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Sample records for advancing stem cell

  1. Advances in stem cell therapy.

    PubMed

    Pérez López, Silvia; Otero Hernández, Jesús

    2012-01-01

    Since the beginning of stem cell biology, considerable effort has been focused in the translation of scientific insights into new therapies. Cell-based assays represent a new strategy for organ and tissue repair in several pathologies. Moreover, alternative treatment strategies are urgently needed due to donor organ shortage that costs many lives every year and results in lifelong immunosuppression. At the moment, only the use of hematopoietic stem cells is considered as the standard for the treatment of malignant and genetic bone marrow disorders, being all other stem cell applications highly experimental. The present chapter tries to summarize some ongoing approaches of stem cell regenerative medicine and also introduces recent findings from published studies and trials conducted in various tissues such as skeletal muscle, liver and lung.

  2. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease. PMID:26593898

  3. Prostate Cancer Stem Cells: Research Advances.

    PubMed

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease.

  4. Technology Advancement for Integrative Stem Cell Analyses

    PubMed Central

    Jeong, Yoon

    2014-01-01

    Scientists have endeavored to use stem cells for a variety of applications ranging from basic science research to translational medicine. Population-based characterization of such stem cells, while providing an important foundation to further development, often disregard the heterogeneity inherent among individual constituents within a given population. The population-based analysis and characterization of stem cells and the problems associated with such a blanket approach only underscore the need for the development of new analytical technology. In this article, we review current stem cell analytical technologies, along with the advantages and disadvantages of each, followed by applications of these technologies in the field of stem cells. Furthermore, while recent advances in micro/nano technology have led to a growth in the stem cell analytical field, underlying architectural concepts allow only for a vertical analytical approach, in which different desirable parameters are obtained from multiple individual experiments and there are many technical challenges that limit vertically integrated analytical tools. Therefore, we propose—by introducing a concept of vertical and horizontal approach—that there is the need of adequate methods to the integration of information, such that multiple descriptive parameters from a stem cell can be obtained from a single experiment. PMID:24874188

  5. Technology advancement for integrative stem cell analyses.

    PubMed

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

    2014-12-01

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

  6. Advances in Stem Cell Therapy for Leukemia.

    PubMed

    Tian, Hong; Qu, Qi; Liu, Liming; Wu, Depei

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective post remission treatment for leukemia, resulting in lower relapse rates than alternative therapies. However, it is limited by the lack of suitable human leukocyte antigen (HLA) matched donors and high rates of transplant-related morbidity and mortality. Cord blood transplantation (CBT) and haploidentical SCT (haplo-SCT) expand the potential donor pool but are also associated with major complications. Co-infusion of third-party donor stem cells with a CBT/haplo-SCT, which is called "dual transplantation," has been reported to improve the outcome of HSCT by accelerating hematopoietic reconstitution and reducing the incidence of graft-versus-host disease (GVHD). In addition, infusion of HLA-mismatched donor granulocyte colony-stimulating factor-mobilized donor peripheral blood stem cells after chemotherapy, the so called "microtransplantation", has been shown to promote the graft-versus-leukemia effect and hasten hematopoietic recovery without amplifying GVHD. Herein, we review recent advances in stem cell therapy for leukemia with a specific focus on dual transplantation and microtransplantation.

  7. Advances in Reprogramming Somatic Cells to Induced Pluripotent Stem Cells

    PubMed Central

    Patel, Minal; Yang, Shuying

    2010-01-01

    Traditionally, nuclear reprogramming of cells has been performed by transferring somatic cell nuclei into oocytes, by combining somatic and pluripotent cells together through cell fusion and through genetic integration of factors through somatic cell chromatin. All of these techniques changes gene expression which further leads to a change in cell fate. Here we discuss recent advances in generating induced pluripotent stem cells, different reprogramming methods and clinical applications of iPS cells. Viral vectors have been used to transfer transcription factors (Oct4, Sox2, c-myc, Klf4, and nanog) to induce reprogramming of mouse fibroblasts, neural stem cells, neural progenitor cells, keratinocytes, B lymphocytes and meningeal membrane cells towards pluripotency. Human fibroblasts, neural cells, blood and keratinocytes have also been reprogrammed towards pluripotency. In this review we have discussed the use of viral vectors for reprogramming both animal and human stem cells. Currently, many studies are also involved in finding alternatives to using viral vectors carrying transcription factors for reprogramming cells. These include using plasmid transfection, piggyback transposon system and piggyback transposon system combined with a non viral vector system. Applications of these techniques have been discussed in detail including its advantages and disadvantages. Finally, current clinical applications of induced pluripotent stem cells and its limitations have also been reviewed. Thus, this review is a summary of current research advances in reprogramming cells into induced pluripotent stem cells. PMID:20336395

  8. [Advances in Lung Stem Cells and Lung Cancer Stem Cells].

    PubMed

    Yin, Huijing; Deng, Jiong

    2015-10-20

    Cancer stem cells (CSCs) are emerging as a hot topic for cancer research. Lung CSCs share many characteristics with normal lung stem cells (SCs), including self-renewal and multi-potency for differentiation. Many molecular markers expressed in various types of CSCs were also found in lung CSCs, such as CD133, CD44, aldehyde dehydrogenase (ALDH) and ATP-binding cassette sub-family G member 2 (ABCG2). Similarly, proliferation and expansion of lung CSCs are regulated not only by signal transduction pathways functioning in normal lung SCs, such as Notch, Hedgehog and Wnt pathways, but also by those acting in tumor cells, such as epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3) and phosphatidylinositol 3 kinase (PI3K) pathways. As CSC plays an critical role in tumor recurrence, metastasis and drug-resistance, understanding the difference between lung CSCs and normal lung SCs, identifying and targeting CSC markers or related signaling pathways may increase the efficacy of therapy on lung cancer and improved survival of lung cancer patients.

  9. Neural stem cells-trends and advances.

    PubMed

    English, Denis; Sharma, Neel K; Sharma, Kaushal; Anand, Akshay

    2013-04-01

    For many years, accepted dogma held that brain is a static organ with no possibility of regeneration of cells in injured or diseased human brain. However, recent preclinical reports have shown regenerative potential of neural stem cells using various injury models. This has resulted in renewed hope for those suffering from spinal cord injury and neural damage. As the potential of stem cell therapy gained impact, these claims, in particular, led to widespread enthusiasm that acute and chronic injury of the nervous system would soon be a problem of the past. The devastation caused by injury or diseases of the brain and spinal cord led to wide premature acceptance that "neural stem cells (NSCs)" derived from embryonic, fetal or adult sources would soon be effective in reversing neural and spinal trauma. However, neural therapy with stem cells has not been realized to its fullest extent. Although, discrete population of regenerative stem cells seems to be present in specific areas of human brain, the function of these cells is unclear. However, similar cells in animals seem to play important role in postnatal growth as well as recovery of neural tissue from injury, anoxia, or disease.

  10. Personalized nanomedicine advancements for stem cell tracking☆

    PubMed Central

    Janowski, Mirek; Bulte, Jeff W.M.; Walczak, Piotr

    2012-01-01

    Recent technological developments in biomedicine have facilitated the generation of data on the anatomical, physiological and molecular level for individual patients and thus introduces opportunity for therapy to be personalized in an unprecedented fashion. Generation of patient-specific stem cells exemplifies the efforts toward this new approach. Cell-based therapy is a highly promising treatment paradigm; however, due to the lack of consistent and unbiased data about the fate of stem cells in vivo, interpretation of therapeutic remains challenging hampering the progress in this field. The advent of nanotechnology with a wide palette of inorganic and organic nanostructures has expanded the arsenal of methods for tracking transplanted stem cells. The diversity of nanomaterials has revolutionized personalized nanomedicine and enables individualized tailoring of stem cell labeling materials for the specific needs of each patient. The successful implementation of stem cell tracking will likely be a significant driving force that will contribute to the further development of nanotheranostics. The purpose of this review is to emphasize the role of cell tracking using currently available nanoparticles. PMID:22820528

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

    PubMed

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

    2016-04-01

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

  12. Advances and Prospect of Nanotechnology in Stem Cells

    NASA Astrophysics Data System (ADS)

    Wang, Zheng; Ruan, Jing; Cui, Daxiang

    2009-07-01

    In recent years, stem cell nanotechnology has emerged as a new exciting field. Theoretical and experimental studies of interaction between nanomaterials or nanostructures and stem cells have made great advances. The importance of nanomaterials, nanostructures, and nanotechnology to the fundamental developments in stem cells-based therapies for injuries and degenerative diseases has been recognized. In particular, the effects of structure and properties of nanomaterials on the proliferation and differentiation of stem cells have become a new interdisciplinary frontier in regeneration medicine and material science. Here we review some of the main advances in this field over the past few years, explore the application prospects, and discuss the issues, approaches and challenges, with the aim of improving application of nanotechnology in the stem cells research and development.

  13. Advances in culture and manipulation of human pluripotent stem cells.

    PubMed

    Qian, X; Villa-Diaz, L G; Krebsbach, P H

    2013-11-01

    Recent advances in the understanding of pluripotent stem cell biology and emerging technologies to reprogram somatic cells to a stem cell-like state are helping bring stem cell therapies for a range of human disorders closer to clinical reality. Human pluripotent stem cells (hPSCs) have become a promising resource for regenerative medicine and research into early development because these cells are able to self-renew indefinitely and are capable of differentiation into specialized cell types of all 3 germ layers and trophoectoderm. Human PSCs include embryonic stem cells (hESCs) derived from the inner cell mass of blastocyst-stage embryos and induced pluripotent stem cells (hiPSCs) generated via the reprogramming of somatic cells by the overexpression of key transcription factors. The application of hiPSCs and the finding that somatic cells can be directly reprogrammed into different cell types will likely have a significant impact on regenerative medicine. However, a major limitation for successful therapeutic application of hPSCs and their derivatives is the potential xenogeneic contamination and instability of current culture conditions. This review summarizes recent advances in hPSC culture and methods to induce controlled lineage differentiation through regulation of cell-signaling pathways and manipulation of gene expression as well as new trends in direct reprogramming of somatic cells.

  14. Recent Stem Cell Advances: Cord Blood and Induced Pluripotent Stem Cell for Cardiac Regeneration- a Review.

    PubMed

    Medhekar, Sheetal Kashinath; Shende, Vikas Suresh; Chincholkar, Anjali Baburao

    2016-05-30

    Stem cells are primitive self renewing undifferentiated cell that can be differentiated into various types of specialized cells like nerve cell, skin cells, muscle cells, intestinal tissue, and blood cells. Stem cells live in bone marrow where they divide to make new blood cells and produces peripheral stem cells in circulation. Under proper environment and in presence of signaling molecules stem cells begin to develop into specialized tissues and organs. These unique characteristics make them very promising entities for regeneration of damaged tissue. Day by day increase in incidence of heart diseases including left ventricular dysfunction, ischemic heart disease (IHD), congestive heart failure (CHF) are the major cause of morbidity and mortality. However infracted tissue cannot regenerate into healthy tissue. Heart transplantation is only the treatment for such patient. Due to limitation of availability of donor for organ transplantation, a focus is made for alternative and effective therapy to treat such condition. In this review we have discussed the new advances in stem cells such as use of cord stem cells and iPSC technology in cardiac repair. Future approach of CB cells was found to be used in tissue repair which is specifically observed for improvement of left ventricular function and myocardial infarction. Here we have also focused on how iPSC technology is used for regeneration of cardiomyocytes and intiating neovascularization in myocardial infarction and also for study of pathophysiology of various degenerative diseases and genetic disease in research field.

  15. Recent Stem Cell Advances: Cord Blood and Induced Pluripotent Stem Cell for Cardiac Regeneration- a Review

    PubMed Central

    Medhekar, Sheetal Kashinath; Shende, Vikas Suresh; Chincholkar, Anjali Baburao

    2016-01-01

    Stem cells are primitive self renewing undifferentiated cell that can be differentiated into various types of specialized cells like nerve cell, skin cells, muscle cells, intestinal tissue, and blood cells. Stem cells live in bone marrow where they divide to make new blood cells and produces peripheral stem cells in circulation. Under proper environment and in presence of signaling molecules stem cells begin to develop into specialized tissues and organs. These unique characteristics make them very promising entities for regeneration of damaged tissue. Day by day increase in incidence of heart diseases including left ventricular dysfunction, ischemic heart disease (IHD), congestive heart failure (CHF) are the major cause of morbidity and mortality. However infracted tissue cannot regenerate into healthy tissue. Heart transplantation is only the treatment for such patient. Due to limitation of availability of donor for organ transplantation, a focus is made for alternative and effective therapy to treat such condition. In this review we have discussed the new advances in stem cells such as use of cord stem cells and iPSC technology in cardiac repair. Future approach of CB cells was found to be used in tissue repair which is specifically observed for improvement of left ventricular function and myocardial infarction. Here we have also focused on how iPSC technology is used for regeneration of cardiomyocytes and intiating neovascularization in myocardial infarction and also for study of pathophysiology of various degenerative diseases and genetic disease in research field. PMID:27426082

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

    PubMed

    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.

  17. Advancements in stem cells treatment of skeletal muscle wasting

    PubMed Central

    Meregalli, Mirella; Farini, Andrea; Sitzia, Clementina; Torrente, Yvan

    2014-01-01

    Muscular dystrophies (MDs) are a heterogeneous group of inherited disorders, in which progressive muscle wasting and weakness is often associated with exhaustion of muscle regeneration potential. Although physiological properties of skeletal muscle tissue are now well known, no treatments are effective for these diseases. Muscle regeneration was attempted by means transplantation of myogenic cells (from myoblast to embryonic stem cells) and also by interfering with the malignant processes that originate in pathological tissues, such as uncontrolled fibrosis and inflammation. Taking into account the advances in the isolation of new subpopulation of stem cells and in the creation of artificial stem cell niches, we discuss how these emerging technologies offer great promises for therapeutic approaches to muscle diseases and muscle wasting associated with aging. PMID:24575052

  18. Advances in genetic modification of pluripotent stem cells.

    PubMed

    Fontes, Andrew; Lakshmipathy, Uma

    2013-11-15

    Genetically engineered stem cells aid in dissecting basic cell function and are valuable tools for drug discovery, in vivo cell tracking, and gene therapy. Gene transfer into pluripotent stem cells has been a challenge due to their intrinsic feature of growing in clusters and hence not amenable to common gene delivery methods. Several advances have been made in the rapid assembly of DNA elements, optimization of culture conditions, and DNA delivery methods. This has lead to the development of viral and non-viral methods for transient or stable modification of cells, albeit with varying efficiencies. Most methods require selection and clonal expansion that demand prolonged culture and are not suited for cells with limited proliferative potential. Choosing the right platform based on preferred length, strength, and context of transgene expression is a critical step. Random integration of the transgene into the genome can be complicated due to silencing or altered regulation of expression due to genomic effects. An alternative to this are site-specific methods that target transgenes followed by screening to identify the genomic loci that support long-term expression with stem cell proliferation and differentiation. A highly precise and accurate editing of the genome driven by homology can be achieved using traditional methods as well as the newer technologies such as zinc finger nuclease, TAL effector nucleases and CRISPR. In this review, we summarize the different genetic engineering methods that have been successfully used to create modified embryonic and induced pluripotent stem cells.

  19. Recent advances in Echinococcus genomics and stem cell research.

    PubMed

    Koziol, U; Brehm, K

    2015-10-30

    Alveolar and cystic echinococcosis, caused by the metacestode larval stages of the tapeworms Echinococcus multilocularis and Echinococcus granulosus, respectively, are life-threatening diseases and very difficult to treat. The introduction of benzimidazole-based chemotherapy, which targets parasite β-tubulin, has significantly improved the life-span and prognosis of echinococcosis patients. However, benzimidazoles show only parasitostatic activity, are associated with serious adverse side effects and have to be administered for very long time periods, underlining the need for new drugs. Very recently, the nuclear genomes of E. multilocularis and E. granulosus have been characterised, revealing a plethora of data for gaining a deeper understanding of host-parasite interaction, parasite development and parasite evolution. Combined with extensive transcriptome analyses of Echinococcus life cycle stages these investigations also yielded novel clues for targeted drug design. Recent years also witnessed significant advancements in the molecular and cellular characterisation of the Echinococcus 'germinative cell' population, which forms a unique stem cell system that differs from stem cells of other organisms in the expression of several genes associated with the maintenance of pluripotency. As the only parasite cell type capable of undergoing mitosis, the germinative cells are central to all developmental transitions of Echinococcus within the host and to parasite expansion via asexual proliferation. In the present article, we will briefly introduce and discuss recent advances in Echinococcus genomics and stem cell research in the context of drug design and development. Interestingly, it turns out that benzimidazoles seem to have very limited effects on Echinococcus germinative cells, which could explain the high recurrence rates observed after chemotherapeutic treatment of echinococcosis patients. This clearly indicates that future efforts into the development of

  20. Recent advances in Echinococcus genomics and stem cell research.

    PubMed

    Koziol, U; Brehm, K

    2015-10-30

    Alveolar and cystic echinococcosis, caused by the metacestode larval stages of the tapeworms Echinococcus multilocularis and Echinococcus granulosus, respectively, are life-threatening diseases and very difficult to treat. The introduction of benzimidazole-based chemotherapy, which targets parasite β-tubulin, has significantly improved the life-span and prognosis of echinococcosis patients. However, benzimidazoles show only parasitostatic activity, are associated with serious adverse side effects and have to be administered for very long time periods, underlining the need for new drugs. Very recently, the nuclear genomes of E. multilocularis and E. granulosus have been characterised, revealing a plethora of data for gaining a deeper understanding of host-parasite interaction, parasite development and parasite evolution. Combined with extensive transcriptome analyses of Echinococcus life cycle stages these investigations also yielded novel clues for targeted drug design. Recent years also witnessed significant advancements in the molecular and cellular characterisation of the Echinococcus 'germinative cell' population, which forms a unique stem cell system that differs from stem cells of other organisms in the expression of several genes associated with the maintenance of pluripotency. As the only parasite cell type capable of undergoing mitosis, the germinative cells are central to all developmental transitions of Echinococcus within the host and to parasite expansion via asexual proliferation. In the present article, we will briefly introduce and discuss recent advances in Echinococcus genomics and stem cell research in the context of drug design and development. Interestingly, it turns out that benzimidazoles seem to have very limited effects on Echinococcus germinative cells, which could explain the high recurrence rates observed after chemotherapeutic treatment of echinococcosis patients. This clearly indicates that future efforts into the development of

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

    PubMed

    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.

  2. Advances in stem cell therapy for cardiovascular disease (Review).

    PubMed

    Sun, Rongrong; Li, Xianchi; Liu, Min; Zeng, Yi; Chen, Shuang; Zhang, Peying

    2016-07-01

    Cardiovascular disease constitutes the primary cause of mortality and morbidity worldwide, and represents a group of disorders associated with the loss of cardiac function. Despite considerable advances in the understanding of the pathologic mechanisms of the disease, the majority of the currently available therapies remain at best palliative, since the problem of cardiac tissue loss has not yet been addressed. Indeed, few therapeutic approaches offer direct tissue repair and regeneration, whereas the majority of treatment options aim to limit scar formation and adverse remodeling, while improving myocardial function. Of all the existing therapeutic approaches, the problem of cardiac tissue loss is addressed uniquely by heart transplantation. Nevertheless, alternative options, particularly stem cell therapy, has emerged as a novel and promising approach. This approach involves the transplantation of healthy and functional cells to promote the renewal of damaged cells and repair injured tissue. Bone marrow precursor cells were the first cell type used in clinical studies, and subsequently, preclinical and clinical investigations have been extended to the use of various populations of stem cells. This review addresses the present state of research as regards stem cell therapy for cardiovascular disease.

  3. Breast cancer stem cells: current advances and clinical implications.

    PubMed

    Luo, Ming; Clouthier, Shawn G; Deol, Yadwinder; Liu, Suling; Nagrath, Sunitha; Azizi, Ebrahim; Wicha, Max S

    2015-01-01

    There is substantial evidence that many cancers, including breast cancer, are driven by a population of cells that display stem cell properties. These cells, termed cancer stem cells (CSCs) or tumor initiating cells, not only drive tumor initiation and growth but also mediate tumor metastasis and therapeutic resistance. In this chapter, we summarize current advances in CSC research with a major focus on breast CSCs (BCSCs). We review the prevailing methods to isolate and characterize BCSCs and recent evidence documenting their cellular origins and phenotypic plasticity that enables them to transition between mesenchymal and epithelial-like states. We describe in vitro and clinical evidence that these cells mediate metastasis and treatment resistance in breast cancer, the development of novel strategies to isolate circulating tumor cells (CTCs) that contain CSCs and the use of patient-derived xenograft (PDX) models in preclinical breast cancer research. Lastly, we highlight several signaling pathways that regulate BCSC self-renewal and describe clinical implications of targeting these cells for breast cancer treatment. The development of strategies to effectively target BCSCs has the potential to significantly improve the outcomes for patients with breast cancer.

  4. A brief review of recent advances in stem cell biology

    PubMed Central

    Chen, Jinhui; Zhou, Libing; Pan, Su-yue

    2014-01-01

    Stem cells have the remarkable potential to develop into many different cell types, essentially without limit to replenish other cells as long as the person or animal is still alive, offering immense hope of curing Alzheimer's disease, repairing damaged spinal cords, treating kidney, liver and lung diseases and making damaged hearts whole. Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic “somatic” or “adult” stem cells. Recent breakthrough make it possible to convert or “reprogram” specialized adult cells to assume a stem stem-like cells with different technologies. The review will briefly discuss the recent progresses in this area. PMID:25206872

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

    PubMed

    Swan, Melanie

    2011-12-01

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

  6. Hematopoietic specification from human pluripotent stem cells: current advances and challenges toward de novo generation of hematopoietic stem cells.

    PubMed

    Slukvin, Igor I

    2013-12-12

    Significant advances in cellular reprogramming technologies and hematopoietic differentiation from human pluripotent stem cells (hPSCs) have already enabled the routine production of multiple lineages of blood cells in vitro and opened novel opportunities to study hematopoietic development, model genetic blood diseases, and manufacture immunologically matched cells for transfusion and cancer immunotherapy. However, the generation of hematopoietic cells with robust and sustained multilineage engraftment has not been achieved. Here, we highlight the recent advances in understanding the molecular and cellular pathways leading to blood development from hPSCs and discuss potential approaches that can be taken to facilitate the development of technologies for de novo production of hematopoietic stem cells.

  7. Stem Cells

    MedlinePlus

    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 ...

  8. Advances in haploidentical stem cell transplantation for hematologic malignancies.

    PubMed

    Montoro, Juan; Sanz, Jaime; Sanz, Guillermo F; Sanz, Miguel A

    2016-08-01

    One of the most important advances in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the use of alternative donors and cell sources, such as haploidentical transplants (haplo-HSCT) from family donors. Several approaches have been developed to overcome the challenging bidirectional alloreactivity. We discuss these approaches, including ex vivo T-cell-depleted grafts with megadose of CD34(+) cells, not requiring immunosuppression after allogeneic transplantation for graft-versus-host disease (GVHD) prophylaxis, and other strategies using unmanipulated T-cell-replete grafts with intensive immunosuppression or post-transplantation cyclophosphamide to minimize the GVHD. We also address the role of other strategies developed in the context of the haplo-HSCT platforms, such as ex vivo selective depletion of alloreactive donor T-cell subpopulations, infusion of antigen-specific T-cells against several pathogens, and infusion of regulatory T-cells, among other experimental approaches. Finally, some considerations about the selection of the most suitable donor, when more than one family member is available, are also addressed.

  9. [Advances in the mechanism of mesenchymal stem cells in promoting wound healing].

    PubMed

    Zhu, Wenjing; Sun, Haobo; Lyu, Guozhong

    2015-12-01

    Mesenchymal stem cells possess the ability of self-renewal and multiple differentiation potential, thus exert immunomodulatory effect during tissue repair. Mesenchymal stem cells can stimulate angiogenesis and promote tissue repair through transdifferentiation and secreting a variety of growth factors and cytokines. This review outlines the advances in the mechanism of mesenchymal stem cells in promoting wound healing, including alleviation of inflammatory response, induction of angiogenesis, and promotion of migration of mesenchymal stem cells to the site of tissue injury.

  10. Hematopoietic Stem-Cell Transplantation for Advanced Systemic Mastocytosis

    PubMed Central

    Ustun, Celalettin; Reiter, Andreas; Scott, Bart L.; Nakamura, Ryotaro; Damaj, Gandhi; Kreil, Sebastian; Shanley, Ryan; Hogan, William J.; Perales, Miguel-Angel; Shore, Tsiporah; Baurmann, Herrad; Stuart, Robert; Gruhn, Bernd; Doubek, Michael; Hsu, Jack W.; Tholouli, Eleni; Gromke, Tanja; Godley, Lucy A.; Pagano, Livio; Gilman, Andrew; Wagner, Eva Maria; Shwayder, Tor; Bornhäuser, Martin; Papadopoulos, Esperanza B.; Böhm, Alexandra; Vercellotti, Gregory; Van Lint, Maria Teresa; Schmid, Christoph; Rabitsch, Werner; Pullarkat, Vinod; Legrand, Faezeh; Yakoub-agha, Ibrahim; Saber, Wael; Barrett, John; Hermine, Olivier; Hagglund, Hans; Sperr, Wolfgang R.; Popat, Uday; Alyea, Edwin P.; Devine, Steven; Deeg, H. Joachim; Weisdorf, Daniel; Akin, Cem; Valent, Peter

    2014-01-01

    Purpose Advanced systemic mastocytosis (SM), a fatal hematopoietic malignancy characterized by drug resistance, has no standard therapy. The effectiveness of allogeneic hematopoietic stem-cell transplantation (alloHCT) in SM remains unknown. Patients and Methods In a global effort to define the value of HCT in SM, 57 patients with the following subtypes of SM were evaluated: SM associated with clonal hematologic non–mast cell disorders (SM-AHNMD; n = 38), mast cell leukemia (MCL; n = 12), and aggressive SM (ASM; n = 7). Median age of patients was 46 years (range, 11 to 67 years). Donors were HLA-identical (n = 34), unrelated (n = 17), umbilical cord blood (n = 2), HLA-haploidentical (n = 1), or unknown (n = 3). Thirty-six patients received myeloablative conditioning (MAC), and 21 patients received reduced-intensity conditioning (RIC). Results Responses in SM were observed in 40 patients (70%), with complete remission in 16 patients (28%). Twelve patients (21%) had stable disease, and five patients (9%) had primary refractory disease. Overall survival (OS) at 3 years was 57% for all patients, 74% for patients with SM-AHNMD, 43% for those with ASM, and 17% for those with MCL. The strongest risk factor for poor OS was MCL. Survival was also lower in patients receiving RIC compared with MAC and in patients having progression compared with patients having stable disease or response. Conclusion AlloHCT was associated with long-term survival in patients with advanced SM. Although alloHCT may be considered as a viable and potentially curative therapeutic option for advanced SM in the meantime, given that this is a retrospective analysis with no control group, the definitive role of alloHCT will need to be determined by a prospective trial. PMID:25154823

  11. ADVANCES IN THE USE OF STEM CELLS IN ORTHOPEDICS

    PubMed Central

    Cristante, Alexandre Fogaça; Narazaki, Douglas Kenji

    2015-01-01

    Primordial cells or stem cells are multipotent undifferentiated cells with the capacity to originate any type of cell in the organism. They may have their origins in the blastocyst and thus are classified as embryonic, or tissues developed in fetuses, newborns or adults and thus are known as somatic stem cells. Bone marrow is one of the main locations for isolating primordial cells, and there are two lineages: hematopoietic and mesenchymal progenitor cells. There are several uses for these undifferentiated cells in orthopedics, going from cartilaginous lesions in osteoarthrosis, osteochondritis dissecans and patellar chondromalacia, to bone lesions like in pseudarthrosis or bone losses, or nerve lesions like in spinal cord trauma. Studying stem cells is probably the most promising field of study of all within medicine, and this is shortly going to revolutionize all medical specialties (both clinical and surgical) and thus provide solutions for diseases that today are difficult to deal with. PMID:27027022

  12. Recent Advances of Stem Cell Therapy for Retinitis Pigmentosa

    PubMed Central

    He, Yuxi; Zhang, Yan; Liu, Xin; Ghazaryan, Emma; Li, Ying; Xie, Jianan; Su, Guanfang

    2014-01-01

    Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by progressive loss of photoreceptors and eventually leads to retina degeneration and atrophy. Until now, the exact pathogenesis and etiology of this disease has not been clear, and many approaches for RP therapies have been carried out in animals and in clinical trials. In recent years, stem cell transplantation-based attempts made some progress, especially the transplantation of bone marrow-derived mesenchymal stem cells (BMSCs). This review will provide an overview of stem cell-based treatment of RP and its main problems, to provide evidence for the safety and feasibility for further clinical treatment. PMID:25141102

  13. Research Advancements in Porcine Derived Mesenchymal Stem Cells.

    PubMed

    Bharti, Dinesh; Shivakumar, Sharath Belame; Subbarao, Raghavendra Baregundi; Rho, Gyu-Jin

    2016-01-01

    In the present era of stem cell biology, various animals such as Mouse, Bovine, Rabbit and Porcine have been tested for the efficiency of their mesenchymal stem cells (MSCs before their actual use for stem cell based application in humans. Among them pigs have many similarities to humans in the form of organ size, physiology and their functioning, therefore they have been considered as a valuable model system for in vitro studies and preclinical assessments. Easy assessability, few ethical issues, successful MSC isolation from different origins like bone marrow, skin, umbilical cord blood, Wharton's jelly, endometrium, amniotic fluid and peripheral blood make porcine a good model for stem cell therapy. Porcine derived MSCs (pMSCs have shown greater in vitro differentiation and transdifferention potential towards mesenchymal lineages and specialized lineages such as cardiomyocytes, neurons, hepatocytes and pancreatic beta cells. Immunomodulatory and low immunogenic profiles as shown by autologous and heterologous MSCs proves them safe and appropriate models for xenotransplantation purposes. Furthermore, tissue engineered stem cell constructs can be of immense importance in relation to various osteochondral defects which are difficult to treat otherwise. Using pMSCs successful treatment of various disorders like Parkinson's disease, cardiac ischemia, hepatic failure, has been reported by many studies. Here, in this review we highlight current research findings in the area of porcine mesenchymal stem cells dealing with their isolation methods, differentiation ability, transplantation applications and their therapeutic potential towards various diseases. PMID:26201864

  14. Advances in Isolation Methods for Spermatogonial Stem Cells.

    PubMed

    Zhang, Rui; Sun, Jin; Zou, Kang

    2016-02-01

    Stem cell research has led to many remarkable achievements in recent years, but progress in the study of spermatogonial stem cells (SSCs) has been relatively slow, partly due to the slow development of techniques for spermatogonial stem cell isolation. The major accomplishments of SSC sorting and identification occurred approximately 10 years ago, and since that time, these techniques have been widely used without major improvements. In this article, we briefly introduce the biological properties of SSCs before reviewing the development of sorting techniques for SSCs in the past decades. We then summarize recent achievements in SSC sorting and finally discuss the advantages and disadvantages of SSC isolation methods, to provide new insight into techniques and research related to spermatogonial stem cells and promote the development of reproductive biology.

  15. Advances in mesenchymal stem cell-based strategies for cartilage repair and regeneration.

    PubMed

    Toh, Wei Seong; Foldager, Casper Bindzus; Pei, Ming; Hui, James Hoi Po

    2014-10-01

    Significant research efforts have been undertaken in the last decade in the development of stem cell-based therapies for cartilage repair. Among the various stem cell sources, mesenchymal stem cells (MSCs) demonstrate great promise and clinical efficacy in cartilage regeneration. With a deeper understanding of stem cell biology, new therapeutics and new bioengineering approaches have emerged and showed potential for further developments. Of note, there has been a paradigm shift in applying MSCs for tissue regeneration from the use of stem cells for transplantation to the use of stem cell-derived matrix and secretome components as therapeutic tools and agents for cartilage regeneration. In this review, we will discuss the emerging role of MSCs in cartilage regeneration and the most recent advances in development of stem cell-based therapeutics for cartilage regeneration.

  16. Recent Advances in Hydroxyapatite Scaffolds Containing Mesenchymal Stem Cells

    PubMed Central

    Michel, John; Penna, Matthew; Kochen, Juan; Cheung, Herman

    2015-01-01

    Modern day tissue engineering and cellular therapies have gravitated toward using stem cells with scaffolds as a dynamic modality to aid in differentiation and tissue regeneration. Mesenchymal stem cells (MSCs) are one of the most studied stem cells used in combination with scaffolds. These cells differentiate along the osteogenic lineage when seeded on hydroxyapatite containing scaffolds and can be used as a therapeutic option to regenerate various tissues. In recent years, the combination of hydroxyapatite and natural or synthetic polymers has been studied extensively. Due to the interest in these scaffolds, this review will cover the wide range of hydroxyapatite containing scaffolds used with MSCs for in vitro and in vivo experiments. Further, in order to maintain a progressive scope of the field this review article will only focus on literature utilizing adult human derived MSCs (hMSCs) published in the last three years. PMID:26106425

  17. Recent Advances in Hydroxyapatite Scaffolds Containing Mesenchymal Stem Cells.

    PubMed

    Michel, John; Penna, Matthew; Kochen, Juan; Cheung, Herman

    2015-01-01

    Modern day tissue engineering and cellular therapies have gravitated toward using stem cells with scaffolds as a dynamic modality to aid in differentiation and tissue regeneration. Mesenchymal stem cells (MSCs) are one of the most studied stem cells used in combination with scaffolds. These cells differentiate along the osteogenic lineage when seeded on hydroxyapatite containing scaffolds and can be used as a therapeutic option to regenerate various tissues. In recent years, the combination of hydroxyapatite and natural or synthetic polymers has been studied extensively. Due to the interest in these scaffolds, this review will cover the wide range of hydroxyapatite containing scaffolds used with MSCs for in vitro and in vivo experiments. Further, in order to maintain a progressive scope of the field this review article will only focus on literature utilizing adult human derived MSCs (hMSCs) published in the last three years.

  18. Invited review: Stem cells and muscle diseases: advances in cell therapy strategies.

    PubMed

    Negroni, Elisa; Gidaro, Teresa; Bigot, Anne; Butler-Browne, Gillian S; Mouly, Vincent; Trollet, Capucine

    2015-04-01

    Despite considerable progress to increase our understanding of muscle genetics, pathophysiology, molecular and cellular partners involved in muscular dystrophies and muscle ageing, there is still a crucial need for effective treatments to counteract muscle degeneration and muscle wasting in such conditions. This review focuses on cell-based therapy for muscle diseases. We give an overview of the different parameters that have to be taken into account in such a therapeutic strategy, including the influence of muscle ageing, cell proliferation and migration capacities, as well as the translation of preclinical results in rodent into human clinical approaches. We describe recent advances in different types of human myogenic stem cells, with a particular emphasis on myoblasts but also on other candidate cells described so far [CD133+ cells, aldehyde dehydrogenase-positive cells (ALDH+), muscle-derived stem cells (MuStem), embryonic stem cells (ES) and induced pluripotent stem cells (iPS)]. Finally, we provide an update of ongoing clinical trials using cell therapy strategies.

  19. Advances and challenges in the differentiation of pluripotent stem cells into pancreatic β cells.

    PubMed

    Abdelalim, Essam M; Emara, Mohamed M

    2015-01-26

    Pluripotent stem cells (PSCs) are able to differentiate into several cell types, including pancreatic β cells. Differentiation of pancreatic β cells depends on certain transcription factors, which function in a coordinated way during pancreas development. The existing protocols for in vitro differentiation produce pancreatic β cells, which are not highly responsive to glucose stimulation except after their transplantation into immune-compromised mice and allowing several weeks for further differentiation to ensure the maturation of these cells in vivo. Thus, although the substantial improvement that has been made for the differentiation of induced PSCs and embryonic stem cells toward pancreatic β cells, several challenges still hindering their full generation. Here, we summarize recent advances in the differentiation of PSCs into pancreatic β cells and discuss the challenges facing their differentiation as well as the different applications of these potential PSC-derived β cells.

  20. Induced Pluripotent Stem Cells in Dermatology: Potentials, Advances, and Limitations

    PubMed Central

    Bilousova, Ganna; Roop, Dennis R.

    2015-01-01

    The discovery of methods for reprogramming adult somatic cells into induced pluripotent stem cells (iPSCs) has raised the possibility of producing truly personalized treatment options for numerous diseases. Similar to embryonic stem cells (ESCs), iPSCs can give rise to any cell type in the body and they are amenable to genetic correction by homologous recombination. These ESC properties of iPSCs allow for the development of permanent corrective therapies for many currently incurable disorders, including inherited skin diseases, without using embryonic tissues or oocytes. Here, we review recent progress and limitations of iPSC research with a focus on clinical applications of iPSCs, and using iPSCs to model human diseases for drug discovery in the field of dermatology. PMID:25368014

  1. Induced pluripotent stem cells in dermatology: potentials, advances, and limitations.

    PubMed

    Bilousova, Ganna; Roop, Dennis R

    2014-11-01

    The discovery of methods for reprogramming adult somatic cells into induced pluripotent stem cells (iPSCs) has raised the possibility of producing truly personalized treatment options for numerous diseases. Similar to embryonic stem cells (ESCs), iPSCs can give rise to any cell type in the body and are amenable to genetic correction by homologous recombination. These ESC properties of iPSCs allow for the development of permanent corrective therapies for many currently incurable disorders, including inherited skin diseases, without using embryonic tissues or oocytes. Here, we review recent progress and limitations of iPSC research with a focus on clinical applications of iPSCs and using iPSCs to model human diseases for drug discovery in the field of dermatology.

  2. Advances in hepatic stem/progenitor cell biology

    PubMed Central

    Verhulst, Stefaan; Best, Jan; van Grunsven, Leo A.; Dollé, Laurent

    2015-01-01

    The liver is famous for its strong regenerative capacity, employing different modes of regeneration according to type and extent of injury. Mature liver cells are able to proliferate in order to replace the damaged tissue allowing the recovery of the parenchymal function. In more severe scenarios hepatocytes are believed to arise also from a facultative liver progenitor cell compartment. In human, severe acute liver failure and liver cirrhosis are also both important clinical targets in which regeneration is impaired, where the role of this stem cell compartment seems more convincing. In animal models, the current state of ambiguity regarding the identity and role of liver progenitor cells in liver physiology dampens the enthusiasm for the potential use of these cells in regenerative medicine. The aim of this review is to give the basics of liver progenitor cell biology and discuss recent results vis-à-vis their identity and contribution to liver regeneration. PMID:26600740

  3. Advances of mesenchymal stem cells derived from bone marrow and dental tissue in craniofacial tissue engineering.

    PubMed

    Yang, Maobin; Zhang, Hongming; Gangolli, Riddhi

    2014-05-01

    Bone and dental tissues in craniofacial region work as an important aesthetic and functional unit. Reconstruction of craniofacial tissue defects is highly expected to ensure patients to maintain good quality of life. Tissue engineering and regenerative medicine have been developed in the last two decades, and been advanced with the stem cell technology. Bone marrow derived mesenchymal stem cells are one of the most extensively studied post-natal stem cell population, and are widely utilized in cell-based therapy. Dental tissue derived mesenchymal stem cells are a relatively new stem cell population that isolated from various dental tissues. These cells can undergo multilineage differentiation including osteogenic and odontogenic differentiation, thus provide an alternative source of mesenchymal stem cells for tissue engineering. In this review, we discuss the important issues in mesenchymal stem cell biology including the origin and functions of mesenchymal stem cells, compare the properties of these two types of mesenchymal cells, update recent basic research and clinic applications in this field, and address important future challenges.

  4. Corneal stem cells and tissue engineering: Current advances and future perspectives.

    PubMed

    de Araujo, Aline Lütz; Gomes, José Álvaro Pereira

    2015-06-26

    Major advances are currently being made in regenerative medicine for cornea. Stem cell-based therapies represent a novel strategy that may substitute conventional corneal transplantation, albeit there are many challenges ahead given the singularities of each cellular layer of the cornea. This review recapitulates the current data on corneal epithelial stem cells, corneal stromal stem cells and corneal endothelial cell progenitors. Corneal limbal autografts containing epithelial stem cells have been transplanted in humans for more than 20 years with great successful rates, and researchers now focus on ex vivo cultures and other cell lineages to transplant to the ocular surface. A small population of cells in the corneal endothelium was recently reported to have self-renewal capacity, although they do not proliferate in vivo. Two main obstacles have hindered endothelial cell transplantation to date: culture protocols and cell delivery methods to the posterior cornea in vivo. Human corneal stromal stem cells have been identified shortly after the recognition of precursors of endothelial cells. Stromal stem cells may have the potential to provide a direct cell-based therapeutic approach when injected to corneal scars. Furthermore, they exhibit the ability to deposit organized connective tissue in vitro and may be useful in corneal stroma engineering in the future. Recent advances and future perspectives in the field are discussed.

  5. Glioblastoma cancer stem cells: Biomarker and therapeutic advances.

    PubMed

    Pointer, Kelli B; Clark, Paul A; Zorniak, Michael; Alrfaei, Bahauddeen M; Kuo, John S

    2014-05-01

    Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in humans. It accounts for fifty-two percent of primary brain malignancies in the United States and twenty percent of all primary intracranial tumors. Despite the current standard therapies of maximal safe surgical resection followed by temozolomide and radiotherapy, the median patient survival is still less than 2 years due to inevitable tumor recurrence. Glioblastoma cancer stem cells (GSCs) are a subgroup of tumor cells that are radiation and chemotherapy resistant and likely contribute to rapid tumor recurrence. In order to gain a better understanding of the many GBM-associated mutations, analysis of the GBM cancer genome is on-going; however, innovative strategies to target GSCs and overcome tumor resistance are needed to improve patient survival. Cancer stem cell biology studies reveal basic understandings of GSC resistance patterns and therapeutic responses. Membrane proteomics using phage and yeast display libraries provides a method to identify novel antibodies and surface antigens to better recognize, isolate, and target GSCs. Altogether, basic GBM and GSC genetics and proteomics studies combined with strategies to discover GSC-targeting agents could lead to novel treatments that significantly improve patient survival and quality of life.

  6. [Prostate cancer stem cells: advances in current research].

    PubMed

    Wu, Gang; Wu, Deng-long

    2015-02-01

    Prostate cancer is one of the most common malignancies threatening men's health, and the mechanisms underlying its initiation and progression are poorly understood. Last decade has witnessed encouraging progress in the studies of prostate cancer stem cells (PCSCs), which are considered to play important roles in tumor initiation, recurrence and metastasis, castration resistance, and drug resistance. Therefore, a deeper insight into PCSCs is of great significance for the successful management of prostate cancer. This article presents an overview on the location, origin, and markers of PCSCs as well as their potential correlation with tumor metastasis and castration resistance.

  7. Advances and perspectives of colorectal cancer stem cell vaccine.

    PubMed

    Guo, Mei; Dou, Jun

    2015-12-01

    Colorectal cancer is essentially an environmental and genetic disease featured by uncontrolled cell growth and the capability to invade other parts of the body by forming metastases, which inconvertibly cause great damage to tissues and organs. It has become one of the leading causes of cancer-related mortality in the developed countries such as United States, and approximately 1.2 million new cases are yearly diagnosed worldwide, with the death rate of more than 600,000 annually and incidence rates are increasing in most developing countries. Apart from the generally accepted theory that pathogenesis of colorectal cancer consists of genetic mutation of a certain target cell and diversifications in tumor microenvironment, the colorectal cancer stem cells (CCSCs) theory makes a different explanation, stating that among millions of colon cancer cells there is a specific and scanty cellular population which possess the capability of self-renewal, differentiation and strong oncogenicity, and is tightly responsible for drug resistance and tumor metastasis. Based on these characteristics, CCSCs are becoming a novel target cells both in the clinical and the basic studies, especially the study of CCSCs vaccines due to induced efficient immune response against CCSCs. This review provides an overview of CCSCs and preparation technics and targeting factors related to CCSCs vaccines in detail.

  8. Generation of skeletal muscle cells from pluripotent stem cells: advances and challenges.

    PubMed

    Abujarour, Ramzey; Valamehr, Bahram

    2015-01-01

    Human pluripotent stem cells (hPSCs) possess unlimited proliferative potential while maintaining the ability to differentiate into any cell type including skeletal muscle cells (SMCs). hPSCs are amenable to genetic editing and can be derived from patient somatic cells, and thus represent a promising option for cell therapies for the treatment of degenerative diseases such as muscular dystrophies. There are unresolved challenges however associated with the derivation and scale-up of hPSCs and generation of differentiated cells in large quantity and high purity. Reported myogenic differentiation protocols are long, require cell sorting and/or rely on ectopic expression of myogenic master regulators. More recent advances have been made with the application of small molecules to enhance the myogenic differentiation efficiency and the identification of more selective markers for the enrichment of myogenic progenitors with enhanced regenerative potential. Here we review the field of myogenic differentiation and highlight areas requiring further research.

  9. Microparticle, nanoparticle, and stem cell-based oxygen carriers as advanced blood substitutes.

    PubMed

    Tao, Zhimin; Ghoroghchian, P Peter

    2014-09-01

    Here, we discuss recent advances in the development of artificial red blood cell (RBC) substitutes, illustrating lessons learned from initial attempts using perfluorocarbon (PFC) emulsions and acellular hemoglobin-based oxygen carriers (HBOCs). We also highlight novel oxygen-containing microparticles, nanoparticles, and stem cell-derived RBC products, with emphasis on improvements in biocompatibility and oxygen delivery. In addition, we envision future developments for the rational design of advanced blood substitutes that aim to address unmet clinical needs.

  10. Helicobacter pylori infection induced gastric cancer; advance in gastric stem cell research and the remaining challenges

    PubMed Central

    2012-01-01

    Helicobacter pylori infection is the major cause of gastric cancer, which remains an important health care challenge. Recent investigation in gastric stem cell or progenitor cell biology has uncovered valuable information in understanding the gastric gland renewal and maintenance of homeostasis, they also provide clues for further defining the mechanisms by which gastric cancer may originate and progress. Lgr5, Villin-promoter, TFF2-mRNA and Mist have recently been identified as gastric stem/progenitor cell markers; their identification enriched our understanding on the gastric stem cell pathobiology during chronic inflammation and metaplasia. In addition, advance in gastric cancer stem cell markers such as CD44, CD90, CD133, Musashi-1 reveal novel information on tumor cell behavior and disease progression implicated for therapeutics. However, two critical questions remain to be of considerable challenges for future exploration; one is how H. pylori or chronic inflammation affects gastric stem cell or their progenitors, which give rise to mucus-, acid-, pepsinogen-, and hormone-secreting cell lineages. Another one is how bacterial infection or inflammation induces oncogenic transformation and propagates into tumors. Focus on the interactions of H. pylori with gastric stem/progenitor cells and their microenvironment will be instrumental to decipher the initiation and origin of gastric cancer. Future studies in these areas will be critical to uncover molecular mechanisms of chronic inflammation-mediated oncogenic transformation and provide options for cancer prevention and intervention. We review recent progress and discuss future research directions in these important research fields. PMID:23217022

  11. Advanced Imaging and Tissue Engineering of the Human Limbal Epithelial Stem Cell Niche

    PubMed Central

    Massie, Isobel; Dziasko, Marc; Kureshi, Alvena; Levis, Hannah J.; Morgan, Louise; Neale, Michael; Sheth, Radhika; Tovell, Victoria E.; Vernon, Amanda J.; Funderburgh, James L.; Daniels, Julie T.

    2015-01-01

    The limbal epithelial stem cell niche provides a unique, physically protective environment in which limbal epithelial stem cells reside in close proximity with accessory cell types and their secreted factors. The use of advanced imaging techniques is described to visualize the niche in three dimensions in native human corneal tissue. In addition, a protocol is provided for the isolation and culture of three different cell types, including human limbal epithelial stem cells from the limbal niche of human donor tissue. Finally, the process of incorporating these cells within plastic compressed collagen constructs to form a tissue-engineered corneal limbus is described and how immunohistochemical techniques may be applied to characterize cell phenotype therein. PMID:25388395

  12. Types of Stem Cells

    MedlinePlus

    ... 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 ...

  13. Advances in understanding the cell types and approaches used for generating induced pluripotent stem cells

    PubMed Central

    2014-01-01

    Successfully reprogramming somatic cells to a pluripotent state generates induced pluripotent stem (iPS) cells (or iPSCs), which have extensive self-renewal capacity like embryonic stem cells (ESCs). iPSCs can also generate daughter cells that can further undergo differentiation into various lineages or terminally differentiate to reach their final functional state. The discovery of how to produce iPSCs opened a new field of stem cell research with both intellectual and therapeutic benefits. The huge potential implications of disease-specific or patient-specific iPSCs have impelled scientists to solve problems hindering their applications in clinical medicine, especially the issues of convenience and safety. To determine the range of tissue types amenable to reprogramming as well as their particular characteristics, cells from three embryonic germ layers have been assessed, and the advantages that some tissue origins have over fibroblast origins concerning efficiency and accessibility have been elucidated. To provide safe iPSCs in an efficient and convenient way, the delivery systems and combinations of inducing factors as well as the chemicals used to generate iPSCs have also been significantly improved in addition to the efforts on finding better donor cells. Currently, iPSCs can be generated without c-Myc and Klf4 oncogenes, and non-viral delivery integration-free chemically mediated reprogramming methods have been successfully employed with relatively satisfactory efficiency. This paper will review recent advances in iPS technology by highlighting tissue origin and generation of iPSCs. The obstacles that need to be overcome for clinical applications of iPSCs are also discussed. PMID:25037625

  14. Advances in understanding the cell types and approaches used for generating induced pluripotent stem cells.

    PubMed

    Li, Jun; Song, Wei; Pan, Guangjin; Zhou, Jun

    2014-01-01

    Successfully reprogramming somatic cells to a pluripotent state generates induced pluripotent stem (iPS) cells (or iPSCs), which have extensive self-renewal capacity like embryonic stem cells (ESCs). iPSCs can also generate daughter cells that can further undergo differentiation into various lineages or terminally differentiate to reach their final functional state. The discovery of how to produce iPSCs opened a new field of stem cell research with both intellectual and therapeutic benefits. The huge potential implications of disease-specific or patient-specific iPSCs have impelled scientists to solve problems hindering their applications in clinical medicine, especially the issues of convenience and safety. To determine the range of tissue types amenable to reprogramming as well as their particular characteristics, cells from three embryonic germ layers have been assessed, and the advantages that some tissue origins have over fibroblast origins concerning efficiency and accessibility have been elucidated. To provide safe iPSCs in an efficient and convenient way, the delivery systems and combinations of inducing factors as well as the chemicals used to generate iPSCs have also been significantly improved in addition to the efforts on finding better donor cells. Currently, iPSCs can be generated without c-Myc and Klf4 oncogenes, and non-viral delivery integration-free chemically mediated reprogramming methods have been successfully employed with relatively satisfactory efficiency. This paper will review recent advances in iPS technology by highlighting tissue origin and generation of iPSCs. The obstacles that need to be overcome for clinical applications of iPSCs are also discussed.

  15. Advances in osteosarcoma stem cell research and opportunities for novel therapeutic targets.

    PubMed

    Yan, Guang-Ning; Lv, Yang-Fan; Guo, Qiao-Nan

    2016-01-28

    Osteosarcoma is the most common type of bone cancer, especially in children and young adults. The primary treatment for osteosarcoma is a combination of surgery and chemotherapy, however prognoses remain poor due to chemoresistance and early metastases. Osteosarcoma stem cells appear to play central roles in tumor recurrence, metastases and chemoresistance via self-renewal and differentiation. Targeting these cells may provide a novel strategy in the treatment of osteosarcoma. This review summarizes current knowledge of this rare phenotype and recent advances in understanding the functions OSCs (osteosarcoma stem cells) in osteosarcoma, with the aim of improving therapies in the future.

