when designed for immune-privileged organs like the brain. The context of this work is to improve deep brain stimulating devices used in a consistently growing spectrum of psychomotor and psychiatric diseases mainly in form of stiff electrodes. Based on the compliance match hypothesis of biocompatibility we present another step forward using flexible implant materials covered with brain cell...

  5. Stem cells and colorectal carcinogenesis

    Science.gov (United States)

    Stoian, M; Stoica, V; Radulian, G

    2016-01-01

    Abstract Colorectal cancer represents an important cause of mortality and morbidity. Unfortunately, the physiopathology is still under study. There are theories about carcinogenesis and it is known that not only a single factor is responsible for the development of a tumor, but several conditions. Stem cells are a promising target for the treatment of colorectal cancer, along with the environment that has an important role. It has been postulated that mutations within the adult colonic stem cells may induce neoplastic changes. 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 tumor and therefore they are responsible for recurrence. It is important to know that a new way of treatment needs to be found, since these cells are resistant to chemotherapy and radiotherapy.

  6. 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....

  7. Stem cells in the human breast

    DEFF Research Database (Denmark)

    Petersen, Ole William; Polyak, Kornelia

    2010-01-01

    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......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...

  8. Depletion of neural stem cells from the subventricular zone of adult mouse brain using cytosine b‐Arabinofuranoside

    OpenAIRE

    Ghanbari, Amir; Esmaeilpour, Tahereh; Bahmanpour, Soghra; Golmohammadi, Mohammad Ghasem; Sharififar, Sharareh; Azari, Hassan

    2015-01-01

    Abstract Introduction Neural stem cells (NSCs) reside along the ventricular axis of the mammalian brain. They divide infrequently to maintain themselves and the down‐stream progenitors. Due to the quiescent property of NSCs, attempts to deplete these cells using antimitotic agents such as cytosine b‐Aarabinofuranoside (Ara‐C) have not been successful. We hypothesized that implementing infusion gaps in Ara‐C kill paradigms would recruit the quiescent NSCs and subsequently eliminate them from t...

  9. Ectopically hTERT expressing adult human mesenchymal stem cells are less radiosensitive than their telomerase negative counterpart

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Graakjaer, Jesper; Cairney, Claire J;

    2007-01-01

    radiosensitivity to other mammalian cells so far tested. In this study, we investigated the genetic effects of ionizing radiation (2.5-15 Gy) on normal human mesenchymal stem cells and their telomerised counterpart hMSC-telo1. We evaluated overall genomic integrity, DNA damage/repair by applying a fluorescence...... and high telomerase activity have the advantage of re-establishing the telomeric caps. Udgivelsesdato: 2007-Mar-10...

  10. Embryonic Stem Cell Markers

    OpenAIRE

    Lan Ma; Liang Li; Wenxiu Zhao; Xiang Ji; Fangfang Zhang

    2012-01-01

    Embryonic stem cell (ESC) markers are molecules specifically expressed in ES cells. Understanding of the functions of these markers is critical for characterization and elucidation for the mechanism of ESC pluripotent maintenance and self-renewal, therefore helping to accelerate the clinical application of ES cells. Unfortunately, different cell types can share single or sometimes multiple markers; thus the main obstacle in the clinical application of ESC is to purify ES cells from other type...

  11. DNA methylation in stem cell renewal and multipotency

    OpenAIRE

    Berdasco, María; Esteller, Manel

    2011-01-01

    Owing to their potential for differentiation into multiple cell types, multipotent stem cells extracted from many adult tissues are an attractive stem cell resource for the replacement of damaged tissues in regenerative medicine. The requirements for cellular differentiation of an adult stem cell are a loss of proliferation potential and a gain of cell-type identity. These processes could be restricted by epigenetic modifications that prevent the risks of lineage-unrelated gene expression or ...

  12. Depolarization Alters Phenotype, Maintains Plasticity of Predifferentiated Mesenchymal Stem Cells

    OpenAIRE

    Sundelacruz, Sarah; Levin, Michael; Kaplan, David L

    2013-01-01

    Although adult stem cell transplantation has been implemented as a therapy for tissue repair, it is limited by the availability of functional adult stem cells. A potential approach to generate stem and progenitor cells may be to modulate the differentiated status of somatic cells. Therefore, there is a need for a better understanding of how the differentiated phenotype of mature cells is regulated. We hypothesize that bioelectric signaling plays an important role in the maintenance of the dif...

  13. 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.