  16. Stem Cells: Taking a Closer Look at the Advancements and Hurdles of Stem Cell Research in Australia

    ERIC Educational Resources Information Center

    Sanderson, Aimee

    2008-01-01

    The technology surrounding stem cells generates great excitement amongst scientists, media and the community. For science teachers, this means not only embracing and keeping track of the rapid growth and ongoing development in this field but also tackling the ethical and legislative issues surrounding the topic. So what are stem cells, what is all…

  17. Advances in Induced Pluripotent Stem Cells, Genomics, Biomarkers, and Antiplatelet Therapy

    PubMed Central

    Barbato, Emanuele; Lara-Pezzi, Enrique; Stolen, Craig; Taylor, Angela; Barton, Paul J.; Bartunek, Jozef; Iaizzo, Paul; Judge, Daniel P.; Kirshenbaum, Lorrie; Blaxall, Burns C.; Terzic, Andre; Hall, Jennifer L.

    2014-01-01

    The Journal provides the clinician and scientist with the latest advances in discovery research, emerging technologies, pre-clinical research design and testing, and clinical trials. We highlight advances in areas of induced pluripotent stem cells, genomics, biomarkers, multi-modality imaging and antiplatelet biology and therapy. The top publications are critically discussed and presented along with anatomical reviews and FDA insight to provide context. PMID:24659088

  18. New advances in the mesenchymal stem cells therapy against skin flaps necrosis.

    PubMed

    Zhang, Fu-Gui; Tang, Xiu-Fa

    2014-09-26

    Mesenchymal stem cells (MSCs), multipotential cells that reside within the bone marrow, can be induced to differentiate into various cells, such as osteoblasts, adipocytes, chondrocytes, vascular endothelial progenitor cells, and other cell types. MSCs are being widely studied as potential cell therapy agents due to their angiogenic properties, which have been well established by in vitro and in vivo researches. Within this context, MSCs therapy appears to hold substantial promise, particularly in the treatment of conditions involving skin grafts, pedicle flaps, as well as free flaps described in literatures. The purpose of this review is to report the new advances and mechanisms underlying MSCs therapy against skin flaps necrosis.

  19. Advances in islet cell biology: from stem cell differentiation to clinical transplantation: conference report.

    PubMed

    Kandeel, Fouad; Smith, Craig V; Todorov, Ivan; Mullen, Yoko

    2003-10-01

    The 3rd Annual Rachmiel Levine Symposium entitled "Advances in Islet Cell Biology-From Stem Cell Differentiation to Clinical Transplantation" was organized by the Department of Diabetes, Endocrinology and Metabolism at the City of Hope National Medical Center, with the support of the Southern California Islet Cell Resources Center, American Diabetes Association-David Shapiro Research Fund, Ross Foundation, the National Center for Research Resources (NCRR), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health. The symposium was held at the Hilton Anaheim Hotel in Anaheim, CA, in October 2002, and was attended by nearly 400 participants from 23 countries and 30 U.S. states. The symposium consisted of 11 sessions focusing on 3 areas: (1) pancreas and islet cell differentiation and islet generation, (2) beta cell biology and insulin synthesis and/or secretion, and (3) pancreatic islet transplantation in patients with type I diabetes. Thirty-nine world experts lectured on the most current information in each field. Fifty-three abstracts were selected for presentation and discussed at the poster session. The first author of each of the top 10 posters received a Young Investigator Travel Award provided by the National Center for Research Resources and the Southern California Islet Cell Resources Center. The symposium also offered special Meet the Professor sessions, which gave the attendees an opportunity to closely interact with the participating speakers of the day.

  20. Pluripotent stem cell derivation and differentiation toward cardiac muscle: novel techniques and advances in patent literature.

    PubMed

    Quattrocelli, Mattia; Thorrez, Lieven; Sampaolesi, Maurilio

    2013-04-01

    Pluripotent stem cells hold unprecedented potential for regenerative medicine, disease modeling and drug screening. Embryonic stem cells (ESCs), standard model for pluripotency studies, have been recently flanked by induced pluripotent stem cells (iPSCs). iPSCs are obtained from somatic cells via epigenetic and transcriptional reprogramming, overcoming ESC-related ethical issues and enabling the possibility of donor-matching pluripotent cell lines. Since the European Court of Justice banned patents involving embryo disaggregation to generate human ESCs, iPSCs can now fuel the willingness of European companies to invest in treatments based on stem cells. Moreover, iPSCs share many unique features of ESCs, such as unlimited self-renewal potential and broad differentiation capability, even though iPSCs seem more susceptible to genomic instability and display epigenetic biases as compared to ESCs. Both ESCs and iPSCs have been intensely investigated for cardiomyocyte production and cardiac muscle regeneration, both in human and animal models. In vitro and in vivo studies are continuously expanding and refining this field via genetic manipulation and cell conditioning, trying to achieve standard and reproducible products, eligible for clinical and biopharmaceutical scopes. This review focuses on the recently growing body of patents, concerning technical advances in production, expansion and cardiac differentiation of ESCs and iPSCs.

  1. Artificial Stem Cell Niches

    PubMed Central

    Lutolf, Matthias P.; Blau, Helen M.

    2011-01-01

    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-intrinsic regulatory networks, control their function and balance their numbers in response to physiologic demands. This progress report provides a perspective on how advanced materials technologies could be used (i) to engineer and systematically analyze specific aspects of functional stem cells niches in a controlled fashion in vitro and (ii) to target stem cell niches in vivo. Such “artificial niches” constitute potent tools for elucidating stem cell regulatory mechanisms with the capacity to directly impact the development of novel therapeutic strategies for tissue regeneration. PMID:20882496

  2. Robotics, Stem Cells and Brain Computer Interfaces in Rehabilitation and Recovery from Stroke; Updates and Advances

    PubMed Central

    Boninger, Michael L; Wechsler, Lawrence R.; Stein, Joel

    2014-01-01

    Objective To describe the current state and latest advances in robotics, stem cells, and brain computer interfaces in rehabilitation and recovery for stroke. Design The authors of this summary recently reviewed this work as part of a national presentation. The paper represents the information included in each area. Results Each area has seen great advances and challenges as products move to market and experiments are ongoing. Conclusion Robotics, stem cells, and brain computer interfaces all have tremendous potential to reduce disability and lead to better outcomes for patients with stroke. Continued research and investment will be needed as the field moves forward. With this investment, the potential for recovery of function is likely substantial PMID:25313662

  3. Some aspects of allogeneic stem cell transplantation in patients with myelodysplastic syndrome: advances and controversy

    PubMed Central

    Blau, Olga; Blau, Igor Wolfgang

    2014-01-01

    Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid disorders. MDS remains a disease of elderly patients; moreover, the incidence of high risk MDS is proportionally greater in elderly patients, with increased frequency of secondary acute myeloid leukemia, as well as adverse cytogenetic abnormalities. Allogeneic stem cell transplantation is a therapeutic approach with known curative potential for patients with MDS that allows the achievement of long-term disease control. Numerous controversies still exist regarding transplantation in MDS: timing of transplantation, disease status at transplantation and comorbidity, conditioning intensity, pretransplant therapy, and stem cell source. Various transplant modalities of different intensities and alternative donor sources are now in use. Current advances in transplant technology are allowing the consideration of older patients. This should result in a greater number of older patients benefiting from this potentially curative treatment modality. Despite advances in transplantation technology, there is still considerable morbidity and mortality associated with this approach. Nevertheless, with the introduction of reduced-intensity conditioning and thereby reduced early mortality, transplant numbers in MDS patients have significantly increased. Moreover, recent new developments with innovative drugs, including hypomethylating agents, have extended the therapeutic alternatives for MDS patients. Hypomethylating agents allow the delay of allogeneic stem cell transplantation by serving as an effective and well-tolerated means to reduce disease burden. PMID:25506229

  4. Advances and Developments in the Use of Human Mesenchymal Stem Cells – A Few Considerations

    PubMed Central

    Kennard, Lucinda; Thanabalasundaram, Gopiga; Tailor, Hiteshkumar D; Khan, Wasim S

    2011-01-01

    One less visited area in musculoskeletal stem cell research is the effects of donor age on quality of stem cells. The prevalence of degenerative orthopaedic conditions is large, and the older population is likely to receive great benefit from stem cell therapies. There are many known growth factors involved in controlling and influencing stem cell growth which are also related to cell senescence. Of which, expressions are found to be altered in mesenchymal stem cells from older donors. Considerations must also be taken of these mechanisms which also have a role in cell cycle and tumour suppression. PMID:21892368

  5. Stem cell therapies for amyotrophic lateral sclerosis: Recent advances and prospects for the future

    PubMed Central

    Lunn, J. Simon; Sakowski, Stacey A.; Feldman, Eva L.

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a lethal disease involving the loss of motor neurons. Although the mechanisms responsible for motor neuron degeneration in ALS remain elusive, the development of stem cell-based therapies for the treatment of ALS has gained widespread support. Here, we review the types of stem cells being considered for therapeutic applications in ALS, and emphasize recent preclinical advances that provide supportive rationale for clinical translation. We also discuss early trials from around the world translating cellular therapies to ALS patients, and offer important considerations for future clinical trial design. Although clinical translation is still in its infancy, and additional insight into the mechanisms underlying therapeutic efficacy and the establishment of long-term safety are required, these studies represent an important first step towards the development of effective cellular therapies for the treatment of ALS. PMID:24448926

  6. Concise review: Stem cell therapies for amyotrophic lateral sclerosis: recent advances and prospects for the future.

    PubMed

    Lunn, J Simon; Sakowski, Stacey A; Feldman, Eva L

    2014-05-01

    Amyotrophic lateral sclerosis (ALS) is a lethal disease involving the loss of motor neurons. Although the mechanisms responsible for motor neuron degeneration in ALS remain elusive, the development of stem cell-based therapies for the treatment of ALS has gained widespread support. Here, we review the types of stem cells being considered for therapeutic applications in ALS, and emphasize recent preclinical advances that provide supportive rationale for clinical translation. We also discuss early trials from around the world translating cellular therapies to ALS patients, and offer important considerations for future clinical trial design. Although clinical translation is still in its infancy, and additional insight into the mechanisms underlying therapeutic efficacy and the establishment of long-term safety are required, these studies represent an important first step toward the development of effective cellular therapies for the treatment of ALS.

  7. Targeting stem cell signaling pathways for drug discovery: advances in the Notch and Wnt pathways.

    PubMed

    An, Songzhu Michael; Ding, Qiang; Zhang, Jie; Xie, JingYi; Li, LingSong

    2014-06-01

    Signaling pathways transduce extracellular stimuli into cells through molecular cascades to regulate cellular functions. In stem cells, a small number of pathways, notably those of TGF-β/BMP, Hedgehog, Notch, and Wnt, are responsible for the regulation of pluripotency and differentiation. During embryonic development, these pathways govern cell fate specifications as well as the formation of tissues and organs. In adulthood, their normal functions are important for tissue homeostasis and regeneration, whereas aberrations result in diseases, such as cancer and degenerative disorders. In complex biological systems, stem cell signaling pathways work in concert as a network and exhibit crosstalk, such as the negative crosstalk between Wnt and Notch. Over the past decade, genetic and genomic studies have identified a number of potential drug targets that are involved in stem cell signaling pathways. Indeed, discovery of new targets and drugs for these pathways has become one of the most active areas in both the research community and pharmaceutical industry. Remarkable progress has been made and several promising drug candidates have entered into clinical trials. This review focuses on recent advances in the discovery of novel drugs which target the Notch and Wnt pathways.

  8. Stem Cell Basics

    MedlinePlus

    ... stem cells? What are the potential uses of human stem cells and the obstacles that must be overcome before ... two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells . ...

  9. Learn About Stem Cells

    MedlinePlus

    ... 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

  10. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells.

    PubMed

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-01-01

    Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies. PMID:26907255

  11. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells

    PubMed Central

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-01-01

    Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies. PMID:26907255

  12. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells.

    PubMed

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-01-01

    Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies.

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

    PubMed

    Aponte, Pedro Manuel

    2015-05-26

    Spermatogonial stem cells (SSCs) are the germ stem cells of the seminiferous epithelium in the testis. Through the process of spermatogenesis, they produce sperm while concomitantly keeping their cellular pool constant through self-renewal. SSC biology offers important applications for animal reproduction and overcoming human disease through regenerative therapies. To this end, several techniques involving SSCs have been developed and will be covered in this article. SSCs convey genetic information to the next generation, a property that can be exploited for gene targeting. Additionally, SSCs can be induced to become embryonic stem cell-like pluripotent cells in vitro. Updates on SSC transplantation techniques with related applications, such as fertility restoration and preservation of endangered species, are also covered on this article. SSC suspensions can be transplanted to the testis of an animal and this has given the basis for SSC functional assays. This procedure has proven technically demanding in large animals and men. In parallel, testis tissue xenografting, another transplantation technique, was developed and resulted in sperm production in testis explants grafted into ectopical locations in foreign species. Since SSC culture holds a pivotal role in SSC biotechnologies, current advances are overviewed. Finally, spermatogenesis in vitro, already demonstrated in mice, offers great promises to cope with reproductive issues in the farm animal industry and human clinical applications. PMID:26029339

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

    PubMed Central

    Aponte, Pedro Manuel

    2015-01-01

    Spermatogonial stem cells (SSCs) are the germ stem cells of the seminiferous epithelium in the testis. Through the process of spermatogenesis, they produce sperm while concomitantly keeping their cellular pool constant through self-renewal. SSC biology offers important applications for animal reproduction and overcoming human disease through regenerative therapies. To this end, several techniques involving SSCs have been developed and will be covered in this article. SSCs convey genetic information to the next generation, a property that can be exploited for gene targeting. Additionally, SSCs can be induced to become embryonic stem cell-like pluripotent cells in vitro. Updates on SSC transplantation techniques with related applications, such as fertility restoration and preservation of endangered species, are also covered on this article. SSC suspensions can be transplanted to the testis of an animal and this has given the basis for SSC functional assays. This procedure has proven technically demanding in large animals and men. In parallel, testis tissue xenografting, another transplantation technique, was developed and resulted in sperm production in testis explants grafted into ectopical locations in foreign species. Since SSC culture holds a pivotal role in SSC biotechnologies, current advances are overviewed. Finally, spermatogenesis in vitro, already demonstrated in mice, offers great promises to cope with reproductive issues in the farm animal industry and human clinical applications. PMID:26029339

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

    PubMed

    Aponte, Pedro Manuel

    2015-05-26

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

  16. Advances in microfluidic platforms for analyzing and regulating human pluripotent stem cells.

    PubMed

    Qian, Tongcheng; Shusta, Eric V; Palecek, Sean P

    2015-10-01

    Microfluidic devices employ submillimeter length scale control of flow to achieve high-resolution spatial and temporal control over the microenvironment, providing powerful tools to elucidate mechanisms of human pluripotent stem cell (hPSC) regulation and to elicit desired hPSC fates. In addition, microfluidics allow control of paracrine and juxtracrine signaling, thereby enabling fabrication of microphysiological systems comprised of multiple cell types organized into organs-on-a-chip. Microfluidic cell culture systems can also be integrated with actuators and sensors, permitting construction of high-density arrays of cell-based biosensors for screening applications. This review describes recent advances in using microfluidics to understand mechanisms by which the microenvironment regulates hPSC fates and applications of microfluidics to realize the potential of hPSCs for in vitro modeling and screening applications.

  17. Advances in pluripotent stem cell-derived endothelial cells: from biomaterials to organ regeneration.

    PubMed

    Lui, Kathy O

    2014-01-01

    Human embryonic stem cells (ESCs), by virtue of their capability to self-renew and differentiate into a variety of cell types, represent the first type of pluripotent stem cells (PSCs) to be used in clinical transplantation during recent phase-I trials; however, it is still unclear whether hESC-derived tissues can self-organize and form part of the vascularized, functional organ following transplantation. Recently, endothelial cells (ECs) or angiogenic factors such as VEGFA have been demonstrated to support development and regeneration of multiple organ systems, including the heart, pancreas, liver, lung and bone marrow. Therefore, co-transplantation of ECs derived from the same parental PSCs that differentiate into cell types of interest; or overexpression of the inductive angiogenic factors responsible for organ regeneration might be beneficial to support function of hPSC-derived tissues. In this special issue, we discuss how protein kinases (Ng and colleagues); DNA methylation and histone modification (Tsui and colleagues) regulate cellular pluripotency and cell-fate specification of PSCs. In addition, we discuss how ECs and angiogenic factors could contribute to repair and regeneration of organs such as the heart (Yuan and colleagues), the cardiovascular system (Tse and colleagues) and the pancreas (Lui). We also discuss the role of mesenchymal stem cells or paracrine factors secreted by them in tissue repair (Li and colleagues). Lastly, we discuss how to generate self-organized and vascularized tissues derived from PSCs in a 2- or 3-dimensional format by fusing tissue bioengineering approaches with stem cell technology (Chen).

  18. Advances in induced pluripotent stem cells, genomics, biomarkers, and antiplatelet therapy highlights of the year in JCTR 2013.

    PubMed

    Barbato, Emanuele; Lara-Pezzi, Enrique; Stolen, Craig; Taylor, Angela; Barton, Paul J; Bartunek, Jozef; Iaizzo, Paul; Judge, Daniel P; Kirshenbaum, Lorrie; Blaxall, Burns C; Terzic, Andre; Hall, Jennifer L

    2014-07-01

    The Journal provides the clinician and scientist with the latest advances in discovery research, emerging technologies, preclinical research design and testing, and clinical trials. We highlight advances in areas of induced pluripotent stem cells, genomics, biomarkers, multimodality imaging, and antiplatelet biology and therapy. The top publications are critically discussed and presented along with anatomical reviews and FDA insight to provide context.

  19. The Effect of Advanced Motherhood on Newborn Offspring's Hippocampal Neural Stem Cell Proliferation

    PubMed Central

    Duan, Ping; Han, Xuefei

    2016-01-01

    Objective. To investigate the effect of advanced motherhood on rat hippocampal neural stem cell proliferation. Methods. Female parents were subdivided into control and old mother group by age, and neural stem cells were cultured from hippocampal tissues for 24 h newborn offspring. The diameter and numbers of neurospheres were examined by microscopy, and differences in proliferation were examined by EdU immunofluorescence, CCK-8 assay, and cell cycle analysis. Results. The number of neurospheres in the old mother group after culture was lower than the control group. Additionally, neurospheres' diameter was smaller than that of the control group (P < 0.05). The EdU positive rate of the old mother group was lower than that of the control group (P < 0.05). CCK-8 assay results showed that the absorbance values for the old mother group were lower than that of the control group at 48 h and 72 h (P < 0.05). The proportions of cells in the S and G2/M phases of the cell cycle for the older mother group were less than that found for the control group (P < 0.05). Conclusion. The proliferation rates of hippocampal NSCs seen in the older mother group were lower than that seen in the control group. PMID:27689086

  20. The Effect of Advanced Motherhood on Newborn Offspring's Hippocampal Neural Stem Cell Proliferation

    PubMed Central

    Duan, Ping; Han, Xuefei

    2016-01-01

    Objective. To investigate the effect of advanced motherhood on rat hippocampal neural stem cell proliferation. Methods. Female parents were subdivided into control and old mother group by age, and neural stem cells were cultured from hippocampal tissues for 24 h newborn offspring. The diameter and numbers of neurospheres were examined by microscopy, and differences in proliferation were examined by EdU immunofluorescence, CCK-8 assay, and cell cycle analysis. Results. The number of neurospheres in the old mother group after culture was lower than the control group. Additionally, neurospheres' diameter was smaller than that of the control group (P < 0.05). The EdU positive rate of the old mother group was lower than that of the control group (P < 0.05). CCK-8 assay results showed that the absorbance values for the old mother group were lower than that of the control group at 48 h and 72 h (P < 0.05). The proportions of cells in the S and G2/M phases of the cell cycle for the older mother group were less than that found for the control group (P < 0.05). Conclusion. The proliferation rates of hippocampal NSCs seen in the older mother group were lower than that seen in the control group.

  1. [Advances in the experimental study of the use of mesenchy- mal stem cells for the treatment of inhalation injury].

    PubMed

    Feng, Zhu; Guanghua, Guo

    2015-06-01

    Inhalation injury seriously threatens the survival and quality of life in burn and trauma patients. So far there is no breakthrough in the treatment of inhalation injury. A significant advance has been witnessed in the experimental study of the use of stem cells in the treatment of lung injury in recent years. In this paper, according to the results of our study in the systemic transplantation of bone marrow mesenchymal stem cells for the treatment of inhalation injury, the effect of mesenchymal stem cells on anti-inflammatory process and repair of lung tissues in inhalation injury, and its possible mechanisms are reviewed.

  2. Intraoperative Stem Cell Therapy

    PubMed Central

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

    2013-01-01

    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 potential regenerative mechanisms and the roles of different cell populations in the regeneration process are discussed. Although intraoperative stem cell therapies have been shown to be safe and effective for several indications, there are still critical challenges to be tackled prior to adoption into the standard surgical armamentarium. PMID:22809140

  3. [Potential of hematopoietic stem cells as the basis for generation of advanced therapy medicinal products].

    PubMed

    Bönig, H; Heiden, M; Schüttrumpf, J; Müller, M M; Seifried, E

    2011-07-01

    Individualized, (stem) cell-based therapies of congenital and acquired illnesses are among the most exciting medical challenges of the twenty-first century. Before the full potential of such therapies can be achieved, many basic scientific and biotechnological questions remain to be answered. What is the ideal source for the generation of such cellular drugs is one of those issues. In many respects, hematopoietic stem cells fulfill the requirements for stem cells as starting material for novel cellular therapeutics, including the simple access to large amounts of stem cells, the availability of good phenotypic markers for their prospective isolation, and an extensive body of knowledge about the in vitro manipulation of these cells. This manuscript discusses the general and specific usability of hematopoietic stem cells as starting material for novel cellular therapeutics and presents some examples of hematological and nonhematological therapeutic approaches which are based on hematopoietic stem cells.

  4. Recent Advances and the Future of Stem Cell Therapies in Amyotrophic Lateral Sclerosis.

    PubMed

    Goutman, Stephen A; Chen, Kevin S; Feldman, Eva L

    2015-04-01

    Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of the motor neurons without a known cure. Based on the possibility of cellular neuroprotection and early preclinical results, stem cells have gained widespread enthusiasm as a potential treatment strategy. Preclinical models demonstrate a protective role of engrafted stem cells and provided the basis for human trials carried out using various types of stem cells, as well as a range of cell delivery methods. To date, no trial has demonstrated a clear therapeutic benefit; however, results remain encouraging and are the basis for ongoing studies. In addition, stem cell technology continues to improve, and induced pluripotent stem cells may offer additional therapeutic options in the future. Improved disease models and clinical trials will be essential in order to validate stem cells as a beneficial therapy.

  5. Biopsy Needle Advancement during Bone Marrow Aspiration Increases Mesenchymal Stem Cell Concentration

    PubMed Central

    Peters, Anne E.; Watts, Ashlee E.

    2016-01-01

    Point-of-care kits to concentrate bone marrow (BM)-derived mesenchymal stem cells (MSCs) are used clinically in horses. A maximal number of MSCs per milliliter of marrow aspirated might be desired prior to use of a point-of-care system to concentrate MSCs. Our objective was to test a method to increase the number of MSCs per milliliter of marrow collected. We collected two BM aspirates using two different collection techniques from 12 horses. The first collection technique was to aspirate BM from a single site without advancement of the biopsy needle. The second collection technique was to aspirate marrow from multiple sites within the same sternal puncture by advancing the needle 5 mm three times for BM aspiration from four sites. Numbers of MSCs in collected BM were assessed by total nucleated cell count of BM after aspiration, total colony-forming unit-fibroblast (CFU-F) assay, and total MSC number at each culture passage. The BM aspiration technique of four needle advancements during BM aspiration resulted in higher initial nucleated cell counts, more CFU-Fs, and more MSCs at the first passage. There were no differences in the number of MSCs at later passages. Multiple advancements of the BM needle during BM aspiration resulted in increased MSC concentration at the time of BM collection. If a point-of-care kit is used to concentrate MSCs, multiple advancements may result in higher MSC numbers in the BM concentrate after preparation by the point-of-care kit. For culture expanded MSCs beyond the first cell passage, the difference is of questionable clinical relevance. PMID:27014705

  6. Mesenchymal Stem Cells in Chronic Wounds: The Spectrum from Basic to Advanced Therapy

    PubMed Central

    Otero-Viñas, Marta; Falanga, Vincent

    2016-01-01

    Significance: Almost 7 million Americans have chronic cutaneous wounds and billions of dollars are spent on their treatment. The number of patients with nonhealing wounds keeps increasing worldwide due to an ever-aging population, increasing number of obese and diabetic patients, and cardiovascular disease. Recent Advances: Advanced treatments for difficult wounds are needed. Therapy with mesenchymal stem cells (MSCs) is attractive due to their differentiating potential, their immunomodulating properties, and their paracrine effects. Critical Issues: New technologies (including growth factors and skin substitutes) are now widely used for stimulating wound healing. However, in spite of these advances, the percentage of complete wound closure in most clinical situations is around 50–60%. Moreover, there is a high rate of wound recurrence. Future Directions: Recently, it has been demonstrated that MSCs speed up wound healing by decreasing inflammation, by promoting angiogenesis, and by decreasing scarring. However, there are some potential limitations to successful MSC therapy. These limitations include the need to improve cell delivery methods, cell viability, heterogeneity in MSC preparations, and suboptimal wound bed preparation. Further large, controlled clinical trials are needed to establish the safety of MSCs before widespread clinical application. PMID:27076993

  7. Advancing drug discovery for neuropsychiatric disorders using patient-specific stem cell models.

    PubMed

    Haggarty, Stephen J; Silva, M Catarina; Cross, Alan; Brandon, Nicholas J; Perlis, Roy H

    2016-06-01

    Compelling clinical, social, and economic reasons exist to innovate in the process of drug discovery for neuropsychiatric disorders. The use of patient-specific, induced pluripotent stem cells (iPSCs) now affords the ability to generate neuronal cell-based models that recapitulate key aspects of human disease. In the context of neuropsychiatric disorders, where access to physiologically active and relevant cell types of the central nervous system for research is extremely limiting, iPSC-derived in vitro culture of human neurons and glial cells is transformative. Potential applications relevant to early stage drug discovery, include support of quantitative biochemistry, functional genomics, proteomics, and perhaps most notably, high-throughput and high-content chemical screening. While many phenotypes in human iPSC-derived culture systems may prove adaptable to screening formats, addressing the question of which in vitro phenotypes are ultimately relevant to disease pathophysiology and therefore more likely to yield effective pharmacological agents that are disease-modifying treatments requires careful consideration. Here, we review recent examples of studies of neuropsychiatric disorders using human stem cell models where cellular phenotypes linked to disease and functional assays have been reported. We also highlight technical advances using genome-editing technologies in iPSCs to support drug discovery efforts, including the interpretation of the functional significance of rare genetic variants of unknown significance and for the purpose of creating cell type- and pathway-selective functional reporter assays. Additionally, we evaluate the potential of in vitro stem cell models to investigate early events of disease pathogenesis, in an effort to understand the underlying molecular mechanism, including the basis of selective cell-type vulnerability, and the potential to create new cell-based diagnostics to aid in the classification of patients and subsequent

  8. Advancing drug discovery for neuropsychiatric disorders using patient-specific stem cell models.

    PubMed

    Haggarty, Stephen J; Silva, M Catarina; Cross, Alan; Brandon, Nicholas J; Perlis, Roy H

    2016-06-01

    Compelling clinical, social, and economic reasons exist to innovate in the process of drug discovery for neuropsychiatric disorders. The use of patient-specific, induced pluripotent stem cells (iPSCs) now affords the ability to generate neuronal cell-based models that recapitulate key aspects of human disease. In the context of neuropsychiatric disorders, where access to physiologically active and relevant cell types of the central nervous system for research is extremely limiting, iPSC-derived in vitro culture of human neurons and glial cells is transformative. Potential applications relevant to early stage drug discovery, include support of quantitative biochemistry, functional genomics, proteomics, and perhaps most notably, high-throughput and high-content chemical screening. While many phenotypes in human iPSC-derived culture systems may prove adaptable to screening formats, addressing the question of which in vitro phenotypes are ultimately relevant to disease pathophysiology and therefore more likely to yield effective pharmacological agents that are disease-modifying treatments requires careful consideration. Here, we review recent examples of studies of neuropsychiatric disorders using human stem cell models where cellular phenotypes linked to disease and functional assays have been reported. We also highlight technical advances using genome-editing technologies in iPSCs to support drug discovery efforts, including the interpretation of the functional significance of rare genetic variants of unknown significance and for the purpose of creating cell type- and pathway-selective functional reporter assays. Additionally, we evaluate the potential of in vitro stem cell models to investigate early events of disease pathogenesis, in an effort to understand the underlying molecular mechanism, including the basis of selective cell-type vulnerability, and the potential to create new cell-based diagnostics to aid in the classification of patients and subsequent

  9. Advanced Properties of Urine Derived Stem Cells Compared to Adipose Tissue Derived Stem Cells in Terms of Cell Proliferation, Immune Modulation and Multi Differentiation.

    PubMed

    Kang, Hye Suk; Choi, Seock Hwan; Kim, Bum Soo; Choi, Jae Young; Park, Gang-Baek; Kwon, Tae Gyun; Chun, So Young

    2015-12-01

    Adipose tissue stem cells (ADSCs) would be an attractive autologous cell source. However, ADSCs require invasive procedures, and has potential complications. Recently, urine stem cells (USCs) have been proposed as an alternative stem cell source. In this study, we compared USCs and ADSCs collected from the same patients on stem cell characteristics and capacity to differentiate into various cell lineages to provide a useful guideline for selecting the appropriate type of cell source for use in clinical application. The urine samples were collected via urethral catheterization, and adipose tissue was obtained from subcutaneous fat tissue during elective laparoscopic kidney surgery from the same patient (n = 10). Both cells were plated for primary culture. Cell proliferation, colony formation, cell surface markers, immune modulation, chromosome stability and multi-lineage differentiation were analyzed for each USCs and ADSCs at cell passage 3, 5, and 7. USCs showed high cell proliferation rate, enhanced colony forming ability, strong positive for stem cell markers expression, high efficiency for inhibition of immune cell activation compared to ADSCs at cell passage 3, 5, and 7. In chromosome stability analysis, both cells showed normal karyotype through all passages. In analysis of multi-lineage capability, USCs showed higher myogenic, neurogenic, and endogenic differentiation rate, and lower osteogenic, adipogenic, and chondrogenic differentiation rate compared to ADSCs. Therefore, we expect that USC can be an alternative autologous stem cell source for muscle, neuron and endothelial tissue reconstruction instead of ADSCs.

  10. Advanced Properties of Urine Derived Stem Cells Compared to Adipose Tissue Derived Stem Cells in Terms of Cell Proliferation, Immune Modulation and Multi Differentiation

    PubMed Central

    2015-01-01

    Adipose tissue stem cells (ADSCs) would be an attractive autologous cell source. However, ADSCs require invasive procedures, and has potential complications. Recently, urine stem cells (USCs) have been proposed as an alternative stem cell source. In this study, we compared USCs and ADSCs collected from the same patients on stem cell characteristics and capacity to differentiate into various cell lineages to provide a useful guideline for selecting the appropriate type of cell source for use in clinical application. The urine samples were collected via urethral catheterization, and adipose tissue was obtained from subcutaneous fat tissue during elective laparoscopic kidney surgery from the same patient (n = 10). Both cells were plated for primary culture. Cell proliferation, colony formation, cell surface markers, immune modulation, chromosome stability and multi-lineage differentiation were analyzed for each USCs and ADSCs at cell passage 3, 5, and 7. USCs showed high cell proliferation rate, enhanced colony forming ability, strong positive for stem cell markers expression, high efficiency for inhibition of immune cell activation compared to ADSCs at cell passage 3, 5, and 7. In chromosome stability analysis, both cells showed normal karyotype through all passages. In analysis of multi-lineage capability, USCs showed higher myogenic, neurogenic, and endogenic differentiation rate, and lower osteogenic, adipogenic, and chondrogenic differentiation rate compared to ADSCs. Therefore, we expect that USC can be an alternative autologous stem cell source for muscle, neuron and endothelial tissue reconstruction instead of ADSCs. PMID:26713051

  11. From discovery to approval of an advanced therapy medicinal product-containing stem cells, in the EU.

    PubMed

    Pellegrini, Graziella; Lambiase, Alessandro; Macaluso, Claudio; Pocobelli, Augusto; Deng, Sophie; Cavallini, Gian Maria; Esteki, Roza; Rama, Paolo

    2016-06-01

    In 1997, the human corneal epithelium was reconstructed in vitro and transplanted on patients. Later, it became a routine treatment, before regulations considered advanced therapy medicinal products and drugs on the same lines. Manufacturing, before and after good manufacturing practice setting, was established in different facilities and the clinical application in several hospitals. Advanced therapy medicinal products, including stem cells, are unique products with different challenges than other drugs: some uncertainties, in addition to benefit, cannot be avoided. This review will focus on all recent developments in the stem cell-based corneal therapy. PMID:27091398

  12. From discovery to approval of an advanced therapy medicinal product-containing stem cells, in the EU.

    PubMed

    Pellegrini, Graziella; Lambiase, Alessandro; Macaluso, Claudio; Pocobelli, Augusto; Deng, Sophie; Cavallini, Gian Maria; Esteki, Roza; Rama, Paolo

    2016-06-01

    In 1997, the human corneal epithelium was reconstructed in vitro and transplanted on patients. Later, it became a routine treatment, before regulations considered advanced therapy medicinal products and drugs on the same lines. Manufacturing, before and after good manufacturing practice setting, was established in different facilities and the clinical application in several hospitals. Advanced therapy medicinal products, including stem cells, are unique products with different challenges than other drugs: some uncertainties, in addition to benefit, cannot be avoided. This review will focus on all recent developments in the stem cell-based corneal therapy.

  13. Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells

    PubMed Central

    LABSCH, SABRINA; LIU, LI; BAUER, NATHALIE; ZHANG, YIYAO; ALEKSANDROWICZ, EWA; GLADKICH, JURY; SCHÖNSIEGEL, FRANK; HERR, INGRID

    2014-01-01

    Advanced androgen-independent prostate cancer (AIPC) is an aggressive malignancy with a poor prognosis. Apoptosis-resistant cancer stem cells (CSCs) have been identified in AIPC and are not eliminated by current therapeutics. Novel therapeutic options, which are currently being evaluated in patient studies, include TRAIL and the broccoli-derived isothiocyanate sulforaphane. Although neither agent targets normal cells, TRAIL induces apoptosis in most cancer cells, and sulforaphane eliminates CSCs. In this study, the established AIPC cell lines DU145 and PC3, with enriched CSC features, and primary patient-derived prostate CSCs were treated with sulforaphane and recombinant soluble TRAIL. We examined the effects of these drugs on NF-κB activity, self-renewal and differentiation potential, and stem cell signaling via spheroid- and colony-forming assays, FACS and western blot analyses, immunohistochemistry, and an antibody protein array in vitro and after xenotransplantation. We largely found a stronger effect of sulforaphane on CSC properties compared to TRAIL, though the agents acted synergistically when applied in combination. This was associated with the inhibition of TRAIL-induced NF-κB binding; CXCR4, Jagged1, Notch 1, SOX 2, and Nanog expression; ALDH1 activity inhibition; and the elimination of differentiation and self-renewal potential. In vivo, tumor engraftment and tumor growth were strongly inhibited, without the induction of liver necrosis or other obvious side effects. These findings suggest that sulforaphane shifts the balance from TRAIL-induced survival signals to apoptosis and thus explains the observed synergistic effect. A nutritional strategy for high sulforaphane intake may target the cancer-specific activity of TRAIL in CSCs. PMID:24626333

  14. Experimental Advances Towards Neural Regeneration from Induced Stem Cells to Direct In Vivo Reprogramming.

    PubMed

    Dametti, Sara; Faravelli, Irene; Ruggieri, Margherita; Ramirez, Agnese; Nizzardo, Monica; Corti, Stefania

    2016-05-01

    Neuronal loss is a common substrate of many neurological diseases that still lack effective treatments and highly burden lives of affected individuals. The discovery of self-renewing stem cells within the central nervous system (CNS) has opened the doors to the possibility of using the plasticity of CNS as a potential strategy for the development of regenerative therapies after injuries. The role of neural progenitor cells appears to be crucial, but insufficient in reparative processes after damage. In addition, the mechanisms that regulate these events are still largely unknown. Stem cell-based therapeutic approaches have primarily focused on the use of either induced pluripotent stem cells or induced neural stem cells as sources for cell transplantation. More recently, in vivo direct reprogramming of endogenous CNS cells into multipotent neural stem/progenitor cells has been proposed as an alternative strategy that could overcome the limits connected with both the invasiveness of exogenous cell transplantation and the technical issues of in vitro reprogramming (i.e., the time requested and the limited available amount of directly induced neuronal cells). In this review, we aim to highlight the recent studies on in vivo direct reprogramming, focusing on astrocytes conversion to neurons or to neural stem/precursors cells, in the perspective of future therapeutic purposes for neurological disorders.

  15. Stem cells for regenerative medicine: advances in the engineering of tissues and organs

    NASA Astrophysics Data System (ADS)

    Ringe, Jochen; Kaps, Christian; Burmester, Gerd-Rüdiger; Sittinger, Michael

    2002-07-01

    The adult bone marrow stroma contains a subset of nonhematopoietic cells referred to as mesenchymal stem or mesenchymal progenitor cells (MSC). These cells have the capacity to undergo extensive replication in an undifferentiated state ex vivo. In addition, MSC have the potential to develop either in vitro or in vivo into distinct mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma, which suggest these cells as an attractive cell source for tissue engineering approaches. The interest in modern biological technologies such as tissue engineering has dramatically increased since it is feasible to isolate living, healthy cells from the body, expand them under cell culture conditions, combine them with biocompatible carrier materials and retransplant them into patients. Therefore, tissue engineering gives the opportunity to generate living substitutes for tissues and organs, which may overcome the drawbacks of classical tissue reconstruction: lacking quality and quantity of autologous grafts, immunogenicity of allogenic grafts and loosening of alloplastic implants. Due to the prerequisite for tissue engineering to ensure a sufficient number of tissue specific cells without donor site morbidity, much attention has been drawn to multipotential progenitor cells such as embryonic stem cells, periosteal cells and mesenchymal stem cells. In this report we review the state of the art in tissue engineering with mesenchymal stem and mesenchymal progenitor cells with emphasis on bone and cartilage reconstruction. Furthermore, several issues of importance, especially with regard to the clinical application of mesenchymal stem cells, are discussed.

  16. In utero stem cell transplantation and gene therapy: rationale, history, and recent advances toward clinical application

    PubMed Central

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

    2016-01-01

    Recent advances in high-throughput molecular testing have made it possible to diagnose most genetic disorders relatively early in gestation with minimal risk to the fetus. These advances should soon allow widespread prenatal screening for the majority of human genetic diseases, opening the door to the possibility of treatment/correction prior to birth. In addition to the obvious psychological and financial benefits of curing a disease in utero, and thereby enabling the birth of a healthy infant, there are multiple biological advantages unique to fetal development, which provide compelling rationale for performing potentially curative treatments, such as stem cell transplantation or gene therapy, prior to birth. Herein, we briefly review the fields of in utero transplantation (IUTx) and in utero gene therapy and discuss the biological hurdles that have thus far restricted success of IUTx to patients with immunodeficiencies. We then highlight several recent experimental breakthroughs in immunology, hematopoietic/marrow ontogeny, and in utero cell delivery, which have collectively provided means of overcoming these barriers, thus setting the stage for clinical application of these highly promising therapies in the near future. PMID:27069953

  17. Recent advances in haploidentical hematopoietic stem cell transplantation using ex vivo T cell-depleted graft in children and adolescents

    PubMed Central

    Koh, Kyung-Nam; Seo, Jong Jin

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for children and adolescents with various malignant and non-malignant diseases. While human leukocyte antigen (HLA)-identical sibling donor is the preferred choice, matched unrelated volunteer donor is another realistic option for successful HSCT. Unfortunately, it is not always possible to find a HLA-matched donor for patients requiring HSCT, leading to a considerable number of deaths of patients without undergoing transplantation. Alternatively, allogeneic HSCT from haploidentical family members could provide donors for virtually all patients who need HSCT. Although the early attempts at allogeneic HSCT from haploidentical family donor (HFD) were disappointing, recent advances in the effective ex vivo depletion of T cells or unmanipulated in vivo regulation of T cells, better supportive care, and optimal conditioning regimens have significantly improved the outcomes of haploidentical HSCT. The ex vivo techniques used to remove T cells have evolved from the selection of CD34+ hematopoietic stem cell progenitors to the depletion of CD3+ cells, and more recently to the depletion of αβ+ T cells. The recent emerging evidence for ex vivo T cell-depleted haploidentical HSCT has provided additional therapeutic options for pediatric patients with diseases curable by HSCT but has not found a suitable related or unrelated donor. This review discusses recent advances in haploidentical HSCT, focusing on transplant using ex vivo T cell-depleted grafts. In addition, our experiences with this novel approach for the treatment of pediatric patients with malignant and non-malignant diseases are described. PMID:27104186

  18. Recent advances in haploidentical hematopoietic stem cell transplantation using ex vivo T cell-depleted graft in children and adolescents.

    PubMed

    Im, Ho Joon; Koh, Kyung-Nam; Seo, Jong Jin

    2016-03-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for children and adolescents with various malignant and non-malignant diseases. While human leukocyte antigen (HLA)-identical sibling donor is the preferred choice, matched unrelated volunteer donor is another realistic option for successful HSCT. Unfortunately, it is not always possible to find a HLA-matched donor for patients requiring HSCT, leading to a considerable number of deaths of patients without undergoing transplantation. Alternatively, allogeneic HSCT from haploidentical family members could provide donors for virtually all patients who need HSCT. Although the early attempts at allogeneic HSCT from haploidentical family donor (HFD) were disappointing, recent advances in the effective ex vivo depletion of T cells or unmanipulated in vivo regulation of T cells, better supportive care, and optimal conditioning regimens have significantly improved the outcomes of haploidentical HSCT. The ex vivo techniques used to remove T cells have evolved from the selection of CD34(+) hematopoietic stem cell progenitors to the depletion of CD3(+) cells, and more recently to the depletion of αβ(+) T cells. The recent emerging evidence for ex vivo T cell-depleted haploidentical HSCT has provided additional therapeutic options for pediatric patients with diseases curable by HSCT but has not found a suitable related or unrelated donor. This review discusses recent advances in haploidentical HSCT, focusing on transplant using ex vivo T cell-depleted grafts. In addition, our experiences with this novel approach for the treatment of pediatric patients with malignant and non-malignant diseases are described.

  19. Advanced feeder-free generation of induced pluripotent stem cells directly from blood cells.

    PubMed

    Trokovic, Ras; Weltner, Jere; Nishimura, Ken; Ohtaka, Manami; Nakanishi, Mahito; Salomaa, Veikko; Jalanko, Anu; Otonkoski, Timo; Kyttälä, Aija

    2014-12-01

    Generation of validated human induced pluripotent stem cells (iPSCs) for biobanking is essential for exploring the full potential of iPSCs in disease modeling and drug discovery. Peripheral blood mononuclear cells (PBMCs) are attractive targets for reprogramming, because blood is collected by a routine clinical procedure and is a commonly stored material in biobanks. Generation of iPSCs from blood cells has previously been reported using integrative retroviruses, episomal Sendai viruses, and DNA plasmids. However, most of the published protocols require expansion and/or activation of a specific cell population from PBMCs. We have recently collected a PBMC cohort from the Finnish population containing more than 2,000 subjects. Here we report efficient generation of iPSCs directly from PBMCs in feeder-free conditions in approximately 2 weeks. The produced iPSC clones are pluripotent and transgene-free. Together, these properties make this novel method a powerful tool for large-scale reprogramming of PBMCs and for iPSC biobanking.

  20. Advances in tissue engineering through stem cell-based co-culture.

    PubMed

    Paschos, Nikolaos K; Brown, Wendy E; Eswaramoorthy, Rajalakshmanan; Hu, Jerry C; Athanasiou, Kyriacos A

    2015-05-01

    Stem cells are the future in tissue engineering and regeneration. In a co-culture, stem cells not only provide a target cell source with multipotent differentiation capacity, but can also act as assisting cells that promote tissue homeostasis, metabolism, growth and repair. Their incorporation into co-culture systems seems to be important in the creation of complex tissues or organs. In this review, critical aspects of stem cell use in co-culture systems are discussed. Direct and indirect co-culture methodologies used in tissue engineering are described, along with various characteristics of cellular interactions in these systems. Direct cell-cell contact, cell-extracellular matrix interaction and signalling via soluble factors are presented. The advantages of stem cell co-culture strategies and their applications in tissue engineering and regenerative medicine are portrayed through specific examples for several tissues, including orthopaedic soft tissues, bone, heart, vasculature, lung, kidney, liver and nerve. A concise review of the progress and the lessons learned are provided, with a focus on recent developments and their implications. It is hoped that knowledge developed from one tissue can be translated to other tissues. Finally, we address challenges in tissue engineering and regenerative medicine that can potentially be overcome via employing strategies for stem cell co-culture use.

  1. [Ethical aspects of human embryonic stem cell use and commercial umbilical cord blood stem cell banking. Ethical reflections on the occasion of the regulation of the European Council and Parliament on advanced therapy medicinal products].

    PubMed

    Virt, G

    2010-01-01

    The regulation of the European Council and Parliament on advanced therapy medicinal products also includes therapies with human embryonic stem cells. The use of these stem cells is controversially and heavily discussed. Contrary to the use of adult stem cells, medical and ethical problems concerning the use of human embryonic stem cells persists, because this use is based on the destruction of human life at the very beginning. The regulation foresees, therefore, subsidiarity within the European Member States. Although there are no ethical problems in principle with the use of stem cells from the umbilical cord blood, there are social ethical doubts with the banking of these stem cells for autologous use without any currently foreseeable medical advantage by commercial blood banks. Also in this case subsidiarity is valid.

  2. Concise Review: Advances in Generating Hepatocytes from Pluripotent Stem Cells for Translational Medicine.

    PubMed

    Szkolnicka, Dagmara; Hay, David C

    2016-06-01

    The liver is one of the major organs in the human body. Severe or prolonged exposure of the liver to different factors may cause life-threatening disease, which necessitates donor organ transplantation. While orthotopic liver transplantation can be used to effectively treat liver failure, it is an invasive procedure, which is severely limited by organ donation. Therefore, alternative sources of liver support have been proposed and studied. This includes the use of pluripotent stem cell-derived hepatocytes as a renewable source of cells for therapy. In addition to cell-based therapies, in vitro engineered liver tissue provides powerful models for human drug discovery and disease modeling. This review focuses on the generation of hepatocyte-like cells from pluripotent stem cells and their application in translational medicine. Stem Cells 2016;34:1421-1426.

  3. "The state of the heart": Recent advances in engineering human cardiac tissue from pluripotent stem cells.

    PubMed

    Sirabella, Dario; Cimetta, Elisa; Vunjak-Novakovic, Gordana

    2015-08-01

    The pressing need for effective cell therapy for the heart has led to the investigation of suitable cell sources for tissue replacement. In recent years, human pluripotent stem cell research expanded tremendously, in particular since the derivation of human-induced pluripotent stem cells. In parallel, bioengineering technologies have led to novel approaches for in vitro cell culture. The combination of these two fields holds potential for in vitro generation of high-fidelity heart tissue, both for basic research and for therapeutic applications. However, this new multidisciplinary science is still at an early stage. Many questions need to be answered and improvements need to be made before clinical applications become a reality. Here we discuss the current status of human stem cell differentiation into cardiomyocytes and the combined use of bioengineering approaches for cardiac tissue formation and maturation in developmental studies, disease modeling, drug testing, and regenerative medicine.

  4. Advances in the Use of Stem Cells in Veterinary Medicine: From Basic Research to Clinical Practice.

    PubMed

    Markoski, Melissa Medeiros

    2016-01-01

    Today, several veterinary diseases may be treated with the administration of stem cells. This is possible because these cells present a high therapeutic potential and may be injected as autologous or allogenic, freshly isolated, or previously cultured. The literature supports that the process is safe and brings considerable benefits to animal health. Knowledge about how adult stem cells modulate the molecular signals to activate cell homing has also been increasingly determined, evidencing the mechanisms which enable cells to repair and regenerate injured tissues. Preclinical studies were designed for many animal models and they have contributed to the translation to the human clinic. This review shows the most commonly used stem cell types, with emphasis on mesenchymal stem cells and their mechanistic potential to repair, as well as the experimental protocols, studied diseases, and species with the highest amount of studies and applications. The relationship between stem cell protocols utilized on clinics, molecular mechanisms, and the physiological responses may offer subsidies to new studies and therefore improve the therapeutic outcome for both humans and animals. PMID:27379197

  5. Advances in the Use of Stem Cells in Veterinary Medicine: From Basic Research to Clinical Practice

    PubMed Central

    2016-01-01

    Today, several veterinary diseases may be treated with the administration of stem cells. This is possible because these cells present a high therapeutic potential and may be injected as autologous or allogenic, freshly isolated, or previously cultured. The literature supports that the process is safe and brings considerable benefits to animal health. Knowledge about how adult stem cells modulate the molecular signals to activate cell homing has also been increasingly determined, evidencing the mechanisms which enable cells to repair and regenerate injured tissues. Preclinical studies were designed for many animal models and they have contributed to the translation to the human clinic. This review shows the most commonly used stem cell types, with emphasis on mesenchymal stem cells and their mechanistic potential to repair, as well as the experimental protocols, studied diseases, and species with the highest amount of studies and applications. The relationship between stem cell protocols utilized on clinics, molecular mechanisms, and the physiological responses may offer subsidies to new studies and therefore improve the therapeutic outcome for both humans and animals. PMID:27379197

  6. Advances in the Use of Stem Cells in Veterinary Medicine: From Basic Research to Clinical Practice.

    PubMed

    Markoski, Melissa Medeiros

    2016-01-01

    Today, several veterinary diseases may be treated with the administration of stem cells. This is possible because these cells present a high therapeutic potential and may be injected as autologous or allogenic, freshly isolated, or previously cultured. The literature supports that the process is safe and brings considerable benefits to animal health. Knowledge about how adult stem cells modulate the molecular signals to activate cell homing has also been increasingly determined, evidencing the mechanisms which enable cells to repair and regenerate injured tissues. Preclinical studies were designed for many animal models and they have contributed to the translation to the human clinic. This review shows the most commonly used stem cell types, with emphasis on mesenchymal stem cells and their mechanistic potential to repair, as well as the experimental protocols, studied diseases, and species with the highest amount of studies and applications. The relationship between stem cell protocols utilized on clinics, molecular mechanisms, and the physiological responses may offer subsidies to new studies and therefore improve the therapeutic outcome for both humans and animals.

  7. Recent advances in mesenchymal stem cell immunomodulation: the role of microvesicles.

    PubMed

    Fierabracci, Alessandra; Del Fattore, Andrea; Luciano, Rosa; Muraca, Marta; Teti, Anna; Muraca, Maurizio

    2015-01-01

    Mesenchymal stem cells are the most widely used cell phenotype for therapeutic applications, the main reasons being their well-established abilities to promote regeneration of injured tissues and to modulate immune responses. Efficacy was reported in the treatment of several animal models of inflammatory and autoimmune diseases and, in clinical settings, for the management of disorders such as GVHD, systemic lupus erythematosus, multiple sclerosis, and inflammatory bowel disease. The effects of mesenchymal stem cells are believed to be largely mediated by paracrine signals, and several secreted molecules have been identified as contributors to the net biological effect. Recently, it has been recognized that bioactive molecules can be shuttled from cell to cell packed in microvesicles, tiny portions of cytoplasm surrounded by a membrane. Coding and noncoding RNAs are also carried in such microvesicles, transferring relevant biological activity to target cells. Several reports indicate that the regenerative effect of mesenchymal stem cells can be reproduced by microvesicles isolated from their culture medium. More recent evidence suggests that the immunomodulatory effects of mesenchymal stem cells are also at least partially mediated by secreted microvesicles. These findings allow better understanding of the mechanisms involved in cell-to-cell interaction and may have interesting implications for the development of novel therapeutic tools in place of the parent cells.

  8. Advances in the knowledge of breast cancer stem cells. A review.

    PubMed

    Schwarz-Cruz Y Celis, Angela; Espinosa, Magali; Maldonado, Vilma; Melendez-Zajgla, Jorge

    2016-06-01

    Much effort has been made by researchers to elucidate the complex biology of breast cancer stem cells (BCSCs), a small subset of breast tumor cells that display stem cell properties, drive tumor initiation, and growth. In recent years, it has been suggested that BCSCs could be responsible for the process of metastasis and the development of drug resistance. These findings make the need to find the distinguishing blend of markers that can recognize only BCSCs of the utmost importance in order to be able to design new targeted therapies. This review will summarize BCSCs' main features as well as the cell surface markers that are currently used to identify them.

  9. [Stem cells and cancer].

    PubMed

    Arvelo, Francisco; Cotte, Carlos; Sojo, Felipe

    2014-12-01

    Surgery, radiotherapy and chemotherapy are universally recognized as the most effective anti-cancer therapies. Despite significant advances directed towards elucidating molecular mechanisms and developing clinical trials, cancer still remains a major public health issue. Cancer stem cells are a subpopulation of the cells that form the tumor. The discovery of these human cancer cells opens a perspective for understanding tumor recurrence, drug resistance and metastasis; and opens up new research directions on how cancer cells are capable of switching from dormancy to malignancy. Therapeutic alternatives emerge from a better understanding of the biology and the environment of tumor stem cells. The present paper aims to summarize the characteristics and properties of cancer stem cells, the ongoing research, as well as the best strategies for prevention and control of the mechanisms of tumor recurrence.

  10. Advances in homology directed genetic engineering of human pluripotent and adult stem cells.

    PubMed

    Ramamoorthi, Kalpith; Curtis, Donald; Asuri, Prashanth

    2013-10-26

    The ability to introduce precise genomic modifications in human cells has profound implications for both basic and applied research in stem cells, ranging from identification of genes regulating stem cell self-renewal and multilineage differentiation to therapeutic gene correction and creation of in vitro models of human diseases. However, the overall efficiency of this process is challenged by several factors including inefficient gene delivery into stem cells and low rates of homology directed site-specific targeting. Recent studies report the development of novel techniques to improve gene targeting efficiencies in human stem cells; these methods include molecular engineering of viral vectors to efficiently deliver episomal genetic sequences that can participate in homology directed targeting, as well as the design of synthetic proteins that can introduce double-stranded breaks in DNA to initiate such recombination events. This review focuses on the potential of these new technologies to precisely alter the human stem cell genome and also highlights the possibilities offered by the combination of these complementary strategies.

  11. Concise Review: Advances in Generating Hepatocytes from Pluripotent Stem Cells for Translational Medicine

    PubMed Central

    Szkolnicka, Dagmara

    2016-01-01

    Abstract The liver is one of the major organs in the human body. Severe or prolonged exposure of the liver to different factors may cause life‐threatening disease, which necessitates donor organ transplantation. While orthotopic liver transplantation can be used to effectively treat liver failure, it is an invasive procedure, which is severely limited by organ donation. Therefore, alternative sources of liver support have been proposed and studied. This includes the use of pluripotent stem cell‐derived hepatocytes as a renewable source of cells for therapy. In addition to cell‐based therapies, in vitro engineered liver tissue provides powerful models for human drug discovery and disease modeling. This review focuses on the generation of hepatocyte‐like cells from pluripotent stem cells and their application in translational medicine. Stem Cells 2016;34:1421–1426 PMID:27015786

  12. Stem Cell Sciences plc.

    PubMed

    Daniels, Sebnem

    2006-09-01

    Stem Cell Sciences' core objective is to develop safe and effective stem cell-based therapies for currently incurable diseases. In order to achieve this goal, Stem Cell Sciences recognizes the need for multiple technologies and a globally integrated stem cell initiative. The key challenges for the successful application of stem cells in the clinic is the need for a reproducible supply of pure, fully characterized stem cells that have been grown in suitable conditions for use in the clinic.

  13. New advances of microRNAs in glioma stem cells, with special emphasis on aberrant methylation of microRNAs.

    PubMed

    Zhao, Bing; Bian, Er-Bao; Li, Jia; Li, Jun

    2014-09-01

    Malignant brain tumors are thought to be originate from a small population of cells that display stem cell properties, including the capacity of self-renewal, multipotent differentiation, initiation of tumor tissues. Cancer stem cells (CSCs) have been identified in gliomas in which they are named as glioma stem cells (GSCs). GSCs, sharing some characteristics with normal neural stem cells (NSCs), contribute to the cellular origin for primary gliomas and the recurrence of malignant gliomas after current conventional therapy. Recently, increasing evidences have showed that miRNAs play a central role in GSCs. In this review we focus on the role of GSCs in gliomas and in the abnomal expression of miRNAs in GSCs. Furthermore, we also discuss epigenetic dysregulation of tumor-suppressor miRNAs by promoter DNA methylation is involved in the regulation of GSCs biology. Recent advances in understanding dysregulated expression of miRNAs and methylation of tumor-suppressor miRNAs in GSCs and their possible use as new therapeutic targets of gliomas.

  14. The advancement of human pluripotent stem cell-derived therapies into the clinic.

    PubMed

    Thies, R Scott; Murry, Charles E

    2015-09-15

    Human pluripotent stem cells (hPSCs) offer many potential applications for drug screening and 'disease in a dish' assay capabilities. However, a more ambitious goal is to develop cell therapeutics using hPSCs to generate and replace somatic cells that are lost as a result of disease or injury. This Spotlight article will describe the state of progress of some of the hPSC-derived therapeutics that offer the most promise for clinical use. Lessons from developmental biology have been instrumental in identifying signaling molecules that can guide these differentiation processes in vitro, and will be described in the context of these cell therapy programs.

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

    PubMed

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

    2010-05-15

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

  16. Stem cells supporting other stem cells

    PubMed Central

    Leatherman, Judith

    2013-01-01

    Adult stem cell therapies are increasingly prevalent for the treatment of damaged or diseased tissues, but most of the improvements observed to date are attributed to the ability of stem cells to produce paracrine factors that have a trophic effect on existing tissue cells, improving their functional capacity. It is now clear that this ability to produce trophic factors is a normal and necessary function for some stem cell populations. In vivo adult stem cells are thought to self-renew due to local signals from the microenvironment where they live, the niche. Several niches have now been identified which harbor multiple stem cell populations. In three of these niches – the Drosophila testis, the bulge of the mammalian hair follicle, and the mammalian bone marrow – one type of stem cell has been found to produce factors that contribute to the maintenance of a second stem cell population in the shared niche. In this review, I will examine the architecture of these three niches and discuss the molecular signals involved. Together, these examples establish a new paradigm for stem cell behavior, that stem cells can promote the maintenance of other stem cells. PMID:24348512

  17. Stem cells and neurodegenerative diseases.

    PubMed

    Hou, LingLing; Hong, Tao

    2008-04-01

    Neurodegenerative diseases are characterized by the neurodegenerative changes or apoptosis of neurons involved in networks, which are important to specific physiological functions. With the development of old-aging society, the incidence of neurodegenerative diseases is on the increase. However, it is difficult to diagnose for most of neurodegenerative diseases. At present, there are too few effective therapies. Advances in stem cell biology have raised the hope and possibility for the therapy of neurodegenerative diseases. Recently, stem cells have been widely attempted to treat neurodegenerative diseases of animal model. Here we review the progress and prospects of various stem cells, including embryonic stem cells, mesenchymal stem cell and neural stem cells and so on, for the treatments of neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, Huntington' disease and Amyotrophic lateral sclerosis/Lou Gehrig's disease.

  18. Targeting Head and Neck Cancer Stem Cells: Current Advances and Future Challenges.

    PubMed

    Birkeland, A C; Owen, J H; Prince, M E

    2015-11-01

    Cancer stem cells (CSCs), or tumor-initiating cells, comprise a subset of tumor cells with demonstrated ability for tumor growth, invasion, metastasis, and resistance to chemotherapy and radiation. Targeting of CSCs remains an attractive yet elusive therapeutic option, with the goal of increasing specificity and effectiveness in tumor eradication, as well as decreasing off-target or systemic toxicity. Research into further characterization and targeted therapy toward head and neck CSCs is an active and rapidly evolving field. This review discusses the current state of research into therapy against head and neck CSCs and future directions for targeted therapy.

  19. Advances in Liver Regeneration: Revisiting Hepatic Stem/Progenitor Cells and Their Origin.

    PubMed

    Sadri, Ali-Reza; Jeschke, Marc G; Amini-Nik, Saeid

    2016-01-01

    The liver has evolved to become a highly plastic organ with extraordinary regenerative capabilities. What drives liver regeneration is still being debated. Adult liver stem/progenitor cells have been characterized and used to produce functional hepatocytes and biliary cells in vitro. However, in vivo, numerous studies have questioned whether hepatic progenitor cells have a significant role in liver regeneration. Mature hepatocytes have recently been shown to be more plastic than previously believed and give rise to new hepatocytes after acute and chronic injury. In this review, we discuss current knowledge in the field of liver regeneration and the importance of the serotonin pathway as a clinical target for patients with liver dysfunction.

  20. Advances in Adipose-Derived Stem Cells Isolation, Characterization, and Application in Regenerative Tissue Engineering

    PubMed Central

    Wankhade, Umesh D.; Shen, Michael; Kolhe, Ravindra; Fulzele, Sadanand

    2016-01-01

    Obesity is a complex, multifactorial disease that has been extensively researched in recent times. Obesity is characterized by excess deposition of adipose tissue in response to surplus energy. Despite the negative connotations of adipose tissue (AT), it serves as a critical endocrine organ. Adipose tissue is a source of several adipokines and cytokines which have been deemed important for both normal metabolic function and disease formation. The discoveries of metabolically active brown AT in adult humans and adipose tissue derived stem cells (ADSC) have been key findings in the past decade with potential therapeutic implications. ADSCs represent an enticing pool of multipotent adult stem cells because of their noncontroversial nature, relative abundance, ease of isolation, and expandability. A decade and a half since the discovery of ADSCs, the scientific community is still working to uncover their therapeutic potential in a wide range of diseases. In this review, we provide an overview of the recent developments in the field of ADSCs and examine their potential use in transplantation and cell-based therapies for the regeneration of diseased organs and systems. We also hope to provide perspective on how to best utilize this readily available, powerful pool of stem cells in the future. PMID:26981130

  1. Advances in Adipose-Derived Stem Cells Isolation, Characterization, and Application in Regenerative Tissue Engineering.

    PubMed

    Wankhade, Umesh D; Shen, Michael; Kolhe, Ravindra; Fulzele, Sadanand

    2016-01-01

    Obesity is a complex, multifactorial disease that has been extensively researched in recent times. Obesity is characterized by excess deposition of adipose tissue in response to surplus energy. Despite the negative connotations of adipose tissue (AT), it serves as a critical endocrine organ. Adipose tissue is a source of several adipokines and cytokines which have been deemed important for both normal metabolic function and disease formation. The discoveries of metabolically active brown AT in adult humans and adipose tissue derived stem cells (ADSC) have been key findings in the past decade with potential therapeutic implications. ADSCs represent an enticing pool of multipotent adult stem cells because of their noncontroversial nature, relative abundance, ease of isolation, and expandability. A decade and a half since the discovery of ADSCs, the scientific community is still working to uncover their therapeutic potential in a wide range of diseases. In this review, we provide an overview of the recent developments in the field of ADSCs and examine their potential use in transplantation and cell-based therapies for the regeneration of diseased organs and systems. We also hope to provide perspective on how to best utilize this readily available, powerful pool of stem cells in the future.

  2. Stem cell biobanks.

    PubMed

    Bardelli, Silvana

    2010-04-01

    Stem cells contribute to innate healing and harbor a promising role for regenerative medicine. Stem cell banking through long-term storage of different stem cell platforms represents a fundamental source to preserve original features of stem cells for patient-specific clinical applications. Stem cell research and clinical translation constitute fundamental and indivisible modules catalyzed through biobanking activity, generating a return of investment. PMID:20560026

  3. Recent Advances and Future Direction in Lyophilisation and Desiccation of Mesenchymal Stem Cells

    PubMed Central

    Bissoyi, Akalabya; Gusev, Oleg; Patra, Pradeep Kumar

    2016-01-01

    Mesenchymal Stem Cells (MSCs) are a promising mammalian cell type as they can be used for the reconstruction of human tissues and organs. MSCs are shown to form bone, cartilage, fat, and muscle-like cells under specific cultivation conditions. Current technology of MSCs cryopreservation has significant disadvantages. Alternative technologies of mammalian cells preservation through lyophilisation or desiccation (air-drying) are among the upcoming domains of investigation in the field of cryobiology. Different protectants and their combinations were studied in this context. Loading of the protectant in the live cell can be a challenging issue but recent studies have shown encouraging results. This paper deals with a review of the protectants, methods of their delivery, and physical boundary conditions adopted for the desiccation and lyophilisation of mammalian cells, including MSCs. A hybrid technique combining both methods is also proposed as a promising way of MSCs dry preservation. PMID:27597869

  4. Recent Advances and Future Direction in Lyophilisation and Desiccation of Mesenchymal Stem Cells

    PubMed Central

    Bissoyi, Akalabya; Gusev, Oleg; Patra, Pradeep Kumar

    2016-01-01

    Mesenchymal Stem Cells (MSCs) are a promising mammalian cell type as they can be used for the reconstruction of human tissues and organs. MSCs are shown to form bone, cartilage, fat, and muscle-like cells under specific cultivation conditions. Current technology of MSCs cryopreservation has significant disadvantages. Alternative technologies of mammalian cells preservation through lyophilisation or desiccation (air-drying) are among the upcoming domains of investigation in the field of cryobiology. Different protectants and their combinations were studied in this context. Loading of the protectant in the live cell can be a challenging issue but recent studies have shown encouraging results. This paper deals with a review of the protectants, methods of their delivery, and physical boundary conditions adopted for the desiccation and lyophilisation of mammalian cells, including MSCs. A hybrid technique combining both methods is also proposed as a promising way of MSCs dry preservation.

  5. Recent Advances and Future Direction in Lyophilisation and Desiccation of Mesenchymal Stem Cells.

    PubMed

    Bissoyi, Akalabya; Kumar, Awanish; Rizvanov, Albert A; Nesmelov, Alexander; Gusev, Oleg; Patra, Pradeep Kumar; Bit, Arindam

    2016-01-01

    Mesenchymal Stem Cells (MSCs) are a promising mammalian cell type as they can be used for the reconstruction of human tissues and organs. MSCs are shown to form bone, cartilage, fat, and muscle-like cells under specific cultivation conditions. Current technology of MSCs cryopreservation has significant disadvantages. Alternative technologies of mammalian cells preservation through lyophilisation or desiccation (air-drying) are among the upcoming domains of investigation in the field of cryobiology. Different protectants and their combinations were studied in this context. Loading of the protectant in the live cell can be a challenging issue but recent studies have shown encouraging results. This paper deals with a review of the protectants, methods of their delivery, and physical boundary conditions adopted for the desiccation and lyophilisation of mammalian cells, including MSCs. A hybrid technique combining both methods is also proposed as a promising way of MSCs dry preservation.

  6. Recent Advances and Future Direction in Lyophilisation and Desiccation of Mesenchymal Stem Cells.

    PubMed

    Bissoyi, Akalabya; Kumar, Awanish; Rizvanov, Albert A; Nesmelov, Alexander; Gusev, Oleg; Patra, Pradeep Kumar; Bit, Arindam

    2016-01-01

    Mesenchymal Stem Cells (MSCs) are a promising mammalian cell type as they can be used for the reconstruction of human tissues and organs. MSCs are shown to form bone, cartilage, fat, and muscle-like cells under specific cultivation conditions. Current technology of MSCs cryopreservation has significant disadvantages. Alternative technologies of mammalian cells preservation through lyophilisation or desiccation (air-drying) are among the upcoming domains of investigation in the field of cryobiology. Different protectants and their combinations were studied in this context. Loading of the protectant in the live cell can be a challenging issue but recent studies have shown encouraging results. This paper deals with a review of the protectants, methods of their delivery, and physical boundary conditions adopted for the desiccation and lyophilisation of mammalian cells, including MSCs. A hybrid technique combining both methods is also proposed as a promising way of MSCs dry preservation. PMID:27597869

  7. Recent advances in cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers.

    PubMed

    Mimeault, M; Hauke, R; Mehta, P P; Batra, S K

    2007-01-01

    Overcoming intrinsic and acquired resistance of cancer stem/progenitor cells to current clinical treatments represents a major challenge in treating and curing the most aggressive and metastatic cancers. This review summarizes recent advances in our understanding of the cellular origin and molecular mechanisms at the basis of cancer initiation and progression as well as the heterogeneity of cancers arising from the malignant transformation of adult stem/progenitor cells. We describe the critical functions provided by several growth factor cascades, including epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), stem cell factor (SCF) receptor (KIT), hedgehog and Wnt/beta-catenin signalling pathways that are frequently activated in cancer progenitor cells and are involved in their sustained growth, survival, invasion and drug resistance. Of therapeutic interest, we also discuss recent progress in the development of new drug combinations to treat the highly aggressive and metastatic cancers including refractory/relapsed leukaemias, melanoma and head and neck, brain, lung, breast, ovary, prostate, pancreas and gastrointestinal cancers which remain incurable in the clinics. The emphasis is on new therapeutic strategies consisting of molecular targeting of distinct oncogenic signalling elements activated in the cancer progenitor cells and their local microenvironment during cancer progression. These new targeted therapies should improve the efficacy of current therapeutic treatments against aggressive cancers, and thereby preventing disease relapse and enhancing patient survival. PMID:17979879

  8. DNA methylation and hydroxymethylation in stem cells.

    PubMed

    Cheng, Ying; Xie, Nina; Jin, Peng; Wang, Tao

    2015-06-01

    In mammals, DNA methylation and hydroxymethylation are specific epigenetic mechanisms that can contribute to the regulation of gene expression and cellular functions. DNA methylation is important for the function of embryonic stem cells and adult stem cells (such as haematopoietic stem cells, neural stem cells and germline stem cells), and changes in DNA methylation patterns are essential for successful nuclear reprogramming. In the past several years, the rediscovery of hydroxymethylation and the TET enzymes expanded our insights tremendously and uncovered more dynamic aspects of cytosine methylation regulation. Here, we review the current knowledge and highlight the most recent advances in DNA methylation and hydroxymethylation in embryonic stem cells, induced pluripotent stem cells and several well-studied adult stems cells. Our current understanding of stem cell epigenetics and new advances in the field will undoubtedly stimulate further clinical applications of regenerative medicine in the future.

  9. [Recent Advances on the Immunoregulation of MicroRNA-155 in Mesenchymal Stem Cells--Review].

    PubMed

    Han, Xiao; Wang, Lei; Wu, Tao; Bai, Hai

    2016-02-01

    Mesenchymal stem cells (MSC) are capable of immunosuppression and differentiating into multiple cell lineages. MSC, which are accessed easily and less side-effects, have been a source of seed cells in tissue-engineering and cell-therapy. However, the application of MSC are limited by their differentiation of instability and easy aging. MicroRNA-155 (miR-155) is one of microRNA, which has powerful regulatory potential in a wide variety of immune cells through degrading specific mRNA after transcription and inhibiting translation of the target genes. Following the research of miR-155 deeply, it has an indispensable role in the proliferation, differentiation and immunoregulation of MSC. This review discusses the current understandings for the role of miR-155 in MSC.

  10. Advances in cryopreservation of spermatogonial stem cells and restoration of male fertility.

    PubMed

    Aliakbari, Fereshte; Yazdekhasti, Hosein; Abbasi, Mehdi; Hajian Monfared, Mahdieh; Baazm, Maryam

    2016-02-01

    Spermatogenesis is a highly complicated process which initiated by spermatogonial stem cells (SSCs). SSCs are the only cell type that can restore fertility in infertile recipient after SSCs transplantation. SSCs damage during cancer diagnosis and therapy and their depletion may be cause of male infertility in cancer survivors. In this review, used experimental methods regarding SSCs and testis tissue cryopreservation have been reviewed with a special focus on animal models and human which have generated the majority of data about SSCs and the cryopreservation process.

  11. Advanced Cell Technology, Inc.

    PubMed

    Caldwell, William M

    2007-03-01

    Advanced Cell Technology, Inc. (OTCBB: ACTC) is a biotechnology company applying novel human embryonic stem cell technologies in the emerging field of regenerative medicine. We believe that regenerative medicine has the potential to revolutionize the field by enabling scientists to produce human cells of any kind for use in a wide array of therapies.

  12. Donor Natural Killer Cells After Donor Stem Cell Transplant in Treating Patients With Advanced Cancer

    ClinicalTrials.gov

    2013-02-18

    Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Unspecified Adult Solid Tumor, Protocol Specific

  13. Dental mesenchymal stem cells.

    PubMed

    Sharpe, Paul T

    2016-07-01

    Mammalian teeth harbour mesenchymal stem cells (MSCs), which contribute to tooth growth and repair. These dental MSCs possess many in vitro features of bone marrow-derived MSCs, including clonogenicity, expression of certain markers, and following stimulation, differentiation into cells that have the characteristics of osteoblasts, chondrocytes and adipocytes. Teeth and their support tissues provide not only an easily accessible source of MSCs but also a tractable model system to study their function and properties in vivo In addition, the accessibility of teeth together with their clinical relevance provides a valuable opportunity to test stem cell-based treatments for dental disorders. This Review outlines some recent discoveries in dental MSC function and behaviour and discusses how these and other advances are paving the way for the development of new biologically based dental therapies. PMID:27381225

  14. Advances in umbilical cord blood stem cell expansion and clinical translation.

    PubMed

    Pineault, Nicolas; Abu-Khader, Ahmad

    2015-07-01

    Umbilical cord blood (CB) is a rich source of hematopoietic stem cells (HSCs) with important applications in allogeneic stem cell transplantation. However, the low numbers of hematopoietic stem and progenitor cells (HSPCs) in banked units remain a major limitation. Protocols developed for HSPC expansion ex vivo or to improve HSPC homing to the marrow represent solutions to overcome this shortcoming. In recent decades, wide arrays of functionally divergent approaches were developed for the amplification of HSPCs. These include optimization of cytokine cocktails, coculture systems, small molecules, and delivery systems for HSPC-expansion genes. Herein, we review past and current strategies, focusing on studies that characterize the contribution of expanded CB HSPC to short- and long-term engraftment in transplantation models or in clinical trials. Also discussed are homing effectors used to promote engraftment. In summary, these studies underscore that early-acting cytokines alone can expand HSPC with short-term engraftment activity, but that robust expansion of HSPCs with long-term engraftment necessitates the synergistic action of multiple HSC-expansion agonists. In support of this, early clinical trials based on cytokine-driven HSPC-expansion protocols delivered disappointing results, whereas recent trials based on the synergistic action of cytokines and HSPC-expansion agonists reported significant improvements in engraftment and therapeutic outcomes. Conversely, molecules that enhance homing of HSPC may represent a complementary approach to improve and perhaps accelerate engraftment. Optimization of the next generation of HSPC-expansion and priming strategies should support a paradigm shift in CB transplantation in which smaller, better matched units may preferentially be used.

  15. Application of biomaterials to advance induced pluripotent stem cell research and therapy

    PubMed Central

    Tong, Zhixiang; Solanki, Aniruddh; Hamilos, Allison; Levy, Oren; Wen, Kendall; Yin, Xiaolei; Karp, Jeffrey M

    2015-01-01

    Derived from any somatic cell type and possessing unlimited self-renewal and differentiation potential, induced pluripotent stem cells (iPSCs) are poised to revolutionize stem cell biology and regenerative medicine research, bringing unprecedented opportunities for treating debilitating human diseases. To overcome the limitations associated with safety, efficiency, and scalability of traditional iPSC derivation, expansion, and differentiation protocols, biomaterials have recently been considered. Beyond addressing these limitations, the integration of biomaterials with existing iPSC culture platforms could offer additional opportunities to better probe the biology and control the behavior of iPSCs or their progeny in vitro and in vivo. Herein, we discuss the impact of biomaterials on the iPSC field, from derivation to tissue regeneration and modeling. Although still exploratory, we envision the emerging combination of biomaterials and iPSCs will be critical in the successful application of iPSCs and their progeny for research and clinical translation. PMID:25766254

  16. Application of biomaterials to advance induced pluripotent stem cell research and therapy

    PubMed Central

    Tong, Zhixiang; Solanki, Aniruddh; Hamilos, Allison; Levy, Oren; Wen, Kendall; Yin, Xiaolei; Karp, Jeffrey M

    2015-01-01

    Derived from any somatic cell type and possessing unlimited self-renewal and differentiation potential, induced pluripotent stem cells (iPSCs) are poised to revolutionize stem cell biology and regenerative medicine research, bringing unprecedented opportunities for treating debilitating human diseases. To overcome the limitations associated with safety, efficiency, and scalability of traditional iPSC derivation, expansion, and differentiation protocols, biomaterials have recently been considered. Beyond addressing these limitations, the integration of biomaterials with existing iPSC culture platforms could offer additional opportunities to better probe the biology and control the behavior of iPSCs or their progeny in vitro and in vivo. Herein, we discuss the impact of biomaterials on the iPSC field, from derivation to tissue regeneration and modeling. Although still exploratory, we envision the emerging combination of biomaterials and iPSCs will be critical in the successful application of iPSCs and their progeny for research and clinical translation. PMID:25766254

  17. Stem Cells, Redox Signaling, and Stem Cell Aging

    PubMed Central

    Liang, Raymond

    2014-01-01

    Abstract Significance: Functional stem cell decline has been postulated to result in loss of maintenance of tissue homeostasis leading to organismal decline and diseases of aging. Recent Advances: Recent findings implicate redox metabolism in the control of stem cell pool and stem cell aging. Although reactive oxygen species (ROS) are better known for their damaging properties to DNA, proteins and lipids, recent findings suggest that ROS may also be an integral physiological mediator of cellular signaling in primary cells. Critical Issues: Here we review recent published work on major signaling pathways and transcription factors that are regulated by ROS and mediate ROS regulation of stem cell fate. We will specifically focus on how alterations in this regulation may be implicated in disease and particularly in diseases of stem cell aging. In general, based on the work described here we propose a model in which ROS function as stem cell rheostat. Future Directions: Future work in elucidating how ROS control stem cell cycling, apoptotic machinery, and lineage determination should shed light on mechanisms whereby ROS may control stem cell aging. Antioxid. Redox Signal. 20, 1902–1916. PMID:24383555

  18. Bone regeneration and stem cells

    PubMed Central

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

    2011-01-01

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

  19. Introduction to stem cells and regenerative medicine.

    PubMed

    Kolios, George; Moodley, Yuben

    2013-01-01

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

  20. Stem cells: review and update.

    PubMed

    Sylvester, Karl G; Longaker, Michael T

    2004-01-01

    Regenerative medicine and emerging biotechnologies stand to revolutionize the practice of medicine. Advancements in stem cell biology, including embryonic and postnatal somatic stem cells, have made the prospect of tissue regeneration a potential clinical reality. Short of reproductive cloning, these same technologies, properly used, could allow for the creation of replacement tissue for the deficient host. To provide a concise review for surgeons on the current science and biology of stem cells, we surveyed the scientific literature, MEDLINE, and relevant political headlines that illuminate the stem cell discussion; the issues are summarized in this review. Building on this conceptual framework, the related issues of clinical promise and the political debate enveloping this emerging technology are examined. A basic understanding of stem cell biology is paramount to stay informed of this emerging technology and the national debate.

  1. Stem Cell Research.

    PubMed

    Trounson, Alan; Kolaja, Kyle; Petersen, Thomas; Weber, Klaus; McVean, Maralee; Funk, Kathleen A

    2015-01-01

    Stem cells have great potential in basic research and are being slowly integrated into toxicological research. This symposium provided an overview of the state of the field, stem cell models, described allogenic stem cell treatments and issues of immunogenicity associated with protein therapeutics, and tehn concentrated on stem cell uses in regenerative medicine focusing on lung and testing strategies on engineered tissues from a pathologist's perspective.

  2. Inducing pluripotency in vitro: recent advances and highlights in induced pluripotent stem cells generation and pluripotency reprogramming.

    PubMed

    Rony, I K; Baten, A; Bloomfield, J A; Islam, M E; Billah, M M; Islam, K D

    2015-04-01

    Induced pluripotent stem cells (iPSCs) are considered patient-specific counterparts of embryonic stem cells as they originate from somatic cells after forced expression of pluripotency reprogramming factors Oct4, Sox2, Klf4 and c-Myc. iPSCs offer unprecedented opportunity for personalized cell therapies in regenerative medicine. In recent years, iPSC technology has undergone substantial improvement to overcome slow and inefficient reprogramming protocols, and to ensure clinical-grade iPSCs and their functional derivatives. Recent developments in iPSC technology include better reprogramming methods employing novel delivery systems such as non-integrating viral and non-viral vectors, and characterization of alternative reprogramming factors. Concurrently, small chemical molecules (inhibitors of specific signalling or epigenetic regulators) have become crucial to iPSC reprogramming; they have the ability to replace putative reprogramming factors and boost reprogramming processes. Moreover, common dietary supplements, such as vitamin C and antioxidants, when introduced into reprogramming media, have been found to improve genomic and epigenomic profiles of iPSCs. In this article, we review the most recent advances in the iPSC field and potent application of iPSCs, in terms of cell therapy and tissue engineering.

  3. Information on Stem Cell Research

    MedlinePlus

    ... 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 ...

  4. Plant stem cell niches.

    PubMed

    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.

  5. Advances in the Treatment of Ischemic Diseases by Mesenchymal Stem Cells

    PubMed Central

    Li, Shujing; Wang, Xianyun; Li, Jing; Zhang, Jun; Zhang, Fan; Hu, Jie; Qi, Yixin; Yan, Baoyong; Li, Quanhai

    2016-01-01

    Ischemic diseases are a group of diseases, including ischemic cerebrovascular disease, ischemic cardiomyopathy (ICM), and diabetic foot as well as other diseases which are becoming a leading cause of morbidity and mortality in the whole world. Mesenchymal stem cells (MSCs) have been used to treat a variety of ischemic diseases in animal models and clinical trials. Lots of recent publications demonstrated that MSCs therapy was safe and relieved symptoms in patients of ischemic disease. However, many factors could influence therapeutic efficacy including route of delivery, MSCs' survival and residential rate in vivo, timing of transplantation, particular microenvironment, and patient's clinical condition. In this review, the current status, therapeutic potential, and the detailed factors of MSCs-based therapeutics for ischemic cerebrovascular disease, ICM, and diabetic foot are presented and discussed. We think that MSCs transplantation would constitute an ideal option for patients with ischemic diseases. PMID:27293445

  6. Advances in the Treatment of Ischemic Diseases by Mesenchymal Stem Cells.

    PubMed

    Li, Shujing; Wang, Xianyun; Li, Jing; Zhang, Jun; Zhang, Fan; Hu, Jie; Qi, Yixin; Yan, Baoyong; Li, Quanhai

    2016-01-01

    Ischemic diseases are a group of diseases, including ischemic cerebrovascular disease, ischemic cardiomyopathy (ICM), and diabetic foot as well as other diseases which are becoming a leading cause of morbidity and mortality in the whole world. Mesenchymal stem cells (MSCs) have been used to treat a variety of ischemic diseases in animal models and clinical trials. Lots of recent publications demonstrated that MSCs therapy was safe and relieved symptoms in patients of ischemic disease. However, many factors could influence therapeutic efficacy including route of delivery, MSCs' survival and residential rate in vivo, timing of transplantation, particular microenvironment, and patient's clinical condition. In this review, the current status, therapeutic potential, and the detailed factors of MSCs-based therapeutics for ischemic cerebrovascular disease, ICM, and diabetic foot are presented and discussed. We think that MSCs transplantation would constitute an ideal option for patients with ischemic diseases. PMID:27293445

  7. Admixed human embryos and stem cells: legislative, ethical and scientific advances.

    PubMed

    Bahadur, G; Iqbal, M; Malik, S; Sanyal, A; Wafa, R; Noble, R

    2008-01-01

    This paper examines the regulatory framework currently governing the creation of animal-human hybrids and chimera embryos in stem cell research, and some of the ethical implications of such research. It discusses the findings of a recent government select committee that considered the topic. It considers the debate around the precise definition of a human embryo, and whether such hybrids therefore fall within the remit of the Human Fertilisation and Embryology Authority. It outlines the advantages of such hybrids, in lessening the need for human egg donors, as well as the moral objections to species boundary violation. It calls for an examination of the scientific benefits of such research to inform debate on the question, and argues for the need to take genuine account of the public's views on this matter.

  8. Advances in the Treatment of Ischemic Diseases by Mesenchymal Stem Cells.

    PubMed

    Li, Shujing; Wang, Xianyun; Li, Jing; Zhang, Jun; Zhang, Fan; Hu, Jie; Qi, Yixin; Yan, Baoyong; Li, Quanhai

    2016-01-01

    Ischemic diseases are a group of diseases, including ischemic cerebrovascular disease, ischemic cardiomyopathy (ICM), and diabetic foot as well as other diseases which are becoming a leading cause of morbidity and mortality in the whole world. Mesenchymal stem cells (MSCs) have been used to treat a variety of ischemic diseases in animal models and clinical trials. Lots of recent publications demonstrated that MSCs therapy was safe and relieved symptoms in patients of ischemic disease. However, many factors could influence therapeutic efficacy including route of delivery, MSCs' survival and residential rate in vivo, timing of transplantation, particular microenvironment, and patient's clinical condition. In this review, the current status, therapeutic potential, and the detailed factors of MSCs-based therapeutics for ischemic cerebrovascular disease, ICM, and diabetic foot are presented and discussed. We think that MSCs transplantation would constitute an ideal option for patients with ischemic diseases.

  9. [Advances in the research of treating refractory diabetic wounds with stem cells].

    PubMed

    Gong, Jiahong; Lu, Shuliang

    2014-12-01

    With the growth of aging society, China has become the country of population with the highest incidence of diabetes in the world. Diabetes leads to pathological changes in vascular and nervous system, rendering the diabetic skin fragile and hard to heal if wounded; in the end most diabetic wounds tend to become chronic skin ulcers. The refractory diabetic wound is the result of various endogenous and exogenous factors. It is a quite complicated pathophysiologic event which lacks an effective and specific therapeutic method in clinic. The use of stem cells could be a new approach of treating diabetic chronic wounds since they have a potential ability of self-renovation and multi-directional differentiation which will promote angiogenesis and wound healing process, thus be beneficial in the care of ischemia diseases of the lower limb. This article reviews basic theory of treating diabetic wound and the changes in microenvironment, and prompts many successful cases in curing refractory diabetic wounds.

  10. Stem Cell Information: Glossary

    MedlinePlus

    ... based therapies Cell culture Cell division Chromosome Clone Cloning Cord blood stem cells Culture medium Differentiation Directed ... Pluripotent Polar body Preimplantation Proliferation Regenerative medicine Reproductive cloning Signals Somatic cell Somatic cell nuclear transfer (SCNT) ...

  11. Patient-Specific Age: The Other Side of the Coin in Advanced Mesenchymal Stem Cell Therapy

    PubMed Central

    Schimke, Magdalena M.; Marozin, Sabrina; Lepperdinger, Günter

    2015-01-01

    Multipotential mesenchymal stromal cells (MSC) are present as a rare subpopulation within any type of stroma in the body of higher animals. Prominently, MSC have been recognized to reside in perivascular locations, supposedly maintaining blood vessel integrity. During tissue damage and injury, MSC/pericytes become activated, evade from their perivascular niche and are thus assumed to support wound healing and tissue regeneration. In vitro MSC exhibit demonstrated capabilities to differentiate into a wide variety of tissue cell types. Hence, many MSC-based therapeutic approaches have been performed to address bone, cartilage, or heart regeneration. Furthermore, prominent studies showed efficacy of ex vivo expanded MSC to countervail graft-vs.-host-disease. Therefore, additional fields of application are presently conceived, in which MSC-based therapies potentially unfold beneficial effects, such as amelioration of non-healing conditions after tendon or spinal cord injury, as well as neuropathies. Working along these lines, MSC-based scientific research has been forged ahead to prominently occupy the clinical stage. Aging is to a great deal stochastic by nature bringing forth changes in an individual fashion. Yet, is aging of stem cells or/and their corresponding niche considered a determining factor for outcome and success of clinical therapies? PMID:26696897

  12. The regulatory niche of intestinal stem cells.

    PubMed

    Sailaja, Badi Sri; He, Xi C; Li, Linheng

    2016-09-01

    The niche constitutes a unique category of cells that support the microenvironment for the maintenance and self-renewal of stem cells. Intestinal stem cells reside at the base of the crypt, which contains adjacent epithelial cells, stromal cells and smooth muscle cells, and soluble and cell-associated growth and differentiation factors. We summarize here recent advances in our understanding of the crucial role of the niche in regulating stem cells. The stem cell niche maintains a balance among quiescence, proliferation and regeneration of intestinal stem cells after injury. Mesenchymal cells, Paneth cells, immune cells, endothelial cells and neural cells are important regulatory components that secrete niche ligands, growth factors and cytokines. Intestinal homeostasis is regulated by niche signalling pathways, specifically Wnt, bone morphogenetic protein, Notch and epidermal growth factor. These insights into the regulatory stem cell niche during homeostasis and post-injury regeneration offer the potential to accelerate development of therapies for intestine-related disorders.

  13. The regulatory niche of intestinal stem cells.

    PubMed

    Sailaja, Badi Sri; He, Xi C; Li, Linheng

    2016-09-01

    The niche constitutes a unique category of cells that support the microenvironment for the maintenance and self-renewal of stem cells. Intestinal stem cells reside at the base of the crypt, which contains adjacent epithelial cells, stromal cells and smooth muscle cells, and soluble and cell-associated growth and differentiation factors. We summarize here recent advances in our understanding of the crucial role of the niche in regulating stem cells. The stem cell niche maintains a balance among quiescence, proliferation and regeneration of intestinal stem cells after injury. Mesenchymal cells, Paneth cells, immune cells, endothelial cells and neural cells are important regulatory components that secrete niche ligands, growth factors and cytokines. Intestinal homeostasis is regulated by niche signalling pathways, specifically Wnt, bone morphogenetic protein, Notch and epidermal growth factor. These insights into the regulatory stem cell niche during homeostasis and post-injury regeneration offer the potential to accelerate development of therapies for intestine-related disorders. PMID:27060879

  14. Recent advances in animal and human pluripotent stem cell modeling of cardiac laminopathy.

    PubMed

    Lee, Yee-Ki; Jiang, Yu; Ran, Xin-Ru; Lau, Yee-Man; Ng, Kwong-Man; Lai, Wing-Hon Kevin; Siu, Chung-Wah; Tse, Hung-Fat

    2016-01-01

    Laminopathy is a disease closely related to deficiency of the nuclear matrix protein lamin A/C or failure in prelamin A processing, and leads to accumulation of the misfold protein causing progeria. The resultant disrupted lamin function is highly associated with abnormal nuclear architecture, cell senescence, apoptosis, and unstable genome integrity. To date, the effects of loss in nuclear integrity on the susceptible organ, striated muscle, have been commonly associated with muscular dystrophy, dilated cardiac myopathy (DCM), and conduction defeats, but have not been studied intensively. In this review, we aim to summarize recent breakthroughs in an in vivo laminopathy model and in vitro study using patient-specific human induced pluripotent stem cells (iPSCs) that reproduce the pathophysiological phenotype for further drug screening. We describe several in-vivo transgenic mouse models to elucidate the effects of Lmna H222P, N195K mutations, and LMNA knockout on cardiac function, in terms of hemodynamic and electrical signal propagation; certain strategies targeted on stress-related MAPK are mentioned. We will also discuss human iPSC cardiomyocytes serving as a platform to reveal the underlying mechanisms, such as the altered mechanical sensation in electrical coupling of the heart conduction system and ion channel alternation in relation to altered nuclear architecture, and furthermore to enable screening of drugs that can attenuate this cardiac premature aging phenotype by inhibition of prelamin misfolding and oxidative stress, and also enhancement of autophagy protein clearance and cardiac-protective microRNA. PMID:27649756

  15. Recent advances in animal and human pluripotent stem cell modeling of cardiac laminopathy.

    PubMed

    Lee, Yee-Ki; Jiang, Yu; Ran, Xin-Ru; Lau, Yee-Man; Ng, Kwong-Man; Lai, Wing-Hon Kevin; Siu, Chung-Wah; Tse, Hung-Fat

    2016-09-20

    Laminopathy is a disease closely related to deficiency of the nuclear matrix protein lamin A/C or failure in prelamin A processing, and leads to accumulation of the misfold protein causing progeria. The resultant disrupted lamin function is highly associated with abnormal nuclear architecture, cell senescence, apoptosis, and unstable genome integrity. To date, the effects of loss in nuclear integrity on the susceptible organ, striated muscle, have been commonly associated with muscular dystrophy, dilated cardiac myopathy (DCM), and conduction defeats, but have not been studied intensively. In this review, we aim to summarize recent breakthroughs in an in vivo laminopathy model and in vitro study using patient-specific human induced pluripotent stem cells (iPSCs) that reproduce the pathophysiological phenotype for further drug screening. We describe several in-vivo transgenic mouse models to elucidate the effects of Lmna H222P, N195K mutations, and LMNA knockout on cardiac function, in terms of hemodynamic and electrical signal propagation; certain strategies targeted on stress-related MAPK are mentioned. We will also discuss human iPSC cardiomyocytes serving as a platform to reveal the underlying mechanisms, such as the altered mechanical sensation in electrical coupling of the heart conduction system and ion channel alternation in relation to altered nuclear architecture, and furthermore to enable screening of drugs that can attenuate this cardiac premature aging phenotype by inhibition of prelamin misfolding and oxidative stress, and also enhancement of autophagy protein clearance and cardiac-protective microRNA.

  16. Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells.

    PubMed

    Singh, Jagdeep K; Simões, Bruno M; Howell, Sacha J; Farnie, Gillian; Clarke, Robert B

    2013-01-01

    Breast cancer stem-like cells (CSCs) are an important therapeutic target as they are purported to be responsible for tumor initiation, maintenance, metastases, and disease recurrence. Interleukin-8 (IL-8) is upregulated in breast cancer compared with normal breast tissue and is associated with poor prognosis. IL-8 is reported to promote breast cancer progression by increasing cell invasion, angiogenesis, and metastases and is upregulated in HER2-positive cancers. Recently, we and others have established that IL-8 via its cognate receptors, CXCR1 and CXCR2, is also involved in regulating breast CSC activity. Our work demonstrates that in metastatic breast CSCs, CXCR1/2 signals via transactivation of HER2. Given the importance of HER2 in breast cancer and in regulating CSC activity, a pathway driving the activation of these receptors would have important biological and clinical consequences, especially in tumors that express high levels of IL-8 and other CXCR1/2-activating ligands. Here, we review the IL-8 signaling pathway and the role of HER2 in maintaining an IL-8 inflammatory loop and discuss the potential of combining CXCR1/2 inhibitors with other treatments such as HER2-targeted therapy as a novel approach to eliminate CSCs and improve patient survival.

  17. Signaling involved in stem cell reprogramming and differentiation

    PubMed Central

    Tanabe, Shihori

    2015-01-01

    Stem cell differentiation is regulated by multiple signaling events. Recent technical advances have revealed that differentiated cells can be reprogrammed into stem cells. The signals involved in stem cell programming are of major interest in stem cell research. The signaling mechanisms involved in regulating stem cell reprogramming and differentiation are the subject of intense study in the field of life sciences. In this review, the molecular interactions and signaling pathways related to stem cell differentiation are discussed. PMID:26328015

  18. Stem cells and repair of lung injuries

    PubMed Central

    Neuringer, Isabel P; Randell, Scott H

    2004-01-01

    Fueled by the promise of regenerative medicine, currently there is unprecedented interest in stem cells. Furthermore, there have been revolutionary, but somewhat controversial, advances in our understanding of stem cell biology. Stem cells likely play key roles in the repair of diverse lung injuries. However, due to very low rates of cellular proliferation in vivo in the normal steady state, cellular and architectural complexity of the respiratory tract, and the lack of an intensive research effort, lung stem cells remain poorly understood compared to those in other major organ systems. In the present review, we concisely explore the conceptual framework of stem cell biology and recent advances pertinent to the lungs. We illustrate lung diseases in which manipulation of stem cells may be physiologically significant and highlight the challenges facing stem cell-related therapy in the lung. PMID:15285789

  19. Stem cell technology for neurodegenerative diseases.

    PubMed

    Lunn, J Simon; Sakowski, Stacey A; Hur, Junguk; Feldman, Eva L

    2011-09-01

    Over the past 20 years, stem cell technologies have become an increasingly attractive option to investigate and treat neurodegenerative diseases. In the current review, we discuss the process of extending basic stem cell research into translational therapies for patients suffering from neurodegenerative diseases. We begin with a discussion of the burden of these diseases on society, emphasizing the need for increased attention toward advancing stem cell therapies. We then explain the various types of stem cells utilized in neurodegenerative disease research, and outline important issues to consider in the transition of stem cell therapy from bench to bedside. Finally, we detail the current progress regarding the applications of stem cell therapies to specific neurodegenerative diseases, focusing on Parkinson disease, Huntington disease, Alzheimer disease, amyotrophic lateral sclerosis, and spinal muscular atrophy. With a greater understanding of the capacity of stem cell technologies, there is growing public hope that stem cell therapies will continue to progress into realistic and efficacious treatments for neurodegenerative diseases.

  20. Delivery of Differentiation Factors by Mesoporous Silica Particles Assists Advanced Differentiation of Transplanted Murine Embryonic Stem Cells

    PubMed Central

    Kozhevnikova, Mariya; König, Niclas; Zhou, Chunfang; Leao, Richardson; Knöpfel, Thomas; Pankratova, Stanislava; Trolle, Carl; Berezin, Vladimir; Bock, Elisabeth; Aldskogius, Håkan

    2013-01-01

    Stem cell transplantation holds great hope for the replacement of damaged cells in the nervous system. However, poor long-term survival after transplantation and insufficiently robust differentiation of stem cells into specialized cell types in vivo remain major obstacles for clinical application. Here, we report the development of a novel technological approach for the local delivery of exogenous trophic factor mimetics to transplanted cells using specifically designed silica nanoporous particles. We demonstrated that delivering Cintrofin and Gliafin, established peptide mimetics of the ciliary neurotrophic factor and glial cell line-derived neurotrophic factor, respectively, with these particles enabled not only robust functional differentiation of motor neurons from transplanted embryonic stem cells but also their long-term survival in vivo. We propose that the delivery of growth factors by mesoporous nanoparticles is a potentially versatile and widely applicable strategy for efficient differentiation and functional integration of stem cell derivatives upon transplantation. PMID:24089415

  1. Stem cells sources for intervertebral disc regeneration.

    PubMed

    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.

  2. Stem cells sources for intervertebral disc regeneration

    PubMed Central

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-01-01

    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

  3. Stem cells sources for intervertebral disc regeneration.

    PubMed

    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

  4. Advances in conditioning regimens for older adults undergoing allogeneic stem cell transplantation to treat hematologic malignancies.

    PubMed

    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.

  5. Hematopoietic stem and progenitor cell harvesting: technical advances and clinical utility

    PubMed Central

    Hequet, Olivier

    2015-01-01

    Hematopoietic stem and progenitor cell (HSPC) transplantations require prior harvesting of allogeneic or autologous HSPCs. HSPCs are usually present in bone marrow (BM) during the entire life, in cord blood (CB) at birth, or in peripheral blood (PB) under particular circumstances. HSPCs were first harvested in BM and later in CB and PB, as studies showed interesting features of such grafts. All harvesting methods were in use throughout the years, except BM harvesting for HSPC autologous transplantation, which was replaced by PB harvesting. BM, CB, and PB harvesting methods have been developed, and materials and devices technically improved to increase the number of HSPCs harvested. In parallel, knowing the features of the donors or patients associated with successful numbers of HSPCs allows the adaptation of appropriate harvesting methods. Moreover, it is important to ensure the safety of donors or patients while harvesting. This review describes the methods used for harvesting based on recent studies or developments around these methods, and more particularly, the means developed to increase the numbers of HSPCs harvested in each method. It also explains briefly the influence of technical improvements in HSPC harvesting on potential changes in HSPC graft composition. PMID:25733943

  6. Stem cells and reproduction

    PubMed Central

    Du, Hongling; Taylor, Hugh S.

    2011-01-01

    Purpose of review To review the latest developments in reproductive tract stem cell biology. Recent findings In 2004, two studies indicated that ovaries contain stem cells which form oocytes in adults and that can be cultured in vitro into mature oocytes. A live birth after orthotopic transplantation of cyropreserved ovarian tissue in a woman whose ovaries were damaged by chemotherapy demonstrates the clinical potential of these cells. In the same year, another study provided novel evidence of endometrial regeneration by stem cells in women who received bone marrow transplants. This finding has potential for the use in treatment of uterine disorders. It also supports a new theory for the cause of endometriosis, which may have its origin in ectopic transdifferentiation of stem cells. Several recent studies have demonstrated that fetal cells enter the maternal circulation and generate microchimerism in the mother. The uterus is a dynamic organ permeable to fetal stem cells, capable of transdifferentiation and an end organ in which bone marrow stem cells may differentiate. Finally stem cell transformation can be an underlying cause of ovarian cancer. Summary Whereas we are just beginning to understand stem cells, the potential implications of stem cells to reproductive biology and medicine are apparent. PMID:20305558

  7. Stem cells in urology.

    PubMed

    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.

  8. Stem cells - biological update and cell therapy progress.

    PubMed

    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.

  9. Vascular Smooth Muscle Cells From Hypertensive Patient-Derived Induced Pluripotent Stem Cells to Advance Hypertension Pharmacogenomics

    PubMed Central

    Biel, Nikolett M.; Santostefano, Katherine E.; DiVita, Bayli B.; El Rouby, Nihal; Carrasquilla, Santiago D.; Simmons, Chelsey; Nakanishi, Mahito; Cooper-DeHoff, Rhonda M.; Johnson, Julie A.