  14. The new stem cell biology.

    OpenAIRE

    Quesenberry, Peter J.; Colvin, Gerald A; Lambert, Jean-Francois; Frimberger, Angela E.; Dooner, Mark S.; Mcauliffe, Christina I.; Miller, Caroline; Becker, Pamela; Badiavas, Evangelis; Falanga, Vincent J.; Elfenbein, Gerald; Lum, Lawrence G.

    2002-01-01

    Recent studies have indicated that bone marrow stem cells are capable of generating muscle, cardiac, hepatic, renal, and bone cells. Purified hematopoietic stem cells have generated cardiac and hepatic cells and reversed disease manifestations in these tissues. Hematopoietic stem cells also alter phenotype with cell cycle transit or circadian phase. During a cytokine stimulated cell cycle transit, reversible alterations of differentiation and engraftment occur. Primitive hematopoietic stem ce...

  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. Protease-activated receptor-1 negatively regulates proliferation of neural stem/progenitor cells derived from the hippocampal dentate gyrus of the adult mouse.

    Science.gov (United States)

    Tanaka, Masayuki; Yoneyama, Masanori; Shiba, Tatsuo; Yamaguchi, Taro; Ogita, Kiyokazu

    2016-07-01

    Thrombin-activated protease-activated receptor (PAR)-1 regulates the proliferation of neural cells following brain injury. To elucidate the involvement of PAR-1 in the neurogenesis that occurs in the adult hippocampus, we examined whether PAR-1 regulated the proliferation of neural stem/progenitor cells (NPCs) derived from the murine hippocampal dentate gyrus. NPC cultures expressed PAR-1 protein and mRNA encoding all subtypes of PAR. Direct exposure of the cells to thrombin dramatically attenuated the cell proliferation without causing cell damage. This thrombin-induced attenuation was almost completely abolished by the PAR antagonist RWJ 56110, as well as by dabigatran and 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), which are selective and non-selective thrombin inhibitors, respectively. Expectedly, the PAR-1 agonist peptide (AP) SFLLR-NH2 also attenuated the cell proliferation. The cell proliferation was not affected by the PAR-1 negative control peptide RLLFT-NH2, which is an inactive peptide for PAR-1. Independently, we determined the effect of in vivo treatment with AEBSF or AP on hippocampal neurogenesis in the adult mouse. The administration of AEBSF, but not that of AP, significantly increased the number of newly-generated cells in the hippocampal subgranular zone. These data suggest that PAR-1 negatively regulated adult neurogenesis in the hippocampus by inhibiting the proliferative activity of the NPCs. PMID:27426918

  17. 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.

  18. Current Stem Cell Delivery Methods for Myocardial Repair

    OpenAIRE

    Sheng, Calvin C.; Li Zhou; Jijun Hao

    2013-01-01

    Heart failure commonly results from an irreparable damage due to cardiovascular diseases (CVDs), the leading cause of morbidity and mortality in the United States. In recent years, the rapid advancements in stem cell research have garnered much praise for paving the way to novel therapies in reversing myocardial injuries. Cell types currently investigated for cellular delivery include embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cell lineages such as ske...

  19. Stem Cell Therapy: A New Treatment for Burns?

    OpenAIRE

    Gauglitz, Gerd G.; Marc G. Jeschke; Mohammed Al Shehab; Anna Arno; Blit, Patrick H.; Smith, Alexandra H.

    2011-01-01

    Stem cell therapy has emerged as a promising new approach in almost every medicine specialty. This vast, heterogeneous family of cells are now both naturally (embryonic and adult stem cells) or artificially obtained (induced pluripotent stem cells or iPSCs) and their fates have become increasingly controllable, thanks to ongoing research in this passionate new field. We are at the beginning of a new era in medicine, with multiple applications for stem cell therapy, not only as a monotherapy, ...

  20. The role of dental stem cells in regeneration

    OpenAIRE

    MAXIM, MONICA ANGELA; Soritau, Olga; BACIUT, MIHAELA; BRAN, SIMION; BACIUT, GRIGORE

    2015-01-01

    Mesenchymal stem cells (MSCs) are adult stem cells that have the capacity of rising multiple cell types. A rich source of mesenchymal stem cells is represented by the dental tissues: the periodontal ligament, the dental pulp, the apical papilla, the dental follicle and the deciduous teeth. The aim of this review is to characterize the main dental- derived mesenchymal stem cell population, and to show their important role in tissue regeneration based on their properties : the multi-potency, th...