    2015-01-01

    Studies in hypertension (HTN) pharmacogenomics seek to identify genetic sources of variable antihypertensive drug response. Genetic association studies have detected single-nucleotide polymorphisms (SNPs) that link to drug responses; however, to understand mechanisms underlying how genetic traits alter drug responses, a biological interface is needed. Patient-derived induced pluripotent stem cells (iPSCs) provide a potential source for studying otherwise inaccessible tissues that may be important to antihypertensive drug response. The present study established multiple iPSC lines from an HTN pharmacogenomics cohort. We demonstrated that established HTN iPSCs can robustly and reproducibly differentiate into functional vascular smooth muscle cells (VSMCs), a cell type most relevant to vasculature tone control. Moreover, a sensitive traction force microscopy assay demonstrated that iPSC-derived VSMCs show a quantitative contractile response on physiological stimulus of endothelin-1. Furthermore, the inflammatory chemokine tumor necrosis factor α induced a typical VSMC response in iPSC-derived VSMCs. These studies pave the way for a large research initiative to decode biological significance of identified SNPs in hypertension pharmacogenomics. Significance Treatment of hypertension remains suboptimal, and a pharmacogenomics approach seeks to identify genetic biomarkers that could be used to guide treatment decisions; however, it is important to understand the biological underpinnings of genetic associations. Mouse models do not accurately recapitulate individual patient responses based on their genetics, and hypertension-relevant cells are difficult to obtain from patients. Induced pluripotent stem cell (iPSC) technology provides a great interface to bring patient cells with their genomic data into the laboratory and to study hypertensive responses. As an initial step, the present study established an iPSC bank from patients with primary hypertension and demonstrated

  10. Cell motion predicts human epidermal stemness

    PubMed Central

    Toki, Fujio; Tate, Sota; Imai, Matome; Matsushita, Natsuki; Shiraishi, Ken; Sayama, Koji; Toki, Hiroshi; Higashiyama, Shigeki

    2015-01-01

    Image-based identification of cultured stem cells and noninvasive evaluation of their proliferative capacity advance cell therapy and stem cell research. Here we demonstrate that human keratinocyte stem cells can be identified in situ by analyzing cell motion during their cultivation. Modeling experiments suggested that the clonal type of cultured human clonogenic keratinocytes can be efficiently determined by analysis of early cell movement. Image analysis experiments demonstrated that keratinocyte stem cells indeed display a unique rotational movement that can be identified as early as the two-cell stage colony. We also demonstrate that α6 integrin is required for both rotational and collective cell motion. Our experiments provide, for the first time, strong evidence that cell motion and epidermal stemness are linked. We conclude that early identification of human keratinocyte stem cells by image analysis of cell movement is a valid parameter for quality control of cultured keratinocytes for transplantation. PMID:25897083

  11. Brain tumor stem cells.

    PubMed

    Palm, Thomas; Schwamborn, Jens C

    2010-06-01

    Since the end of the 'no-new-neuron' theory, emerging evidence from multiple studies has supported the existence of stem cells in neurogenic areas of the adult brain. Along with this discovery, neural stem cells became candidate cells being at the origin of brain tumors. In fact, it has been demonstrated that molecular mechanisms controlling self-renewal and differentiation are shared between brain tumor stem cells and neural stem cells and that corruption of genes implicated in these pathways can direct tumor growth. In this regard, future anticancer approaches could be inspired by uncovering such redundancies and setting up treatments leading to exhaustion of the cancer stem cell pool. However, deleterious effects on (normal) neural stem cells should be minimized. Such therapeutic models underline the importance to study the cellular mechanisms implicated in fate decisions of neural stem cells and the oncogenic derivation of adult brain cells. In this review, we discuss the putative origins of brain tumor stem cells and their possible implications on future therapies.

  12. Fish stem cell cultures.

    PubMed

    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. Stem cells in dermatology.

    PubMed

    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.

  14. SL-401 and SL-501, targeted therapeutics directed at the interleukin-3 receptor, inhibit the growth of leukaemic cells and stem cells in advanced phase chronic myeloid leukaemia.

    PubMed

    Frolova, Olga; Benito, Juliana; Brooks, Chris; Wang, Rui-Yu; Korchin, Borys; Rowinsky, Eric K; Cortes, Jorge; Kantarjian, Hagop; Andreeff, Michael; Frankel, Arthur E; Konopleva, Marina

    2014-09-01

    While imatinib and other tyrosine kinase inhibitors (TKIs) are highly efficacious in the treatment of chronic myeloid leukaemia (CML), some patients become refractory to these therapies. After confirming that interleukin-3 receptor (IL3R, CD123) is highly expressed on CD34(+) /CD38(-) BCR-ABL1(+) CML stem cells, we investigated whether targeting IL3R with diphtheria toxin (DT)-IL3 fusion proteins SL-401 (DT388 -IL3) and SL-501 (DT388 -IL3[K116W]) could eradicate these stem cells. SL-401 and SL-501 inhibited cell growth and induced apoptosis in the KBM5 cell line and its TKI-resistant KBM5-STI subline. Combinations of imatinib with these agents increased apoptosis in KBM5 and in primary CML cells. In six primary CML samples, including CML cells harbouring the ABL1 T315I mutation, SL-401 and SL-501 decreased the absolute numbers of viable CD34(+) /CD38(-) /CD123(+) CML progenitor cells by inducing apoptosis. IL3-targeting agents reduced clonogenic growth and diminished the fraction of primitive long-term culture-initiating cells in samples from patients with advanced phase CML that were resistant to TKIs or harboured an ABL1 mutation. Survival was also extended in a mouse model of primary TKI-resistant CML blast crisis. These data suggest that the DT-IL3 fusion proteins, SL-401 and SL-501, deplete CML stem cells and may increase the effectiveness of current CML treatment, which principally targets tumour bulk.

  15. Stem Cell Transplants (For Teens)

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants Print ... Does it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  16. Stem cells in cardiac repair.

    PubMed

    Henning, Robert J

    2011-01-01

    Myocardial infarction is the leading cause of death among people in industrialized nations. Although the heart has some ability to regenerate after infarction, myocardial restoration is inadequate. Consequently, investigators are currently exploring the use of human embryonic stem cells (hESCs), skeletal myoblasts and adult bone marrow stem cells to limit infarct size. hESCs are pluripotent cells that can regenerate myocardium in infarcted hearts, attenuate heart remodeling and contribute to left ventricle (LV) systolic force development. Since hESCs can form heart teratomas, investigators are differentiating hESCs toward cardiac progenitor cells prior to transplantation into hearts. Large quantities of hESCs cardiac progenitor cells, however, must be generated, immune rejection must be prevented and grafts must survive over the long term to significantly improve myocardial performance. Transplanted autologous skeletal myoblasts can survive in infarcted myocardium in small numbers, proliferate, differentiate into skeletal myofibers and increase the LV ejection fraction. These cells, however, do not form electromechanical connections with host cardiomyocytes. Consequently, electrical re-entry can occur and cause cardiac arrhythmias. Autologous bone marrow mononuclear cells contain hematopoietic and mesenchymal stem cells. In several meta-analyses, patients with coronary disease who received autologous bone marrow cells by intracoronary injection show significant 3.7% (range: 1.9-5.4%) increases in LV ejection fraction, decreases in LV end-systolic volume of -4.8 ml (range: -1.4 to -8.2 ml) and reductions in infarct size of 5.5% (-1.9 to -9.1%), without experiencing arrhythmias. Bone marrow cells appear to release biologically active factors that limit myocardial damage. Unfortunately, bone marrow cells from patients with chronic diseases propagate poorly and can die prematurely. Substantial challenges must be addressed and resolved to advance the use of stem cells

  17. Autophagy in stem cells

    PubMed Central

    Guan, Jun-Lin; Simon, Anna Katharina; Prescott, Mark; Menendez, Javier A.; Liu, Fei; Wang, Fen; Wang, Chenran; Wolvetang, Ernst; Vazquez-Martin, Alejandro; Zhang, Jue

    2013-01-01

    Autophagy is a highly conserved cellular process by which cytoplasmic components are sequestered in autophagosomes and delivered to lysosomes for degradation. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis as well as remodeling during normal development, and dysfunctions in autophagy have been associated with a variety of pathologies including cancer, inflammatory bowel disease and neurodegenerative disease. Stem cells are unique in their ability to self-renew and differentiate into various cells in the body, which are important in development, tissue renewal and a range of disease processes. Therefore, it is predicted that autophagy would be crucial for the quality control mechanisms and maintenance of cellular homeostasis in various stem cells given their relatively long life in the organisms. In contrast to the extensive body of knowledge available for somatic cells, the role of autophagy in the maintenance and function of stem cells is only beginning to be revealed as a result of recent studies. Here we provide a comprehensive review of the current understanding of the mechanisms and regulation of autophagy in embryonic stem cells, several tissue stem cells (particularly hematopoietic stem cells), as well as a number of cancer stem cells. We discuss how recent studies of different knockout mice models have defined the roles of various autophagy genes and related pathways in the regulation of the maintenance, expansion and differentiation of various stem cells. We also highlight the many unanswered questions that will help to drive further research at the intersection of autophagy and stem cell biology in the near future. PMID:23486312

  18. Stem cell transplantation for neuroblastoma.

    PubMed

    Fish, J D; Grupp, S A

    2008-01-01

    High-risk neuroblastoma is a childhood malignancy with a poor prognosis. Gradual improvements in survival have correlated with therapeutic intensity, and the ability to harvest, process and store autologous hematopoietic stem cells has allowed for dose intensification beyond marrow tolerance. The use of high-dose chemotherapy with autologous hematopoietic stem cell rescue in consolidation has resulted in improvements in survival, although further advances are still needed. Newer approaches to SCT and supportive care, most notably the transition to PBSC, have resulted in further improvement in survival and decreases in treatment-related mortality. Research into experimental approaches to hematopoietic SCT is ongoing.

  19. Effect of advanced oxidation protein products on the proliferation and osteogenic differentiation of rat mesenchymal stem cells.

    PubMed

    Sun, Nan; Yang, Li; Li, Yingbin; Zhang, Hua; Chen, Hong; Liu, Duan; Li, Qingnan; Cai, Dehong

    2013-08-01

    Advanced oxidation protein products (AOPPs) as a novel marker of oxidative stress, are involved in a variety of diseases, including osteoporosis. Although a number of studies have shown the possible functions of AOPPs in biological processes, little is known about the role of AOPPs in the pathogenesis of osteoporosis. In this study, we aimed to investigate the effect of AOPPs on the proliferation and osteogenic differentiation of rat mesenchymal stem cells (MSCs). MSCs, isolated from bone marrow, were cultured in the absence or presence of AOPPs (50, 100, 200 and 400 mg/ml). MTT assay was used to determine the proliferative ability of the cells. Alkaline phosphatase (ALP) activity, the mRNA expression of ALP and collagen I and bone nodule formation were detected to assess osteogenic differentiation. Reactive oxygen species (ROS) generation was analyzed with the probe 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The expression of receptor of advanced glycation end-products (RAGE) at the mRNA and protein level was detected by real-time PCR and western blot analysis, respectively. Compared with the control group, AOPPs inhibited MSC proliferation in a dose- and time-dependent manner. Moreover, AOPPs induced a significant reduction in ALP activity, as well as a decrease in ALP and collagen I mRNA levels in the MSCs; bone nodule formation was also inhibited. Furthermore, AOPPs increased ROS generation in the MSCs, and upregulated the expression of RAGE at the mRNA and protein level. These results suggest that AOPPs inhibit the proliferation and osteogenic differentiation of MSCs, possibly through the AOPPs-RAGE-ROS pathway; this may be an important mechanism in the development of osteoporosis.

  20. Stem cells and kidney regeneration.

    PubMed

    Chou, Yu-Hsiang; Pan, Szu-Yu; Yang, Chian-Huei; Lin, Shuei-Liong

    2014-04-01

    Kidney disease is an escalating burden all over the world. In addition to preventing kidney injury, regenerating damaged renal tissue is as important as to retard the progression of chronic kidney disease to end stage renal disease. Although the kidney is a delicate organ and has only limited regenerative capacity compared to the other organs, an increasing understanding of renal development and renal reprogramming has kindled the prospects of regenerative options for kidney disease. Here, we will review the advances in the kidney regeneration including the manipulation of renal tubular cells, fibroblasts, endothelial cells, and macrophages in renal disease. Several types of stem cells, such as bone marrow-derived cells, adipocyte-derived mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells are also applied for renal regeneration. Endogenous or lineage reprogrammed renal progenitor cells represent an attractive possibility for differentiation into multiple renal cell types. Angiogenesis can ameliorate hypoxia and renal fibrosis. Based on these studies and knowledge, we hope to innovate more reliable pharmacological or biotechnical methods for kidney regeneration medicine.

  1. SMOOTH MUSCLE STEM CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  2. Donor Peripheral Stem Cell Transplant in Treating Patients With Advanced Hematologic Cancer or Other Disorders

    ClinicalTrials.gov

    2016-09-16

    Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Precancerous/Nonmalignant Condition

  3. Infusing CD19-directed T cells to augment disease control in patients undergoing autologous hematopoietic stem-cell transplantation for advanced B-lymphoid malignancies.

    PubMed

    Kebriaei, Partow; Huls, Helen; Jena, Bipulendu; Munsell, Mark; Jackson, Rineka; Lee, Dean A; Hackett, Perry B; Rondon, Gabriela; Shpall, Elizabeth; Champlin, Richard E; Cooper, Laurence J N

    2012-05-01

    Limited curative treatment options exist for patients with advanced B-lymphoid malignancies, and new therapeutic approaches are needed to augment the efficacy of hematopoietic stem-cell transplantation (HSCT). Cellular therapies, such as adoptive transfer of T cells that are being evaluated to target malignant disease, use mechanisms independent of chemo- and radiotherapy with nonoverlapping toxicities. Gene therapy is employed to generate tumor-specific T cells, as specificity can be redirected through enforced expression of a chimeric antigen receptor (CAR) to achieve antigen recognition based on the specificity of a monoclonal antibody. By combining cell and gene therapies, we have opened a new Phase I protocol at the MD Anderson Cancer Center (Houston, TX) to examine the safety and feasibility of administering autologous genetically modified T cells expressing a CD19-specific CAR (capable of signaling through chimeric CD28 and CD3-ζ) into patients with high-risk B-lymphoid malignancies undergoing autologous HSCT. The T cells are genetically modified by nonviral gene transfer of the Sleeping Beauty system and CAR(+) T cells selectively propagated in a CAR-dependent manner on designer artificial antigen-presenting cells. The results of this study will lay the foundation for future protocols including CAR(+) T-cell infusions derived from allogeneic sources. PMID:22107246

  4. Infusing CD19-Directed T Cells to Augment Disease Control in Patients Undergoing Autologous Hematopoietic Stem-Cell Transplantation for Advanced B-Lymphoid Malignancies

    PubMed Central

    Kebriaei, Partow; Huls, Helen; Jena, Bipulendu; Munsell, Mark; Jackson, Rineka; Lee, Dean A.; Hackett, Perry B.; Rondon, Gabriela; Shpall, Elizabeth; Champlin, Richard E.

    2012-01-01

    Abstract Limited curative treatment options exist for patients with advanced B-lymphoid malignancies, and new therapeutic approaches are needed to augment the efficacy of hematopoietic stem-cell transplantation (HSCT). Cellular therapies, such as adoptive transfer of T cells that are being evaluated to target malignant disease, use mechanisms independent of chemo- and radiotherapy with nonoverlapping toxicities. Gene therapy is employed to generate tumor-specific T cells, as specificity can be redirected through enforced expression of a chimeric antigen receptor (CAR) to achieve antigen recognition based on the specificity of a monoclonal antibody. By combining cell and gene therapies, we have opened a new Phase I protocol at the MD Anderson Cancer Center (Houston, TX) to examine the safety and feasibility of administering autologous genetically modified T cells expressing a CD19-specific CAR (capable of signaling through chimeric CD28 and CD3-ζ) into patients with high-risk B-lymphoid malignancies undergoing autologous HSCT. The T cells are genetically modified by nonviral gene transfer of the Sleeping Beauty system and CAR+ T cells selectively propagated in a CAR-dependent manner on designer artificial antigen-presenting cells. The results of this study will lay the foundation for future protocols including CAR+ T-cell infusions derived from allogeneic sources. PMID:22107246

  5. Plant Stem Cells.

    PubMed

    Greb, Thomas; Lohmann, Jan U

    2016-09-12

    Among the trending topics in the life sciences, stem cells have received a fair share of attention in the public debate - mostly in connection with their potential for biomedical application and therapies. While the promise of organ regeneration and the end of cancer have captured our imagination, it has gone almost unnoticed that plant stem cells represent the ultimate origin of much of the food we eat, the oxygen we breathe, as well the fuels we burn. Thus, plant stem cells may be ranked among the most important cells for human well-being. Research by many labs in the last decades has uncovered a set of independent stem cell systems that fulfill the specialized needs of plant development and growth in four dimensions. Surprisingly, the cellular and molecular design of these systems is remarkably similar, even across diverse species. In some long-lived plants, such as trees, plant stem cells remain active over hundreds or even thousands of years, revealing the exquisite precision in the underlying control of proliferation, self-renewal and differentiation. In this minireview, we introduce the basic features of the three major plant stem cell systems building on these facts, highlight their modular design at the level of cellular layout and regulatory underpinnings and briefly compare them with their animal counterparts. PMID:27623267

  6. Stem cell niche engineering through droplet microfluidics.

    PubMed

    Allazetta, Simone; Lutolf, Matthias P

    2015-12-01

    Stem cells reside in complex niches in which their behaviour is tightly regulated by various biochemical and biophysical signals. In order to unveil some of the crucial stem cell-niche interactions and expedite the implementation of stem cells in clinical and pharmaceutical applications, in vitro methodologies are being developed to reconstruct key features of stem cell niches. Recently, droplet-based microfluidics has emerged as a promising strategy to build stem cell niche models in a miniaturized and highly precise fashion. This review highlights current advances in using droplet microfluidics in stem cell biology. We also discuss recent efforts in which microgel technology has been interfaced with high-throughput analyses to engender screening paradigms with an unparalleled potential for basic and applied biological studies.

  7. Fueling Hope: Stem Cells in Social Media.

    PubMed

    Robillard, Julie M; Cabral, Emanuel; Hennessey, Craig; Kwon, Brian K; Illes, Judy

    2015-08-01

    Social media is broadening opportunities to engage in discussions about biomedical advances such as stem cell research. However, little is known about how information pertaining to stem cells is disseminated on platforms such as Twitter. To fill this gap, we conducted a content analysis of tweets containing (i) a stem cell keyword, and (ii) a keyword related to either spinal cord injury (SCI) or Parkinson disease (PD). We found that the discussion about stem cells and SCI or PD revolves around different aspects of the research process. We also found that the tone of most tweets about stem cells is either positive or neutral. The findings contribute new knowledge about Twitter as a connecting platform for many voices and as a key tool for the dissemination of information about stem cells and disorders of the central nervous system.

  8. Aneuploidy in stem cells

    PubMed Central

    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 blueprint for the tissue to be generated, or worse, become at risk of adopting a malignant fate. In this review, we discuss the contribution of aneuploidy to healthy tissues and how aneuploidy can lead to disease. Furthermore, we review the differences between how somatic cells and stem cells respond to aneuploidy. PMID:27354891

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

    PubMed Central

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

    2016-01-01

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

  10. Dental pulp stem cells

    PubMed Central

    Ashri, Nahid Y.; Ajlan, Sumaiah 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 their relative accessibility and pleasant handling properties. The purpose of this article is to review the biological principles of periodontal tissue engineering, along with the challenges facing the development of a consistent and clinically relevant tissue regeneration platform. This article includes an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors. PMID:26620980

  11. Patenting human genes and stem cells.

    PubMed

    Martin-Rendon, Enca; Blake, Derek J

    2007-01-01

    Cell lines and genetically modified single cell organisms have been considered patentable subjects for the last two decades. However, despite the technical patentability of genes and stem cell lines, social and legal controversy concerning their 'ownership' has surrounded stem cell research in recent years. Some granted patents on stem cells with extremely broad claims are casting a shadow over the commercialization of these cells as therapeutics. However, in spite of those early patents, the number of patent applications related to stem cells is growing exponentially. Both embryonic and adult stem cells have the ability to differentiate into several cell lineages in an organism as a result of specific genetic programs that direct their commitment and cell fate. Genes that control the pluripotency of stem cells have been recently identified and the genetic manipulation of these cells is becoming more efficient with the advance of new technologies. This review summarizes some of the recent published patents on pluripotency genes, gene transfer into stem cells and genetic reprogramming and takes the hematopoietic and embryonic stem cell as model systems.

  12. Stem cells in microfluidics

    PubMed Central

    Wu, Huei-Wen; Lin, Chun-Che; Lee, Gwo-Bin

    2011-01-01

    Microfluidic techniques have been recently developed for cell-based assays. In microfluidic systems, the objective is for these microenvironments to mimic in vivo surroundings. With advantageous characteristics such as optical transparency and the capability for automating protocols, different types of cells can be cultured, screened, and monitored in real time to systematically investigate their morphology and functions under well-controlled microenvironments in response to various stimuli. Recently, the study of stem cells using microfluidic platforms has attracted considerable interest. Even though stem cells have been studied extensively using bench-top systems, an understanding of their behavior in in vivo-like microenvironments which stimulate cell proliferation and differentiation is still lacking. In this paper, recent cell studies using microfluidic systems are first introduced. The various miniature systems for cell culture, sorting and isolation, and stimulation are then systematically reviewed. The main focus of this review is on papers published in recent years studying stem cells by using microfluidic technology. This review aims to provide experts in microfluidics an overview of various microfluidic systems for stem cell research. PMID:21522491

  13. Stem Cell Research

    SciTech Connect

    Verfaillie, Catherine

    2009-01-23

    We have identified a population of primitive cells in normal human post-natal bone marrow that can, at the single cell level, differentiate in many ways and also proliferate extensively. These cells can differentiate in vitro into most mesodermal cell types (for example, bone cells, and others), as well as cells into cells of the nervous system. The finding that stem cells exist in post-natal tissues with previously unknown proliferation and differentiation potential opens up the possibility of using them to treat a host of degenerative, traumatic or congenital diseases.

  14. Stem Cell Research

    SciTech Connect

    Verfaillie, Catherine

    2002-01-23

    We have identified a population of primitive cells in normal human post-natal bone marrow that can, at the single cell level, differentiate in many ways and also proliferate extensively. These cells can differentiate in vitro into most mesodermal cell types (for example, bone cells, and others), as well as cells into cells of the nervous system. The finding that stem cells exist in post-natal tissues with previously unknown proliferation and differentiation potential opens up the possibility of using them to treat a host of degenerative, traumatic or congenital diseases.

  15. Advancing practical usage of microtechnology: a study of the functional consequences of dielectrophoresis on neural stem cells

    PubMed Central

    Lu, Jente; Barrios, Chesca A.; Dickson, Amanda R.; Nourse, Jamison L.; Lee, Abraham P.; Flanagan, Lisa A.

    2012-01-01

    The integration of microscale engineering, microfluidics, and AC electrokinetics such as dielectrophoresis has generated novel microsystems that enable quantitative analysis of cellular phenotype, function, and physiology. These systems are increasingly being used to assess diverse cell types, such as stem cells, so it becomes critical to thoroughly evaluate whether the systems themselves impact cell function. For example, engineered microsystems have been utilized to investigate neural stem/progenitor cells (NSPCs), which are of interest due to their potential to treat CNS disease and injury. Analysis by dielectrophoresis (DEP) microsystems determined that unlabeled NSPCs with distinct fate potential have previously unrecognized distinguishing electrophysiological characteristics, suggesting that NSPCs could be isolated by DEP microsystems without the use of cell type specific labels. To gauge the potential impact of DEP sorting on NSPCs, we investigated whether electric field exposure of varying times affected survival, proliferation, or fate potential of NSPCs in suspension. We found short-term DEP exposure (1 min or less) had no effect on NSPC survival, proliferation, or fate potential revealed by differentiation. Moreover, NSPC proliferation (measured by DNA synthesis and cell cycle kinetics) and fate potential were not altered by any length of DEP exposure (up to 30 min). However, lengthy exposure (> 5 min) to frequencies near the crossover frequency (50–100 kHz) led to decreased survival of NSPCs (maximum ~30% cell loss after 30 min). Based on experimental observations and mathematical simulations of cells in suspension, we find that frequencies near the crossover frequency generate an induced transmembrane potential that results in cell swelling and rupture. This is in contrast to the case for adherent cells since negative DEP frequencies lower than the crossover frequency generate the highest induced transmembrane potential and damage for these cells. We

  16. Catalyzing stem cell research.

    PubMed

    Willemse, Lisa; Lyall, Drew; Rudnicki, Michael

    2008-09-01

    In 2001, the Stem Cell Network was the first of its kind, a bold initiative to forge and nurture pan-Canadian collaborations involving researchers, engineers, clinicians and private and public sector partners. Canada's broad and deep pool of stem cell talent proved to be a fertile ground for such an initiative, giving rise to a strong, thriving network that, 7 years later, can list innovative cell expansion and screening technologies, early-phase clinical trials for stroke, pulmonary hypertension, muscular dystrophy and cornea replacement, and leading discourse on ethical, legal and social issues among its accomplishments. As it moves into its second and final phase of funding, the Stem Cell Network continues to push boundaries and has set its sights on overcoming the obstacles that impede the transfer of research findings to clinical applications, commercial products and public policy. PMID:18729799

  17. Catalyzing stem cell research.

    PubMed

    Willemse, Lisa; Lyall, Drew; Rudnicki, Michael

    2008-09-01

    In 2001, the Stem Cell Network was the first of its kind, a bold initiative to forge and nurture pan-Canadian collaborations involving researchers, engineers, clinicians and private and public sector partners. Canada's broad and deep pool of stem cell talent proved to be a fertile ground for such an initiative, giving rise to a strong, thriving network that, 7 years later, can list innovative cell expansion and screening technologies, early-phase clinical trials for stroke, pulmonary hypertension, muscular dystrophy and cornea replacement, and leading discourse on ethical, legal and social issues among its accomplishments. As it moves into its second and final phase of funding, the Stem Cell Network continues to push boundaries and has set its sights on overcoming the obstacles that impede the transfer of research findings to clinical applications, commercial products and public policy.

  18. Chemotherapy targeting cancer stem cells.

    PubMed

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future.

  19. Chemotherapy targeting cancer stem cells

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future. PMID:26045975

  20. Epidermal Stem Cells in Orthopaedic Regenerative Medicine

    PubMed Central

    Li, Jin; Zhen, Gehua; Tsai, Shin-Yi; Jia, Xiaofeng

    2013-01-01

    In the last decade, great advances have been made in epidermal stem cell studies at the cellular and molecular level. These studies reported various subpopulations and differentiations existing in the epidermal stem cell. Although controversies and unknown issues remain, epidermal stem cells possess an immune-privileged property in transplantation together with easy accessibility, which is favorable for future clinical application. In this review, we will summarize the biological characteristics of epidermal stem cells, and their potential in orthopedic regenerative medicine. Epidermal stem cells play a critical role via cell replacement, and demonstrate significant translational potential in the treatment of orthopedic injuries and diseases, including treatment for wound healing, peripheral nerve and spinal cord injury, and even muscle and bone remodeling. PMID:23727934

  1. Cancer stem cells of the digestive system.

    PubMed

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

    2014-12-01

    Stem cells of the digestive system are ideal in many ways for research, given they are abundant, highly proliferative and have a uniform structural arrangement. This in turn has enormously aided the research of cancer stem cells of the digestive system, which is now shaping our understanding of cancer stem cells. In this review, the recent advances in the understanding of cancer stem cells of the digestive system have been summarized, including aspects such as their identification, origin, cell-cycle dormancy, relationship with epithelial-mesenchymal transition, cellular metabolism and the underlying molecular mechanisms. Newly acquired knowledge concerning cancer stem cells have led to the development of novel cancer therapeutics with provisional yet encouraging results.

  2. Stem cells and transplant arteriosclerosis.

    PubMed

    Xu, Qingbo

    2008-05-01

    Stem cells can differentiate into a variety of cells to replace dead cells or to repair damaged tissues. Recent evidence indicates that stem cells are involved in the pathogenesis of transplant arteriosclerosis, an alloimmune initiated vascular stenosis that often results in transplant organ failure. Although the pathogenesis of transplant arteriosclerosis is not yet fully understood, recent developments in stem cell research have suggested novel mechanisms of vascular remodeling in allografts. For example, stem cells derived from the recipient may repair damaged endothelial cells of arteries in transplant organs. Further evidence suggests that stem cells or endothelial progenitor cells may be released from both bone marrow and non-bone marrow tissues. Vascular stem cells appear to replenish cells that died in donor vessels. Concomitantly, stem/progenitor cells may also accumulate in the intima, where they differentiate into smooth muscle cells. However, several issues concerning the contribution of stem cells to the pathogenesis of transplant arteriosclerosis are controversial, eg, whether bone marrow-derived stem cells can differentiate into smooth muscle cells that form neointimal lesions of the vessel wall. This review summarizes recent research on the role of stem cells in transplant arteriosclerosis, discusses the mechanisms of stem cell homing and differentiation into mature endothelial and smooth muscle cells, and highlights the controversial issues in the field.

  3. Laser biomodulation on stem cells

    NASA Astrophysics Data System (ADS)

    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.

  4. Bioreactor Engineering of Stem Cell Environments

    PubMed Central

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

    2013-01-01

    Stem cells hold promise to revolutionize modern medicine by development of new therapies, disease models and drug screening systems. Standard cell culture systems have limited biological relevance because they do not recapitulate the complex 3-dimensional interactions and biophysical cues that characterize the in vivo environment. In this review, we discuss the current advances in engineering stem cell environments using novel biomaterials and bioreactor technologies. We also reflect on the challenges the field is currently facing with regard to translation of stem cell based therapies into the clinic. PMID:23531529

  5. Current Biosafety Considerations in Stem Cell Therapy.

    PubMed

    Mousavinejad, Masoumeh; Andrews, Peter W; Shoraki, Elham Kargar

    2016-01-01

    Stem cells can be valuable model systems for drug discovery and modelling human diseases as well as to investigate cellular interactions and molecular events in the early stages of development. Controlling the differentiation of stem cells into specific germ layers provides a potential source of highly specialized cells for therapeutic applications. In recent years, finding individual properties of stem cells such as their ultimate self-renewal capacity and the generation of particular cell lines by differentiation under specific culture conditions underpins the development of regenerative therapies. These futures make stem cells a leading candidate to treat a wide range of diseases. Nevertheless, as with all novel treatments, safety issues are one of the barriers that should be overcome to guarantee the quality of a patient's life after stem cell therapy. Many studies have pointed to a large gap in our knowledge about the therapeutic applications of these cells. This gap clearly shows the importance of biosafety concerns for the current status of cell-based therapies, even more than their therapeutic efficacy. Currently, scientists report that tumorigenicity and immunogenicity are the two most important associated cell-based therapy risks. In principle, intrinsic factors such as cell characteristics and extrinsic elements introduced by manufacturing of stem cells can result in tumor formation and immunological reactions after stem cell transplantation. Therapeutic research shows there are many biological questions regarding safety issues of stem cell clinical applications. Stem cell therapy is a rapidly advancing field that needs to focus more on finding a comprehensive technology for assessing risk. A variety of risk factors (from intrinsic to extrinsic) should be considered for safe clinical stem cell therapies. PMID:27540533

  6. Current Biosafety Considerations in Stem Cell Therapy

    PubMed Central

    Mousavinejad, Masoumeh; Andrews, Peter W.; Shoraki, Elham Kargar

    2016-01-01

    Stem cells can be valuable model systems for drug discovery and modelling human diseases as well as to investigate cellular interactions and molecular events in the early stages of development. Controlling the differentiation of stem cells into specific germ layers provides a potential source of highly specialized cells for therapeutic applications. In recent years, finding individual properties of stem cells such as their ultimate self-renewal capacity and the generation of particular cell lines by differentiation under specific culture conditions underpins the development of regenerative therapies. These futures make stem cells a leading candidate to treat a wide range of diseases. Nevertheless, as with all novel treatments, safety issues are one of the barriers that should be overcome to guarantee the quality of a patient’s life after stem cell therapy. Many studies have pointed to a large gap in our knowledge about the therapeutic applications of these cells. This gap clearly shows the importance of biosafety concerns for the current status of cell-based therapies, even more than their therapeutic efficacy. Currently, scientists report that tumorigenicity and immunogenicity are the two most important associated cell-based therapy risks. In principle, intrinsic factors such as cell characteristics and extrinsic elements introduced by manufacturing of stem cells can result in tumor formation and immunological reactions after stem cell transplantation. Therapeutic research shows there are many biological questions regarding safety issues of stem cell clinical applications. Stem cell therapy is a rapidly advancing field that needs to focus more on finding a comprehensive technology for assessing risk. A variety of risk factors (from intrinsic to extrinsic) should be considered for safe clinical stem cell therapies. PMID:27540533

  7. Translational research of adult stem cell therapy.

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    Montaser, Laila M.; Fawzy, Sherin M.

    2015-08-01

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

  9. Stem Cells in Mammalian Gonads.

    PubMed

    Wu, Ji; Ding, Xinbao; Wang, Jian

    2016-01-01

    Stem cells have great value in clinical application because of their ability to self-renew and their potential to differentiate into many different cell types. Mammalian gonads, including testes for males and ovaries for females, are composed of germline and somatic cells. In male mammals, spermatogonial stem cells maintain spermatogenesis which occurs continuously in adult testis. Likewise, a growing body of evidence demonstrated that female germline stem cells could be found in mammalian ovaries. Meanwhile, prior studies have shown that somatic stem cells exist in both testes and ovaries. In this chapter, we focus on mammalian gonad stem cells and discuss their characteristics as well as differentiation potentials.

  10. Stem cells and small molecule screening: haploid embryonic stem cells as a new tool.

    PubMed

    Wu, Bi; Li, Wei; Wang, Liu; Liu, Zhong-hua; Zhao, Xiao-yang

    2013-06-01

    Stem cells can both self-renew and differentiate into various cell types under certain conditions, which makes them a good model for development and disease studies. Recently, chemical approaches have been widely applied in stem cell biology by promoting stem cell self-renewal, proliferation, differentiation and somatic cell reprogramming using specific small molecules. Conversely, stem cells and their derivatives also provide an efficient and robust platform for small molecule and drug screening. Here, we review the current research and applications of small molecules that modulate stem cell self-renewal and differentiation and improve reprogramming, as well as the applications that use stem cells as a tool for small molecule screening. Moreover, we introduce the recent advance in haploid embryonic stem cells research. Haploid embryonic stem cells maintain haploidy and stable growth over extensive passages, possess the ability to differentiate into all three germ layers in vitro and in vivo, and contribute to the germlines of chimeras when injected into blastocysts. Androgenetic haploid stem cells can also be used in place of sperm to produce fertile progeny after intracytoplasmic injection into mature oocytes. Such characteristics demonstrate that haploid stem cells are a new approach for genetic studies at both the cellular and animal levels and that they are a valuable platform for future small molecule screening.

  11. The decision on the "optimal" human pluripotent stem cell.

    PubMed

    Rosner, Margit; Schipany, Katharina; Hengstschläger, Markus

    2014-05-01

    Because of recent advances, the array of human pluripotent stem cells now contains embryonic stem cells, derived from "surplus" in vitro fertilization embryos or from cloned embryos; induced pluripotent stem cells; and amniotic fluid stem cells. Here, we compare these stem cell types regarding ethical and legal concerns, cultivation conditions, genomic stability, tumor developing potentials, and applicability for disease modeling and human therapy. This overview highlights that in the future appropriate methodological management must include a decision on the "optimal" stem cell to use before the specific application.

  12. Characterization of amniotic stem cells.

    PubMed

    Koike, Chika; Zhou, Kaixuan; Takeda, Yuji; Fathy, Moustafa; Okabe, Motonori; Yoshida, Toshiko; Nakamura, Yukio; Kato, Yukio; Nikaido, Toshio

    2014-08-01

    The amnion membrane is developed from embryo-derived cells, and amniotic cells have been shown to exhibit multidifferentiation potential. These cells represent a desirable source for stem cells for a variety of reasons. However, to date very few molecular analyses of amnion-derived cells have been reported, and efficient markers for isolating the stem cells remain unclear. This paper assesses the characterization of amnion-derived cells as stem cells by examining stemness marker expressions for amnion-derived epithelial cells and mesenchymal cells by flow cytometry, immunocytochemistry, and quantitative PCR. Flow cytometry revealed that amnion epithelial cells expressed CD133, CD 271, and TRA-1-60, whereas mecenchymal cells expressed CD44, CD73, CD90, and CD105. Immunohistochemistry showed that both cells expressed the stemness markers Oct3/4, Sox2, Klf4, and SSEA4. Stemness genes' expression in amnion epithelial cells, mesenchymal cells, fibroblast, bone marrow-derived mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs) was compared by quantitative reverse-transcription polymerase chain reaction (RT-PCR). Amnion-derived epithelial cells and mesenchymal cells expressed Oct3/4, Nanog, and Klf4 more than bone marrow-derived MSCs. The sorted TRA1-60-positive cells expressed Oct3/4, Nanog, and Klf4 more than unsorted cells or TRA1-60-negative cells. TRA1-60 can be a marker for isolating amnion epithelial stem cells.

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

    PubMed

    Schultz, Michael B; Sinclair, David A

    2016-01-01

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

  14. Materials as stem cell regulators

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

  15. Materials as stem cell regulators

    PubMed Central

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

    2014-01-01

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

  16. Glial cell derived neurotrophic factor induces spermatogonial stem cell marker genes in chicken mesenchymal stem cells.

    PubMed

    Boozarpour, Sohrab; Matin, Maryam M; Momeni-Moghaddam, Madjid; Dehghani, Hesam; Mahdavi-Shahri, Naser; Sisakhtnezhad, Sajjad; Heirani-Tabasi, Asieh; Irfan-Maqsood, Muhammad; Bahrami, Ahmad Reza

    2016-06-01

    Mesenchymal stem cells (MSCs) are known with the potential of multi-lineage differentiation. Advances in differentiation technology have also resulted in the conversion of MSCs to other kinds of stem cells. MSCs are considered as a suitable source of cells for biotechnology purposes because they are abundant, easily accessible and well characterized cells. Nowadays small molecules are introduced as novel and efficient factors to differentiate stem cells. In this work, we examined the potential of glial cell derived neurotrophic factor (GDNF) for differentiating chicken MSCs toward spermatogonial stem cells. MSCs were isolated and characterized from chicken and cultured under treatment with all-trans retinoic acid (RA) or glial cell derived neurotrophic factor. Expression analysis of specific genes after 7days of RA treatment, as examined by RT-PCR, proved positive for some germ cell markers such as CVH, STRA8, PLZF and some genes involved in spermatogonial stem cell maintenance like BCL6b and c-KIT. On the other hand, GDNF could additionally induce expression of POU5F1, and NANOG as well as other genes which were induced after RA treatment. These data illustrated that GDNF is relatively more effective in diverting chicken MSCs towards Spermatogonial stem cell -like cells in chickens and suggests GDNF as a new agent to obtain transgenic poultry, nevertheless, exploitability of these cells should be verified by more experiments. PMID:27026484

  17. Glial cell derived neurotrophic factor induces spermatogonial stem cell marker genes in chicken mesenchymal stem cells.

    PubMed

    Boozarpour, Sohrab; Matin, Maryam M; Momeni-Moghaddam, Madjid; Dehghani, Hesam; Mahdavi-Shahri, Naser; Sisakhtnezhad, Sajjad; Heirani-Tabasi, Asieh; Irfan-Maqsood, Muhammad; Bahrami, Ahmad Reza

    2016-06-01

    Mesenchymal stem cells (MSCs) are known with the potential of multi-lineage differentiation. Advances in differentiation technology have also resulted in the conversion of MSCs to other kinds of stem cells. MSCs are considered as a suitable source of cells for biotechnology purposes because they are abundant, easily accessible and well characterized cells. Nowadays small molecules are introduced as novel and efficient factors to differentiate stem cells. In this work, we examined the potential of glial cell derived neurotrophic factor (GDNF) for differentiating chicken MSCs toward spermatogonial stem cells. MSCs were isolated and characterized from chicken and cultured under treatment with all-trans retinoic acid (RA) or glial cell derived neurotrophic factor. Expression analysis of specific genes after 7days of RA treatment, as examined by RT-PCR, proved positive for some germ cell markers such as CVH, STRA8, PLZF and some genes involved in spermatogonial stem cell maintenance like BCL6b and c-KIT. On the other hand, GDNF could additionally induce expression of POU5F1, and NANOG as well as other genes which were induced after RA treatment. These data illustrated that GDNF is relatively more effective in diverting chicken MSCs towards Spermatogonial stem cell -like cells in chickens and suggests GDNF as a new agent to obtain transgenic poultry, nevertheless, exploitability of these cells should be verified by more experiments.

  18. Melanocytes, melanocyte stem cells, and melanoma stem cells.

    PubMed

    Lang, Deborah; Mascarenhas, Joseph B; Shea, Christopher R

    2013-01-01

    Melanocyte stem cells differ greatly from melanoma stem cells; the former provide pigmented cells during normal tissue homeostasis and repair, and the latter play an active role in a lethal form of cancer. These 2 cell types share several features and can be studied by similar methods. Aspects held in common by both melanocyte stem cells and melanoma stem cells include their expression of shared biochemical markers, a system of similar molecular signals necessary for their maintenance, and a requirement for an ideal niche microenvironment for providing these factors. This review provides a perspective of both these cell types and discusses potential models of stem cell growth and propagation. Recent findings provide a strong foundation for the development of new therapeutics directed at isolating and manipulating melanocyte stem cells for tissue engineering or at targeting and eradicating melanoma specifically, while sparing nontumor cells.

  19. Engineering stem cells for future medicine.

    PubMed

    Ricotti, Leonardo; Menciassi, Arianna

    2013-03-01

    Despite their great potential in regenerative medicine applications, stem cells (especially pluripotent ones) currently show a limited clinical success, partly due to a lack of biological knowledge, but also due to a lack of specific and advanced technological instruments able to overcome the current boundaries of stem cell functional maturation and safe/effective therapeutic delivery. This paper aims at describing recent insights, current limitations, and future horizons related to therapeutic stem cells, by analyzing the potential of different bioengineering disciplines in bringing stem cells toward a safe clinical use. First, we clarify how and why stem cells should be properly engineered and which could be in a near future the challenges and the benefits connected with this process. Second, we identify different routes toward stem cell differentiation and functional maturation, relying on chemical, mechanical, topographical, and direct/indirect physical stimulation. Third, we highlight how multiscale modeling could strongly support and optimize stem cell engineering. Finally, we focus on future robotic tools that could provide an added value to the extent of translating basic biological knowledge into clinical applications, by developing ad hoc enabling technologies for stem cell delivery and control.

  20. Autologous Stem Cell Mobilization and Collection.

    PubMed

    Hsu, Yen-Michael S; Cushing, Melissa M

    2016-06-01

    Peripheral blood stem cell collection is an effective approach to obtain a hematopoietic graft for stem cell transplantation. Developing hematopoietic stem/progenitor cell (HSPC) mobilization methods and collection algorithms have improved efficiency, clinical outcomes, and cost effectiveness. Differences in mobilization mechanisms may change the HSPC content harvested and result in different engraftment kinetics and complications. Patient-specific factors can affect mobilization. Incorporating these factors in collection algorithms and improving assays for evaluating mobilization further extend the ability to obtain sufficient HSPCs for hematopoietic repopulation. Technological advance and innovations in leukapheresis have improved collection efficiency and reduced adverse effects. PMID:27112997

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

    NASA Astrophysics Data System (ADS)

    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.

  2. [Perinatal sources of stem cells].

    PubMed

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

    2015-03-08

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

  3. Ionizing radiation promotes advanced malignant traits in nasopharyngeal carcinoma via activation of epithelial-mesenchymal transition and the cancer stem cell phenotype

    PubMed Central

    SU, ZHONGWU; LI, GUO; LIU, CHAO; REN, SHULING; TIAN, YONGQUAN; LIU, YONG; QIU, YUANZHENG

    2016-01-01

    Post-irradiation residual mass and recurrence always suggest a worse prognosis for nasopharyngeal carcinoma (NPC). Our study aimed to investigate the malignant behaviors of post-irradiation residual NPC cells, to identify the potential underlying mechanisms and to search for appropriate bio-targets to overcome this malignancy. Two NPC cell lines were firstly exposed to 60 Gy irradiation, and residual cells were collected. In our previous study, colony formation assay detected the radioresistance of these cells. Here, the CCK-8 assay examined the cell sensitivity to paclitaxel and cisplatin. Wound-healing and Transwell assays were performed to investigate cell motility and invasion capabilities. Inverted phase-contrast microscopy was used to observe and photograph the morphology of cells. Expression levels of epithelial-mesenchymal transition (EMT)-related proteins were detected by western blot assay in NPC cells and tissues. The mRNA levels of cancer stem cell (CSC)-related genes were detected via qRT-PCR. The results revealed that residual NPC cells exhibited enhanced radioresistance and cross-resistance to paclitaxel and cisplatin. Higher capacities of invasion and migration were also observed. An elongated morphology with pseudopodia formation and broadening in the intercellular space was observed in the residual cells. Downregulation of E-cadherin and upregulation of vimentin were detected in the residual NPC cells and tissues. CSC-related Lgr5 and c-myc were significantly upregulated in the CNE-2-Rs and 6-10B-Rs radioresistance cells. Higher proportions of Lgr5+ cells were observed in radioresistant cells via immunofluorescent staining and flow cytometry. In conclusion, our study demonstrated that residual NPC cells had an advanced malignant transition and presented with both EMT and a CSC phenotype. This provides a possible clue and treatment strategy for advanced and residual NPC. PMID:27108809

  4. Seeing Stem Cells at Work In Vivo

    PubMed Central

    Srivastava, Amit K.; Bulte, Jeff W. M.

    2013-01-01

    Stem cell based-therapies are novel therapeutic strategies that hold key for developing new treatments for diseases conditions with very few or no cures. Although there has been an increase in the number of clinical trials involving stem cell-based therapies in the last few years, the long-term risks and benefits of these therapies are still unknown. Detailed in vivo studies are needed to monitor the fate of transplanted cells, including their distribution, differentiation, and longevity over time. Advancements in non-invasive cellular imaging techniques to track engrafted cells in real-time present a powerful tool for determining the efficacy of stem cell-based therapies. In this review, we describe the latest approaches to stem cell labeling and tracking using different imaging modalities. PMID:23975604

  5. Stem cell aging

    PubMed Central

    Muller-Sieburg, Christa; Sieburg, Hans B.

    2009-01-01

    The question whether stem cells age remains an enigma. Traditionally, aging was thought to change the properties of hematopoietic stem cells (HSC). We discuss here a new model of stem cell aging that challenges this view. It is now well-established that the HSC compartment is heterogeneous, consisting of epigenetically fixed subpopulations of HSC that differ in self-renewal and differentiation capacity. New data show that the representation of these HSC subsets changes during aging. HSC that generate lymphocyte-rich progeny are depleted, while myeloid-biased HSC are enriched in the aged HSC compartment. Myeloid-biased HSC, even when isolated from young donors, have most of the characteristics that had been attributed to aged HSC. Thus, the distinct behavior of the HSC isolated from aged hosts is due to the accumulation of myeloid-biased HSC. By extension this means that the properties of individual HSC are not substantially changed during the lifespan of the organism and that aged hosts do not contain many aged HSC. Myeloid-biased HSC give rise to mature cells slowly but contribute for a long time to peripheral hematopoiesis. We propose that such slow, “lazy” HSC are less likely to be transformed and therefore may safely sustain hematopoiesis for a long time. PMID:19066464

  6. Statins and stem cell modulation.

    PubMed

    Xu, Hui; Yang, Yue-Jin; Yang, Tao; Qian, Hai-Yan

    2013-01-01

    Stem cell-based therapy is a promising option for the treatment of ischemic heart diseases. As to a successful stem cell-based therapy, one of the most important issues is that the stable engraftment and survival of implanted stem cells in cardiac microenvironment. There are evidences suggest that pharmacological treatment devoted to regulate stem cell function might represent a potential new therapeutic strategy and are drawing nearer to becoming a part of treatment in clinical settings. Statins could exert cholesterol-independent or pleiotropic effects to cardiovascular system. Recent studies have shown that statins could modulate the biological characteristics and function of various stem cells, thus could be an effective method to facilitate stem cell therapy. This review will focus on statins and their modulation effects on various stem cells.

  7. Successful isolation of viable adipose-derived stem cells from human adipose tissue subject to long-term cryopreservation: positive implications for adult stem cell-based therapeutics in patients of advanced age.

    PubMed

    Devitt, Sean M; Carter, Cynthia M; Dierov, Raia; Weiss, Scott; Gersch, Robert P; Percec, Ivona

    2015-01-01

    We examined cell isolation, viability, and growth in adipose-derived stem cells harvested from whole adipose tissue subject to different cryopreservation lengths (2-1159 days) from patients of varying ages (26-62 years). Subcutaneous abdominal adipose tissue was excised during abdominoplasties and was cryopreserved. The viability and number of adipose-derived stem cells isolated were measured after initial isolation and after 9, 18, and 28 days of growth. Data were analyzed with respect to cryopreservation duration and patient age. Significantly more viable cells were initially isolated from tissue cryopreserved <1 year than from tissue cryopreserved >2 years, irrespective of patient age. However, this difference did not persist with continued growth and there were no significant differences in cell viability or growth at subsequent time points with respect to cryopreservation duration or patient age. Mesenchymal stem cell markers were maintained in all cohorts tested throughout the duration of the study. Consequently, longer cryopreservation negatively impacts initial live adipose-derived stem cell isolation; however, this effect is neutralized with continued cell growth. Patient age does not significantly impact stem cell isolation, viability, or growth. Cryopreservation of adipose tissue is an effective long-term banking method for isolation of adipose-derived stem cells in patients of varying ages.

  8. Successful Isolation of Viable Adipose-Derived Stem Cells from Human Adipose Tissue Subject to Long-Term Cryopreservation: Positive Implications for Adult Stem Cell-Based Therapeutics in Patients of Advanced Age

    PubMed Central

    Devitt, Sean M.; Carter, Cynthia M.; Dierov, Raia; Weiss, Scott; Percec, Ivona

    2015-01-01

    We examined cell isolation, viability, and growth in adipose-derived stem cells harvested from whole adipose tissue subject to different cryopreservation lengths (2–1159 days) from patients of varying ages (26–62 years). Subcutaneous abdominal adipose tissue was excised during abdominoplasties and was cryopreserved. The viability and number of adipose-derived stem cells isolated were measured after initial isolation and after 9, 18, and 28 days of growth. Data were analyzed with respect to cryopreservation duration and patient age. Significantly more viable cells were initially isolated from tissue cryopreserved <1 year than from tissue cryopreserved >2 years, irrespective of patient age. However, this difference did not persist with continued growth and there were no significant differences in cell viability or growth at subsequent time points with respect to cryopreservation duration or patient age. Mesenchymal stem cell markers were maintained in all cohorts tested throughout the duration of the study. Consequently, longer cryopreservation negatively impacts initial live adipose-derived stem cell isolation; however, this effect is neutralized with continued cell growth. Patient age does not significantly impact stem cell isolation, viability, or growth. Cryopreservation of adipose tissue is an effective long-term banking method for isolation of adipose-derived stem cells in patients of varying ages. PMID:25945096

  9. Ovarian cancer stem cells enrichment.

    PubMed

    Yang, Lijuan; Lai, Dongmei

    2013-01-01

    The concept of cancer stem cells (CSCs) provides a new paradigm for understanding cancer biology. Cancer stem cells are defined as a minority of cancer cells with stem cell properties responsible for maintenance and growth of tumors. The targeting of CSCs is a potential therapeutic strategy to combat ovarian cancer. Ovarian epithelial cancer cells cultured in serum-free medium can form sphere cells. These sphere cells may be enriched for cancer stem cells (CSCs). The isolation of sphere cells from solid tumors is an important technique in studying cancer cell biology. Here we describe the isolation of sphere cells from primary ovarian cancer tissue, ascites fluid, and the cancer cell line SKOV3 with stem cell selection medium. PMID:23913228

  10. High Throughput Optimization of Stem Cell Microenvironments

    PubMed Central

    Yang, Fan; Mei, Ying; Langer, Robert; Anderson, Daniel G.

    2009-01-01

    Stem cells have great potential as cell sources for regenerative medicine due to both their self-renewal and multi-lineage differentiation capacity. Despite advances in the field of stem cell biology, major challenges remain before stem cells can be widely used for therapeutic purposes. One challenge is to develop reproducible methods to control stem cell growth and differentiation. The niche in which stem cells reside is a complex, multi-factorial environment. In contrast to using cells alone, biomaterials can provide initial structural support, and allow cells to adhere, proliferate and differentiate in a three-dimensional environment. Researchers have incorporated signals into the biomaterials that can promote desired cell functions in a spatially and temporally controlled manner. Despite progress in biomaterial design and methods to modulate cellular behavior, many of the complex signal networks that regulate cell-material interactions remain unclear. Due to the vast numbers of material properties to be explored and the complexity of cell-surface interactions, it is often difficult to optimize stem cell microenvironments using conventional, iterative approaches. To address these challenges, high throughput screening of combinatorial libraries has emerged as a novel approach to achieve rapid screening with reduced materials and costs. In this review, we discuss recent research in the area of high throughput approaches for characterization and optimization of cellular interactions with their microenvironments. In contrast to conventional approaches, screening combinatorial libraries can result in the discovery of unexpected material solutions to these complex problems. PMID:19601753

  11. Stem cells and somatic cells: reprogramming and plasticity.

    PubMed

    Estrov, Zeev

    2009-01-01

    Recent seminal discoveries have significantly advanced the field of stem cell research and received worldwide attention. Improvements in somatic cell nuclear transfer (SCNT) technology, enabling the cloning of Dolly the sheep, and the derivation and differentiation of human embryonic stem cells raised hopes that normal cells could be generated to replace diseased or injured tissue. At the same time, in vitro and in vivo studies demonstrated that somatic cells of one tissue are capable of generating cells of another tissue. It was theorized that any cell might be reprogrammed, by exposure to a new environment, to become another cell type. This concept contradicts two established hypotheses: (1) that only specific tissues are generated from the endoderm, mesoderm, and ectoderm and (2) that tissue cells arise from a rare population of tissue-specific stem cells in a hierarchical fashion. SCNT, cell fusion experiments, and most recent gene transfer studies also contradict these hypotheses, as they demonstrate that mature somatic cells can be reprogrammed to regain pluripotent (or even totipotent) stem cell capacity. On the basis of the stem cell theory, hierarchical cancer stem cell differentiation models have been proposed. Cancer cell plasticity is an established phenomenon that supports the notion that cellular phenotype and function might be altered. Therefore, mechanisms of cellular plasticity should be exploited and the clinical significance of the cancer stem cell theory cautiously assessed. PMID:19778860

  12. Nanotechnology in the regulation of stem cell behavior

    NASA Astrophysics Data System (ADS)

    Wu, King-Chuen; Tseng, Ching-Li; Wu, Chi-Chang; Kao, Feng-Chen; Tu, Yuan-Kun; So, Edmund C.; Wang, Yang-Kao

    2013-10-01

    Stem cells are known for their potential to repair damaged tissues. The adhesion, growth and differentiation of stem cells are likely controlled by the surrounding microenvironment which contains both chemical and physical cues. Physical cues in the microenvironment, for example, nanotopography, were shown to play important roles in stem cell fate decisions. Thus, controlling stem cell behavior by nanoscale topography has become an important issue in stem cell biology. Nanotechnology has emerged as a new exciting field and research from this field has greatly advanced. Nanotechnology allows the manipulation of sophisticated surfaces/scaffolds which can mimic the cellular environment for regulating cellular behaviors. Thus, we summarize recent studies on nanotechnology with applications to stem cell biology, including the regulation of stem cell adhesion, growth, differentiation, tracking and imaging. Understanding the interactions of nanomaterials with stem cells may provide the knowledge to apply to cell-scaffold combinations in tissue engineering and regenerative medicine.

  13. Stem cell tracking using iron oxide nanoparticles.

    PubMed

    Bull, Elizabeth; Madani, Seyed Yazdan; Sheth, Roosey; Seifalian, Amelia; Green, Mark; Seifalian, Alexander M

    2014-01-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) are an exciting advancement in the field of nanotechnology. They expand the possibilities of noninvasive analysis and have many useful properties, making them potential candidates for numerous novel applications. Notably, they have been shown that they can be tracked by magnetic resonance imaging (MRI) and are capable of conjugation with various cell types, including stem cells. In-depth research has been undertaken to establish these benefits, so that a deeper level of understanding of stem cell migratory pathways and differentiation, tumor migration, and improved drug delivery can be achieved. Stem cells have the ability to treat and cure many debilitating diseases with limited side effects, but a main problem that arises is in the noninvasive tracking and analysis of these stem cells. Recently, researchers have acknowledged the use of SPIONs for this purpose and have set out to establish suitable protocols for coating and attachment, so as to bring MRI tracking of SPION-labeled stem cells into common practice. This review paper explains the manner in which SPIONs are produced, conjugated, and tracked using MRI, as well as a discussion on their limitations. A concise summary of recently researched magnetic particle coatings is provided, and the effects of SPIONs on stem cells are evaluated, while animal and human studies investigating the role of SPIONs in stem cell tracking will be explored.

  14. Reduced Intensity Conditioning Before Partially Matched Donor Stem Cell Transplant in Treating Patients With Advanced Cutaneous T Cell Lymphoma

    ClinicalTrials.gov

    2016-10-19

    Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Stage IIB Mycosis Fungoides and Sezary Syndrome; Stage IIIA Mycosis Fungoides and Sezary Syndrome; Stage IIIB Mycosis Fungoides and Sezary Syndrome; Stage IVA Mycosis Fungoides and Sezary Syndrome; Stage IVB Mycosis Fungoides and Sezary Syndrome

  15. Breast Cancer Stem Cells

    PubMed Central

    Velasco-Velázquez, Marco A.; Homsi, Nora; De La Fuente, Marisol; Pestell, Richard G.

    2012-01-01

    Breast cancer stem cells (BCSCs) constitute a subpopulation of tumor cells that express stem cell-associated markers and have a high capacity for tumor generation in vivo. Identification of BCSCs from tumor samples or breast cancer cell lines has been based mainly on CD44+/CD24−/low or ALDH+ phenotypes. BCSCs isolation has allowed the analysis of the molecular mechanisms involved in their origin, self-renewal, differentiation into tumor cells, resistance to radiation therapy and chemotherapy, and invasiveness and metastatic ability. Molecular genetic analysis using knockout animals and inducible transgenics have identified NF-κB, c-Jun, p21CIP1, and Forkhead-like-protein Dach1 in BCSC expansion and fate. Clinical analyses of BCSCs in breast tumors have found a correlation between the proportion of BCSCs and poor prognosis. Therefore, new therapies that specifically target BCSCs are an urgent need. We summarize recent evidence that partially explain the biological characteristics of BCSCs. PMID:22249027

  16. Analytical strategies for studying stem cell metabolism

    PubMed Central

    Arnold, James M.; Choi, William T.; Sreekumar, Arun

    2015-01-01

    Owing to their capacity for self-renewal and pluripotency, stem cells possess untold potential for revolutionizing the field of regenerative medicine through the development of novel therapeutic strategies for treating cancer, diabetes, cardiovascular and neurodegenerative diseases. Central to developing these strategies is improving our understanding of biological mechanisms responsible for governing stem cell fate and self-renewal. Increasing attention is being given to the significance of metabolism, through the production of energy and generation of small molecules, as a critical regulator of stem cell functioning. Rapid advances in the field of metabolomics now allow for in-depth profiling of stem cells both in vitro and in vivo, providing a systems perspective on key metabolic and molecular pathways which influence stem cell biology. Understanding the analytical platforms and techniques that are currently used to study stem cell metabolomics, as well as how new insights can be derived from this knowledge, will accelerate new research in the field and improve future efforts to expand our understanding of the interplay between metabolism and stem cell biology. PMID:26213533

  17. Stem cell bioprocessing: fundamentals and principles

    PubMed Central

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

    2008-01-01

    In recent years, the potential of stem cell research for tissue engineering-based therapies and regenerative medicine clinical applications has become well established. In 2006, Chung pioneered the first entire organ transplant using adult stem cells and a scaffold for clinical evaluation. With this a new milestone was achieved, with seven patients with myelomeningocele receiving stem cell-derived bladder transplants resulting in substantial improvements in their quality of life. While a bladder is a relatively simple organ, the breakthrough highlights the incredible benefits that can be gained from the cross-disciplinary nature of tissue engineering and regenerative medicine (TERM) that encompasses stem cell research and stem cell bioprocessing. Unquestionably, the development of bioprocess technologies for the transfer of the current laboratory-based practice of stem cell tissue culture to the clinic as therapeutics necessitates the application of engineering principles and practices to achieve control, reproducibility, automation, validation and safety of the process and the product. The successful translation will require contributions from fundamental research (from developmental biology to the ‘omics’ technologies and advances in immunology) and from existing industrial practice (biologics), especially on automation, quality assurance and regulation. The timely development, integration and execution of various components will be critical—failures of the past (such as in the commercialization of skin equivalents) on marketing, pricing, production and advertising should not be repeated. This review aims to address the principles required for successful stem cell bioprocessing so that they can be applied deftly to clinical applications. PMID:19033137

  18. Stem cell bioprocessing: fundamentals and principles.

    PubMed

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

    2009-03-01

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

  19. Hematopoietic stem cell mobilization: updated conceptual renditions

    PubMed Central

    Bonig, H; Papayannopoulou, T

    2013-01-01

    Despite its specific clinical relevance, the field of hematopoietic stem cell mobilization has received broad attention, owing mainly to the belief that pharmacologic stem cell mobilization might provide clues as to how stem cells are retained in their natural environment, the bone marrow ‘niche’. Inherent to this knowledge is also the desire to optimally engineer stem cells to interact with their target niche (such as after transplantation), or to lure malignant stem cells out of their protective niches (in order to kill them), and in general to decipher the niche’s structural components and its organization. Whereas, with the exception of the recent addition of CXCR4 antagonists to the armamentarium for mobilization of patients refractory to granulocyte colony-stimulating factor alone, clinical stem cell mobilization has not changed significantly over the last decade or so, much effort has been made trying to explain the complex mechanism(s) by which hematopoietic stem and progenitor cells leave the marrow. This brief review will report some of the more recent advances about mobilization, with an attempt to reconcile some of the seemingly inconsistent data in mobilization and to interject some commonalities among different mobilization regimes. PMID:22951944

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

    PubMed Central

    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

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

    PubMed

    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.

  2. Antioxidants inhibit advanced glycosylation end-product-induced apoptosis by downregulation of miR-223 in human adipose tissue-derived stem cells

    PubMed Central

    Wang, Zhe; Li, Hongqiu; Guo, Ran; Wang, Qiushi; Zhang, Dianbao

    2016-01-01

    Advanced glycosylation end products (AGEs) are endogenous inflammatory mediators that induce apoptosis of mesenchymal stem cells. A potential mechanism includes increased generation of reactive oxygen species (ROS). MicroRNA-223 (miR-223) is implicated in the regulation of cell growth and apoptosis in several cell types. Here, we tested the hypothesis that antioxidants N-acetylcysteine (NAC) and ascorbic acid 2-phosphate (AAP) inhibit AGE-induced apoptosis via a microRNA-dependent mechanism in human adipose tissue-derived stem cells (ADSCs). Results showed that AGE-HSA enhanced apoptosis and caspase-3 activity in ADSCs. AGE-HSA also increased ROS generation and upregulated the expression of miR-223. Interestingly, reductions in ROS generation and apoptosis, and upregulation of miR-223 were found in ADSCs treated with antioxidants NAC and AAP. Furthermore, miR-223 mimics blocked antioxidant inhibition of AGE-induced apoptosis and ROS generation. Knockdown of miR-223 amplified the protective effects of antioxidants on apoptosis induced by AGE-HSA. miR-223 acted by targeting fibroblast growth factor receptor 2. These results indicate that NAC and AAP suppress AGE-HSA-induced apoptosis of ADSCs, possibly through downregulation of miR-223. PMID:26964642

  3. Pancreatic cancer stem cells

    PubMed Central

    Zhu, Ya-Yun; Yuan, Zhou

    2015-01-01

    Studies are emerging in support of the cancer stem cells (CSCs) theory which considers that a tiny subset of cancer cells is exclusively responsible for the initiation and malignant behavior of a cancer. This cell population, also termed CSCs, possesses the capacity both to self-renew, producing progeny that have the identical tumorigenic potential, and to differentiate into the bulk of cancer cells, helping serve the formation of the tumor entities, which, altogether, build the hierarchically organized structure of a cancer. In this review, we try to articulate the complicated signaling pathways regulating the retention of the characteristics of pancreatic CSCs, and in the wake of which, we seek to offer insights into the CSCs-relevant targeted therapeutics which are, in the meantime, confronted with bigger challenges than ever. PMID:26045976

  4. Role of liver stem cells in hepatocarcinogenesis

    PubMed Central

    Xu, Lei-Bo; Liu, Chao

    2014-01-01

    Liver cancer is an aggressive disease with a high mortality rate. Management of liver cancer is strongly dependent on the tumor stage and underlying liver disease. Unfortunately, most cases are discovered when the cancer is already advanced, missing the opportunity for surgical resection. Thus, an improved understanding of the mechanisms responsible for liver cancer initiation and progression will facilitate the detection of more reliable tumor markers and the development of new small molecules for targeted therapy of liver cancer. Recently, there is increasing evidence for the “cancer stem cell hypothesis”, which postulates that liver cancer originates from the malignant transformation of liver stem/progenitor cells (liver cancer stem cells). This cancer stem cell model has important significance for understanding the basic biology of liver cancer and has profound importance for the development of new strategies for cancer prevention and treatment. In this review, we highlight recent advances in the role of liver stem cells in hepatocarcinogenesis. Our review of the literature shows that identification of the cellular origin and the signaling pathways involved is challenging issues in liver cancer with pivotal implications in therapeutic perspectives. Although the dedifferentiation of mature hepatocytes/cholangiocytes in hepatocarcinogenesis cannot be excluded, neoplastic transformation of a stem cell subpopulation more easily explains hepatocarcinogenesis. Elimination of liver cancer stem cells in liver cancer could result in the degeneration of downstream cells, which makes them potential targets for liver cancer therapies. Therefore, liver stem cells could represent a new target for therapeutic approaches to liver cancer in the near future. PMID:25426254

  5. Hematopoietic stem cell engineering at a crossroads.

    PubMed

    Rivière, Isabelle; Dunbar, Cynthia E; Sadelain, Michel

    2012-02-01

    The genetic engineering of hematopoietic stem cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm for stem cell engineering in general. Recent clinical reports support the formidable promise of this approach but also highlight the limitations of the technologies used to date, which have on occasion resulted in clonal expansion, myelodysplasia, or leukemogenesis. New research directions, predicated on improved vector designs, targeted gene delivery or the therapeutic use of pluripotent stem cells, herald the advent of safer and more effective hematopoietic stem cell therapies that may transform medical practice. In this review, we place these recent advances in perspective, emphasizing the solutions emerging from a wave of new technologies and highlighting the challenges that lie ahead.

  6. Hematopoietic stem cell engineering at a crossroads

    PubMed Central

    Rivière, Isabelle; Dunbar, Cynthia E.

    2012-01-01

    The genetic engineering of hematopoietic stem cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm for stem cell engineering in general. Recent clinical reports support the formidable promise of this approach but also highlight the limitations of the technologies used to date, which have on occasion resulted in clonal expansion, myelodysplasia, or leukemogenesis. New research directions, predicated on improved vector designs, targeted gene delivery or the therapeutic use of pluripotent stem cells, herald the advent of safer and more effective hematopoietic stem cell therapies that may transform medical practice. In this review, we place these recent advances in perspective, emphasizing the solutions emerging from a wave of new technologies and highlighting the challenges that lie ahead. PMID:22096239

  7. [Cancer stem cell research toward therapeutics].

    PubMed

    Ito, Keisuke

    2015-05-01

    The capacity of cancer stem cells, or cancer-initiating cells, to both provide mature tumor cells and perpetuate themselves through self-renewal is crucial to initiate and maintain tumorigenesis, and has become the focus of intense research interest as a promising source of new therapeutic strategies. However, many scientific challenges and technical barriers remain to be solved before recent findings can be translated into effective therapeutics. Here we highlight the latest advances in our knowledge of cancer stem cells, and provide a critical perspective on the clinical benefits promised by this developing area of research.

  8. Science and society: a stem cell technology model.

    PubMed

    Kiatpongsan, Sorapop

    2008-02-01

    Stem cell technology has been recognized as an emerging technology that could transform current supportive approach toward curing many chronic disorders and degenerative conditions. Regenerative medicine is the promising area of medical practice in the coming decade. However, stem cell technology also brings up controversial issues from the bioethical perspective such as the destruction of human embryos to derive embryonic stem cells or putting the egg donors at risk when retrieving oocytes used in somatic cell nuclear transfer technique. Recently, scientists have discovered a novel method to derive human embryonic stem cell-like cells (iPS; induced pluripotent stem cells) from human skin cells. This innovative approach would not only be a breakthrough discovery to advance the knowledge of stem cell research and the landmark for future stem cell-based therapy but will also provide viable solutions for social concerns on bioethical issues.

  9. Human pluripotent stem cell-derived products: Advances towards robust, scalable and cost-effective manufacturing strategies

    PubMed Central

    Jenkins, Michael J; Farid, Suzanne S

    2015-01-01

    The ability to develop cost-effective, scalable and robust bioprocesses for human pluripotent stem cells (hPSCs) will be key to their commercial success as cell therapies and tools for use in drug screening and disease modelling studies. This review outlines key process economic drivers for hPSCs and progress made on improving the economic and operational feasibility of hPSC bioprocesses. Factors influencing key cost metrics, namely capital investment and cost of goods, for hPSCs are discussed. Step efficiencies particularly for differentiation, media requirements and technology choice are amongst the key process economic drivers identified for hPSCs. Progress made to address these cost drivers in hPSC bioprocessing strategies is discussed. These include improving expansion and differentiation yields in planar and bioreactor technologies, the development of xeno-free media and microcarrier coatings, identification of optimal bioprocess operating conditions to control cell fate and the development of directed differentiation protocols that reduce reliance on expensive morphogens such as growth factors and small molecules. These approaches offer methods to further optimise hPSC bioprocessing in terms of its commercial feasibility. PMID:25524780

  10. Skeletal stem cells

    PubMed Central

    Bianco, Paolo; Robey, Pamela G.

    2015-01-01

    Skeletal stem cells (SSCs) reside in the postnatal bone marrow and give rise to cartilage, bone, hematopoiesis-supportive stroma and marrow adipocytes in defined in vivo assays. These lineages emerge in a specific sequence during embryonic development and post natal growth, and together comprise a continuous anatomical system, the bone-bone marrow organ. SSCs conjoin skeletal and hematopoietic physiology, and are a tool for understanding and ameliorating skeletal and hematopoietic disorders. Here and in the accompanying poster, we concisely discuss the biology of SSCs in the context of the development and postnatal physiology of skeletal lineages, to which their use in medicine must remain anchored. PMID:25758217

  11. European stem cell research in legal shackles.

    PubMed

    Nielen, Myrthe G; de Vries, Sybe A; Geijsen, Niels

    2013-12-11

    Advances in stem cell biology have raised legal challenges to the patentability of stem cells and any derived technologies and processes. In 1999, Oliver Brüstle was granted a patent for the generation and therapeutic use of neural cells derived from human embryonic stem cells (hESCs). The patent was challenged and put before the European Court of Justice, which ruled that inventions involving the prior destruction of human embryos cannot be patented. The legal maneuvering around this case demonstrates that the future of stem cell-based patents in Europe remains unsettled. Furthermore, owing to the European Court's broad definition of hESC as 'any cell that is capable of commencing development into a human being,' novel technologies that could eliminate the need for hESCs, such as induced pluripotent stem cells (iPSCs), are at risk of being included under the same ruling. Advances in the in vitro development of germ cells from pluripotent stem cells may one day provide a direct developmental path from iPSC to oocyte and sperm, and, according to the European Court's reasoning, legally equate iPSCs with human embryos. In this review, we will briefly discuss the Brüstle v Greenpeace case and the implications of the European Court of Justice's ruling. We will identify potential risks for stem cell research and future therapeutics resulting from the broad legal definition of the human embryo. Finally, we will broach the current legal landscape, as this broad definition has also created great uncertainty about the status of human iPSCs.

  12. Mechanotransduction: Tuning Stem Cells Fate

    PubMed Central

    D'Angelo, Francesco; Tiribuzi, Roberto; Armentano, Ilaria; Kenny, Josè Maria; Martino, Sabata; Orlacchio, Aldo

    2011-01-01

    It is a general concern that the success of regenerative medicine-based applications is based on the ability to recapitulate the molecular events that allow stem cells to repair the damaged tissue/organ. To this end biomaterials are designed to display properties that, in a precise and physiological-like fashion, could drive stem cell fate both in vitro and in vivo. The rationale is that stem cells are highly sensitive to forces and that they may convert mechanical stimuli into a chemical response. In this review, we describe novelties on stem cells and biomaterials interactions with more focus on the implication of the mechanical stimulation named mechanotransduction. PMID:24956164

  13. Advanced flow cytometric analysis of nanoparticle targeting to rare leukemic stem cells in peripheral human blood in a defined model system

    NASA Astrophysics Data System (ADS)

    Cooper, Christy L.; Leary, James F.

    2015-03-01

    Leukemia stem cells are both stem-like and leukemic-like. This complicates their detection as rare circulating tumor cells in the peripheral blood of leukemia patients. Since leukemic stem cells are also resistant to standard chemotherapeutic regimens, new therapeutic strategies need to be designed to kill the leukemic stem cells without killing normal stem cells. In these initial targeting studies we utilized a bioinformatics approach to design an antibodyfluorescent nanoparticle conjugate for targeting to these leukemic stem cells and to minimize targeting to normal stemprogenitor cells. Multicolor flow cytometric analyses were performed on a BD FACS Aria III. Human leukemic stem cell-like cell RS4;11 (with putative immunophenotype CD133+/CD24+/-, CD34+/-, CD38+, CD10-/Flt3+) was spiked into normal hematopoietic stem-progenitor cells obtained from a "buffy coat" prep (with putative immunophenotype CD133- /CD34+/CD38-/CD10-/Flt-3-) to be used as a model human leukemia patient. To analyze the model system, digital data mixtures of the two cell types were first created and assigned classifiers in order to create truth sets. ROC (Receiver Operating Characteristic) and multidimensional cluster analyses were used to evaluate the specificity and sensitivity of the immunophenotyping panel and for automated cell population identification, respectively. Costs of misclassification (false targeting) were also accounted for by this analysis scheme. Ultimately, this analysis scheme will be applied to use of nanoparticle-antibody conjugates at therapeutic doses for targeted killing of leukemia stem cells preferentially to normal stem -progenitor cells.

  14. Autophagy in stem and progenitor cells.

    PubMed

    Rodolfo, Carlo; Di Bartolomeo, Sabrina; Cecconi, Francesco

    2016-02-01

    Autophagy is a highly conserved cellular process, responsible for the degradation and recycling of damaged and/or outlived proteins and organelles. This is the major cellular pathway, acting throughout the formation of cytosolic vesicles, called autophagosomes, for the delivering to lysosome. Recycling of cellular components through autophagy is a crucial step for cell homeostasis as well as for tissue remodelling during development. Impairment of this process has been related to the pathogenesis of various diseases, such as cancer and neurodegeneration, to the response to bacterial and viral infections, and to ageing. The ability of stem cells to self-renew and differentiate into the mature cells of the body renders this unique type of cell highly crucial to development and tissue renewal, not least in various diseases. During the last two decades, extensive knowledge about autophagy roles and regulation in somatic cells has been acquired; however, the picture about the role and the regulation of autophagy in the different types of stem cells is still largely unknown. Autophagy is a major player in the quality control and maintenance of cellular homeostasis, both crucial factors for stem cells during an organism's life. In this review, we have highlighted the most significant advances in the comprehension of autophagy regulation in embryonic and tissue stem cells, as well as in cancer stem cells and induced pluripotent cells.

  15. [Stem cells and cardiac regeneration].

    PubMed

    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.

  16. The ethics of stem cells revisited.

    PubMed

    de Miguel-Beriain, Iñigo

    2015-03-01

    Stem cells constitute one of the most promising tools for regenerative medicine. Thus, it seems morally compelling to explore all the sources that might provide us with them. However, some of these sources, such as somatic cell nuclear transfer, embryo destruction, or even induced pluripotency obtained by reprogramming have raised deep ethical issues. The aim of this paper is to reflect on the stem cell ethical debate at the current moment through an analysis of the academic literature. It will also provide an analysis of the ethical implications of the most relevant scientific advances that have happened in recent months or those which seem about to merge. PMID:25446134

  17. The ethics of stem cells revisited.

    PubMed

    de Miguel-Beriain, Iñigo

    2015-03-01

    Stem cells constitute one of the most promising tools for regenerative medicine. Thus, it seems morally compelling to explore all the sources that might provide us with them. However, some of these sources, such as somatic cell nuclear transfer, embryo destruction, or even induced pluripotency obtained by reprogramming have raised deep ethical issues. The aim of this paper is to reflect on the stem cell ethical debate at the current moment through an analysis of the academic literature. It will also provide an analysis of the ethical implications of the most relevant scientific advances that have happened in recent months or those which seem about to merge.

  18. A Prospective Study of an Alemtuzumab Containing Reduced-intensity Allogeneic Stem Cell Transplantation Program in Patients with Poor-Risk and Advanced Lymphoid Malignancies

    PubMed Central

    Sauter, Craig S.; Chou, Joanne F.; Papadopoulos, Esperanza B.; Perales, Miguel-Angel; Jakubowski, Ann A.; Young, James W.; Scordo, Michael; Giralt, Sergio; Castro-Malaspina, Hugo

    2015-01-01

    Reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT) have used alemtuzumab to abrogate the risk of graft-versus-host disease (GVHD). Thirty-eight advanced lymphoma patients underwent a prospective phase II study of melphalan, fludarabine and alemtuzumab containing RIC allo-SCT from 20 matched related and 18 unrelated donors with cyclosporin-A as GVHD prophylaxis. The cumulative incidence of grade II-IV acute GVHD at 3 months was 10.5% and three evaluable patients experienced chronic GVHD. Progression-free (PFS) and overall (OS) survival at 5 years is 25% (95% CI: 13-40) and 44% (95% CI: 28-59%) respectively. Previous high-dose therapy and autologous stem cell transplantation (HDT-ASCT) and elevated LDH at the time of allo-SCT resulted in inferior OS. Within this cohort of high-risk lymphoma patients, alemtuzumab containing RIC resulted in a low risk of GVHD and a high incidence of POD, especially in those with poor-risk features defined by elevated LDH pre-allo-SCT and previous HDT-ASCT. PMID:24528216

  19. A prospective study of an alemtuzumab containing reduced-intensity allogeneic stem cell transplant program in patients with poor-risk and advanced lymphoid malignancies.

    PubMed

    Sauter, Craig S; Chou, Joanne F; Papadopoulos, Esperanza B; Perales, Miguel-Angel; Jakubowski, Ann A; Young, James W; Scordo, Michael; Giralt, Sergio; Castro-Malaspina, Hugo

    2014-12-01

    Reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplant (allo-SCT) have used alemtuzumab to abrogate the risk of graft-versus-host disease (GVHD). Thirty-eight patients with advanced lymphoma underwent a prospective phase II study of melphalan, fludarabine and alemtuzumab containing RIC allo-SCT from 20 matched related and 18 unrelated donors with cyclosporine-A as GVHD prophylaxis. The cumulative incidence of grade II-IV acute GVHD at 3 months was 10.5% and three evaluable patients experienced chronic GVHD. Progression-free (PFS) and overall (OS) survival at 5 years was 25% (95% confidence interval [CI]: 13-40%) and 44% (95% CI: 28-59%), respectively. Previous high-dose therapy and autologous stem cell transplant (HDT-ASCT) and elevated lactate dehydrogenase (LDH) at the time of allo-SCT resulted in inferior OS. Within this cohort of patients with high-risk lymphoma, alemtuzumab containing RIC resulted in a low risk of GVHD and a high incidence of progression of disease, especially in those with poor-risk features defined by elevated LDH pre-allo-SCT and previous HDT-ASCT.

  20. Involvement of Plant Stem Cells or Stem Cell-Like Cells in Dedifferentiation.

    PubMed

    Jiang, Fangwei; Feng, Zhenhua; Liu, Hailiang; Zhu, Jian

    2015-01-01

    Dedifferentiation is the transformation of cells from a given differentiated state to a less differentiated or stem cell-like state. Stem cell-related genes play important roles in dedifferentiation, which exhibits similar histone modification and DNA methylation features to stem cell maintenance. Hence, stem cell-related factors possibly synergistically function to provide a specific niche beneficial to dedifferentiation. During callus formation in Arabidopsis petioles, cells adjacent to procambium cells (stem cell-like cells) are dedifferentiated and survive more easily than other cell types. This finding indicates that stem cells or stem cell-like cells may influence the dedifferentiating niche. In this paper, we provide a brief overview of stem cell maintenance and dedifferentiation regulation. We also summarize current knowledge of genetic and epigenetic mechanisms underlying the balance between differentiation and dedifferentiation. Furthermore, we discuss the correlation of stem cells or stem cell-like cells with dedifferentiation. PMID:26635851

  1. Adult Stem and Progenitor Cells

    NASA Astrophysics Data System (ADS)

    Geraerts, Martine; Verfaillie, Catherine M.

    The discovery of adult stem cells in most adult tissues is the basis of a number of clinical studies that are carried out, with therapeutic use of hematopoietic stem cells as a prime example. Intense scientific debate is still ongoing as to whether adult stem cells may have a greater plasticity than previously thought. Although cells with some features of embryonic stem cells that, among others, express Oct4, Nanog and SSEA1 are isolated from fresh tissue, it is not clear if the greater differentiation potential is acquired during cell culture. Moreover, adult more pluripotent cells do not have all pluripotent characteristics typical for embryonic stem cells. Recently, some elegant studies were published in which adult cells could be completely reprogrammed to embryonic stem cell-like cells by overexpression of some key transcription factors for pluripotency (Oct4, Sox2, Klf4 and c-Myc). It will be interesting for the future to investigate the exact mechanisms underlying this reprogramming and whether similar transcription factor pathways are present and/or can be activated in adult more pluripotent stem cells.

  2. The new stem cell biology.

    PubMed Central

    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 cells express a wide variety of adhesion and cytokine receptors and respond quickly with migration and podia extensions on exposure to cytokines. These data suggest an "Open Chromatin" model of stem cell regulation in which there is a fluctuating continuum in the stem cell/progenitor cell compartments, rather than a hierarchical relationship. These observations, along with progress in using low dose treatments and tolerization approaches, suggest many new therapeutic strategies involving stem cells and the creation of a new medical specialty; stemology. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:12053709

  3. Stem cells in pharmaceutical biotechnology.

    PubMed

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

    2011-11-01

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

  4. Bioprinting for stem cell research

    PubMed Central

    Tasoglu, Savas; Demirci, Utkan

    2012-01-01

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

  5. Stem cells for spine surgery.

    PubMed

    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.

  6. Myocardial infarction: stem cell transplantation for cardiac regeneration.

    PubMed

    Carvalho, Edmund; Verma, Paul; Hourigan, Kerry; Banerjee, Rinti

    2015-11-01

    It is estimated that by 2030, almost 23.6 million people will perish from cardiovascular disease, according to the WHO. The review discusses advances in stem cell therapy for myocardial infarction, including cell sources, methods of differentiation, expansion selection and their route of delivery. Skeletal muscle cells, hematopoietic cells and mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs)-derived cardiomyocytes have advanced to the clinical stage, while induced pluripotent cells (iPSCs) are yet to be considered clinically. Delivery of cells to the sites of injury and their subsequent retention is a major issue. The development of supportive scaffold matrices to facilitate stem cell retention and differentiation are analyzed. The review outlines clinical translation of conjugate stem cell-based cellular therapeutics post-myocardial infarction.

  7. What Undergraduates Misunderstand about Stem Cell Research

    ERIC Educational Resources Information Center

    Halverson, Kristy Lynn; Freyermuth, Sharyn K.; Siegel, Marcelle A.; Clark, Catharine G.

    2010-01-01

    As biotechnology-related scientific advances, such as stem cell research (SCR), are increasingly permeating the popular media, it has become ever more important to understand students' ideas about this issue. Very few studies have investigated learners' ideas about biotechnology. Our study was designed to understand the types of alternative…

  8. Pluripotent Stem Cells from Domesticated Mammals.

    PubMed

    Ezashi, Toshihiko; Yuan, Ye; Roberts, R Michael

    2016-01-01

    This review deals with the latest advances in the study of embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) from domesticated species, with a focus on pigs, cattle, sheep, goats, horses, cats, and dogs. Whereas the derivation of fully pluripotent ESC from these species has proved slow, reprogramming of somatic cells to iPSC has been more straightforward. However, most of these iPSC depend on the continued expression of the introduced transgenes, a major drawback to their utility. The persistent failure in generating ESC and the dependency of iPSC on ectopic genes probably stem from an inability to maintain the stability of the endogenous gene networks necessary to maintain pluripotency. Based on work in humans and rodents, achievement of full pluripotency will likely require fine adjustments in the growth factors and signaling inhibitors provided to the cells. Finally, we discuss the future utility of these cells for biomedical and agricultural purposes. PMID:26566158

  9. The advantages of hair follicle pluripotent stem cells over embryonic stem cells and induced pluripotent stem cells for regenerative medicine.

    PubMed

    Amoh, Yasuyuki; Katsuoka, Kensei; Hoffman, Robert M

    2010-12-01

    Multipotent adult stem cells have many potential therapeutic applications. Our recent findings suggest that hair follicles are a promising source of easily accessible multipotent stem cells. Stem cells in the hair follicle area express the neural stem cell marker nestin, suggesting that hair-follicle stem cells and neural stem cells have common features. Nestin-expressing hair follicle stem cells can form neurons and other cell types, and thus adult hair follicle stem cells could have important therapeutic applications, particularly for neurologic diseases. Transplanted hair follicle stem cells promote the functional recovery of injured peripheral nerve and spinal cord. Recent findings suggest that direct transplantation of hair-follicle stem cells without culture can promote nerve repair, which makes them potentially clinically practical. Human hair follicle stem cells as well as mouse hair follicle stem cells promote nerve repair and can be applied to test the hypothesis that human hair follicle stem cells can provide a readily available source of neurologically therapeutic stem cells. The use of hair follicle stem cells for nerve regeneration overcomes critical problems of embryonic stem cells or induced pluripotent stem cells in that the hair follicle stem cells are multipotent, readily accessible, non-oncogenic, and are not associated with ethical issues.

  10. Stem cells, colorectal cancer and cancer stem cell markers correlations.

    PubMed

    Cherciu, Irina; Bărbălan, A; Pirici, D; Mărgăritescu, C; Săftoiu, A

    2014-01-01

    : The idea of stem cells as being progenitors of cancer was initially controversial, but later supported by research in the field of leukemia and solid tumors. Afterwards, it was established that genetic abnormalities can affect the stem and progenitor cells, leading to uncontrolled replication and deregulated differentiation. These alterations will cause the changeover to cancerous stem cells (CSC) having two main characteristics: tumor initiation and maintenance. This review will focus on the colorectal cancer stem cell (CR-CSCs) theory which provides a better understanding of different tumor processes: initiation, aggressive growth, recurrence, treatment resistance and metastasis. A search in PubMed/Medline was performed using the following keywords: colorectal cancer stem cells (CR-CSCs), colorectal neoplasms stem cells, colorectal cancer stem cell (CR-CSCs) markers, etc. Electronic searches were supplemented by hand searching reference lists, abstracts and proceedings from meetings. Isolation of CR-CSCs can be achieved by targeting and selecting subpopulation of tumor cells based on expression of one or multiple cell surface markers associated with cancer self-renewal, markers as: CD133, CD166, CD44, CD24, beta1 integrin-CD29, Lgr5, EpCAM (ESA), ALDH-1, Msi-1, DCAMLK1 or EphB receptors. The identification and localization of CR-CSCs through different markers will hopefully lead to a better stratification of prognosis and treatment response, as well as the development of new effective strategies for cancer management.

  11. FDA Warns About Stem Cell Claims

    MedlinePlus

    ... Home For Consumers Consumer Updates FDA Warns About Stem Cell Claims Share Tweet Linkedin Pin it More sharing ... blood-forming system. back to top Regulation of Stem Cells FDA regulates stem cells in the U.S. to ...

  12. LncRNAs in Stem Cells

    PubMed Central

    Hu, Shanshan; Shan, Ge

    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 summarized, and insights into current and future studies are presented. PMID:26880946

  13. Engineering Approaches Toward Deconstructing and Controlling the Stem Cell Environment

    PubMed Central

    Edalat, Faramarz; Bae, Hojae; Manoucheri, Sam; Cha, Jae Min; Khademhosseini, Ali

    2012-01-01

    Stem cell-based therapeutics have become a vital component in tissue engineering and regenerative medicine. The microenvironment within which stem cells reside, i.e. the niche, plays a crucial role in regulating stem cell self-renewal and differentiation. However, current biological techniques lack the means to recapitulate the complexity of this microenvironment. Nano- and microengineered materials offer innovative methods to: (1) deconstruct the stem cell niche to understand the effects of individual elements; (2) construct complex tissue-like structures resembling the niche to better predict and control cellular processes; and (3) transplant stem cells or activate endogenous stem cell populations for regeneration of aged or diseased tissues. Here, we highlight some of the latest advances in this field and discuss future applications and directions of the use of nano- and microtechnologies for stem cell engineering. PMID:22101755

  14. Stem Cells, Retinal Ganglion Cells, and Glaucoma

    PubMed Central

    Sluch, Valentin M.; Zack, Donald J.

    2015-01-01

    Retinal ganglion cells represent an essential neuronal cell type for vision. These cells receive inputs from light-sensing photoreceptors via retinal interneurons and then relay these signals to the brain for further processing. Retinal ganglion cell diseases that result in cell death, e.g. glaucoma, often lead to permanent damage since mammalian nerves do not regenerate. Stem cell differentiation can generate cells needed for replacement or can be used to generate cells capable of secreting protective factors to promote survival. In addition, stem cell-derived cells can be used in drug screening research. Here, we discuss the current state of stem cell research potential for interference in glaucoma and other optic nerve diseases with a focus on stem cell differentiation to retinal ganglion cells. PMID:24732765

  15. Gastrointestinal stem cell up-to-date.

    PubMed

    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.

  16. Keratinocyte stem cells: a commentary.

    PubMed

    Potten, Christopher S; Booth, Catherine

    2002-10-01

    For many years it has been widely accepted that stem cells play a crucial role in adult tissue maintenance. The concept that the renewing tissues of the body contain a small subcompartment of self-maintaining stem cells, upon which the entire tissue is dependent, is also now accepted as applicable to all renewing tissues. Gene therapy and tissue engineering are driving considerable interest in the clinical application of such hierarchically organized cellular compartments. Recent initial observations have provided a tantalizing insight into the large pluripotency of these cells. Indeed, scientists are now beginning to talk about the possible totipotency of some adult tissue stem cells. Such work is currently phenomenologic, but analysis of data derived from genomics and proteomics, identifying the crucial control signals involved, will soon provide a further impetus to stem cell biology with far reaching applications. The epidermis with its relatively simple structure, ease of accessibility, and the ability to grow its cells in vitro is one obvious target tissue for testing stem cell manipulation theories. It is crucial, however, that the normal keratinocyte stem cell is thoroughly characterized prior to attempting to manipulate its pluripotency. This commentary assesses the data generated to date and critically discusses the conclusions that have been drawn. Our current level of understanding, or lack of understanding, of the keratinocyte stem cell is reviewed.

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

    PubMed

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

    2015-04-01

    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 stem cells and amniotic stem cells, with respect to their differentiation lineages, passage numbers and animal model studies. Amniotic stem cells have a greater number of differentiation lineages than dental stem cells. On the contrary, dental stem cells showed the highest number of passages compared to amniotic stem cells. For tissue regeneration based on animal studies, amniotic stem cells showed the shortest time to regenerate in comparison with dental stem cells.

  18. Cell rheology: Stressed-out stem cells

    NASA Astrophysics Data System (ADS)

    Holle, Andrew W.; Engler, Adam J.

    2010-01-01

    Experiments have shown that the physical characteristics of the matrix surrounding a stem cell can affect its behaviour. This picture gets further complicated by studies of stem cells and their differentiated counterparts that show that the cells' own softness also has a clear role in how they respond to stress.

  19. Stem cells and ethics: current issues.

    PubMed

    McCormick, Jennifer Blair; Huso, Holly A

    2010-04-01

    Much attention has recently turned to the promise and potential of human stem cells in therapeutic applications for the repair of cardiac tissue. The advances being made in the laboratory are exciting, and the pace at which research using human stem cells is moving from bench to bedside is extraordinary. The social, ethical, and policy considerations embedded within this area of research also require a large amount of attention and deliberation so that the scientific progress is able to successfully continue without social backlash.

  20. Stem cells as drug delivery methods: application of stem cell secretome for regeneration.

    PubMed

    Tran, Christine; Damaser, Margot S

    2015-03-01

    Mesenchymal stem cells (MSCs) are a unique cell population defined by their ability to indefinitely self-renew, differentiate into multiple cell lineages, and form clonal cell populations. It was originally thought that this ability for broad plasticity defined the therapeutic potential of MSCs. However, an expanding body of recent literature has brought growing awareness to the remarkable array of bioactive molecules produced by stem cells. This protein milieu or "secretome" comprises a diverse host of cytokines, chemokines, angiogenic factors, and growth factors. The autocrine/paracrine role of these molecules is being increasingly recognized as key to the regulation of many physiological processes including directing endogenous and progenitor cells to sites of injury as well as mediating apoptosis, scarring, and tissue revascularization. In fact, the immunomodulatory and paracrine role of these molecules may predominantly account for the therapeutic effects of MSCs given that many in vitro and in vivo studies have demonstrated limited stem cell engraftment at the site of injury. While the study of such a vast protein array remains challenging, technological advances in the field of proteomics have greatly facilitated our ability to analyze and characterize the stem cell secretome. Thus, stem cells can be considered as tunable pharmacological storehouses useful for combinatorial drug manufacture and delivery. As a cell-free option for regenerative medicine therapies, stem cell secretome has shown great potential in a variety of clinical applications including the restoration of function in cardiovascular, neurodegenerative, oncologic, and genitourinary pathologies.

  1. Stem cell therapy without the cells

    PubMed Central

    Maguire, Greg

    2013-01-01

    As an example of the burgeoning importance of stem cell therapy, this past month the California Institute for Regenerative Medicine (CIRM) has approved $70 million to create a new network of stem cell clinical trial centers. Much work in the last decade has been devoted to developing the use of autologous and allogeneic adult stem cell transplants to treat a number of conditions, including heart attack, dementia, wounds, and immune system-related diseases. The standard model teaches us that adult stem cells exists throughout most of the body and provide a means to regenerate and repair most tissues through replication and differentiation. Although we have often witnessed the medical cart placed in front of the scientific horse in the development of stem cell therapies outside of academic circles, great strides have been made, such as the use of purified stem cells1 instead of whole bone marrow transplants in cancer patients, where physicians avoid re-injecting the patients with their own cancer cells.2 We most often think of stem cell therapy acting to regenerate tissue through replication and then differentiation, but recent studies point to the dramatic effects adult stem cells exert in the repair of various tissues through the release of paracrine and autocrine substances, and not simply through differentiation. Indeed, up to 80% of the therapeutic effect of adult stem cells has been shown to be through paracrine mediated actions.3 That is, the collected types of molecules released by the stem cells, called the secretome, or stem cell released molecules (SRM), number in the 100s, including proteins, microRNA, growth factors, antioxidants, proteasomes, and exosomes, and target a multitude of biological pathways through paracrine actions. The composition of the different molecule types in SRM is state dependent, and varies with cell type and conditions such as age and environment. PMID:24567776

  2. Microbioreactors for Stem Cell Research

    NASA Astrophysics Data System (ADS)

    Freytes, Donald O.; Vunjak-Novakovic, Gordana

    During tissue development and regeneration, stem cells respond to the entire milieu of their environment, through dynamic interactions with the surrounding cells, extracellular matrix, and cascades of molecular and physical regulatory factors. A new generation of culture systems is emerging to offer some of the biological fidelity of a whole organism within highly controllable in vitro settings and provide the cultured cells with the combinations of factors they normally encounter in vivo. There is a growing notion that such "biomimetic" systems are essential for unlocking the full potential of stem cells - for tissue regeneration as well as biological research. In this chapter, we discuss the biological principles for designing biologically inspired culture systems for stem cell research and focus on the control of stem cell microenvironment through surface patterning, microfluidics, and electrical stimulation.

  3. Stem cells and combinatorial science.

    PubMed

    Fang, Yue Qin; Wong, Wan Qing; Yap, Yan Wen; Orner, Brendan P

    2007-09-01

    Stem cell-based technologies have the potential to help cure a number of cell degenerative diseases. Combinatorial and high throughput screening techniques could provide tools to control and manipulate the self-renewal and differentiation of stem cells. This review chronicles historic and recent progress in the stem cell field involving both pluripotent and multipotent cells, and it highlights relevant cellular signal transduction pathways. This review further describes screens using libraries of soluble, small-molecule ligands, and arrays of molecules immobilized onto surfaces while proposing future trends in similar studies. It is hoped that by reviewing both the stem cell and the relevant high throughput screening literature, this paper can act as a resource to the combinatorial science community.

  4. The embryonic stem cell test.

    PubMed

    Schulpen, Sjors H W; Piersma, Aldert H

    2013-01-01

    The embryonic stem cell test is an animal-free alternative test method for developmental toxicity. Mouse embryonic stem cells are cultured in a hanging drop method to form embryoid bodies. These embryoid bodies, when plated on tissue culture dishes, differentiate to form contracting myocardial cell foci within 10 days. Inhibition of cardiomyocyte differentiation by test compounds serves as the end point of the assay, as monitored by counting contracting muscle foci under the microscope.

  5. Application of stem cells for articular cartilage regeneration.

    PubMed

    Hwang, Nathaniel S; Elisseeff, Jennifer

    2009-01-01

    Articular cartilage is a highly organized tissue lacking self-regeneration capacity upon lesion. Current surgical intervention by application of in vitro-expanded autologous chondrocytes transplantation procedure is associated with several disadvantages, including donor-site morbidity and inferior fibrocartilage formation at the defect site. However, recent advancements in tissue engineering have provided notable strategies for stem cell-based therapies and articular cartilage tissue engineering. In this review, we discuss the current strategies to engineer cartilage tissues from adult stem cells and human embryonic stem cell-derived cells. The characteristics of adult stem cells, the microenvironmental control of cell fate determination, and the limitation imposed by the intrinsic nature of stem cells are discussed. The strategy to commit the stem cells for functional cartilage tissues in vivo is also discussed.

  6. Harvesting dental stem cells - Overview

    PubMed Central

    Sunil, P. M.; Manikandan, Ramanathan; Muthumurugan; Yoithapprabhunath, Thukanayakanpalayam Ragunathan; Sivakumar, Muniapillai

    2015-01-01

    Dental stem cells have recently become one of the widely researched areas in dentistry. Ever since the identification of stem cells from various dental tissues like deciduous teeth, dental papilla, periodontal ligament and third molars, storing them for future use for various clinical applications was being explored. Dental stem cells were harvested and isolated using various techniques by different investigators and laboratories. This article explains the technical aspects of preparing the patient, atraumatic and aseptic removal of the tooth and its safe transportation and preservation for future expansion. PMID:26538883

  7. Stem cells, dot-com.

    PubMed

    Liang, Bryan A; Mackey, Tim K

    2012-09-12

    Direct-to-consumer (DTC) advertising of suspect goods and services has burgeoned because of the Internet. Despite very limited approval for use, DTC stem cell-marketed "treatments" have emerged for an array of conditions, creating global public health and safety risks. However, it remains unclear whether such use of stem cells is subject to drugs or biologics regulations. To address this gap, regulatory agencies should be given clear authority, and the international community should create a framework for appropriate stem cell use. In addition, consumer protection laws should be used to scrutinize providers.

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

    PubMed

    Mahla, Ranjeet Singh

    2016-01-01

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

  9. Stem Cells Applications in Regenerative Medicine and Disease Therapeutics

    PubMed Central

    2016-01-01

    Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation. PMID:27516776

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

    PubMed

    Mahla, Ranjeet Singh

    2016-01-01

    Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation. PMID:27516776

  11. Engineering the niche for stem cells.

    PubMed

    Tan, Shawna; Barker, Nicholas

    2013-12-01

    Much has been made about the potential for stem cells in regenerative medicine but the reality is that the development of actual therapies has been slow. Adult stem cells rely heavily on the assortment of biochemical and biophysical elements that constitute the local microenvironment in which they exist. One goal of biomedicine is to create an artificial yet biofunctional niche to support multipotency, differentiation and proliferation. Such tools would facilitate more conclusive experimentation by biologists, pharmaceutical scientists and tissue engineers. While many bioengineering techniques and platforms are already in use, technological innovations now allow this to be done at a higher resolution and specificity. Ultimately, the multidisciplinary integration of engineering and biology will allow the niche to be generated at a scale that can be clinically exploited. Using the systems that constitute the intestinal, hematopoietic and epidermal tissues, this article summarizes the various approaches and tools currently employed to recreate stem cell niches and also explores recent advances in the field. PMID:24274105

  12. Engineering the niche for stem cells.

    PubMed

    Tan, Shawna; Barker, Nicholas

    2013-12-01

    Much has been made about the potential for stem cells in regenerative medicine but the reality is that the development of actual therapies has been slow. Adult stem cells rely heavily on the assortment of biochemical and biophysical elements that constitute the local microenvironment in which they exist. One goal of biomedicine is to create an artificial yet biofunctional niche to support multipotency, differentiation and proliferation. Such tools would facilitate more conclusive experimentation by biologists, pharmaceutical scientists and tissue engineers. While many bioengineering techniques and platforms are already in use, technological innovations now allow this to be done at a higher resolution and specificity. Ultimately, the multidisciplinary integration of engineering and biology will allow the niche to be generated at a scale that can be clinically exploited. Using the systems that constitute the intestinal, hematopoietic and epidermal tissues, this article summarizes the various approaches and tools currently employed to recreate stem cell niches and also explores recent advances in the field.

  13. A perspective on stem cell modeling of amyotrophic lateral sclerosis.

    PubMed

    de Boer, A Sophie; Eggan, Kevin

    2015-01-01

    Amyotrophic lateral sclerosis is a complex neurodegenerative disease. Limitations in animal models have impeded progress in studying disease pathology and potential drug discovery. Here, we will review recent advances in the development of stem cell models for the study of ALS. Additionally, we will discuss the progress toward therapeutic development derived from these stem cell based assays.

  14. Advances in cell culture

    SciTech Connect

    Maramorosch, K. )

    1987-01-01

    This book presents papers on advances in cell culture. Topics covered include: Genetic changes in the influenza viruses during growth in cultured cells; The biochemistry and genetics of mosquito cells in culture; and Tree tissue culture applications.

  15. The Clinical Status of Stem Cell Therapy for Ischemic Cardiomyopathy

    PubMed Central

    Wang, Xianyun; Zhang, Jun; Zhang, Fan; Li, Jing; Li, Yaqi; Tan, Zirui; Hu, Jie; Qi, Yixin; Yan, Baoyong

    2015-01-01

    Ischemic cardiomyopathy (ICM) is becoming a leading cause of morbidity and mortality in the whole world. Stem cell-based therapy is emerging as a promising option for treatment of ICM. Several stem cell types including cardiac-derived stem cells (CSCs), bone marrow-derived stem cells, mesenchymal stem cells (MSCs), skeletal myoblasts (SMs), and CD34+ and CD 133+ stem cells have been applied in clinical researches. The clinical effect produced by stem cell administration in ICM mainly depends on the transdifferentiation and paracrine effect. One important issue is that low survival and residential rate of transferred stem cells in the infracted myocardium blocks the effective advances in cardiac improvement. Many other factors associated with the efficacy of cell replacement therapy for ICM mainly including the route of delivery, the type and number of stem cell infusion, the timing of injection, patient's physical condition, the particular microenvironment onto which the cells are delivered, and clinical condition remain to be addressed. Here we provide an overview of the pros and cons of these transferred cells and discuss the current state of their therapeutic potential. We believe that stem cell translation will be an ideal option for patients following ischemic heart disease in the future. PMID:26101528

  16. Neural stem cell-based treatment for neurodegenerative diseases.

    PubMed

    Kim, Seung U; Lee, Hong J; Kim, Yun B

    2013-10-01

    Human neurodegenerative diseases such as Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) are caused by a loss of neurons and glia in the brain or spinal cord. Neurons and glial cells have successfully been generated from stem cells such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs) and neural stem cells (NSCs), and stem cell-based cell therapies for neurodegenerative diseases have been developed. A recent advance in generation of a new class of pluripotent stem cells, induced pluripotent stem cells (iPSCs), derived from patients' own skin fibroblasts, opens doors for a totally new field of personalized medicine. Transplantation of NSCs, neurons or glia generated from stem cells in animal models of neurodegenerative diseases, including PD, HD, ALS and AD, demonstrates clinical improvement and also life extension of these animals. Additional therapeutic benefits in these animals can be provided by stem cell-mediated gene transfer of therapeutic genes such as neurotrophic factors and enzymes. Although further research is still needed, cell and gene therapy based on stem cells, particularly using neurons and glia derived from iPSCs, ESCs or NSCs, will become a routine treatment for patients suffering from neurodegenerative diseases and also stroke and spinal cord injury.

  17. Drosophila's contribution to stem cell research

    PubMed Central

    Singh, Gyanesh

    2016-01-01

    The discovery of Drosophila stem cells with striking similarities to mammalian stem cells has brought new hope for stem cell research. Recent developments in Drosophila stem cell research is bringing wider opportunities for contemporary stem cell biologists. In this regard, Drosophila germ cells are becoming a popular model of stem cell research. In several cases, genes that controlled Drosophila stem cells were later discovered to have functional homologs in mammalian stem cells. Like mammals, Drosophila germline stem cells (GSCs) are controlled by both intrinsic as well as external signals. Inside the Drosophila testes, germline and somatic stem cells form a cluster of cells (the hub). Hub cells depend on JAK-STAT signaling, and, in absence of this signal, they do not self-renew. In Drosophila, significant changes occur within the stem cell niche that contributes to a decline in stem cell number over time. In case of aging Drosophila, somatic niche cells show reduced DE-cadherin and unpaired (Upd) proteins. Unpaired proteins are known to directly decrease stem cell number within the niches, and, overexpression of upd within niche cells restored GSCs in older males also . Stem cells in the midgut of Drosophila are also very promising. Reduced Notch signaling was found to increase the number of midgut progenitor cells. On the other hand, activation of the Notch pathway decreased proliferation of these cells. Further research in this area should lead to the discovery of additional factors that regulate stem and progenitor cells in Drosophila. PMID:26180635

  18. Drosophila's contribution to stem cell research.

    PubMed

    Singh, Gyanesh

    2015-01-01

    The discovery of Drosophila stem cells with striking similarities to mammalian stem cells has brought new hope for stem cell research. Recent developments in Drosophila stem cell research is bringing wider opportunities for contemporary stem cell biologists. In this regard, Drosophila germ cells are becoming a popular model of stem cell research. In several cases, genes that controlled Drosophila stem cells were later discovered to have functional homologs in mammalian stem cells. Like mammals, Drosophila germline stem cells (GSCs) are controlled by both intrinsic as well as external signals. Inside the Drosophila testes, germline and somatic stem cells form a cluster of cells (the hub). Hub cells depend on JAK-STAT signaling, and, in absence of this signal, they do not self-renew. In Drosophila, significant changes occur within the stem cell niche that contributes to a decline in stem cell number over time. In case of aging Drosophila, somatic niche cells show reduced DE-cadherin and unpaired (Upd) proteins. Unpaired proteins are known to directly decrease stem cell number within the niches, and, overexpression of upd within niche cells restored GSCs in older males also . Stem cells in the midgut of Drosophila are also very promising. Reduced Notch signaling was found to increase the number of midgut progenitor cells. On the other hand, activation of the Notch pathway decreased proliferation of these cells. Further research in this area should lead to the discovery of additional factors that regulate stem and progenitor cells in Drosophila. PMID:26180635

  19. Improved survival of children with advanced neuroblastoma treated by intensified therapy including myeloablative chemotherapy with stem cell transplantation: a retrospective analysis from the Tohoku Neuroblastoma Study Group.

    PubMed

    Imaizumi, M; Watanabe, A; Kikuta, A; Takano, T; Ito, E; Shimizu, T; Tsuchiya, S; Iinuma, K; Konno, T; Ohi, R; Hayashi, Y

    2001-10-01

    In the hospitals of the Tohoku Neuroblastoma Study Group (TNBSG), treatment for children with advanced neuroblastoma (NB) was intensified in the mid-1990's with the introduction of myeloablative therapy (MT) with stem cell transplantation (SCT) including the use of autologous peripheral blood stem cells (PBSC) and bone marrow transplantation (BMT). In this report, we examined whether the intensified therapy improved the outcome of children with advanced NB (age> 12 months) who were diagnosed between 1991 and 1997. Patients were 36 children (23 boys and 13 girls) with an average age of 3.4 years (range; 1 to 14 years). Six of them had stage III disease, and the other 30 had stage IV. They were treated initially with induction chemotherapy, surgery, and post-operative chemoradiotherapy, after which 17 of them continued further chemotherapy and the other 19 received MT/SCT (18 with PBSCT and 1 with BMT). Progression-free survival (PFS) rate at seven years from diagnosis was 43.5% for all patients, 66.7% for stage III patients and 38.2% for stage IV patients. The difference between stage III and IV patients was not significant. Among the 30 patients with stage IV disease, PFS at seven years was significantly higher in the 19 patients who received MT/SCT (55.6%) than in the 11 patients who did not receive it (12.5%). There was no difference in clinical and biological risk factors between these two groups, except for the proportion of patients with favorable response to initial therapy (36% and 80% for patients without and with MT/SCT, respectively). Furthermore, the proportion of patients with N-myc amplification was significantly higher in patients with progressive disease (PD) after MT/SCT than in those in CR after MT/SCT. The results of this retrospective study of children with advanced NB suggest that therapy intensification involving MT/SCT might result in lengthened survival time for patients with stage IV disease, and that post-transplant PD remains a risk for

  20. Diabetes and stem cell function.

    PubMed

    Fujimaki, Shin; Wakabayashi, Tamami; Takemasa, Tohru; Asashima, Makoto; Kuwabara, Tomoko

    2015-01-01

    Diabetes mellitus is one of the most common serious metabolic diseases that results in hyperglycemia due to defects of insulin secretion or insulin action or both. The present review focuses on the alterations to the diabetic neuronal tissues and skeletal muscle, including stem cells in both tissues, and the preventive effects of physical activity on diabetes. Diabetes is associated with various nervous disorders, such as cognitive deficits, depression, and Alzheimer's disease, and that may be caused by neural stem cell dysfunction. Additionally, diabetes induces skeletal muscle atrophy, the impairment of energy metabolism, and muscle weakness. Similar to neural stem cells, the proliferation and differentiation are attenuated in skeletal muscle stem cells, termed satellite cells. However, physical activity is very useful for preventing the diabetic alteration to the neuronal tissues and skeletal muscle. Physical activity improves neurogenic capacity of neural stem cells and the proliferative and differentiative abilities of satellite cells. The present review proposes physical activity as a useful measure for the patients in diabetes to improve the physiological functions and to maintain their quality of life. It further discusses the use of stem cell-based approaches in the context of diabetes treatment.

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

    PubMed

    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

  2. Autologous stem cells for personalised medicine.

    PubMed

    Prasongchean, Weerapong; Ferretti, Patrizia

    2012-09-15

    Increasing understanding of stem cell biology, the ability to reprogramme differentiated cells to a pluripotent state and evidence of multipotency in certain adult somatic stem cells has opened the door to exciting therapeutic advances as well as a great deal of regulatory and ethical issues. Benefits will come from the possibility of modelling human diseases and develop individualised therapies, and from their use in transplantation and bioengineering. The use of autologous stem cells is highly desirable, as it avoids the problem of tissue rejection, and also reduces ethical and regulatory issues. Identification of the most appropriate cell sources for different potential applications, development of appropriate clinical grade methodologies and large scale well controlled clinical trials will be essential to assess safety and value of cell based therapies, which have been generating much hope, but are by and large not yet close to becoming standard clinical practice. We briefly discuss stem cells in the context of tissue repair and regenerative medicine, with a focus on individualised clinical approaches, and give examples of sources of autologous cells with potential for clinical intervention.

  3. Large animal models for stem cell therapy.

    PubMed

    Harding, John; Roberts, R Michael; Mirochnitchenko, Oleg

    2013-03-28

    for the future development of large animal models to facilitate advances in stem cell-based regenerative medicine.

  4. Large animal models for stem cell therapy

    PubMed Central

    2013-01-01

    for the future development of large animal models to facilitate advances in stem cell-based regenerative medicine. PMID:23672797

  5. Intestinal Stem Cells: Got Calcium?

    PubMed

    Nászai, Máté; Cordero, Julia B

    2016-02-01

    Calcium ions are well-known intracellular signalling molecules. A new study identifies local cytoplasmic calcium as a central integrator of metabolic and proliferative signals in Drosophila intestinal stem cells. PMID:26859268

  6. The reprogramming therapy for a patient with advanced hepatocellular carcinoma by using human-induced pluripotent stem (iPS) cells technology.

    PubMed

    Moriguchi, Hisashi; Madson, Joren

    2013-01-01

    Therapeutic methods to reprogramme and destroy human solid tumour cells have not been developed. We show a proof-of-concept for the direct reprogramming therapy of human solid tumour cells. Furthermore, our study is the first to report on the development of a new treatment by using human-induced pluripotent stem cells technology.

  7. Stem Cell Models of Human Brain Development.

    PubMed

    Kelava, Iva; Lancaster, Madeline A

    2016-06-01

    Recent breakthroughs in pluripotent stem cell technologies have enabled a new class of in vitro systems for functional modeling of human brain development. These advances, in combination with improvements in neural differentiation methods, allow the generation of in vitro systems that reproduce many in vivo features of the brain with remarkable similarity. Here, we describe advances in the development of these methods, focusing on neural rosette and organoid approaches, and compare their relative capabilities and limitations. We also discuss current technical hurdles for recreating the cell-type complexity and spatial architecture of the brain in culture and offer potential solutions.

  8. Stem cell potential of the mammalian gonad

    PubMed Central

    Liu, Chia-Feng; Barsoum, Ivraym; Gupta, Rupesh; Hofmann, Marie-Claude; Yao, Humphrey Hung-Chang

    2010-01-01

    Stem cells have enormous potential for therapeutic application because of their ability to self-renew and differentiate into different cell types. Gonads, which consist of somatic cells and germ cells, are the only organs capable of transmitting genetic materials to the offspring. Germ-line stem cells and somatic stem cells have been found in the testis; however, the presence of stem cells in the ovary remains controversial. In this review, we discuss studies focusing on whether stem cell properties are present in the different cell types of male and female gonads and their implications on stem cell research. PMID:19482665

  9. Pancreatic stem cells remain unresolved.

    PubMed

    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.

  10. Gene and stem cell therapy for diabetes.

    PubMed

    Calne, Roy Y; Ghoneim, Mohamed A; Lee, K O; Uin, Gan Shu

    2013-01-01

    Gene and stem cell therapy has been on the scientific agenda in many laboratories for more than 20 years. The literature is enormous, but practical applications have been few. Recently advances in stem cell biology and gene therapy are clarifying some of the issues. I have made a few observations concerning our own studies on bone marrow mesenchymal stem cells cultured to produce a small percentage of insulin-producing cells and human insulin gene engineered into Lenti and AA viruses. The aim of clinical application would still seem to be several years away, if all goes well. The first step will be to produce enough insulin-secreting cells to be of potential value to patients. The next crucial question will be how to persuade the cells to respond to blood glucose levels swiftly and appropriately. With both stem cell and gene therapy, another important factor will be to ensure that any positive results will continue long enough to be preferable to insulin injections. PMID:25095498

  11. MS Stem Cell Therapy Succeeds but Poses Risks

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_159285.html MS Stem Cell Therapy Succeeds But Poses Risks Toxic ... transplant could represent a major advance against aggressive multiple sclerosis, experts say. This new treatment destroys the immune ...

  12. Stem cell applications in diabetes.

    PubMed

    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.

  13. Targeting Breast Cancer Stem Cells

    PubMed Central

    McDermott, Sean P.; Wicha, Max S.

    2010-01-01

    The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self renewing cell populations that constitute the bulk of the tumor. Although, the CSC hypothesis does not directly address the cell of origin of cancer, it is postulated that tissue-resident stem or progenitors are the most common targets of transformation. Clinically, CSCs are predicted to mediate tumor recurrence after chemo- and radiation-therapy due to the relative inability of these modalities to effectively target CSCs. If this is the case, then CSC must be efficiently targeted to achieve a true cure. Similarities between normal and malignant stem cells, at the levels of cell-surface proteins, molecular pathways, cell cycle quiescence, and microRNA signaling present challenges in developing CSC-specific therapeutics. Approaches to targeting CSCs include the development of agents targeting known stem cell regulatory pathways as well as unbiased high-throughput siRNA or small-molecule screening. Based on studies of pathways present in normal stem cells, recent work has identified potential “Achilles heals” of CSC, whereas unbiased screening provides opportunities to identify new pathways utilized by CSC as well as develop potential therapeutic agents. Here, we review both approaches and their potential to effectively target breast CSC. PMID:20599450

  14. [Cell transplant and regenerative therapy with stem cells].

    PubMed

    Prósper, F; Gavira, J J; Herreros, J; Rábago, G; Luquin, R; Moreno, J; Robles, J E; Redondo, P

    2006-01-01

    One of the fields of medicine that has raised the most expectations in recent years is cell therapy with stem cells. The isolation of human embryo cells, the apparent and unexpected potentiality of adult stem cells and the development of gene therapy lead us to imagine a hopeful future for a significant number of diseases that are at present incurable. In this article we will sketch out the panorama of stem cell research, describing the main achievements in this field as well as some of the questions that await an answer. In spite of the great expectations, it is essential that we maintain a critical and realistic spirit when it comes to analysing the scientific advances in this area.

  15. Redox Regulation in Cancer Stem Cells

    PubMed Central

    Ding, Shijie; Li, Chunbao; Cheng, Ninghui; Cui, Xiaojiang; Xu, Xinglian; Zhou, Guanghong

    2015-01-01

    Reactive oxygen species (ROS) and ROS-dependent (redox regulation) signaling pathways and transcriptional activities are thought to be critical in stem cell self-renewal and differentiation during growth and organogenesis. Aberrant ROS burst and dysregulation of those ROS-dependent cellular processes are strongly associated with human diseases including many cancers. ROS levels are elevated in cancer cells partially due to their higher metabolism rate. In the past 15 years, the concept of cancer stem cells (CSCs) has been gaining ground as the subpopulation of cancer cells with stem cell-like properties and characteristics have been identified in various cancers. CSCs possess low levels of ROS and are responsible for cancer recurrence after chemotherapy or radiotherapy. Unfortunately, how CSCs control ROS production and scavenging and how ROS-dependent signaling pathways contribute to CSCs function remain poorly understood. This review focuses on the role of redox balance, especially in ROS-dependent cellular processes in cancer stem cells (CSCs). We updated recent advances in our understanding of ROS generation and elimination in CSCs and their effects on CSC self-renewal and differentiation through modulating signaling pathways and transcriptional activities. The review concludes that targeting CSCs by manipulating ROS metabolism/dependent pathways may be an effective approach for improving cancer treatment. PMID:26273424

  16. Application of Stem Cell Technology in Dental Regenerative Medicine

    PubMed Central

    Feng, Ruoxue; Lengner, Chistopher

    2013-01-01

    Significance In this review, we summarize the current literature regarding the isolation and characterization of dental tissue-derived stem cells and address the potential of these cell types for use in regenerative cell transplantation therapy. Recent Advances Looking forward, platforms for the delivery of stem cells via scaffolds and the use of growth factors and cytokines for enhancing dental stem cell self-renewal and differentiation are discussed. Critical Issues We aim to understand the developmental origins of dental tissues in an effort to elucidate the molecular pathways governing the genesis of somatic dental stem cells. The advantages and disadvantages of several dental stem cells are discussed, including the developmental stage and specific locations from which these cells can be purified. In particular, stem cells from human exfoliated deciduous teeth may act as a very practical and easily accessibly reservoir for autologous stem cells and hold the most value in stem cell therapy. Dental pulp stem cells and periodontal ligament stem cells should also be considered for their triple lineage differentiation ability and relative ease of isolation. Further, we address the potentials and limitations of induced pluripotent stem cells as a cell source in dental regenerative. Future Directions From an economical and a practical standpoint, dental stem cell therapy would be most easily applied in the prevention of periodontal ligament detachment and bone atrophy, as well as in the regeneration of dentin-pulp complex. In contrast, cell-based tooth replacement due to decay or other oral pathology seems, at the current time, an untenable approach. PMID:24527351

  17. Dormancy activation mechanism of tracheal stem cells

    PubMed Central

    Li, Xin; Xu, Jing-xian; Jia, Xin-Shan; Li, Wen-ya; Han, Yi-chen; Wang, En-hua; Li, Fang

    2016-01-01

    Accurate markers and molecular mechanisms of stem cell dormancy and activation are poorly understood. In this study, the anti-cancer drug, 5-fluorouracil, was used to selectively kill proliferating cells of human bronchial epithelial (HBE) cell line. This method can enrich and purify stem cell population. The dormant versus active status of stem cells was determined by phosphorylation of RNAp II Ser2. The surviving stem cells were cultured to form stem cell spheres expressing stem cell markers and transplanted into nude mice to form a teratoma. The results demonstrated the properties of stem cells and potential for multi-directional differentiation. Bisulfite sequencing polymerase chain reaction showed that demethylation of the Sox2 promoter by 5-FU resulted in Sox2 expression in the dormant stem cells. This study shows that the dormancy and activation of HBE stem cells is closely related to epigenetic modification. PMID:27009861

  18. Stem cell regulation: Implications when differentiated cells regulate symmetric stem cell division.

    PubMed

    Høyem, Marte Rørvik; Måløy, Frode; Jakobsen, Per; Brandsdal, Bjørn Olav

    2015-09-01

    We use a mathematical model to show that if symmetric stem cell division is regulated by differentiated cells, then changes in the population dynamics of the differentiated cells can lead to changes in the population dynamics of the stem cells. More precisely, the relative fitness of the stem cells can be affected by modifying the death rate of the differentiated cells. This result is interesting because stem cells are less sensitive than differentiated cells to environmental factors, such as medical therapy. Our result implies that stem cells can be manipulated indirectly by medical treatments that target the differentiated cells. PMID:25997796

  19. Clinical translation of stem cells: insight for cartilage therapies

    PubMed Central

    Lee, Jennifer K.; Responte, Donald J.; Cissell, Derek D.; Hu, Jerry C.; Nolta, Jan A.; Athanasiou, Kyriacos A.

    2015-01-01

    The limited regenerative capacity of articular cartilage and deficiencies of current treatments have motivated the investigation of new repair technologies. In vitro cartilage generation using primary cell sources is limited by cell availability and expansion potential. Pluripotent stem cells possess the capacity for chondrocytic differentiation and extended expansion, providing a potential future solution to cell-based cartilage regeneration. However, despite successes in producing cartilage using adult and embryonic stem cells, the translation of these technologies to the clinic has been severely limited. This review discusses recent advances in stem cell-based cartilage tissue engineering and the major current limitations to clinical translation of these products. Concerns regarding appropriate animal models and studies, stem cell manufacturing, and relevant regulatory processes and guidelines will be addressed. Understanding the significant hurdles limiting the clinical use of stem cell-based cartilage may guide future developments in the fields of tissue engineering and regenerative medicine. PMID:24083452

  20. Engineering stem cell niches in bioreactors

    PubMed Central

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

    2013-01-01

    Stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the body. Efficient differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as “niches”, to impact stem cell fate decision. The niche factors include the regulatory factors such as oxygen, extracellular matrix (synthetic and decellularized), paracrine/autocrine signaling and physical forces (i.e., mechanical force, electrical force and flow shear). The use of novel bioreactors with precise control and recapitulation of niche factors through modulating reactor operation parameters can enable efficient stem cell expansion and differentiation. Recently, the development of microfluidic devices and microbioreactors also provides powerful tools to manipulate the stem cell microenvironment by adjusting flow rate and cytokine gradients. In general, bioreactor engineering can be used to better modulate stem cell niches critical for stem cell expansion, differentiation and applications as novel cell-based biomedicines. This paper reviews important factors that can be more precisely controlled in bioreactors and their effects on stem cell engineering. PMID:24179601

  1. Stem Cell-based Tissue Engineering Approaches for Musculoskeletal Regeneration

    PubMed Central

    Brown, Patrick T.; Handorf, Andrew M.; Jeon, Won Bae; Li, Wan-Ju

    2014-01-01

    The field of regenerative medicine and tissue engineering is an ever evolving field that holds promise in treating numerous musculoskeletal diseases and injuries. An important impetus in the development of the field was the discovery and implementation of stem cells. The utilization of mesenchymal stem cells, and later embryonic and induced pluripotent stem cells, opens new arenas for tissue engineering and presents the potential of developing stem cell-based therapies for disease treatment. Multipotent and pluripotent stem cells can produce various lineage tissues, and allow for derivation of a tissue that may be comprised of multiple cell types. As the field grows, the combination of biomaterial scaffolds and bioreactors provides methods to create an environment for stem cells that better represent their microenvironment for new tissue formation. As technologies for the fabrication of biomaterial scaffolds advance, the ability of scaffolds to modulate stem cell behavior advances as well. The composition of scaffolds could be of natural or synthetic materials and could be tailored to enhance cell self-renewal and/or direct cell fates. In addition to biomaterial scaffolds, studies of tissue development and cellular microenvironments have determined other factors, such as growth factors and oxygen tension, that are crucial to the regulation of stem cell activity. The overarching goal of stem cell-based tissue engineering research is to precisely control differentiation of stem cells in culture. In this article, we review current developments in tissue engineering, focusing on several stem cell sources, induction factors including growth factors, oxygen tension, biomaterials, and mechanical stimulation, and the internal and external regulatory mechanisms that govern proliferation and differentiation. PMID:23432679

  2. Stem Cells and Liver Regeneration

    PubMed Central

    DUNCAN, ANDREW W.; DORRELL, CRAIG; GROMPE, MARKUS

    2011-01-01

    One of the defining features of the liver is the capacity to maintain a constant size despite injury. Although the precise molecular signals involved in the maintenance of liver size are not completely known, it is clear that the liver delicately balances regeneration with overgrowth. Mammals, for example, can survive surgical removal of up to 75% of the total liver mass. Within 1 week after liver resection, the total number of liver cells is restored. Moreover, liver overgrowth can be induced by a variety of signals, including hepatocyte growth factor or peroxisome proliferators; the liver quickly returns to its normal size when the proliferative signal is removed. The extent to which liver stem cells mediate liver regeneration has been hotly debated. One of the primary reasons for this controversy is the use of multiple definitions for the hepatic stem cell. Definitions for the liver stem cell include the following: (1) cells responsible for normal tissue turnover, (2) cells that give rise to regeneration after partial hepatectomy, (3) cells responsible for progenitor-dependent regeneration, (4) cells that produce hepatocyte and bile duct epithelial phenotypes in vitro, and (5) transplantable liver-repopulating cells. This review will consider liver stem cells in the context of each definition. PMID:19470389

  3. Molecular Culprits Generating Brain Tumor Stem Cells

    PubMed Central

    Oh, Se-Yeong

    2013-01-01

    Despite current advances in multimodality therapies, such as surgery, radiotherapy, and chemotherapy, the outcome for patients with high-grade glioma remains fatal. Understanding how glioma cells resist various therapies may provide opportunities for developing new therapies. Accumulating evidence suggests that the main obstacle for successfully treating high-grade glioma is the existence of brain tumor stem cells (BTSCs), which share a number of cellular properties with adult stem cells, such as self-renewal and multipotent differentiation capabilities. Owing to their resistance to standard therapy coupled with their infiltrative nature, BTSCs are a primary cause of tumor recurrence post-therapy. Therefore, BTSCs are thought to be the main glioma cells representing a novel therapeutic target and should be eliminated to obtain successful treatment outcomes. PMID:24904883

  4. Current Stem Cell Delivery Methods for Myocardial Repair

    PubMed Central

    Sheng, Calvin C.; Zhou, Li; Hao, Jijun

    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 skeletal myoblasts, bone-marrow-derived stem cells (BMSCs), mesenchymal stem cells (MSCs), and cardiac stem cells (CSCs). To engraft these cells into patients' damaged myocardium, a variety of approaches (intramyocardial, transendocardial, transcoronary, venous, intravenous, intracoronary artery and retrograde venous administrations and bioengineered tissue transplantation) have been developed and explored. In this paper, we will discuss the pros and cons of these delivery modalities, the current state of their therapeutic potentials, and a multifaceted evaluation of their reported clinical feasibility, safety, and efficacy. While the issues of optimal delivery approach, the best progenitor stem cell type, the most effective dose, and timing of administration remain to be addressed, we are highly optimistic that stem cell therapy will provide a clinically viable option for myocardial regeneration. PMID:23509740

  5. Current stem cell delivery methods for myocardial repair.

    PubMed

    Sheng, Calvin C; Zhou, Li; Hao, Jijun

    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 skeletal myoblasts, bone-marrow-derived stem cells (BMSCs), mesenchymal stem cells (MSCs), and cardiac stem cells (CSCs). To engraft these cells into patients' damaged myocardium, a variety of approaches (intramyocardial, transendocardial, transcoronary, venous, intravenous, intracoronary artery and retrograde venous administrations and bioengineered tissue transplantation) have been developed and explored. In this paper, we will discuss the pros and cons of these delivery modalities, the current state of their therapeutic potentials, and a multifaceted evaluation of their reported clinical feasibility, safety, and efficacy. While the issues of optimal delivery approach, the best progenitor stem cell type, the most effective dose, and timing of administration remain to be addressed, we are highly optimistic that stem cell therapy will provide a clinically viable option for myocardial regeneration.

  6. Embryonic stem cells: prospects for developmental biology and cell therapy.

    PubMed

    Wobus, Anna M; Boheler, Kenneth R

    2005-04-01

    Stem cells represent natural units of embryonic development and tissue regeneration. Embryonic stem (ES) cells, in particular, possess a nearly unlimited self-renewal capacity and developmental potential to differentiate into virtually any cell type of an organism. Mouse ES cells, which are established as permanent cell lines from early embryos, can be regarded as a versatile biological system that has led to major advances in cell and developmental biology. Human ES cell lines, which have recently been derived, may additionally serve as an unlimited source of cells for regenerative medicine. Before therapeutic applications can be realized, important problems must be resolved. Ethical issues surround the derivation of human ES cells from in vitro fertilized blastocysts. Current techniques for directed differentiation into somatic cell populations remain inefficient and yield heterogeneous cell populations. Transplanted ES cell progeny may not function normally in organs, might retain tumorigenic potential, and could be rejected immunologically. The number of human ES cell lines available for research may also be insufficient to adequately determine their therapeutic potential. Recent molecular and cellular advances with mouse ES cells, however, portend the successful use of these cells in therapeutics. This review therefore focuses both on mouse and human ES cells with respect to in vitro propagation and differentiation as well as their use in basic cell and developmental biology and toxicology and presents prospects for human ES cells in tissue regeneration and transplantation.

  7. Pluripotent stem cells from germ cells.

    PubMed

    Kerr, Candace L; Shamblott, Michael J; Gearhart, John D

    2006-01-01

    To date, stem cells have been derived from three sources of germ cells. These include embryonic germ cells (EGCs), embryonal carcinoma cells (ECCs), and multipotent germ line stem cells (GSCs). EGCs are derived from primordial germ cells that arise in the late embryonic and early fetal period of development. ECCs are derived from adult testicular tumors whereas GSCs have been derived by culturing spermatogonial stem cells from mouse neonates and adults. For each of these lines, their pluripotency has been demonstrated by their ability to differentiate into cell types derived from the three germ layers in vitro and in vivo and in chimeric animals, including germ line transmission. These germ line-derived stem cells have been generated from many species including human, mice, porcine, and chicken albeit with only slight modifications. This chapter describes general considerations regarding critical aspects of their derivation compared with their counterpart, embryonic stem cells (ESCs). Detailed protocols for EGC derivation and maintenance from human and mouse primordial germ cells (PGCs) will be presented.

  8. Recent advances in phytoplasma research: from genetic diversity and genome evolution to pathogenic redirection of plant stem cell fate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Parasitizing phloem sieve cells and being transmitted by insects, phytoplasmas are a unique group of cell wall-less bacteria responsible for numerous plant diseases worldwide. Due to difficulties in establishing axenic culture of phytoplasmas, phenotypic characters suitable for conventional microbia...

  9. Rituximab, fludarabine, and total body irradiation as conditioning regimen before allogeneic hematopoietic stem cell transplantation for advanced chronic lymphocytic leukemia: long-term prospective multicenter study.

    PubMed

    Michallet, Mauricette; Socié, Gerard; Mohty, Mohamad; Sobh, Mohamad; Bay, Jacques-O; Morisset, Stéphane; Labussière-Wallet, Hélène; Tabrizi, Reza; Milpied, Noel; Bordigoni, Pierre; El-Cheikh, Jean; Blaise, Didier

    2013-02-01

    To evaluate the efficacy and toxicity of reduced-intensity conditioning (RIC) combining fludarabine, low-dose total body irradiation (TBI) and rituximab before allogeneic hematopoietic stem cell transplantation (allo-HSCT) from human leucocyte antigen (HLA) identical siblings, we conducted a prospective study in patients ≤65 years old with advanced chronic lymphocytic leukemia (CLL) stage B or C in response after a salvage treatment. Conditioning included rituximab (375 mg/m² on day 5), fludarabine (30 mg/m² from day 4 to day 2), TBI (2 Gy on day 0), and rituximab (500 mg/m² on days 1 and 8). Forty patients were included, 34 (85%) were male with a median age of 54 years (range, 35-65 years), 38 (95%) were in B stage, and 2 were in stage C; only 7 patients (17%) were in complete response. Seven (17%) patients did not receive rituximab. Thirty-nine (98%) patients engrafted, 17 patients developed acute graft-versus-host disease (GVHD) grade ≥II with a cumulative incidence at 3 months of 44% (36-52) with a significant protective effect of rituximab (p = 0.02). The cumulative incidence of chronic GVHD was 29% (21-36) at 12 months for both limited and extensive forms. The median overall survival was not reached with 5-years probability of 55% (41-74). The multivariate analysis showed a positive effect of rituximab on overall survival and event-free survival (hazard ratio [HR] = 0.1 [0-0.6], p = 0.02; and HR = 0.1 [0-0.4], p = 0.035, respectively). The association of fludarabine, TBI, and rituximab is feasible, well tolerated, and allows better outcomes in advanced CLL.

  10. Clinical results of high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation in children with advanced stage rhabdomyosarcoma.

    PubMed

    Kim, Nam Kyun; Kim, Hyo Sun; Suh, Chang-Ok; Kim, Hyun Ok; Lyu, Chuhl Joo

    2012-09-01

    Regardless of improvement in cure of Rhabdomyosarcoma (RMS), the results in treatment of advanced stage of RMS in children are still dismal. Recently, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (HDC/APBSCT) has been tried to manage the advanced high-risk RMS patients. We investigated the effectiveness of HDC/APBSCT by reviewing the clinical records of high-risk pediatric RMS patients in single institute database. Over twenty years, 37 patients were diagnosed as RMS with high-risk at the time of first diagnosis. These patients were classified as two groups according to treatment method. The first group was HDC/APBSCT and the other was conventional multi-agent chemotherapy group. Differences of clinical results between the two groups were analyzed. The median age of patients was 5 yr, ranging from 6 months to 15 yr. The 5-yr event free survival rate (EFS) of all patients was 24.8% ± 4.8%. HDC/APBSCT group and conventional multi-agent chemotherapy group were 41.3% ± 17.8% and 16.7% ± 7.6% for 5-yr EFS, respectively (P = 0.023). There was a significant difference in the result of HDC/APBSCT between complete remission or very good partial response group and poor response group (50% ± 20.4% vs 37.5% ± 28.6%, P = 0.018). HDC/APBSCT can be a promising treatment modality in high-risk RMS patients. PMID:22969254

  11. Concise review: mesenchymal stem cells for diabetes.

    PubMed

    Domínguez-Bendala, Juan; Lanzoni, Giacomo; Inverardi, Luca; Ricordi, Camillo

    2012-01-01

    Mesenchymal stem cells (MSCs) have already made their mark in the young field of regenerative medicine. Easily derived from many adult tissues, their therapeutic worth has already been validated for a number of conditions. Unlike embryonic stem cells, neither their procurement nor their use is deemed controversial. Here we review the potential use of MSCs for the treatment of type 1 diabetes mellitus, a devastating chronic disease in which the insulin-producing cells of the pancreas (the β-cells) are the target of an autoimmune process. It has been hypothesized that stem cell-derived β-cells may be used to replenish the islet mass in diabetic patients, making islet transplantation (a form of cell therapy that has already proven effective at clinically restoring normoglycemia) available to millions of prospective patients. Here we review the most current advances in the design and application of protocols for the differentiation of transplantable β-cells, with a special emphasis in analyzing MSC potency according to their tissue of origin. Although no single method appears to be ripe enough for clinical trials yet, recent progress in reprogramming (a biotechnological breakthrough that relativizes the thus far insurmountable barriers between embryonal germ layers) bodes well for the rise of MSCs as a potential weapon of choice to develop personalized therapies for type 1 diabetes. PMID:23197641

  12. Stem cells' exodus: a journey to immortality.

    PubMed

    Zhou, Yi; Lewallen, Michelle; Xie, Ting

    2013-01-28

    Stem cell niches provide a regulatory microenvironment that retains stem cells and promotes self-renewal. Recently in Developmental Cell, Rinkevich et al. (2013) showed that cell islands (CIs) of Botryllus schlosseri, a colonial chordate, provide niches for maintaining cycling stem cells that migrate from degenerated CIs to newly formed buds.

  13. Human stem cell ethics: beyond the embryo.

    PubMed

    Sugarman, Jeremy

    2008-06-01

    Human embryonic stem cell research has elicited powerful debates about the morality of destroying human embryos. However, there are important ethical issues related to stem cell research that are unrelated to embryo destruction. These include particular issues involving different types of cells used, the procurement of such cells, in vivo use of stem cells, intellectual property, and conflicts of interest.

  14. Stem-cell ecology and stem cells in motion

    PubMed Central

    Scadden, David T.

    2008-01-01

    This review highlights major scientific developments over the past 50 years or so in concepts related to stem-cell ecology and to stem cells in motion. Many thorough and eloquent reviews have been presented in the last 5 years updating progress in these issues. Some paradigms have been challenged, others validated, or new ones brought to light. In the present review, we will confine our remarks to the historical development of progress. In doing so, we will refrain from a detailed analysis of controversial data, emphasizing instead widely accepted views and some challenging novel ones. PMID:18398055

  15. Stem cells for the treatment of neurological disorders

    NASA Astrophysics Data System (ADS)

    Lindvall, Olle; Kokaia, Zaal

    2006-06-01

    Many common neurological disorders, such as Parkinson's disease, stroke and multiple sclerosis, are caused by a loss of neurons and glial cells. In recent years, neurons and glia have been generated successfully from stem cells in culture, fuelling efforts to develop stem-cell-based transplantation therapies for human patients. More recently, efforts have been extended to stimulating the formation and preventing the death of neurons and glial cells produced by endogenous stem cells within the adult central nervous system. The next step is to translate these exciting advances from the laboratory into clinically useful therapies.

  16. Common stemness regulators of embryonic and cancer stem cells.

    PubMed

    Hadjimichael, Christiana; Chanoumidou, Konstantina; Papadopoulou, Natalia; Arampatzi, Panagiota; Papamatheakis, Joseph; Kretsovali, Androniki

    2015-10-26

    Pluripotency of embryonic stem cells (ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal transducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors (cancer stem cells), provides a common conceptual and research framework for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies.

  17. Common stemness regulators of embryonic and cancer stem cells

    PubMed Central

    Hadjimichael, Christiana; Chanoumidou, Konstantina; Papadopoulou, Natalia; Arampatzi, Panagiota; Papamatheakis, Joseph; Kretsovali, Androniki

    2015-01-01

    Pluripotency of embryonic stem cells (ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal transducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors (cancer stem cells), provides a common conceptual and research framework for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies. PMID:26516408

  18. Transplant related ocular surface disorders: Advanced techniques for ocular surface rehabilitation after ocular complications secondary to hematopoietic stem cell transplantation.

    PubMed

    Stahl, Erin D; Mahomed, Faheem; Hans, Amneet K; Dalal, Jignesh D

    2016-05-01

    HSCT has been linked to the development of an assortment of ocular surface complications with the potential to lead to permanent visual impairment if left untreated or if not treated early in the course of disease. Strategies for therapy include maintenance of lubrication and tear preservation, prevention of evaporation, decreasing inflammation, and providing epithelial support. The ultimate aim of treatment is to prevent permanent ocular sequelae through prompt ophthalmology consultation and the use of advanced techniques for ocular surface rehabilitation. We describe several rehabilitation options of ocular surface complications occurring secondarily during the post-HSCT course.

  19. Cancer stem cell signaling pathways.

    PubMed

    Matsui, William H

    2016-09-01

    Tissue development and homeostasis are governed by the actions of stem cells. Multipotent cells are capable of self-renewal during the course of one's lifetime. The accurate and appropriate regulation of stem cell functions is absolutely critical for normal biological activity. Several key developmental or signaling pathways have been shown to play essential roles in this regulatory capacity. Specifically, the Janus-activated kinase/signal transducer and activator of transcription, Hedgehog, Wnt, Notch, phosphatidylinositol 3-kinase/phosphatase and tensin homolog, and nuclear factor-κB signaling pathways have all been shown experimentally to mediate various stem cell properties, such as self-renewal, cell fate decisions, survival, proliferation, and differentiation. Unsurprisingly, many of these crucial signaling pathways are dysregulated in cancer. Growing evidence suggests that overactive or abnormal signaling within and among these pathways may contribute to the survival of cancer stem cells (CSCs). CSCs are a relatively rare population of cancer cells capable of self-renewal, differentiation, and generation of serially transplantable heterogeneous tumors of several types of cancer. PMID:27611937

  20. Satellite Cells and the Muscle Stem Cell Niche

    PubMed Central

    Yin, Hang; Price, Feodor

    2013-01-01

    Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process involving the activation of various cellular and molecular responses. As skeletal muscle stem cells, satellite cells play an indispensible role in this process. The self-renewing proliferation of satellite cells not only maintains the stem cell population but also provides numerous myogenic cells, which proliferate, differentiate, fuse, and lead to new myofiber formation and reconstitution of a functional contractile apparatus. The complex behavior of satellite cells during skeletal muscle regeneration is tightly regulated through the dynamic interplay between intrinsic factors within satellite cells and extrinsic factors constituting the muscle stem cell niche/microenvironment. For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved our understanding of skeletal muscle biology. Here, we review some recent advances, with focuses on functions of satellite cells and their niche during the process of skeletal muscle regeneration. PMID:23303905

  1. [Leukemia stem cells and their targeted clearance].

    PubMed

    Liu, Bo; Shi, Ce; Zhou, Jin

    2014-08-01

    Leukemia stem cells(LSC) are the root causes of the leukemia, and are also the main reason for the leukemia relapse. Researchers hope that there are some methods to specifically mark the LSC and to clear them for promoting the advancements in the treatment of leukemia. This review discusses the biological characteristics of LSC and its microenvironment, the current internationally recognized main methods for specific marking of LSC, including marking LSC self-renewal, apoptosis signaling pathways, microenvironment, cell cycle-related signaling pathways and LSC-specific immune phenotype, so as to eliminate LSC and minimal residual disease through these marking ways. But, at present, there are no specific methods to remove leukaemia stem cells independently, possibly the combination of LSC immune phenotype with blocking the microenvironment signaling pathways can target at and remove LSC, thus improving the prognosis of leukemia.

  2. Stem cells in the diabetic infarcted heart

    PubMed Central

    Glass, Carley E.; Singal, Pawan K.

    2010-01-01

    Diabetes mellitus is one of the leading causes of death, and the majority of these deaths are associated with cardiovascular diseases. Development and progression of myocardial infarction leading to heart failure is much more complex and multifactorial in diabetics compared with non-diabetics. Despite significant advances in pharmacological interventions and surgical techniques, the disease progression leading to diabetic end-stage heart failure remains very high. Recently, cell therapy has gained much attention as an alternative approach to treat various heart diseases. However, transplanted stem cell studies in diabetic animal models are very limited. In this review, we discuss the pathogenesis of the diabetic infarcted heart and the potential of stem cell therapy to repair and regenerate. PMID:20559720

  3. Mechanism of regulation of stem cell differentiation by matrix stiffness.

    PubMed

    Lv, Hongwei; Li, Lisha; Sun, Meiyu; Zhang, Yin; Chen, Li; Rong, Yue; Li, Yulin

    2015-05-27

    Stem cell behaviors are regulated by multiple microenvironmental cues. As an external signal, mechanical stiffness of the extracellular matrix is capable of governing stem cell fate determination, but how this biophysical cue is translated into intracellular signaling remains elusive. Here, we elucidate mechanisms by which stem cells respond to microenvironmental stiffness through the dynamics of the cytoskeletal network, leading to changes in gene expression via biophysical transduction signaling pathways in two-dimensional culture. Furthermore, a putative rapid shift from original mechanosensing to de novo cell-derived matrix sensing in more physiologically relevant three-dimensional culture is pointed out. A comprehensive understanding of stem cell responses to this stimulus is essential for designing biomaterials that mimic the physiological environment and advancing stem cell-based clinical applications for tissue engineering.

  4. Regulation of stem cells in the zebra fish hematopoietic system.

    PubMed

    Huang, H-T; Zon, L I

    2008-01-01

    Hematopoietic stem cells (HSCs) have been used extensively as a model for stem cell biology. Stem cells share the ability to self-renew and differentiate into multiple cell types, making them ideal candidates for tissue regeneration or replacement therapies. Current applications of stem cell technology are limited by our knowledge of the molecular mechanisms that control their proliferation and differentiation, and various model organisms have been used to fill these gaps. This chapter focuses on the contributions of the zebra fish model to our understanding of stem cell regulation within the hematopoietic system. Studies in zebra fish have been valuable for identifying new genetic and signaling factors that affect HSC formation and development with important implications for humans, and new advances in the zebra fish toolbox will allow other aspects of HSC behavior to be investigated as well, including migration, homing, and engraftment.

  5. Alternative splicing: An important mechanism in stem cell biology

    PubMed Central

    Chen, Kenian; Dai, Xiaojing; Wu, Jiaqian

    2015-01-01

    Alternative splicing (AS) is an essential mechanism in post-transcriptional regulation and leads to protein diversity. It has been shown that AS is prevalent in metazoan genomes, and the splicing pattern is dynamically regulated in different tissues and cell types, including embryonic stem cells. These observations suggest that AS may play critical roles in stem cell biology. Since embryonic stem cells and induced pluripotent stem cells have the ability to give rise to all types of cells and tissues, they hold the promise of future cell-based therapy. Many efforts have been devoted to understanding the mechanisms underlying stem cell self-renewal and differentiation. However, most of the studies focused on the expression of a core set of transcription factors and regulatory RNAs. The role of AS in stem cell differentiation was not clear. Recent advances in high-throughput technologies have allowed the profiling of dynamic splicing patterns and cis-motifs that are responsible for AS at a genome-wide scale, and provided novel insights in a number of studies. In this review, we discuss some recent findings involving AS and stem cells. An emerging picture from these findings is that AS is integrated in the transcriptional and post-transcriptional networks and together they control pluripotency maintenance and differentiation of stem cells. PMID:25621101

  6. Alternative sources of pluripotent stem cells: ethical and scientific issues revisited.

    PubMed

    Condic, Maureen L; Rao, Mahendra

    2010-08-01

    Stem cell researchers in the United States continue to face an uncertain future, because of the changing federal guidelines governing this research, the restrictive patent situation surrounding the generation of new human embryonic stem cell lines, and the ethical divide over the use of embryos for research. In this commentary, we describe how recent advances in the derivation of induced pluripotent stem cells and the isolation of germ-line-derived pluripotent stem cells resolve a number of these uncertainties. The availability of patient-matched, pluripotent stem cells that can be obtained by ethically acceptable means provides important advantages for stem cell researchers, by both avoiding protracted ethical debates and giving U.S. researchers full access to federal funding. Thus, ethically uncompromised stem cells, such as those derived by direct reprogramming or from germ-cell precursors, are likely to yield important advances in stem cell research and move the field rapidly toward clinical applications.

  7. Enrichment of spermatogonial stem cells using side population in teleost.

    PubMed

    Hayashi, Makoto; Sato, Masanao; Nagasaka, Yasuhiko; Sadaie, Sakiko; Kobayashi, Satoru; Yoshizaki, Goro

    2014-07-01

    Spermatogenesis originates from a small population of spermatogonial stem cells; this population can maintain continuous sperm production throughout the life of fish via self-renewal and differentiation. Despite their biological importance, spermatogonial stem cells are not thoroughly characterized because they are difficult to distinguish from their progeny cells that become committed to differentiation. We previously established a novel technique for germ cell transplantation to identify spermatogonial stem cells based on their colonizing activity and their ability to initiate donor-derived gametogenesis in the rainbow trout (Oncorhynchus mykiss). Although spermatogonial stem cells can be retrospectively identified after transplantation, there is currently no technique to prospectively enrich for or purify spermatogonial stem cells. Here, we describe a method for spermatogonial stem cell enrichment using a side population. With optimized Hoechst 33342 staining conditions, we successfully identified side-population cells among type A spermatogonia. Side-population cells were transcriptomically and morphologically distinct from non-side-population cells. To functionally determine whether the transplantable spermatogonial stem cells were enriched in the side-population fraction, we compared the colonization activity of side-population cells with that of non-side-population cells. Colonization efficiency was significantly higher with side-population cells than with non-side-population cells or with total type A spermatogonia. In addition, side-population cells could produce billions of sperm in recipients. These results indicated that transplantable spermatogonial stem cells were enriched in the side-population fraction. This method will provide biological information that may advance our understanding of spermatogonial stem cells in teleosts. Additionally, this technique will increase the efficiency of germ cell transplantation used in surrogate broodstock

  8. Allogenic banking of dental pulp stem cells for innovative therapeutics.

    PubMed

    Collart-Dutilleul, Pierre-Yves; Chaubron, Franck; De Vos, John; Cuisinier, Frédéric J

    2015-08-26

    Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat.

  9. Allogenic banking of dental pulp stem cells for innovative therapeutics

    PubMed Central

    Collart-Dutilleul, Pierre-Yves; Chaubron, Franck; De Vos, John; Cuisinier, Frédéric J

    2015-01-01

    Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat. PMID:26328017

  10. Monitoring stem cells in phase contrast imaging

    NASA Astrophysics Data System (ADS)

    Lam, K. P.; Dempsey, K. P.; Collins, D. J.; Richardson, J. B.

    2016-04-01

    Understanding the mechanisms behind the proliferation of Mesenchymal Stem cells (MSCs) can offer a greater insight into the behaviour of these cells throughout their life cycles. Traditional methods of determining the rate of MSC differentiation rely on population based studies over an extended time period. However, such methods can be inadequate as they are unable to track cells as they interact; for example, in autologous cell therapies for osteoarthritis, the development of biological assays that could predict in vivo functional activity and biological action are particularly challenging. Here further research is required to determine non-histochemical biomarkers which provide correlations between cell survival and predictive functional outcome. This paper proposes using a (previously developed) advanced texture-based analysis algorithm to facilitate in vitro cells tracking using time-lapsed microscopy. The technique was adopted to monitor stem cells in the context of unlabelled, phase contrast imaging, with the goal of examining the cell to cell interactions in both monoculture and co-culture systems. The results obtained are analysed using established exploratory procedures developed for time series data and compared with the typical fluorescent-based approach of cell labelling. A review of the progress and the lessons learned are also presented.

  11. Biomaterials Approach to Expand and Direct Differentiation of Stem Cells

    PubMed Central

    Chai, Chou; Leong, Kam W

    2008-01-01

    Stem cells play increasingly prominent roles in tissue engineering and regenerative medicine. Pluripotent embryonic stem (ES) cells theoretically allow every cell type in the body to be regenerated. Adult stem cells have also been identified and isolated from every major tissue and organ, some possessing apparent pluripotency comparable to that of ES cells. However, a major limitation in the translation of stem cell technologies to clinical applications is the supply of cells. Advances in biomaterials engineering and scaffold fabrication enable the development of ex vivo cell expansion systems to address this limitation. Progress in biomaterial design has also allowed directed differentiation of stem cells into specific lineages. In addition to delivering biochemical cues, various technologies have been developed to introduce micro- and nano-scale features onto culture surfaces to enable the study of stem cell responses to topographical cues. Knowledge gained from these studies portends the alteration of stem cell fate in the absence of biological factors, which would be valuable in the engineering of complex organs comprising multiple cell types. Biomaterials may also play an immunoprotective role by minimizing host immunoreactivity toward transplanted cells or engineered grafts. PMID:17264853

  12. Clinical Trials of Adult Stem Cell Therapy in Patients with Ischemic Stroke.

    PubMed

    Bang, Oh Young

    2016-01-01

    Stem cell therapy is considered a potential regenerative strategy for patients with neurologic deficits. Studies involving animal models of ischemic stroke have shown that stem cells transplanted into the brain can lead to functional improvement. With current advances in the understanding regarding the effects of introducing stem cells and their mechanisms of action, several clinical trials of stem cell therapy have been conducted in patients with stroke since 2005, including studies using mesenchymal stem cells, bone marrow mononuclear cells, and neural stem/progenitor cells. In addition, several clinical trials of the use of adult stem cells to treat ischemic stroke are ongoing. This review presents the status of our understanding of adult stem cells and results from clinical trials, and introduces ongoing clinical studies of adult stem cell therapy in the field of stroke.

  13. Becoming a Blood Stem Cell Donor

    MedlinePlus

    ... total__ Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Subscribe Subscribed Unsubscribe 359 359 Loading... ... Ever considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  14. Stem Cell Transplant Patients and Fungal Infections

    MedlinePlus

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

  15. Adult Stem Cells and Diabetes Therapy

    PubMed Central

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

    2016-01-01

    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 cells. In this review, we focus on adult stem cells, especial human bone marrow stem cells (BM) for diabetes therapy, its history, and current development. We discuss prospects for future diabetes therapy such as induced pluripotent stem cells which have popularity in stem cell research area. PMID:27123495

  16. Perspectives on human stem cell research.

    PubMed

    Jung, Kyu Won

    2009-09-01

    Human stem cell research draws not only scientists' but the public's attention. Human stem cell research is considered to be able to identify the mechanism of human development and change the paradigm of medical practices. However, there are heated ethical and legal debates about human stem cell research. The core issue is that of human dignity and human life. Some prefer human adult stem cell research or iPS cell research, others hES cell research. We do not need to exclude any type of stem cell research because each has its own merits and issues, and they can facilitate the scientific revolution when working together.

  17. [Bone and Stem Cells. Immune cell regulation by the bone marrow niche].

    PubMed

    Terashima, Asuka; Takayanagi, Hiroshi

    2014-04-01

    Adult hematopoietic stem cells (HSCs) are maintained in the bone marrow and give rise to all blood cell types. The maintenance and the differentiation of blood cells including immune cells are essential for host defense and oxygen delivery. HSCs are maintained in microenvironments called stem cell niches, which consists of various cell types in bone marrow. Recently, new visualization technologies and assay systems brought advances in studies on the stem cell niche. In addition, several reports demonstrated that osteoblasts and osteocytes regulate not only HSC homeostasis but also immune cell differentiation, suggesting a close relationship between bone cells and HSCs.

  18. A highly selective fluorescent probe for direct detection and isolation of mouse embryonic stem cells.

    PubMed

    Chandran, Yogeswari; Kang, Nam-Young; Park, Sung-Jin; Alamudi, Samira Husen; Kim, Jun-Young; Sahu, Srikanta; Su, Dongdong; Lee, Jungyeol; Vendrell, Marc; Chang, Young-Tae

    2015-11-01

    Stem cell research has gathered immense attention in the past decade due to the remarkable ability of stem cells for self-renewal and tissue-specific differentiation. Despite having numerous advancements in stem cell isolation and manipulation techniques, there is a need for highly reliable probes for the specific detection of live stem cells. Herein we developed a new fluorescence probe (CDy9) with high selectivity for mouse embryonic stem cells. CDy9 allows the detection and isolation of intact stem cells with marginal impact on their function and capabilities. PMID:26115574

  19. Ex vivo expansion of hematopoietic stem cells.

    PubMed

    Xie, JingJing; Zhang, ChengCheng

    2015-09-01

    Ex vivo expansion of hematopoietic stem cells (HSCs) would benefit clinical applications in several aspects, to improve patient survival, utilize cord blood stem cells for adult applications, and selectively propagate stem cell populations after genetic manipulation. In this review we summarize and discuss recent advances in the culture systems of mouse and human HSCs, which include stroma/HSC co-culture, continuous perfusion and fed-batch cultures, and those supplemented with extrinsic ligands, membrane transportable transcription factors, complement components, protein modification enzymes, metabolites, or small molecule chemicals. Some of the expansion systems have been tested in clinical trials. The optimal condition for ex vivo expansion of the primitive and functional human HSCs is still under development. An improved understanding of the mechanisms for HSC cell fate determination and the HSC culture characteristics will guide development of new strategies to overcome difficulties. In the future, development of a combination treatment regimen with agents that enhance self-renewal, block differentiation, and improve homing will be critical. Methods to enhance yields and lower cost during collection and processing should be employed. The employment of an efficient system for ex vivo expansion of HSCs will facilitate the further development of novel strategies for cell and gene therapies including genome editing.

  20. Identify multiple myeloma stem cells: Utopia?

    PubMed Central

    Saltarella, Ilaria; Lamanuzzi, Aurelia; Reale, Antonia; Vacca, Angelo; Ria, Roberto

    2015-01-01

    Multiple myeloma (MM) is a hematologic malignancy of monoclonal plasma cells which remains incurable despite recent advances in therapies. The presence of cancer stem cells (CSCs) has been demonstrated in many solid and hematologic tumors, so the idea of CSCs has been proposed for MM, even if MM CSCs have not been define yet. The existence of myeloma CSCs with clonotypic B and clonotypic non B cells was postulated by many groups. This review aims to focus on these distinct clonotypic subpopulations and on their ability to develop and sustain MM. The bone marrow microenvironment provides to MM CSCs self-renewal, survival and drug resistance thanks to the presence of normal and cancer stem cell niches. The niches and CSCs interact each other through adhesion molecules and the interplay between ligands and receptors activates stemness signaling (Hedgehog, Wnt and Notch pathways). MM CSCs are also supposed to be responsible for drug resistance that happens in three steps from the initial cancer cell homing microenvironment-mediated to development of microenvironment-independent drug resistance. In this review, we will underline all these aspects of MM CSCs. PMID:25621108

  1. Identify multiple myeloma stem cells: Utopia?

    PubMed

    Saltarella, Ilaria; Lamanuzzi, Aurelia; Reale, Antonia; Vacca, Angelo; Ria, Roberto

    2015-01-26

    Multiple myeloma (MM) is a hematologic malignancy of monoclonal plasma cells which remains incurable despite recent advances in therapies. The presence of cancer stem cells (CSCs) has been demonstrated in many solid and hematologic tumors, so the idea of CSCs has been proposed for MM, even if MM CSCs have not been define yet. The existence of myeloma CSCs with clonotypic B and clonotypic non B cells was postulated by many groups. This review aims to focus on these distinct clonotypic subpopulations and on their ability to develop and sustain MM. The bone marrow microenvironment provides to MM CSCs self-renewal, survival and drug resistance thanks to the presence of normal and cancer stem cell niches. The niches and CSCs interact each other through adhesion molecules and the interplay between ligands and receptors activates stemness signaling (Hedgehog, Wnt and Notch pathways). MM CSCs are also supposed to be responsible for drug resistance that happens in three steps from the initial cancer cell homing microenvironment-mediated to development of microenvironment-independent drug resistance. In this review, we will underline all these aspects of MM CSCs. PMID:25621108

  2. Identify multiple myeloma stem cells: Utopia?

    PubMed

    Saltarella, Ilaria; Lamanuzzi, Aurelia; Reale, Antonia; Vacca, Angelo; Ria, Roberto

    2015-01-26

    Multiple myeloma (MM) is a hematologic malignancy of monoclonal plasma cells which remains incurable despite recent advances in therapies. The presence of cancer stem cells (CSCs) has been demonstrated in many solid and hematologic tumors, so the idea of CSCs has been proposed for MM, even if MM CSCs have not been define yet. The existence of myeloma CSCs with clonotypic B and clonotypic non B cells was postulated by many groups. This review aims to focus on these distinct clonotypic subpopulations and on their ability to develop and sustain MM. The bone marrow microenvironment provides to MM CSCs self-renewal, survival and drug resistance thanks to the presence of normal and cancer stem cell niches. The niches and CSCs interact each other through adhesion molecules and the interplay between ligands and receptors activates stemness signaling (Hedgehog, Wnt and Notch pathways). MM CSCs are also supposed to be responsible for drug resistance that happens in three steps from the initial cancer cell homing microenvironment-mediated to development of microenvironment-independent drug resistance. In this review, we will underline all these aspects of MM CSCs.

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

    PubMed

    Al'bert, E V; Ezhova, T A

    2013-02-01

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

  4. Stem Cell Research Policies around the World

    PubMed Central

    Dhar, Deepali; Hsi-en Ho, John

    2009-01-01

    The proliferation of stem cell research, conflated with its ethical and moral implications, has led governments to attempt regulation of both the science and funding of stem cells. Due to a diversity of opinions and cultural viewpoints, no single policy or set of rules exist to govern stem cell research. Instead, each country has developed its own policy. The following map catalogs the general legal and political milleu regarding stem cell research by country. PMID:19774124

  5. Stem cells and colorectal carcinogenesis

    PubMed Central

    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. Application of stems cells in wound healing--an update.

    PubMed

    Teng, Miao; Huang, Yuesheng; Zhang, Hengshu

    2014-01-01

    Wound healing is a complex but well-orchestrated tissue repair process composed of a series of molecular and cellular events conducted by various types of cells and extracellular matrix. Despite a variety of therapeutic strategies proposed to accelerate the healing of acute and/or chronic wounds over the past few decades, effective treatment of chronic nonhealing wounds still remains a challenge. Due to the recent advances in stem cell research, a dramatic enthusiasm has been drawn to the application of stem cells in regenerative medicine. Both embryonic and adult stem cells have prolonged self-renewal capacity and are able to differentiate into various tissue types. Nevertheless, use of embryonic stem cells is limited, owing to ethical concerns and legal restrictions. Adult stem cells, which could be isolated from bone marrow, umbilical cord blood, adipose tissue, skin and hair follicles,are being explored extensively to facilitate the healing of both acute and chronic wounds. The current article summarizes recent research on various types of stem cell-based strategies applied to improve wound healing. In addition, future directions of stem cell-based therapy in wound healing have also been discussed. Finally, despite its apparent advantages, limitations and challenges of stem cell therapy are discussed.

  7. Stem/Progenitor cells in vascular regeneration.

    PubMed

    Zhang, Li; Xu, Qingbo

    2014-06-01

    A series of studies has been presented in the search for proof of circulating and resident vascular progenitor cells, which can differentiate into endothelial and smooth muscle cells and pericytes in animal and human studies. In terms of pluripotent stem cells, including embryonic stem cells, iPS, and partial-iPS cells, they display a great potential for vascular lineage differentiation. Development of stem cell therapy for treatment of vascular and ischemic diseases remains a major challenging research field. At the present, there is a clear expansion of research into mechanisms of stem cell differentiation into vascular lineages that are tested in animal models. Although there are several clinical trials ongoing that primarily focus on determining the benefits of stem cell transplantation in ischemic heart or peripheral ischemic tissues, intensive investigation for translational aspects of stem cell therapy would be needed. It is a hope that stem cell therapy for vascular diseases could be developed for clinic application in the future.

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  9. Control of stem cell fate by engineering their micro and nanoenvironment

    PubMed Central

    Griffin, Michelle F; Butler, Peter E; Seifalian, Alexander M; Kalaskar, Deepak M

    2015-01-01

    Stem cells are capable of long-term self-renewal and differentiation into specialised cell types, making them an ideal candidate for a cell source for regenerative medicine. The control of stem cell fate has become a major area of interest in the field of regenerative medicine and therapeutic intervention. Conventional methods of chemically inducing stem cells into specific lineages is being challenged by the advances in biomaterial technology, with evidence highlighting that material properties are capable of driving stem cell fate. Materials are being designed to mimic the clues stem cells receive in their in vivo stem cell niche including topographical and chemical instructions. Nanotopographical clues that mimic the extracellular matrix (ECM) in vivo have shown to regulate stem cell differentiation. The delivery of ECM components on biomaterials in the form of short peptides sequences has also proved successful in directing stem cell lineage. Growth factors responsible for controlling stem cell fate in vivo have also been delivered via biomaterials to provide clues to determine stem cell differentiation. An alternative approach to guide stem cells fate is to provide genetic clues including delivering DNA plasmids and small interfering RNAs via scaffolds. This review, aims to provide an overview of the topographical, chemical and molecular clues that biomaterials can provide to guide stem cell fate. The promising features and challenges of such approaches will be highlighted, to provide directions for future advancements in this exciting area of stem cell translation for regenerative medicine. PMID:25621104

  10. Setting FIRES to Stem Cell Research

    ERIC Educational Resources Information Center

    Miller, Roxanne Grietz

    2005-01-01

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

  11. Blood-Forming Stem Cell Transplants

    MedlinePlus

    ... Health Professionals Questions to Ask about Your Treatment Research Blood-Forming Stem Cell Transplants On This Page What are bone marrow ... are evaluating BMT and PBSCT in clinical trials (research studies) for the treatment ... are the donor’s stem cells matched to the patient’s stem cells in allogeneic ...

  12. Developing neural stem cell-based treatments for neurodegenerative diseases.

    PubMed

    Byrne, James A

    2014-05-30

    Owing to the aging of the population, our society now faces an impending wave of age-related neurodegenerative pathologies, the most significant of which is Alzheimer's disease. Currently, no effective therapies for Alzheimer's disease have been developed. However, recent advances in the fields of neural stem cells and human induced pluripotent stem cells now provide us with the first real hope for a cure. The recent discovery by Blurton-Jones and colleagues that neural stem cells can effectively deliver disease-modifying therapeutic proteins throughout the brains of our best rodent models of Alzheimer's disease, combined with recent advances in human nuclear reprogramming, stem cell research, and highly customized genetic engineering, may represent a potentially revolutionary personalized cellular therapeutic approach capable of effectively curing, ameliorating, and/or slowing the progression of Alzheimer's disease.

  13. Extinction models for cancer stem cell therapy

    PubMed Central

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

    2012-01-01

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

  14. Methods for Stem Cell Production and Therapy

    NASA Technical Reports Server (NTRS)

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

    2015-01-01

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

  15. Stem cell therapy for voiding and erectile dysfunction

    PubMed Central

    Vaegler, Martin; Lenis, Andrew T; Daum, Lisa; Renninger, M; Bastian, Amend; Stenzl, Arnulf; Damaser, Margot S; Sievert, Karl-Dietrich

    2013-01-01

    Voiding dysfunction comprises a variety of disorders, including stress urinary incontinence and overactive bladder, and affects millions of men and women worldwide. Erectile dysfunction (ED) also decreases quality of life for millions of men, as well as for their partners. Advanced age and diabetes are common comorbidities that can exacerbate and negatively impact upon the development of these disorders. Therapies that target the pathophysiology of these conditions to halt progression are not currently available. However, stem cell therapy could fill this therapeutic void. Stem cells can reduce inflammation, prevent fibrosis, promote angiogenesis, recruit endogenous progenitor cells, and differentiate to replace damaged cells. Adult multipotent stem cell therapy, in particular, has shown promise in case reports and preclinical animal studies. Stem cells have also enabled advances in urological tissue engineering by facilitating ex vivo construction of bladder wall and urethral tissue (using a patient's own cells) prior to transplantation. More recent studies have focused on bioactive factor secretion and homing of stem cells. In the future, clinicians are likely to utilize allogeneic stem cell sources, intravenous systemic delivery, and ex vivo cell enhancement to treat voiding dysfunction and ED. PMID:22710667

  16. Microfluidic systems for stem cell-based neural tissue engineering.

    PubMed

    Karimi, Mahdi; Bahrami, Sajad; Mirshekari, Hamed; Basri, Seyed Masoud Moosavi; Nik, Amirala Bakhshian; Aref, Amir R; Akbari, Mohsen; Hamblin, Michael R

    2016-07-01

    Neural tissue engineering aims at developing novel approaches for the treatment of diseases of the nervous system, by providing a permissive environment for the growth and differentiation of neural cells. Three-dimensional (3D) cell culture systems provide a closer biomimetic environment, and promote better cell differentiation and improved cell function, than could be achieved by conventional two-dimensional (2D) culture systems. With the recent advances in the discovery and introduction of different types of stem cells for tissue engineering, microfluidic platforms have provided an improved microenvironment for the 3D-culture of stem cells. Microfluidic systems can provide more precise control over the spatiotemporal distribution of chemical and physical cues at the cellular level compared to traditional systems. Various microsystems have been designed and fabricated for the purpose of neural tissue engineering. Enhanced neural migration and differentiation, and monitoring of these processes, as well as understanding the behavior of stem cells and their microenvironment have been obtained through application of different microfluidic-based stem cell culture and tissue engineering techniques. As the technology advances it may be possible to construct a "brain-on-a-chip". In this review, we describe the basics of stem cells and tissue engineering as well as microfluidics-based tissue engineering approaches. We review recent testing of various microfluidic approaches for stem cell-based neural tissue engineering.

  17. Advancing the STEM Workforce through STEM-Centric Career Development

    ERIC Educational Resources Information Center

    Feller, Rich

    2011-01-01

    Preparing for the future is not what it used to be. Yet, advising students, preparing lessons, and promoting the value of STEM options remains constant. As a result, technical and engineering educators seek clarity about the future of careers, career development, and ways to promote STEM options. Recently, the ITEEA conference allowed the author…

  18. Modern stem cell therapy: approach to disease.

    PubMed

    Zemljic, Mateja; Pejkovic, Bozena; Krajnc, Ivan; Kocbek, Lidija

    2015-12-01

    Various types of stem cells exist, each with their own advantages and disadvantages. Considering the current available evidence, important preclinical and clinical studies regarding the therapeutic potential of stem cells, stem cell therapy might be the important strategy for tissue repair. The development of stem cell therapy for tissue repair has primarily relied on stem cells, especially mesenchymal stem cells. Multilineage differentiation into all of the described cells are considered as important candidates for a range of diseases like neurological diseases, cardiovascular diseases, gastrointestinal cancer and genetic defects, as well as for acute and chronic wounds healing and pharmaceutical treatment. We review the properties and multipotency of stem cells and their differentiation potential, once cultured under specific growth conditions, for use in cell-based therapies and functional tissue replacement.

  19. Nuclear Mechanics and Stem Cell Differentiation.

    PubMed

    Mao, Xinjian; Gavara, Nuria; Song, Guanbin

    2015-12-01

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

  20. Our Fat Future: Translating Adipose Stem Cell Therapy

    PubMed Central

    Nordberg, Rachel C.

    2015-01-01

    Summary Human adipose stem cells (hASCs) have the potential to treat patients with a variety of clinical conditions. Recent advancements in translational research, regulatory policy, and industry have positioned hASCs on the threshold of clinical translation. We discuss the progress and challenges of bringing adipose stem cell therapy into mainstream clinical use. Significance This article details the advances made in recent years that have helped move human adipose stem cell therapy toward mainstream clinical use from a translational research, regulatory policy, and industrial standpoint. Four recurrent themes in translational technology as they pertain to human adipose stem cells are discussed: automated closed-system operations, biosensors and real-time monitoring, biomimetics, and rapid manufacturing. In light of recent FDA guidance documents, regulatory concerns about adipose stem cell therapy are discussed. Finally, an update is provided on the current state of clinical trials and the emerging industry that uses human adipose stem cells. This article is expected to stimulate future studies in translational adipose stem cell research. PMID:26185256

  1. Advancing STEM Education: A 2020 Vision

    ERIC Educational Resources Information Center

    Bybee, Rodger W.

    2010-01-01

    STEM (an acronym for science, technology, engineering and mathematics) had its origins in the 1990s at the National Science Foundation (NSF) and has been used as a generic label for any event, policy, program, or practice that involves one or several of the STEM disciplines. However, a recent survey on the "perception of STEM" found that most…

  2. Role of adipose-derived stem cells in wound healing.

    PubMed

    Hassan, Waqar Ul; Greiser, Udo; Wang, Wenxin

    2014-01-01

    Impaired wound healing remains a challenge to date and causes debilitating effects with tremendous suffering. Recent advances in tissue engineering approaches in the area of cell therapy have provided promising treatment options to meet the challenges of impaired skin wound healing such as diabetic foot ulcers. Over the last few years, stem cell therapy has emerged as a novel therapeutic approach for various diseases including wound repair and tissue regeneration. Several different types of stem cells have been studied in both preclinical and clinical settings such as bone marrow-derived stem cells, adipose-derived stem cells (ASCs), circulating angiogenic cells (e.g., endothelial progenitor cells), human dermal fibroblasts, and keratinocytes for wound healing. Adipose tissue is an abundant source of mesenchymal stem cells, which have shown an improved outcome in wound healing studies. ASCs are pluripotent stem cells with the ability to differentiate into different lineages and to secrete paracrine factors initiating tissue regeneration process. The abundant supply of fat tissue, ease of isolation, extensive proliferative capacities ex vivo, and their ability to secrete pro-angiogenic growth factors make them an ideal cell type to use in therapies for the treatment of nonhealing wounds. In this review, we look at the pathogenesis of chronic wounds, role of stem cells in wound healing, and more specifically look at the role of ASCs, their mechanism of action and their safety profile in wound repair and tissue regeneration.

  3. Stem cells: science, policy, and ethics.

    PubMed

    Fischbach, Gerald D; Fischbach, Ruth L

    2004-11-01

    Human embryonic stem cells offer the promise of a new regenerative medicine in which damaged adult cells can be replaced with new cells. Research is needed to determine the most viable stem cell lines and reliable ways to promote the differentiation of pluripotent stem cells into specific cell types (neurons, muscle cells, etc). To create new cell lines, it is necessary to destroy preimplantation blastocysts. This has led to an intense debate that threatens to limit embryonic stem cell research. The profound ethical issues raised call for informed, dispassionate debate.

  4. Muscle stem cells at a glance

    PubMed Central

    Wang, Yu Xin; Dumont, Nicolas A.; Rudnicki, Michael A.

    2014-01-01

    ABSTRACT Muscle stem cells facilitate the long-term regenerative capacity of skeletal muscle. This self-renewing population of satellite cells has only recently been defined through genetic and transplantation experiments. Although muscle stem cells remain in a dormant quiescent state in uninjured muscle, they are poised to activate and produce committed progeny. Unlike committed myogenic progenitor cells, the self-renewal capacity gives muscle stem cells the ability to engraft as satellite cells and capitulate long-term regeneration. Similar to other adult stem cells, understanding the molecular regulation of muscle stem cells has significant implications towards the development of pharmacological or cell-based therapies for muscle disorders. This Cell Science at a Glance article and accompanying poster will review satellite cell characteristics and therapeutic potential, and provide an overview of the muscle stem cell hallmarks: quiescence, self-renewal and commitment. PMID:25300792

  5. Is Transforming Stem Cells to Pancreatic Beta Cells Still the Holy Grail for Type 2 Diabetes?

    PubMed

    Kahraman, Sevim; Okawa, Erin R; Kulkarni, Rohit N

    2016-08-01

    Diabetes is a progressive disease affecting millions of people worldwide. There are several medications and treatment options to improve the life quality of people with diabetes. One of the strategies for the treatment of diabetes could be the use of human pluripotent stem cells or induced pluripotent stem cells. The recent advances in differentiation of stem cells into insulin-secreting beta-like cells in vitro make the transplantation of the stem cell-derived beta-like cells an attractive approach for treatment of type 1 and type 2 diabetes. While stem cell-derived beta-like cells provide an unlimited cell source for beta cell replacement therapies, these cells can also be used as a platform for drug screening or modeling diseases.

  6. Drosophila neural stem cells in brain development and tumor formation.

    PubMed

    Jiang, Yanrui; Reichert, Heinrich

    2014-01-01

    Neuroblasts, the neural stem cells in Drosophila, generate the complex neural structure of the central nervous system. Significant progress has been made in understanding the mechanisms regulating the self-renewal, proliferation, and differentiation in Drosophila neuroblast lineages. Deregulation of these mechanisms can lead to severe developmental defects and the formation of malignant brain tumors. Here, the authors review the molecular genetics of Drosophila neuroblasts and discuss some recent advances in stem cell and cancer biology using this model system.

  7. Cell sources and support programs for stem cell research and cell-based therapy in the USA.

    PubMed

    Thomas, John W

    2004-01-01

    In August 2002, the Health & Human Services Secretary Tommy Thompson and National Institutes of Health (NIH) Director Elias Zerhouni announced the creation of a new NIH Task Force to advance stem cell research. The National Heart, Lung, and Blood Institute (NHLBI), with a long history of sponsored research programs for stem cell biology, is participating in the NIH Stem Cell Task Force to facilitate stem cell and embryonic stem (ES) cell research including programs to improve access to cell sources. Programs being implemented include infrastructure enhancement awards to develop eligible human ES cell lines into distribution-quality cell lines, grant supplements for human ES cell line research, an educational program to provide laboratory courses on human ES cell culture techniques, and a new training program to assist investigators wishing to re-direct their laboratories into stem cell research.

  8. Biology of hematopoietic stem cells and progenitors: implications for clinical application.

    PubMed

    Kondo, Motonari; Wagers, Amy J; Manz, Markus G; Prohaska, Susan S; Scherer, David C; Beilhack, Georg F; Shizuru, Judith A; Weissman, Irving L

    2003-01-01

    Stem cell biology is scientifically, clinically, and politically a current topic. The hematopoietic stem cell, the common ancestor of all types of blood cells, is one of the best-characterized stem cells in the body and the only stem cell that is clinically applied in the treatment of diseases such as breast cancer, leukemias, and congenital immunodeficiencies. Multicolor cell sorting enables the purification not only of hematopoietic stem cells, but also of their downstream progenitors such as common lymphoid progenitors and common myeloid progenitors. Recent genetic approaches including gene chip technology have been used to elucidate the gene expression profile of hematopoietic stem cells and other progenitors. Although the mechanisms that control self-renewal and lineage commitment of hematopoietic stem cells are still ambiguous, recent rapid advances in understanding the biological nature of hematopoietic stem and progenitor cells have broadened the potential application of these cells in the treatment of diseases. PMID:12615892

  9. CMV in Hematopoietic Stem Cell Transplantation

    PubMed Central

    de la Cámara, Rafael

    2016-01-01

    Due to its negative impact on the outcome of stem cell transplant (SCT) and solid organ transplant patients (SOT) CMV has been called “the troll of transplantation”. One of the greatest advances in the management of SCT has been the introduction of the preemptive strategy. Since its introduction, the incidence of the viremia, as expected, remains unchanged but there has been a marked decline in the incidence of early CMV disease. However, in spite of the advances in prevention of CMV disease, CMV is still today an important cause of morbidity and mortality. Late CMV disease is still occurring in a significant proportion of patients and the so-called indirect effects of CMV are causing significant morbidity and mortality. Fortunately there have been several advances in the development of new antivirals, adoptive immunotherapy and DNA-CMV vaccines that might transform the management of CMV in the near future. PMID:27413524

  10. Synthetic Extracellular Microenvironment for Modulating Stem Cell Behaviors

    PubMed Central

    Chandra, Prafulla; Lee, Sang Jin

    2015-01-01

    The innate ability of stem cells to self-renew and differentiate into multiple cell types makes them a promising source for tissue engineering and regenerative medicine applications. Their capacity for self-renewal and differentiation is largely influenced by the combination of physical, chemical, and biological signals found in the stem cell niche, both temporally and spatially. Embryonic and adult stem cells are potentially useful for cell-based approaches; however, regulating stem cell behavior remains a major challenge in their clinical use. Most of the current approaches for controlling stem cell fate do not fully address all of the complex signaling pathways that drive stem cell behaviors in their natural microenvironments. To overcome this limitation, a new generation of biomaterials is being developed for use as three-dimensional synthetic microenvironments that can mimic the regulatory characteristics of natural extracellular matrix (ECM) proteins and ECM-bound growth factors. These synthetic microenvironments are currently being investigated as a substrate with surface immobilization and controlled release of bioactive molecules to direct the stem cell fate in vitro, as a tissue template to guide and improve the neo-tissue formation both in vitro and in vivo, and as a delivery vehicle for cell therapy in vivo. The continued advancement of such an intelligent biomaterial system as the synthetic extracellular microenvironment holds the promise of improved therapies for numerous debilitating medical conditions for which no satisfactory cure exists today. PMID:26106260

  11. Embryonic Stem Cell Patents and Human Dignity

    PubMed Central

    Resnik, David B.

    2009-01-01

    This article examines the assertion that human embryonic stem cells patents are immoral because they violate human dignity. After analyzing the concept of human dignity and its role in bioethics debates, this article argues that patents on human embryos or totipotent embryonic stem cells violate human dignity, but that patents on pluripotent or multipotent stem cells do not. Since patents on pluripotent or multipotent stem cells may still threaten human dignity by encouraging people to treat embryos as property, patent agencies should carefully monitor and control these patents to ensure that patents are not inadvertently awarded on embryos or totipotent stem cells. PMID:17922198

  12. Stem cell maintenance in a different niche

    PubMed Central

    Ahn, Ji Yeon; Lee, Seung Tae

    2013-01-01

    To overcome the difficulty of controlling stem cell fate and function in applications to regenerative medicine, a number of alternative approaches have been made. Recent reports demonstrate that a non-cellular niche modulating the biophysical microenvironment with chemical factors can support stem cell self-renewal. In our previous studies, early establishment was executed to optimize biophysical factors and it was subsequently found that the microgeometry of the extracellular matrix made huge differences in stem cell behavior and phenotype. We review here a three-dimensional, non-cellular niche designed to support stem cell self-renewal. The characteristics of stem cells under the designed system are further discussed. PMID:23875159

  13. Advanced glycation end product 3 (AGE3) suppresses the mineralization of mouse stromal ST2 cells and human mesenchymal stem cells by increasing TGF-β expression and secretion.

    PubMed

    Notsu, Masakazu; Yamaguchi, Toru; Okazaki, Kyoko; Tanaka, Ken-ichiro; Ogawa, Noriko; Kanazawa, Ippei; Sugimoto, Toshitsugu

    2014-07-01

    In diabetic patients, advanced glycation end products (AGEs) cause bone fragility because of deterioration of bone quality. We previously showed that AGEs suppressed the mineralization of mouse stromal ST2 cells. TGF-β is abundant in bone, and enhancement of its signal causes bone quality deterioration. However, whether TGF-β signaling is involved in the AGE-induced suppression of mineralization during the osteoblast lineage remains unknown. We therefore examined the roles of TGF-β in the AGE-induced suppression of mineralization of ST2 cells and human mesenchymal stem cells. AGE3 significantly (P < .001) inhibited mineralization in both cell types, whereas transfection with small interfering RNA for the receptor for AGEs (RAGEs) significantly (P < .05) recovered this process in ST2 cells. AGE3 increased (P < .001) the expression of TGF-β mRNA and protein, which was partially antagonized by transfection with RAGE small interfering RNA. Treatment with a TGF-β type I receptor kinase inhibitor, SD208, recovered AGE3-induced decreases in osterix (P < .001) and osteocalcin (P < .05) and antagonized the AGE3-induced increase in Runx2 mRNA expression in ST2 cells (P < .001). Moreover, SD208 completely and dose dependently rescued AGE3-induced suppression of mineralization in both cell types. In contrast, SD208 intensified AGE3-induced suppression of cell proliferation as well as AGE3-induced apoptosis in proliferating ST2 cells. These findings indicate that, after cells become confluent, AGE3 partially inhibits the differentiation and mineralization of osteoblastic cells by binding to RAGE and increasing TGF-β expression and secretion. They also suggest that TGF-β adversely affects bone quality not only in primary osteoporosis but also in diabetes-related bone disorder.

  14. Plasticity of hematopoietic stem cells.

    PubMed

    Ogawa, Makio; LaRue, Amanda C; Mehrotra, Meenal

    2015-01-01

    Almost two decades ago, a number of cell culture and preclinical transplantation studies suggested the striking concept of the tissue-reconstituting ability of hematopoietic stem cells (HSCs). While this heralded an exciting time of radically new therapies for disorders of many organs and tissues, the concept was soon mired by controversy and remained dormant. This chapter provides a brief review of evidence for HSC plasticity including our findings based on single HSC transplantation in mouse. These studies strongly support the concept that HSCs are pluripotent and may be the source for the majority, if not all, of the cell types in our body. PMID:26590762

  15. The gap between law and ethics in human embryonic stem cell research: overcoming the effect of U.S. federal policy on research advances and public benefit.

    PubMed

    Taylor, Patrick L

    2005-10-01

    Key ethical issues arise in association with the conduct of stem cell research by research institutions in the United States. These ethical issues, summarized in detail, receive no adequate translation into federal laws or regulations, also described in this article. U.S. Federal policy takes a passive approach to these ethical issues, translating them simply into limitations on taxpayer funding, and foregoes scientific and ethical leadership while protecting intellectual property interests through a laissez faire approach to stem cell patents and licenses. Those patents and licenses, far from being scientifically and ethically neutral in effect, virtually prohibit commercially sponsored research that could otherwise be a realistic alternative to the federal funding gap. The lack of federal funding and related data-sharing principles, combined with the effect of U.S. patent policy, the lack of key agency guidance, and the proliferation of divergent state laws arising from the lack of Federal leadership, significantly impede ethical stem cell research in the United States, without coherently supporting any consensus ethical vision. Research institutions must themselves implement steps, described in the article, to integrate addressing ethical review with the many legal compliance issues U.S. federal and state laws create.

  16. Klotho, stem cells, and aging

    PubMed Central

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

    2015-01-01

    Aging is an inevitable and progressive biological process involving dysfunction and eventually destruction of every tissue and organ. This process is driven by a tightly regulated and complex interplay between genetic and acquired factors. Klotho is an antiaging gene encoding a single-pass transmembrane protein, klotho, which serves as an aging suppressor through a wide variety of mechanisms, such as antioxidation, antisenescence, antiautophagy, and modulation of many signaling pathways, including insulin-like growth factor and Wnt. Klotho deficiency activates Wnt expression and activity contributing to senescence and depletion of stem cells, which consequently triggers tissue atrophy and fibrosis. In contrast, the klotho protein was shown to suppress Wnt-signaling transduction, and inhibit cell senescence and preserve stem cells. A better understanding of the potential effects of klotho on stem cells could offer novel insights into the cellular and molecular mechanisms of klotho deficiency-related aging and disease. The klotho protein may be a promising therapeutic agent for aging and aging-related disorders. PMID:26346243

  17. Klotho, stem cells, and aging.

    PubMed

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

    2015-01-01

    Aging is an inevitable and progressive biological process involving dysfunction and eventually destruction of every tissue and organ. This process is driven by a tightly regulated and complex interplay between genetic and acquired factors. Klotho is an antiaging gene encoding a single-pass transmembrane protein, klotho, which serves as an aging suppressor through a wide variety of mechanisms, such as antioxidation, antisenescence, antiautophagy, and modulation of many signaling pathways, including insulin-like growth factor and Wnt. Klotho deficiency activates Wnt expression and activity contributing to senescence and depletion of stem cells, which consequently triggers tissue atrophy and fibrosis. In contrast, the klotho protein was shown to suppress Wnt-signaling transduction, and inhibit cell senescence and preserve stem cells. A better understanding of the potential effects of klotho on stem cells could offer novel insights into the cellular and molecular mechanisms of klotho deficiency-related aging and disease. The klotho protein may be a promising therapeutic agent for aging and aging-related disorders. PMID:26346243

  18. Klotho, stem cells, and aging.

    PubMed

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

    2015-01-01

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

  19. Combination Cell Therapy with Mesenchymal Stem Cells and Neural Stem Cells for Brain Stroke in Rats

    PubMed Central

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

    2015-01-01

    Objectives Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. Method and Materials The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. Result The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. Conclusions The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats. PMID:26019759

  20. Stem Cells News Update: A Personal Perspective

    PubMed Central

    Wong, SC

    2013-01-01

    This article is a follow-up to a previous Commentary published in 2011. It updates some of the events mentioned in that Commentary and continues with more interesting and exciting news on stem cell research and the emerging field of Regenerative Medicine. Some of the news includes: 1) the 2012 Nobel Prize for Medicine awarded to John B. Gurdon and Shinya Yamanaka; 2) the cloning of human embryonic stem cells; 3) the continued search for truly pluripotent adult stem cells via in vitro and in vivo protocols; 4) the breakthrough in organ replacements; 5) the global stem cell race; 6) the global stem cell cryo-preservation business; 7) the worldwide stem cell donor registries, and 8) the issue of government regulation on stem cell therapy. PMID:24778557

  1. [Stem cells and tissue engineering techniques].

    PubMed

    Sica, Gigliola

    2013-01-01

    The therapeutic use of stem cells and tissue engineering techniques are emerging in urology. Here, stem cell types, their differentiating potential and fundamental characteristics are illustrated. The cancer stem cell hypothesis is reported with reference to the role played by stem cells in the origin, development and progression of neoplastic lesions. In addition, recent reports of results obtained with stem cells alone or seeded in scaffolds to overcome problems of damaged urinary tract tissue are summarized. Among others, the application of these biotechnologies in urinary bladder, and urethra are delineated. Nevertheless, apart from the ethical concerns raised from the use of embryonic stem cells, a lot of questions need to be solved concerning the biology of stem cells before their widespread use in clinical trials. Further investigation is also required in tissue engineering utilizing animal models.

  2. Stem cell facelift: between reality and fiction.

    PubMed

    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. Stem cells news update: a personal perspective.

    PubMed

    Wong, Sc

    2013-12-01

    This article is a follow-up to a previous Commentary published in 2011. It updates some of the events mentioned in that Commentary and continues with more interesting and exciting news on stem cell research and the emerging field of Regenerative Medicine. Some of the news includes: 1) the 2012 Nobel Prize for Medicine awarded to John B. Gurdon and Shinya Yamanaka; 2) the cloning of human embryonic stem cells; 3) the continued search for truly pluripotent adult stem cells via in vitro and in vivo protocols; 4) the breakthrough in organ replacements; 5) the global stem cell race; 6) the global stem cell cryo-preservation business; 7) the worldwide stem cell donor registries, and 8) the issue of government regulation on stem cell therapy.

  4. Stem cell facelift: between reality and fiction.

    PubMed

    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. PMID:23417722

  5. Optimal stem cell source for allogeneic stem cell transplantation for hematological malignancies

    PubMed Central

    Cheuk, Daniel KL

    2013-01-01

    Hematopoietic stem cell transplant (HSCT) is a standard treatment for many hematological malignancies. Three different sources of stem cells, namely bone marrow (BM), peripheral blood stem cells (PBSC) and cord blood (CB) can be used for HSCT, and each has its own advantages and disadvantages. Randomized controlled trials (RCTs) suggest that there is no significant survival advantage of PBSC over BM in Human Leukocyte Antigen-matched sibling transplant for adult patients with hematological malignancies. PBSC transplant probably results in lower risk of relapse and hence better disease-free survival, especially in patients with high risk disease at the expense of higher risks of both severe acute and chronic graft-versus-host disease (GVHD). In the unrelated donor setting, the only RCT available suggests that PBSC and BM result in comparable overall and disease-free survivals in patients with hematological malignancies; and PBSC transplant results in lower risk of graft failure and higher risk of chronic GVHD. High level evidence is not available for CB in comparison to BM or PBSC. The risks and benefits of different sources of stem cells likely change with different conditioning regimen, strategies for prophylaxis and treatment of GVHD and manipulation of grafts. The recent success and rapid advance of double CB transplant and haploidentical BM and PBSC transplants further complicate the selection of stem cell source. Optimal selection requires careful weighing of the risks and benefits of different stem cell source for each individual recipient and donor. Detailed counseling of patient and donor regarding risks and benefits in the specific context of the patient and transplant method is essential for informed decision making. PMID:24392314

  6. The dynamics of murine mammary stem/progenitor cells

    PubMed Central

    DONG, Qiaoxiang; SUN, Lu-Zhe

    2014-01-01

    The stem/progenitor cells in the murine mammary gland are a highly dynamic population of cells that are responsible for ductal elongation in puberty, homeostasis maintenance in adult, and lobulo-alveolar genesis during pregnancy. In recent years understanding the epithelial cell hierarchy within the mammary gland is becoming particularly important as these different stem/progenitor cells were perceived to be the cells of origin for various subtypes of breast cancer. Although significant advances have been made in enrichment and isolation of stem/progenitor cells by combinations of antibodies against cell surface proteins together with flow cytometry, and in identification of stem/progenitor cells with multi-lineage differentiation and self-renewal using mammary fat pad reconstitution assay and in vivo genetic labeling technique, a clear understanding of how these different stem/progenitors are orchestrated in the mammary gland is still lacking. Here we discuss the different in vivo and in vitro methods currently available for stem/progenitor identification, their associated caveats, and a possible new hierarchy model to reconcile various putative stem/progenitor cell populations identified by different research groups. PMID:25580105

  7. The Role of MicroRNAs in Cardiac Stem Cells

    PubMed Central

    Purvis, Nima; Bahn, Andrew; Katare, Rajesh

    2015-01-01

    Stem cells are considered as the next generation drug treatment in patients with cardiovascular disease who are resistant to conventional treatment. Among several stem cells used in the clinical setting, cardiac stem cells (CSCs) which reside in the myocardium and epicardium of the heart have been shown to be an effective option for the source of stem cells. In normal circumstances, CSCs primarily function as a cell store to replace the physiologically depleted cardiovascular cells, while under the diseased condition they have been shown to experimentally regenerate the diseased myocardium. In spite of their major functional role, molecular mechanisms regulating the CSCs proliferation and differentiation are still unknown. MicroRNAs (miRs) are small, noncoding RNA molecules that regulate gene expression at the posttranscriptional level. Recent studies have demonstrated the important role of miRs in regulating stem cell proliferation and differentiation, as well as other physiological and pathological processes related to stem cell function. This review summarises the current understanding of the role of miRs in CSCs. A deeper understanding of the mechanisms by which miRs regulate CSCs may lead to advances in the mode of stem cell therapies for the treatment of cardiovascular diseases. PMID:25802528

  8. Stem Cell Therapy: A New Treatment for Burns?

    PubMed Central

    Arno, Anna; Smith, Alexandra H.; Blit, Patrick H.; Shehab, Mohammed Al; Gauglitz, Gerd G.; Jeschke, Marc G.

    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, but also as an adjunct to other strategies, such as organ transplantation or standard drug treatment. Regrettably, serious preclinical concerns remain and differentiation, cell fusion, senescence and signalling crosstalk with growth factors and biomaterials are still challenges for this promising multidisciplinary therapeutic modality. Severe burns have several indications for stem cell therapy, including enhancement of wound healing, replacement of damaged skin and perfect skin regeneration – incorporating skin appendages and reduced fibrosis –, as well as systemic effects, such as inflammation, hypermetabolism and immunosuppression. The aim of this review is to describe well established characteristics of stem cells and to delineate new advances in the stem cell field, in the context of burn injury and wound healing.

  9. Stem Cells, Science, and Public Reasoning

    ERIC Educational Resources Information Center

    Hurlbut, J. Benjamin; Robert, Jason Scott

    2012-01-01

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

  10. Pluripotent states of human embryonic stem cells.

    PubMed

    Chen, Yifei; Lai, Dongmei

    2015-02-01

    Since human embryonic stem cells (hESCs) were first isolated and successfully cultured in vitro, the pluripotent potential of hESCs has been underestimated. The pluripotency of mouse embryonic stem cells (mESCs) can be categorized as naïve and primed, depending on their corresponding in vivo developing phases. mESC morphology differs at distinct pluripotent states, which differ in signaling dependence, gene expression, epigenetic features, and developmental potential. hESCs resemble mouse stem cells at primed pluripotency, and consequently are believed to correspond to a later developmental stage in vivo than mESCs. Nevertheless, recent studies indicate that a naïve state of pluripotency may exist in hESCs, and the pluripotency of hESCs also can be enhanced by genetic modification or optimized culture systems. These findings provide novel insight into the properties and differentiation potential of hESCs. Here, we review the recent advances in characterization of ESC states and investigate the mechanisms regulating hESC pluripotency. PMID:25393391

  11. What Undergraduates Misunderstand about Stem Cell Research

    NASA Astrophysics Data System (ADS)

    Halverson, Kristy Lynn; Freyermuth, Sharyn K.; Siegel, Marcelle A.; Clark, Catharine G.

    2010-11-01

    As biotechnology-related scientific advances, such as stem cell research (SCR), are increasingly permeating the popular media, it has become ever more important to understand students' ideas about this issue. Very few studies have investigated learners' ideas about biotechnology. Our study was designed to understand the types of alternative conceptions students hold concerning SCR. The qualitative research design allowed us to examine college students' understandings about stem cells and SCR. More specifically, we addressed the following questions: How can alternative conceptions about stem cell topics be categorized? What types of alternative conceptions are most common? Participants included 132 students enrolled in a biotechnology course that focused on the scientific background of biotechnology applications relevant to citizens. In this study, we used an inductive approach to develop a taxonomy of alternative ideas about SCR by analyzing student responses to multiple open-ended data sources. We identified five categories of conceptions: alternative conceptions about what, alternative conceptions about how, alternative conceptions about medical potential, terminology confusion, and political and legal alternative conceptions. In order to improve instruction, it is important to understand students' ideas when entering the classroom. Our findings highlight a need to teach how science can be applied to societal issues and improve science literacy and citizenship.

  12. Cancer Stem Cells Converted from Pluripotent Stem Cells and the Cancerous Niche

    PubMed Central

    Kasai, T; Chen, L; Mizutani, AZ; Kudoh, T; Murakami, H; Fu, L; Seno, M

    2014-01-01

    Nowadays, the cancer stem cells are considered to be significantly responsible for growth, metastasis, invasion and recurrence of all cancer. Cancer stem cells are typically characterized by continuous proliferation and self-renewal as well as by differentiation potential, while stem cells are considered to differentiate into tissue- specific phenotype of mature cells under the influence of micro-environment. Cancer stem cells should be traced to the stem cells under the influence of a micro-environment, which induces malignant tumors. In this review, we propose this micro-environment as a ‘cancerous niche’ and discuss its importance on the formation and maintenance of cancer stem cells with the recent experimental results to establish cancer stem cell models from induced pluripotent stem cells. These models of cancer stem cell will provide the great advantages in cancer research and its therapeutic applications in the future. PMID:25075155

  13. Learning about Cancer by Studying Stem Cells

    MedlinePlus

    ... About Cancer by Studying Stem Cells Inside Life Science View All Articles | Inside Life Science Home Page Learning About Cancer by Studying Stem ... Once Upon a Stem Cell This Inside Life Science article also appears on LiveScience . Learn about related ...

  14. Stem cells shine in Shanghai.

    PubMed

    Cheng, Linzhao; Xiao, Lei; Zeng, Fanyi; Zhang, Y Alex

    2008-01-10

    From November 6 to 9, 2007, more than 500 scientists from 20 countries and regions gathered in Shanghai, China, to attend the 2007 Shanghai International Symposium on Stem Cell Research. This dynamic meeting was jointly organized by the International Society for Stem Cell Research (ISSCR), the Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (SIBS/CAS), and other institutes in China. For the first time, the ISSCR added its name to a conference other than its own annual meeting, embracing this opportunity to learn more about research that is happening in China and providing a platform for local researchers who do not always have the opportunity to travel internationally to the ISSCR annual meetings. Here we present a sampling of the diverse research presented by the local and international participants during the science-packed 4 day meeting.

  15. Adult stem cells and tissue repair.

    PubMed

    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.

  16. Cancer stem cells and metastasis.

    PubMed

    Sampieri, Katia; Fodde, Riccardo

    2012-06-01

    Cancer stem cells (CSCs) represent a subpopulation of tumour cells endowed with self-renewal and multi-lineage differentiation capacity but also with an innate resistance to cytotoxic agents, a feature likely to pose major clinical challenges towards the complete eradication of minimal residual disease in cancer patients. Operationally, CSCs are defined by their tumour-propagating ability when serially transplanted into immune-compromised mice and by their capacity to fully recapitulate the original heterogeneity of cell types observed in the primary lesions they are derived from. CSCs were first identified in haematopoietic malignancies and later in a broad spectrum of solid tumours including those of the breast, colon and brain. Notably, several CSC characteristics are relevant to metastasis, such as motility, invasiveness and, as mentioned above, resistance to DNA damage-induced apoptosis. Here, we have reviewed the current literature on the relation between CSCs and metastasis formation. Preliminary studies on cancer cell lines and patient-derived material suggest a rate-limiting role for stem-like cells in the processes of tumour cell dissemination and metastasis formation. However, additional studies are needed to deliver formal proof of their identity as the cell of origin of recurrences at distant organ sites. Nevertheless, several studies have already provided pre-clinical evidence of the efficacy of novel therapies directed against disseminated CSCs.

  17. Direct reprogramming of human neural stem cells by OCT4.

    PubMed

    Kim, Jeong Beom; Greber, Boris; Araúzo-Bravo, Marcos J; Meyer, Johann; Park, Kook In; Zaehres, Holm; Schöler, Hans R

    2009-10-01

    Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by ectopic expression of four transcription factors (OCT4 (also called POU5F1), SOX2, c-Myc and KLF4). We previously reported that Oct4 alone is sufficient to reprogram directly adult mouse neural stem cells to iPS cells. Here we report the generation of one-factor human iPS cells from human fetal neural stem cells (one-factor (1F) human NiPS cells) by ectopic expression of OCT4 alone. One-factor human NiPS cells resemble human embryonic stem cells in global gene expression profiles, epigenetic status, as well as pluripotency in vitro and in vivo. These findings demonstrate that the transcription factor OCT4 is sufficient to reprogram human neural stem cells to pluripotency. One-factor iPS cell generation will advance the field further towards understanding reprogramming and generating patient-specific pluripotent stem cells. PMID:19718018

  18. Generalized Potential of Adult Neural Stem Cells

    NASA Astrophysics Data System (ADS)

    Clarke, Diana L.; Johansson, Clas B.; Wilbertz, Johannes; Veress, Biborka; Nilsson, Erik; Karlström, Helena; Lendahl, Urban; Frisén, Jonas

    2000-06-01

    The differentiation potential of stem cells in tissues of the adult has been thought to be limited to cell lineages present in the organ from which they were derived, but there is evidence that some stem cells may have a broader differentiation repertoire. We show here that neural stem cells from the adult mouse brain can contribute to the formation of chimeric chick and mouse embryos and give rise to cells of all germ layers. This demonstrates that an adult neural stem cell has a very broad developmental capacity and may potentially be used to generate a variety of cell types for transplantation in different diseases.

  19. Mesenchymal Stem Cells in Hematopoietic Stem Cell Transplantation

    PubMed Central

    Battiwalla, Minoo; Hematti, Peiman

    2009-01-01

    Mesenchymal stromal/stem cells (MSCs) of bone marrow (BM) origin not only provide the supportive microenvironmental niche for hematopoietic stem cells (HSCs) but are also capable of differentiating into various cell types of mesenchymal origin, such as bone, fat, and cartilage. In vitro and in vivo data suggest that MSCs have low inherent immunogenicity, modulate/suppress immunological responses through interactions with immune cells, and home to damaged tissues to participate in regeneration processes through their diverse biological properties. MSCs derived from BM are being evaluated for a wide range of clinical applications including disorders as diverse as myocardial infarction or newly diagnosed diabetes mellitus type-1. However, their use in HSC transplantation, either for enhancement of hematopoietic engraftment or for treatment/prevention of graft versus host disease, is far ahead of other indications. Ease of isolation and ex vivo expansion of MSCs, combined with their intriguing immunomodulatory properties, and their impressive record of safety in a wide variety of clinical trials make these cells promising candidates for further investigation. PMID:19728189

  20. CANCER STEM CELLS AND RADIORESISTANCE

    PubMed Central

    K, Rycaj; D.G, Tang

    2015-01-01

    Purpose Radiation therapy has made significant contributions to cancer therapy. However, despite continuous improvements, tumor recurrence and therapy resistance still occur in a high proportion of patients. One underlying reason for this radioresistance might be attributable to the presence of cancer stem cells (CSCs). Conclusions This review discusses CSC-specific mechanisms that confer radiation resistance with a focus on breast cancer and glioblastoma multiforme (GBM), thereby emphasizing the addition of these potential therapeutic targets in order to potentiate radiotherapy efficacy. PMID:24527669

  1. Stem cell tracking with optically active nanoparticles

    PubMed Central

    Gao, Yu; Cui, Yan; Chan, Jerry KY; Xu, Chenjie

    2013-01-01

    Stem-cell-based therapies hold promise and potential to address many unmet clinical needs. Cell tracking with modern imaging modalities offers insight into the underlying biological process of the stem-cell-based therapies, with the goal to reveal cell survival, migration, homing, engraftment, differentiation, and functions. Adaptability, sensitivity, resolution, and non-invasiveness have contributed to the longstanding use of optical imaging for stem cell tracking and analysis. To identify transplanted stem cells from the host tissue, optically active probes are usually used to label stem cells before the administration. In comparison to the traditional fluorescent probes like fluorescent proteins and dyes, nanoparticle-based probes are advantageous in terms of the photo-stabilities and minimal changes to the cell phenotype. The main focus here is to overview the recent development of optically active nanoparticles for stem cells tracking. The related optical imaging modalities include fluorescence imaging, photoacoustic imaging, Raman and surface enhanced Raman spectroscopy imaging. PMID:23638335

  2. How stem cells speak with host immune cells in inflammatory brain diseases.

    PubMed

    Pluchino, Stefano; Cossetti, Chiara

    2013-09-01

    Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases.

  3. [Hematopoietic stem cell transplantation: is it an immunologic therapy?].

    PubMed

    Olaya Vargas, Alberto; Pérez Gonzáles, Oscar

    2003-01-01

    The graft-versus-tumor effect occurring after allogeneic (genetically different) haematopoietic cell transplantation for treating human malignancies, represents the clearest example of the power of the human immune system to eradicate cancer. Recent advances in our understanding of the immunobiology of stem-cell engraftment, tolerance and tumor eradication are allowing clinicians to better harness this powerful effect.

  4. Stem cells in the nervous system.

    PubMed

    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.

  5. Stem Cells in the Nervous System

    PubMed Central

    Maldonado-Soto, Angel R.; Oakley, Derek H.; Wichterle, Hynek; Stein, Joel; Doetsch, Fiona K.; Henderson, Christopher E.

    2014-01-01

    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 the field of regenerative medicine. This review focuses on our 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 of 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. PMID:24800720

  6. Engineering Stem Cells for Biomedical Applications.

    PubMed

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

    2016-01-01

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

  7. Stressed stem cells: Temperature response in aged mesenchymal stem cells.

    PubMed

    Stolzing, Alexandra; Sethe, Sebastian; Scutt, Andrew M

    2006-08-01

    Mesenchymal stem cells (MSCs) derived from young (6 week) and aged (56 week) Wistar rats were cultured at standard (37 degrees C) and reduced (32 degrees C) temperature and compared for age markers and stress levels. (ROS, NO, TBARS, carbonyls, lipofuscin, SOD, GPx, apoptosis, proteasome activity) and heat shock proteins (HSP27, -60, -70, -90). Aged MSCs display many of the stress markers associated with aging in other cell types, but results vary across marker categories and are temperature dependant. In young MSCs, culturing at reduced temperature had a generally beneficial effect: the anti-apoptotic heat shock proteins HSP 27, HSP70, and HSP90 were up-regulated; pro-apoptotic HSP60 was downregulated; SOD, GPx increased; and levels in ROS, NO, TBARS, carbonyl, and lipofuscin were diminished. Apoptosis was reduced, but also proteasome activity. In contrast, in aged MSCs, culturing at reduced temperature generally produced no 'beneficial' changes in these parameters, and can even have detrimental effects. Implications for tissue engineering and for stem cell gerontology are discussed. The results suggest that a 'hormesis' theory of stress response can be extended to MSCs, but that cooling cultivation temperature stress produces positive effects in young cells only.

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

    SciTech Connect

    Varga, Nora; Vereb, Zoltan; Rajnavoelgyi, Eva; Nemet, Katalin; Uher, Ferenc; Sarkadi, Balazs; Apati, Agota

    2011-10-28

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

  9. Reforming craniofacial orthodontics via stem cells

    PubMed Central

    Mohanty, Pritam; Prasad, N.K.K.; Sahoo, Nivedita; Kumar, Gunjan; Mohanty, Debapreeti; Sah, Sushila

    2015-01-01

    Stem cells are the most interesting cells in cell biology. They have the potential to evolve as one of the most powerful technologies in the future. The future refers to an age where it will be used extensively in various fields of medical and dental sciences. Researchers have discovered a number of sources from which stem cells can be derived. Craniofacial problems are very common and occur at all ages. Stem cells can be used therapeutically in almost every field of health science. In fact, many procedures will be reformed after stem cells come into play. This article is an insight into the review of the current researches being carried out on stem cells and its use in the field of orthodontics, which is a specialized branch of dentistry. Although the future is uncertain, there is a great possibility that stem cells will be used extensively in almost all major procedures of orthodontics. PMID:25767761

  10. Stem Cells in the Cornea.

    PubMed

    Hertsenberg, Andrew J; Funderburgh, James L

    2015-01-01

    The cornea is the tough, transparent tissue through which light first enters the eye and functions as a barrier to debris and infection as well as two-thirds of the refractive power of the eye. Corneal damage that is not promptly treated will often lead to scarring and vision impairment. Due to the limited options currently available to treat corneal scars, the identification and isolation of stem cells in the cornea has received much attention, as they may have potential for autologous, cell-based approaches to the treatment of damaged corneal tissue.

  11. Stem cell differentiation and human liver disease

    PubMed Central

    Zhou, Wen-Li; Medine, Claire N; Zhu, Liang; Hay, David C

    2012-01-01

    Human stem cells are scalable cell populations capable of cellular differentiation. This makes them a very attractive in vitro cellular resource and in theory provides unlimited amounts of primary cells. Such an approach has the potential to improve our understanding of human biology and treating disease. In the future it may be possible to deploy novel stem cell-based approaches to treat human liver diseases. In recent years, efficient hepatic differentiation from human stem cells has been achieved by several research groups including our own. In this review we provide an overview of the field and discuss the future potential and limitations of stem cell technology. PMID:22563188

  12. Adult Stem Cell Responses to Nanostimuli

    PubMed Central

    Tsimbouri, Penelope M.

    2015-01-01

    Adult or mesenchymal stem cells (MSCs) have been found in different tissues in the body, residing in stem cell microenvironments called “stem cell niches”. They play different roles but their main activity is to maintain tissue homeostasis and repair throughout the lifetime of an organism. Their ability to differentiate into different cell types makes them an ideal tool to study tissue development and to use them in cell-based therapies. This differentiation process is subject to both internal and external forces at the nanoscale level and this response of stem cells to nanostimuli is the focus of this review. PMID:26193326

  13. Stem cells and the Planarian Schmidtea mediterranea.

    PubMed

    Sánchez Alvarado, Alejandro

    2007-01-01

    In recent years, stem cells have been heralded as potential therapeutic agents to address a large number of degenerative diseases. Yet, in order to rationally utilize these cells as effective therapeutic agents, and/or improve treatment of stem-cell-associated malignancies such as leukemias and carcinomas, a better understanding of the basic biological properties of stem cells needs to be acquired. A major limitation in the study of stem cells lies in the difficulty of accessing and studying these cells in vivo. This barrier is further compounded by the limitations of in vitro culture systems, which are unable to emulate the microenvironments in which stem cells reside and which are known to provide critical regulatory signals for their proliferation and differentiation. Given the complexity of vertebrate embryonic and adult stem cell populations and their relative inaccessibility to in vivo molecular analyses, the study of stem cells should benefit from analyzing their counterparts in simpler model organisms. In the past, the use of Drosophila or C. elegans has provided invaluable contributions to our understanding of genes and pathways involved in a variety of human diseases. However, stem cells in these organisms are mostly restricted to the gonads, and more importantly neither Drosophila, nor C. elegans are capable of regenerating body parts lost to injury. Therefore, a simple animal with experimentally accessible stem cells playing a role in tissue maintenance and/or regeneration should be very useful in identifying and functionally testing the mechanisms regulating stem cell activities. The planarian Schmidtea mediterranea is poised to fill this experimental gap. S. mediterranea displays robust regenerative properties driven by a stem cell population capable of producing the approximately 40 different cell types found in this organism, including the germ cells. Given that all known metazoans depend on stem cells for their survival, it is extremely likely that

  14. PEDF & stem cells: niche vs. nurture.

    PubMed

    Fitchev, Philip; Chung, Chuhan; Plunkett, Beth A; Brendler, Charles B; Crawford, Susan E

    2014-01-01

    Anti-angiogenic pigment epithelium-derived factor (PEDF) is a multifunctional 50kD secreted glycoprotein emerging as a key factor in stem cell renewal. Characteristics of the stem cell niche can be highly dependent on location, access to the vasculature, oxygen tension and neighboring cells. In the neural stem cell (NSC) niche, specifically the subventricular zone, PEDF actively participates in the self renewal process and promotes stemness by upregulating Notch signaling effectors Hes1 and Hes5. The local vascular endothelial cells and ependymal cells are the likely sources of PEDF for the NSC while mesenchymal and retinal stem cells can actually produce PEDF. The opposing actions of PEDF and VEGF on various cells are recapitulated in the NSC niche. Intraventricular injection of PEDF promotes stem cell renewal, while injection of VEGF prompts differentiation and neurogenesis in the subventricular zone. Enhancing the expression of PEDF in stem cells has promising therapeutic implications. Bone marrow mesenchymal stem cells overexpressing PEDF effectively inhibited pathologic angiogenesis in the murine eye and these same cells suppressed hepatocellular carcinoma growth. As a protein with bioactivities in nearly all normal organ systems, it is likely that PEDF will continue to gain visibility as an essential component in the development and delivery of novel stem cell-based therapies to combat disease.

  15. Promise of cancer stem cell vaccine

    PubMed Central

    Zhou, Li; Lu, Lin; Wicha, Max S; Chang, Alfred E; Xia, Jian-chuan; Ren, Xiubao; Li, Qiao

    2015-01-01

    Dendritic cell (DC)-based vaccines designed to target cancer stem cells (CSC) can induce significant antitumor responses via conferring host anti-CSC immunity. Our recent studies have demonstrated that CSC-DC vaccine could inhibit metastasis of primary tumors and induce humoral immune responses against cancer stem cells. This approach highlights the promise of cancer stem cell vaccine in cancer immunotherapy. PMID:26337078

  16. Enabling stem cell therapies for tissue repair: current and future challenges

    PubMed Central

    Wong, Victor W.; Sorkin, Michael; Gurtner, Geoffrey C.

    2012-01-01

    Stem cells embody the tremendous potential of the human body to develop, grow, and repair throughout life. Understanding the biologic mechanisms that underlie stem cell-mediated tissue regeneration is key to harnessing this potential. Recent advances in molecular biology, genetic engineering, and material science have broadened our understanding of stem cells and helped bring them closer to widespread clinical application. Specifically, innovative approaches to optimize how stem cells are identified, isolated, grown, and utilized will help translate these advances into effective clinical therapies. Although there is growing interest in stem cells worldwide, this enthusiasm must be tempered by the fact that these treatments remain for the most part clinically unproven. Future challenges include refining the therapeutic manipulation of stem cells, validating these technologies in randomized clinical trials, and regulating the global expansion of regenerative stem cell therapies. PMID:23178704

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

    PubMed

    Loukogeorgakis, Stavros P; De Coppi, Paolo

    2016-02-01

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

  18. The World Stem Cell Summit. Interview with Bernard Siegel.

    PubMed

    Siegel, Bernard

    2011-11-01

    Regenerative Medicine talks to Bernard Siegel, Executive Director of the Genetics Policy Institute (GPI) and founder of the annual World Stem Cell Summit. Bernard Siegel, JD, is the Founder and full-time Executive Director of the nonprofit Genetics Policy Institute (GPI), based in Wellington, FL, USA. He is the creator and co-chair of the World Stem Cell Summit series of global conferences and Editor-in-Chief of the World Stem Cell Report, which he also founded. He traded his 30-year courtroom career to found GPI, which leads the global 'Pro-Cures Movement' and Stem Cell Action Coalition. As a recognized policy expert on to stem cell research, regenerative medicine and cloning, Mr Siegel works with the world's leading stem cell researchers and advocates. Mr Siegel serves on the board of directors of the Coalition for Advancement of Medical Research (CAMR) and Americans for Cures Foundation. He also serves on the executive committee of the Alliance for Regenerative Medicine (ARM). He is a past co-chair of the Governmental Affairs Committee of the International Society for Stem Cell Research (ISSCR).

  19. Stem Cells in Teeth and Craniofacial Bones

    PubMed Central

    Zhao, H.; Chai, Y.

    2015-01-01

    Stem cells are remarkable, and stem cell–based tissue engineering is an emerging field of biomedical science aiming to restore damaged tissue or organs. In dentistry and reconstructive facial surgery, it is of great interest to restore lost teeth or craniofacial bone defects using stem cell–mediated therapy. In the craniofacial region, various stem cell populations have been identified with regeneration potential. In this review, we provide an overview of the current knowledge concerning the various types of tooth- and craniofacial bone–related stem cells and discuss their in vivo identities and regulating mechanisms. PMID:26350960

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

    PubMed

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

    2014-11-01

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

  1. Mammary stem cells have myoepithelial cell properties

    PubMed Central

    Prater, Michael D.; Petit, Valérie; Russell, I. Alasdair; Giraddi, Rajshekhar; Shehata, Mona; Menon, Suraj; Schulte, Reiner; Kalajzic, Ivo; Rath, Nicola; Olson, Michael F.; Metzger, Daniel; Faraldo, Marisa M.; Deugnier, Marie-Ange; Glukhova, Marina A.; Stingl, John

    2014-01-01

    Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt acin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepithelial cells can give rise to a mammary repopulating unit (MRU). We demonstrate that myoepithelial cells, flow-sorted using 2 independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage tracing approach we follow the progeny of α-smooth muscle actin-expressing myoepithelial cells and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy. PMID:25173976

  2. Therapeutic potential of amniotic fluid stem cells.

    PubMed

    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.

  3. Stem Cell Therapy for Autism

    PubMed Central

    Ichim, Thomas E; Solano, Fabio; Glenn, Eduardo; Morales, Frank; Smith, Leonard; Zabrecky, George; Riordan, Neil H

    2007-01-01

    Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions whose incidence is reaching epidemic proportions, afflicting approximately 1 in 166 children. Autistic disorder, or autism is the most common form of ASD. Although several neurophysiological alterations have been associated with autism, immune abnormalities and neural hypoperfusion appear to be broadly consistent. These appear to be causative since correlation of altered inflammatory responses, and hypoperfusion with symptology is reported. Mesenchymal stem cells (MSC) are in late phases of clinical development for treatment of graft versus host disease and Crohn's Disease, two conditions of immune dysregulation. Cord blood CD34+ cells are known to be potent angiogenic stimulators, having demonstrated positive effects in not only peripheral ischemia, but also in models of cerebral ischemia. Additionally, anecdotal clinical cases have reported responses in autistic children receiving cord blood CD34+ cells. We propose the combined use of MSC and cord blood CD34+cells may be useful in the treatment of autism. PMID:17597540

  4. Multiple Myeloma Cancer Stem Cells

    PubMed Central

    Huff, Carol Ann; Matsui, William

    2008-01-01

    Multiple myeloma is characterized by the clonal expansion of neoplastic plasma cells within the bone marrow, elevated serum immunoglobulin, and osteolytic bone disease. The disease is highly responsive to a wide variety of anticancer treatments including conventional cytotoxic chemotherapy, corticosteroids, radiation therapy, and a growing number of agents with novel mechanisms of action. However, few if any patients are cured with these modalities and relapse remains a critical issue. A better understanding of clonogenic multiple myleoma cells is essential to ultimately improving long-term outcomes, but the nature of the cells responsible for myeloma regrowth and disease relapse is unclear. We review evidence that functional heterogeneity exists in multiple myeloma and discuss potential strategies and clinical implications of the stem-cell model of cancer in this disease. PMID:18539970

  5. Stem cell therapy for autism.

    PubMed

    Ichim, Thomas E; Solano, Fabio; Glenn, Eduardo; Morales, Frank; Smith, Leonard; Zabrecky, George; Riordan, Neil H

    2007-06-27

    Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions whose incidence is reaching epidemic proportions, afflicting approximately 1 in 166 children. Autistic disorder, or autism is the most common form of ASD. Although several neurophysiological alterations have been associated with autism, immune abnormalities and neural hypoperfusion appear to be broadly consistent. These appear to be causative since correlation of altered inflammatory responses, and hypoperfusion with symptology is reported. Mesenchymal stem cells (MSC) are in late phases of clinical development for treatment of graft versus host disease and Crohn's Disease, two conditions of immune dysregulation. Cord blood CD34+ cells are known to be potent angiogenic stimulators, having demonstrated positive effects in not only peripheral ischemia, but also in models of cerebral ischemia. Additionally, anecdotal clinical cases have reported responses in autistic children receiving cord blood CD34+ cells. We propose the combined use of MSC and cord blood CD34+cells may be useful in the treatment of autism.

  6. Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass

    PubMed Central

    Guo, Ge; von Meyenn, Ferdinand; Santos, Fatima; Chen, Yaoyao; Reik, Wolf; Bertone, Paul; Smith, Austin; Nichols, Jennifer

    2016-01-01

    Summary Conventional generation of stem cells from human blastocysts produces a developmentally advanced, or primed, stage of pluripotency. In vitro resetting to a more naive phenotype has been reported. However, whether the reset culture conditions of selective kinase inhibition can enable capture of naive epiblast cells directly from the embryo has not been determined. Here, we show that in these specific conditions individual inner cell mass cells grow into colonies that may then be expanded over multiple passages while retaining a diploid karyotype and naive properties. The cells express hallmark naive pluripotency factors and additionally display features of mitochondrial respiration, global gene expression, and genome-wide hypomethylation distinct from primed cells. They transition through primed pluripotency into somatic lineage differentiation. Collectively these attributes suggest classification as human naive embryonic stem cells. Human counterparts of canonical mouse embryonic stem cells would argue for conservation in the phased progression of pluripotency in mammals. PMID:26947977

  7. Establishment of a Mesenchymal Stem Cell Bank

    PubMed Central

    Cooper, Khushnuma; Viswanathan, Chandra

    2011-01-01

    Adult stem cells have generated great amount of interest amongst the scientific community for their potential therapeutic applications for unmet medical needs. We have demonstrated the plasticity of mesenchymal stem cells isolated from the umbilical cord matrix. Their immunological profile makes it even more interesting. We have demonstrated that the umbilical cord is an inexhaustible source of mesenchymal stem cells. Being a very rich source, instead of discarding this tissue, we worked on banking these cells for regenerative medicine application for future use. The present paper gives a detailed account of our experience in the establishment of a mesenchymal stem cell bank at our facility. PMID:21826152

  8. Engineering synthetic hydrogel microenvironments to instruct stem cells

    PubMed Central

    Guvendiren, Murat; Burdick, Jason A

    2013-01-01

    Advances in our understanding and ability to manipulate stem cell behavior are helping to move stem cell-based therapies toward the clinic. However, much of our knowledge has been gained from standard 2-dimensional culture systems, which often misrepresent many of the signals that stem cells receive in their native 3-dimensional environments. Fortunately, the field of synthetic hydrogels is developing to better recapitulate many of these signals to guide stem cell behavior, both as in vitro models and as delivery vehicles for in vivo implantation. These include a multitude of structural and biochemical cues that can be presented on the cellular scale, such as degradation, adhesion, mechanical signals, topography, and the presentation of growth factors, often with precise spatiotemporal control. PMID:23545441

  9. Stem cell therapy in neurodegenerative diseases: From principles to practice.

    PubMed

    Sakthiswary, Rajalingham; Raymond, Azman Ali

    2012-08-15

    The lack of curative therapies for neurodegenerative diseases has high economic impact and places huge burden on the society. The contribution of stem cells to cure neurodegenerative diseases has been unraveled and explored extensively over the past few years. Beyond substitution of the lost neurons, stem cells act as immunomodulators and neuroprotectors. A large number of preclinical and a small number of clinical studies have shown beneficial outcomes in this context. In this review, we have summarized the current concepts of stem cell therapy in neurodegenerative diseases and the recent advances in this field, particularly between 2010 and 2012. Further studies should be encouraged to resolve the clinical issues and vague translational findings for maximum optimization of the efficacy of stem cell therapy in neurodegenerative diseases.

  10. From stem cells to dopamine neurons: developmental biology meets neurodegeneration.

    PubMed

    Tailor, Jignesh; Andreska, Thomas; Kittappa, Raja

    2012-11-01

    Neurodegenerative disease affects tens of millions of people, worldwide, and comes at a cost to the public of billions of dollars. Stem cell therapy, in recent years, has generated a lot of enthusiasm as a novel treatment for neurodegenerative disease. In particular, Parkinson's disease has been identified as the ideal neurodegenerative disease to be treated using stem cells. Despite years of setbacks, recent experimental results have renewed optimism in the validity of stem cell therapy for the treatment of Parkinson's disease. In this review, we discuss advances in our understanding of the embryonic development of the dopamine system and the importance of these discoveries in the continued efforts towards stem cell therapy for Parkinson's disease.

  11. Mesenchymal Stem Cells in Cardiology.

    PubMed

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

    2016-01-01

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

  12. Wnt signaling in adult intestinal stem cells and cancer.

    PubMed

    Krausova, Michaela; Korinek, Vladimir

    2014-03-01

    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 physiological range. In addition, the Wnt pathway involves various feedback loops that balance the opposing processes of cell proliferation and differentiation. Today, we have compelling evidence that mutations causing aberrant activation of the Wnt pathway promote expansion of undifferentiated progenitors and lead to cancer. The review summarizes recent advances in characterization of adult epithelial stem cells in the gut. We mainly focus on discoveries related to molecular mechanisms regulating the output of the Wnt pathway. Moreover, we present novel experimental approaches utilized to investigate the epithelial cell signaling circuitry in vivo and in vitro. Pivotal aspects of tissue homeostasis are often deduced from studies of tumor cells; therefore, we also discuss some latest results gleaned from the deep genome sequencing studies of human carcinomas of the colon and rectum. PMID:24308963

  13. Canine Pluripotent Stem Cells: Are They Ready for Clinical Applications?

    PubMed

    Betts, Dean H; Tobias, Ian C

    2015-01-01

    The derivation of canine embryonic stem cells and generation of canine-induced pluripotent stem cells are significant achievements that have unlocked the potential for developing novel cell-based disease models, drug discovery platforms, and transplantation therapies in the dog. A progression from concept to cure in this clinically relevant companion animal will not only help our canine patients but also help advance human regenerative medicine. Nevertheless, many issues remain to be resolved before pluripotent cells can be used clinically in a safe and reproducible manner. PMID:26664969

  14. Neural Stem Cells (NSCs) and Proteomics*

    PubMed Central

    Shoemaker, Lorelei D.; Kornblum, Harley I.

    2016-01-01

    Neural stem cells (NSCs) can self-renew and give rise to the major cell types of the CNS. Studies of NSCs include the investigation of primary, CNS-derived cells as well as animal and human embryonic stem cell (ESC)-derived and induced pluripotent stem cell (iPSC)-derived sources. NSCs provide a means with which to study normal neural development, neurodegeneration, and neurological disease and are clinically relevant sources for cellular repair to the damaged and diseased CNS. Proteomics studies of NSCs have the potential to delineate molecules and pathways critical for NSC biology and the means by which NSCs can participate in neural repair. In this review, we provide a background to NSC biology, including the means to obtain them and the caveats to these processes. We then focus on advances in the proteomic interrogation of NSCs. This includes the analysis of posttranslational modifications (PTMs); approaches to analyzing different proteomic compartments, such the secretome; as well as approaches to analyzing temporal differences in the proteome to elucidate mechanisms of differentiation. We also discuss some of the methods that will undoubtedly be useful in the investigation of NSCs but which have not yet been applied to the field. While many proteomics studies of NSCs have largely catalogued the proteome or posttranslational modifications of specific cellular states, without delving into specific functions, some have led to understandings of functional processes or identified markers that could not have been identified via other means. Many challenges remain in the field, including the precise identification and standardization of NSCs used for proteomic analyses, as well as how to translate fundamental proteomics studies to functional biology. The next level of investigation will require interdisciplinary approaches, combining the skills of those interested in the biochemistry of proteomics with those interested in modulating NSC function. PMID:26494823

  15. Neural Stem Cells (NSCs) and Proteomics.

    PubMed

    Shoemaker, Lorelei D; Kornblum, Harley I

    2016-02-01

    Neural stem cells (NSCs) can self-renew and give rise to the major cell types of the CNS. Studies of NSCs include the investigation of primary, CNS-derived cells as well as animal and human embryonic stem cell (ESC)-derived and induced pluripotent stem cell (iPSC)-derived sources. NSCs provide a means with which to study normal neural development, neurodegeneration, and neurological disease and are clinically relevant sources for cellular repair to the damaged and diseased CNS. Proteomics studies of NSCs have the potential to delineate molecules and pathways critical for NSC biology and the means by which NSCs can participate in neural repair. In this review, we provide a background to NSC biology, including the means to obtain them and the caveats to these processes. We then focus on advances in the proteomic interrogation of NSCs. This includes the analysis of posttranslational modifications (PTMs); approaches to analyzing different proteomic compartments, such the secretome; as well as approaches to analyzing temporal differences in the proteome to elucidate mechanisms of differentiation. We also discuss some of the methods that will undoubtedly be useful in the investigation of NSCs but which have not yet been applied to the field. While many proteomics studies of NSCs have largely catalogued the proteome or posttranslational modifications of specific cellular states, without delving into specific functions, some have led to understandings of functional processes or identified markers that could not have been identified via other means. Many challenges remain in the field, including the precise identification and standardization of NSCs used for proteomic analyses, as well as how to translate fundamental proteomics studies to functional biology. The next level of investigation will require interdisciplinary approaches, combining the skills of those interested in the biochemistry of proteomics with those interested in modulating NSC function. PMID:26494823

  16. Stem cells in the light of evolution

    PubMed Central

    Chakraborty, Chiranjib; Agoramoorthy, Govindasamy

    2012-01-01

    All organisms depend on stem cells for their survival. As a result, stem cells may be a prerequisite for the evolution of specific characteristics in organisms that include regeneration, multicellularity and coloniality. Stem cells have attracted the attention of biologists and medical scientists for a long time. These provide materials for regenerative medicine. We review in this paper, the link between modern stem cell research and early studies in ancient organisms. It also outlines details on stem cells in the light of evolution with an emphasis on their regeneration potential, coloniality and multicellularity. The information provided might be of use to molecular biologists, medical scientists and developmental biologists who are engaged in integrated research involving the stem cells. PMID:22825600

  17. Two-photon imaging of stem cells

    NASA Astrophysics Data System (ADS)

    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.

  18. Of Microenvironments and Mammary Stem Cells

    SciTech Connect

    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.

  19. Role of stem cells in tooth bioengineering

    PubMed Central

    Singh, Kamleshwar; Mishra, Niraj; Kumar, Lakshya; Agarwal, Kaushal Kishore; Agarwal, Bhaskar

    2012-01-01

    The creation of teeth in the laboratory depends upon the manipulation of stem cells and requires a synergy of all cellular and molecular events that finally lead to the formation of tooth-specific hard tissues, dentin, and enamel. This review focuses on the different sources of stem cells that have been used for making teeth in vitro. The search was performed from 1970 to 2012 and was limited to English language papers. The keywords searched on medline were ‘stem cells and dentistry,’ ‘stem cells and odontoblast,’ ‘stem cells and dentin,’ and ‘stem cells and ameloblasts.’ PMID:25756031

  20. [Stem cell therapy for neurodegenerative disorders].

    PubMed

    Meyer, Morten; Jensen, Pia; Rasmussen, Jens Zimmer

    2010-09-20

    Intrastriatal, foetal neural transplants can ameliorate symptoms in patients with Parkinson's and Huntington's disease, although not stop the primary cell-loss. Several issues must, however, be addressed before general or extended clinical use of cell therapy in neurodegenerative diseases can become a reality. Improvements include standardized and safe master cell-lines derived from human embryonic stem cells, induced pluripotent stem cells and neural stem cells. Cells from these sources are expected to become available for cell replacement therapies or therapeutic production of trophic, anti-inflammatory and restorative factors within a few years.

  1. Human stem cells and articular cartilage regeneration.

    PubMed

    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.

  2. [Bioethical challenges of stem cell tourism].

    PubMed

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

    2013-08-01

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

  3. Stem cells: The Next Therapeutic Frontier

    PubMed Central

    Humes, H. David

    2005-01-01

    Cell therapy is one of the most exciting fields in translational medicine. It stands at the intersection of a variety of rapidly developing scientific disciplines: stem cell biology, immunology, tissue engineering, molecular biology, biomaterials, transplantation biology, regenerative medicine, and clinical research. Cell-based therapy may develop into a new therapeutic platform to treat a vast array of clinical disorders. Blood transfusions and bone marrow transplantation are prime examples of the successful application of cell-based therapeutics; but recent advances in cellular and molecular biology have expanded the potential applications of this approach. Although recombinant genetic engineering to produce a variety of therapeutics such as human erythropoietin and insulin has proven successful, these treatments are unable to completely correct or reverse disease states, because most common disease processes are not due to the deficiency of a single protein but develop due to alterations in the complex interactions of a variety of cell components. In these complex situations, cell-based therapy may be a more successful strategy by providing a dynamic, interactive, and individualized therapeutic approach that responds to the pathophysiological condition of the patient. In this regard, cells may provide innovative methods for drug delivery of biologics, immunotherapy, and tissue regenerative or replacement engineering (1,2). The translation of this discipline to medical practice has tremendous potential, but in many applications technological issues need to be overcome. Since many cell-based indications are already being evaluated in the clinic, the field appears to be on the threshold of a number of successes. This review will focus on our group's use of human stem/progenitor cells in the treatment of acute and chronic renal failure as extensions to the current successful renal substitution processes of hemodialysis and hemofiltration. PMID:16555613

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

    PubMed

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

    2016-09-01

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

  5. Telomeres, stem cells, and hematology

    PubMed Central

    2008-01-01

    Telomeres are highly dynamic structures that adjust the cellular response to stress and growth stimulation based on previous cell divisions. This critical function is accomplished by progressive telomere shortening and DNA damage responses activated by chromosome ends without sufficient telomere repeats. Repair of critically short telomeres by telomerase or recombination is limited in most somatic cells, and apoptosis or cellular senescence is triggered when too many uncapped telomeres accumulate. The chance of the latter increases as the average telomere length decreases. The average telomere length is set and maintained in cells of the germ line that typically express high levels of telomerase. In somatic cells, the telomere length typically declines with age, posing a barrier to tumor growth but also contributing to loss of cells with age. Loss of (stem) cells via telomere attrition provides strong selection for abnormal cells in which malignant progression is facilitated by genome instability resulting from uncapped telomeres. The critical role of telomeres in cell proliferation and aging is illustrated in patients with 50% of normal telomerase levels resulting from a mutation in one of the telomerase genes. Here, the role of telomeres and telomerase in human biology is reviewed from a personal historical perspective. PMID:18263784

  6. The Alpha Stem Cell Clinic: A Model for Evaluating and Delivering Stem Cell-Based Therapies

    PubMed Central

    DeWitt, Natalie D.; Feigal, Ellen G.

    2012-01-01

    Summary Cellular therapies require the careful preparation, expansion, characterization, and delivery of cells in a clinical environment. There are major challenges associated with the delivery of cell therapies and high costs that will limit the companies available to fully evaluate their merit in clinical trials, and will handicap their application at the present financial environment. Cells will be manufactured in good manufacturing practice or near-equivalent facilities with prerequisite safety practices in place, and cell delivery systems will be specialized and require well-trained medical and nursing staff, technicians or nurses trained to handle cells once delivered, patient counselors, as well as statisticians and database managers who will oversee the monitoring of patients in relatively long-term follow-up studies. The model proposed for Alpha Stem Cell Clinics will initially use the capacities and infrastructure that exist in the most advanced tertiary medical clinics for delivery of established bone marrow stem cell therapies. As the research evolves, they will incorporate improved procedures and cell preparations. This model enables commercialization of medical devices, reagents, and other products required for cell therapies. A carefully constructed cell therapy clinical infrastructure with the requisite scientific, technical, and medical expertise and operational efficiencies will have the capabilities to address three fundamental and critical functions: 1) fostering clinical trials; 2) evaluating and establishing safe and effective therapies, and 3) developing and maintaining the delivery of therapies approved by the Food and Drug Administration, or other regulatory agencies. PMID:23197634

  7. The ethics of moral compromise for stem cell research policy.

    PubMed

    Master, Zubin; Crozier, G K D

    2012-03-01

    In the US, stem cell research is at a moral impasse-many see this research as ethically mandated due to its potential for ameliorating major diseases, while others see this research as ethically impermissible because it typically involves the destruction of embryos and use of ova from women. Because their creation does not require embryos or ova, induced pluripotent stem cells offer the most promising path for addressing the main ethical objections to stem cell research; however, this technology is still in development. In order for scientists to advance induced pluripotent stem cell research to a point of translational readiness, they must continue to use ova and embryos in the interim. How then are we to ethically move forward with stem cell research? We argue that there is personal integrity and value in adopting a 'moral compromise' as a means for moving past the moral impasse in stem cell research. In a moral compromise, each party concedes part of their desired outcome in order to engage in a process that respects the values and desires of all parties equitably. Whereas some contend that moral compromise in stem cell research necessarily involves self-contradiction or loss of personal integrity, we argue that in the US context, stem cell research satisfies many of the key pre-conditions of an effective moral compromise. To illustrate our point, we offer a model solution wherein eggs and embryos are temporarily used until non-egg and non-embryonic sources of pluripotent stem cells are developed to a state of translational readiness.

  8. Stem cell reprogramming: A 3D boost

    NASA Astrophysics Data System (ADS)

    Abilez, Oscar J.; Wu, Joseph C.

    2016-03-01

    Biophysical factors in an optimized three-dimensional microenvironment enhance the reprogramming efficiency of human somatic cells into pluripotent stem cells when compared to traditional cell-culture substrates.

  9. Cancer stem cells: progress and challenges in lung cancer.

    PubMed

    Templeton, Amanda K; Miyamoto, Shinya; Babu, Anish; Munshi, Anupama; Ramesh, Rajagopal

    2014-01-01

    The identification of a subpopulation of tumor cells with stem cell-like characteristics first in hematological malignancies and later in solid tumors has emerged into a novel field of cancer research. It has been proposed that this aberrant population of cells now called "cancer stem cells" (CSCs) drives tumor initiation, progression, metastasis, recurrence, and drug resistance. CSCs have been shown to have the capacity of self-renewal and multipotency. Adopting strategies from the field of stem cell research has aided in identification, localization, and targeting of CSCs in many tumors. Despite the huge progress in other solid tumors such as brain, breast, and colon cancers no substantial advancements have been made in lung cancer. This is most likely due to the current rudimentary understanding of lung stem cell hierarchy and heterogeneous nature of lung disease. In this review, we will discuss the most recent findings related to identification of normal lung stem cells and CSCs, pathways involved in regulating the development of CSCs, and the importance of the stem cell niche in development and maintenance of CSCs. Additionally, we will examine the development and feasibility of novel CSC-targeted therapeutic strategies aimed at eradicating lung CSCs. PMID:27358855

  10. Plant stem cells as innovation in cosmetics.

    PubMed

    Moruś, Martyna; Baran, Monika; Rost-Roszkowska, Magdalena; Skotnicka-Graca, Urszula

    2014-01-01

    The stem cells thanks to their ability of unlimited division number or transformation into different cell types creating organs, are responsible for regeneration processes. Depending on the organism in which the stem cells exists, they divide to the plant or animal ones. The later group includes the stem cells existing in both embryo's and adult human's organs. It includes, among others, epidermal stem cells, located in the hair follicle relieves and also in its basal layers, and responsible for permanent regeneration of the epidermis. Temporary science looks for method suitable for stimulation of the epidermis stem cells, amongst the other by delivery of e.g., growth factors for proliferation that decrease with the age. One of the methods is the use of the plant cell culture technology, including a number of methods that should ensure growth of plant cells, issues or organs in the environment with the microorganism-free medium. It uses abilities of the different plant cells to dedifferentiation into stem cells and coming back to the pluripotent status. The extracts obtained this way from the plant stem cells are currently used for production of both common or professional care cosmetics. This work describes exactly impact of the plant stem cell extract, coming from one type of the common apple tree (Uttwiler Spätlauber) to human skin as one of the first plant sorts, which are used in cosmetology and esthetic dermatology.

  11. Prospects of Stem Cells for Retinal Diseases.

    PubMed

    Ng, Tsz Kin; Lam, Dennis S C; Cheung, Herman S

    2013-01-01

    Retinal diseases, including glaucoma, retinitis pigmentosa, diabetic retinopathy, and age-related macular degeneration, are the leading causes of irreversible visual impairment and blindness in developed countries. Traditional and current treatment regimens are based on surgical or medical interventions to slow down the disease progression. However, the number of retinal cells would continue to diminish, and the diseases could not be completely cured. There is an emerging role of stem cells in retinal research. The stem cell therapy on retinal diseases is based on 2 theories: cell replacement therapy and neuroprotective effect. The former hypothesizes that new retinal cells could be regenerated from stem cells to substitute the damaged cells in the diseased retina, whereas the latter believes that the paracrine effects of stem cells modulate the microenvironments of the diseased retina so as to protect the retinal neurons. This article summarizes the choice of stem cells in retinal research. Moreover, the current progress of retinal research on stem cells and the clinical applications of stem cells on retinal diseases are reviewed. In addition, potential challenges and future prospects of retinal stem cell research are discussed.

  12. Burning Fat Fuels Leukemic Stem Cell Heterogeneity.

    PubMed

    Thomas, Daniel; Majeti, Ravindra

    2016-07-01

    Obese leukemia patients exhibit reduced survival after chemotherapy, suggesting an important role of adipose tissue in disease progression. In this issue of Cell Stem Cell, Ye et al. (2016) reveal metabolic heterogeneity in leukemic stem cell (LSC) subpopulations and show that chemotherapy-resistant CD36+ LSCs co-opt gonadal adipose tissue to support their metabolism and survival. PMID:27392217

  13. Ocular stem cells: a status update!

    PubMed Central

    2014-01-01

    Stem cells are unspecialized cells that have been a major focus of the field of regenerative medicine, opening new frontiers and regarded as the future of medicine. The ophthalmology branch of the medical sciences was the first to directly benefit from stem cells for regenerative treatment. The success stories of regenerative medicine in ophthalmology can be attributed to its accessibility, ease of follow-up and the eye being an immune-privileged organ. Cell-based therapies using stem cells from the ciliary body, iris and sclera are still in animal experimental stages but show potential for replacing degenerated photoreceptors. Limbal, corneal and conjunctival stem cells are still limited for use only for surface reconstruction, although they might have potential beyond this. Iris pigment epithelial, ciliary body epithelial and choroidal epithelial stem cells in laboratory studies have shown some promise for retinal or neural tissue replacement. Trabecular meshwork, orbital and sclera stem cells have properties identical to cells of mesenchymal origin but their potential has yet to be experimentally determined and validated. Retinal and retinal pigment epithelium stem cells remain the most sought out stem cells for curing retinal degenerative disorders, although treatments using them have resulted in variable outcomes. The functional aspects of the therapeutic application of lenticular stem cells are not known and need further attention. Recently, embryonic stem cell-derived retinal pigment epithelium has been used for treating patients with Stargardts disease and age-related macular degeneration. Overall, the different stem cells residing in different components of the eye have shown some success in clinical and animal studies in the field of regenerative medicine. PMID:25158127

  14. Ocular stem cells: a status update!

    PubMed

    Dhamodaran, Kamesh; Subramani, Murali; Ponnalagu, Murugeswari; Shetty, Reshma; Das, Debashish

    2014-01-01

    Stem cells are unspecialized cells that have been a major focus of the field of regenerative medicine, opening new frontiers and regarded as the future of medicine. The ophthalmology branch of the medical sciences was the first to directly benefit from stem cells for regenerative treatment. The success stories of regenerative medicine in ophthalmology can be attributed to its accessibility, ease of follow-up and the eye being an immune-privileged organ. Cell-based therapies using stem cells from the ciliary body, iris and sclera are still in animal experimental stages but show potential for replacing degenerated photoreceptors. Limbal, corneal and conjunctival stem cells are still limited for use only for surface reconstruction, although they might have potential beyond this. Iris pigment epithelial, ciliary body epithelial and choroidal epithelial stem cells in laboratory studies have shown some promise for retinal or neural tissue replacement. Trabecular meshwork, orbital and sclera stem cells have properties identical to cells of mesenchymal origin but their potential has yet to be experimentally determined and validated. Retinal and retinal pigment epithelium stem cells remain the most sought out stem cells for curing retinal degenerative disorders, although treatments using them have resulted in variable outcomes. The functional aspects of the therapeutic application of lenticular stem cells are not known and need further attention. Recently, embryonic stem cell-derived retinal pigment epithelium has been used for treating patients with Stargardts disease and age-related macular degeneration. Overall, the different stem cells residing in different components of the eye have shown some success in clinical and animal studies in the field of regenerative medicine.

  15. Hardwiring Stem Cell Communication through Tissue Structure.

    PubMed

    Xin, Tianchi; Greco, Valentina; Myung, Peggy

    2016-03-10

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

  16. Hardwiring Stem Cell Communication through Tissue Structure.

    PubMed

    Xin, Tianchi; Greco, Valentina; Myung, Peggy

    2016-03-10

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

  17. Nanomaterials for Engineering Stem Cell Responses.

    PubMed

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

    2015-08-01

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

  18. Wnt Signaling in Cancer Stem Cell Biology.

    PubMed

    de Sousa E Melo, Felipe; Vermeulen, Louis

    2016-06-27

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer.

  19. Genetic and epigenetic instability of stem cells.

    PubMed

    Rajamani, Karthyayani; Li, Yuan-Sheng; Hsieh, Dean-Kuo; Lin, Shinn-Zong; Harn, Horng-Jyh; Chiou, Tzyy-Wen

    2014-01-01

    Recently, research on stem cells has been receiving an increasing amount of attention, both for its advantages and disadvantages. Genetic and epigenetic instabilities among stem cells have been a recurring obstacle to progress in regenerative medicine using stem cells. Various reports have stated that these instabilities can transform stem cells when transferred in vivo and thus have the potential to develop tumors. Previous research has shown that various extrinsic and intrinsic factors can contribute to the stability of stem cells. The extrinsic factors include growth supplements, growth factors, oxygen tension, passage technique, and cryopreservation. Controlling these factors based on previous reports may assist researchers in developing strategies for the production and clinical application of "safe" stem cells. On the other hand, the intrinsic factors can be unpredictable and uncontrollable; therefore, to ensure the successful use of stem cells in regenerative medicine, it is imperative to develop and implement appropriate strategies and technique for culturing stem cells and to confirm the genetic and epigenetic safety of these stem cells before employing them in clinical trials.

  20. The Patentability of Stem Cells in Australia.

    PubMed

    Petering, Jenny; Cowin, Prue

    2015-07-01

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

  1. Wnt Signaling in Cancer Stem Cell Biology

    PubMed Central

    de Sousa e Melo, Felipe; Vermeulen, Louis

    2016-01-01

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer. PMID:27355964

  2. Stomach development, stem cells and disease.

    PubMed

    Kim, Tae-Hee; Shivdasani, Ramesh A

    2016-02-15

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

  3. [Stem cells - biology and therapeutic application].

    PubMed

    Sikora, Magdalena A; Olszewski, Waldemar L

    2004-04-01

    Enormous hope is connected with stem cells with regard to cell therapy, and this has become one of the most dynamically developing areas of science at the moment. A stem cell has unlimited potential for self-renewal. It appears that it can be a source of in vitro differentiated progeny cells capable of repairing damaged tissue. These review provides information about the biological properties of embryonic stem cells, i.e. ESs (embryonic stem cells), EGs (embryonic germ cells), and ECs (embryonic carcinoma cells). Possible human embryonic stem cell applications are described, with consideration of the desired cell line and the signals involved in their differentiation. The information about adult stem cells present - hemopoietic stem cells and the cells residing in selected tissues and organs: endothelium, pancreas, liver, epithelium, and gastrointestinal tract. Methods of their identification using the cell surfaces are also presented: the possibilities of in vitro transdifferentation, the phenomenon of in vivo plasticity, as well as morphological and genetic properties. Some topics of cell therapy and its clinical application in diabetics amplification are included. PMID:15114255

  4. Induced pluripotent stem cell therapies for retinal disease

    PubMed Central

    Comyn, Oliver; Lee, Edward; MacLaren, Robert E

    2010-01-01

    Purpose of review: This review will discuss how recent advances with induced pluripotent stem (iPS) cells have brought the science of stem cell biology much closer to clinical application for patients with retinal degeneration. Recent findings: The ability to generate embryonic stem (ES) cells by reprogramming DNA taken from adult cells was demonstrated by the cloning of Dolly the sheep by somatic cell nuclear transfer over ten years ago. Recently it has been shown that adult cells can be reprogrammed directly, without the need for a surrogate oocyte through the generation of induced pluripotent stem (iPS) cells. The method of reprogramming has since been optimised to avoid the use of retroviruses, making the process considerably safer. Last year human iPS cells were isolated from an 80 year old patient with neurodegenerative disease and differentiated into neurons in vitro. Summary: For stem cell therapies, the retina has the optimal combination of ease of surgical access, combined with an ability to observe transplanted cells directly through the clear ocular media. The question now is which retinal diseases are most appropriate targets for clinical trials using iPS cell approaches. PMID:19949329

  5. Brain tumour stem cells: possibilities of new therapeutic strategies.

    PubMed

    Piccirillo, Sara G M; Vescovi, Angelo L

    2007-08-01

    Cancers are composed of heterogeneous cell populations, including highly proliferative immature precursors and differentiated cells, which may belong to different lineages. Recent advances in stem cell research have demonstrated the existence of tumour-initiating, cancer stem cells (CSCs) in non-solid and solid tumours. These cells are defined as CSCs because they show functional properties that resemble those of their normal counterpart to a significant extent. This concept applies to CSCs from brain tumours and, particularly, to glioblastoma stem-like cells, which self-renew under clonal conditions and differentiate into neuron- and glia-like cells, and into aberrant cells, with mixed neuronal/astroglia phenotypes. Notably, across serial transplantation into immunodeficient mice, glioblastoma stem-like cells are able to form secondary tumours which are a phenocopy of the human disease. A significant effort is underway to identify both CSC-specific markers and the molecular mechanism that underpin the tumorigenic potential of these cells, for this will have a critical impact on the understanding of the origin of malignant brain tumour and the discovery of new and more specific therapeutic approaches. Lately, the authors have shown that some of the bone morphogenetic proteins can reduce the tumorigenic ability of CSCs in GBMs. This suggests that mechanisms regulating the physiology of normal brain stem cells may be still in place in their cancerous siblings and that this may lead to the development of cures that selectively target the population CSCs found in the patients' tumour mass.

  6. Cancer stem cells: impact, heterogeneity, and uncertainty

    PubMed Central

    Magee, Jeffrey A.; Piskounova, Elena; Morrison, Sean J.

    2015-01-01

    The differentiation of tumorigenic cancer stem cells into non-tumorigenic cancer cells confers heterogeneity to some cancers beyond that explained by clonal evolution or environmental differences. In such cancers, functional differences between tumorigenic and non-tumorigenic cells influence response to therapy and prognosis. However, it remains uncertain whether the model applies to many, or few, cancers due to questions about the robustness of cancer stem cell markers and the extent to which existing assays underestimate the frequency of tumorigenic cells. In cancers with rapid genetic change, reversible changes in cell states, or biological variability among patients the stem cell model may not be readily testable. PMID:22439924

  7. Single-cell sequencing in stem cell biology.

    PubMed

    Wen, Lu; Tang, Fuchou

    2016-04-15

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

  8. Development of Scalable Culture Systems for Human Embryonic Stem Cells

    PubMed Central

    Azarin, Samira M.; Palecek, Sean P.

    2009-01-01

    The use of human pluripotent stem cells, including embryonic and induced pluripotent stem cells, in therapeutic applications will require the development of robust, scalable culture technologies for undifferentiated cells. Advances made in large-scale cultures of other mammalian cells will facilitate expansion of undifferentiated human embryonic stem cells (hESCs), but challenges specific to hESCs will also have to be addressed, including development of defined, humanized culture media and substrates, monitoring spontaneous differentiation and heterogeneity in the cultures, and maintaining karyotypic integrity in the cells. This review will describe our current understanding of environmental factors that regulate hESC self-renewal and efforts to provide these cues in various scalable bioreactor culture systems. PMID:20161686

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

    PubMed

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

    2015-01-01

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

  10. In search of liver cancer stem cells.

    PubMed

    Ma, Stephanie; Chan, Kwok Wah; Guan, Xin-Yuan

    2008-09-01

    Recent research efforts in stem cell and cancer biology have put forth a "stem cell model of carcinogenesis" which stipulates that the capability to maintain tumor formation and growth specifically resides in a small population of cells called cancer stem cells. The stem cell-like characteristics of these cells, including their ability to self-renew and differentiate; and their limited number within the bulk of the tumor mass, are believed to account for their capability to escape conventional therapies. In the past few years, the hypothesis of stem cell-driven tumorigenesis in liver cancer has received substantial support from the recent ability to identify and isolate a subpopulation of liver cancer cells that is not only able to initiate tumor growth, but also serially establish themselves as tumor xenografts with high efficiency and consistency. In this review, stem cell biology that contributes to explain tumor development in the particular context of liver cancer will be discussed. We will begin by briefly considering the knowledge available on normal liver stem cells and their role in tissue renewal and regeneration. We will then summarize the current scientific knowledge of liver cancer stem cells, discuss their relevance to the diagnosis and treatment of the disease and consider the outstanding challenges and potential opportunities that lie ahead of us.

  11. Stem cells in bone tissue engineering.

    PubMed

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

    2010-12-01

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

  12. Deconstructing stem cell population heterogeneity: Single-cell analysis and modeling approaches

    PubMed Central

    Wu, Jincheng; Tzanakakis, Emmanuel S.

    2014-01-01

    Isogenic stem cell populations display cell-to-cell variations in a multitude of attributes including gene or protein expression, epigenetic state, morphology, proliferation and proclivity for differentiation. The origins of the observed heterogeneity and its roles in the maintenance of pluripotency and the lineage specification of stem cells remain unclear. Addressing pertinent questions will require the employment of single-cell analysis methods as traditional cell biochemical and biomolecular assays yield mostly population-average data. In addition to time-lapse microscopy and flow cytometry, recent advances in single-cell genomic, transcriptomic and proteomic profiling are reviewed. The application of multiple displacement amplification, next generation sequencing, mass cytometry and spectrometry to stem cell systems is expected to provide a wealth of information affording unprecedented levels of multiparametric characterization of cell ensembles under defined conditions promoting pluripotency or commitment. Establishing connections between single-cell analysis information and the observed phenotypes will also require suitable mathematical models. Stem cell self-renewal and differentiation are orchestrated by the coordinated regulation of subcellular, intercellular and niche-wide processes spanning multiple time scales. Here, we discuss different modeling approaches and challenges arising from their application to stem cell populations. Integrating single-cell analysis with computational methods will fill gaps in our knowledge about the functions of heterogeneity in stem cell physiology. This combination will also aid the rational design of efficient differentiation and reprogramming strategies as well as bioprocesses for the production of clinically valuable stem cell derivatives. PMID:24035899

  13. Index sorting resolves heterogeneous murine hematopoietic stem cell populations.

    PubMed

    Schulte, Reiner; Wilson, Nicola K; Prick, Janine C M; Cossetti, Chiara; Maj, Michal K; Gottgens, Berthold; Kent, David G

    2015-09-01

    Recent advances in the cellular and molecular biology of single stem cells have uncovered significant heterogeneity in the functional properties of stem cell populations. This has prompted the development of approaches to study single cells in isolation, often performed using multiparameter flow cytometry. However, many stem cell populations are too rare to test all possible cell surface marker combinations, and virtually nothing is known about functional differences associated with varying intensities of such markers. Here we describe the use of index sorting for further resolution of the flow cytometric isolation of single murine hematopoietic stem cells (HSCs). Specifically, we associate single-cell functional assay outcomes with distinct cell surface marker expression intensities. High levels of both CD150 and EPCR associate with delayed kinetics of cell division and low levels of differentiation. Moreover, cells that do not form single HSC-derived clones appear in the 7AAD(dim) fraction, suggesting that even low levels of 7AAD staining are indicative of less healthy cell populations. These data indicate that when used in combination with single-cell functional assays, index sorting is a powerful tool for refining cell isolation strategies. This approach can be broadly applied to other single-cell systems, both to improve isolation and to acquire additional cell surface marker information.