Science.gov

Sample records for stem cell replacement

  1. Stem cell approaches for diabetes: towards beta cell replacement

    PubMed Central

    2011-01-01

    Stem cells hold great promise for pancreatic beta cell replacement therapy for diabetes. In type 1 diabetes, beta cells are mostly destroyed, and in type 2 diabetes beta cell numbers are reduced by 40% to 60%. The proof-of-principle that cellular transplants of pancreatic islets, which contain insulin-secreting beta cells, can reverse the hyperglycemia of type 1 diabetes has been established, and there is now a need to find an adequate source of islet cells. Human embryonic stem cells can be directed to become fully developed beta cells and there is expectation that induced pluripotent stem (iPS) cells can be similarly directed. iPS cells can also be generated from patients with diabetes to allow studies of the genomics and pathogenesis of the disease. Some alternative approaches for replacing beta cells include finding ways to enhance the replication of existing beta cells, stimulating neogenesis (the formation of new islets in postnatal life), and reprogramming of pancreatic exocrine cells to insulin-producing cells. Stem-cell-based approaches could also be used for modulation of the immune system in type 1 diabetes, or to address the problems of obesity and insulin resistance in type 2 diabetes. Herein, we review recent advances in our understanding of diabetes and beta cell biology at the genomic level, and we discuss how stem-cell-based approaches might be used for replacing beta cells and for treating diabetes. PMID:21951399

  2. Patterning discrete stem cell culture environments via localized SAM replacement

    PubMed Central

    Koepsel, Justin T.; Murphy, William L.

    2009-01-01

    Self-assembled monolayers (SAMs) of alkanethiolates on gold have become an important tool for probing cell-material interactions. Emerging studies in stem cell biology are particularly reliant on well-defined model substrates, and rapid and highly controllable fabrication methods may be necessary to characterize the wide array of stem cell-material interactions. Therefore, this study describes a rapid method to create SAM cell culture substrates with multiple discrete regions of controlled peptide identity and density. The approach uses an NaBH4 solution to selectively remove regions of bio-inert, hydroxyl-terminated oligo(ethylene glycol) alkanethiolate SAM, then locally replace them with mixed SAMs of hydroxyl- and carboxylic acid-terminated oligo(ethylene glycol) alkanethiolates. The cell adhesion peptide Arg-Gly-Asp-Ser-Pro (RGDSP) was then covalently linked to carboxylic acid-terminated mixed SAM regions to create cell adhesive environments within a bio-inert background. SAM preparation and peptide immobilization were characterized using polarization modulation–infrared reflection-absorption spectroscopy (PMIRRAS), as well as assays to monitor conjugation of a fluorescently-labeled peptide. This “localized SAM replacement” method was achieved using an array of microchannels, which facilitated rapid and simple processing. Results indicate that immobilized RGDSP promoted spatially localized attachment of human mesenchymal stem cells (hMSCs) within specified regions, while maintaining a stable, bio-inert background in serum-containing cell culture conditions for up to 14 days. Cell attachment to patterned regions presenting a range of cell adhesion peptide densities demonstrated that peptide identity and density strongly influence hMSC spreading and focal adhesion density. These substrates contain discrete, well-defined microenvironments for stem cell culture, which could ultimately enable high-throughput screening for the effects of immobilized signals on stem cell phenotype. PMID:19856996

  3. Combined enzyme replacement and haematopoietic stem cell transplantation in Hurler syndrome.

    PubMed

    Bijarnia, Sunita; Shaw, Peter; Vimpani, Anne; Smith, Robert; Pacey, Verity; O'Grady, Helen; Christodoulou, John; Sillence, David

    2009-01-01

    We report the long-term follow-up of successful treatment of mucopolysaccharidosis type I H (MPS IH, Hurler syndrome) with combined enzyme replacement therapy and haematopoietic progenitor stem cell transplant. PMID:19712183

  4. Adult subventricular zone neural stem cells as a potential source of dopaminergic replacement neurons

    PubMed Central

    Cave, John W.; Wang, Meng; Baker, Harriet

    2014-01-01

    Clinical trials engrafting human fetal ventral mesencephalic tissue have demonstrated, in principle, that cell replacement therapy provides substantial long-lasting improvement of motor impairments generated by Parkinson's Disease (PD). The use of fetal tissue is not practical for widespread clinical implementation of this therapy, but stem cells are a promising alternative source for obtaining replacement cells. The ideal stem cell source has yet to be established and, in this review, we discuss the potential of neural stem cells in the adult subventricular zone (SVZ) as an autologous source of replacement cells. We identify three key challenges for further developing this potential source of replacement cells: (1) improving survival of transplanted cells, (2) suppressing glial progenitor proliferation and survival, and (3) developing methods to efficiently produce dopaminergic neurons. Subventricular neural stem cells naturally produce a dopaminergic interneuron phenotype that has an apparent lack of vulnerability to PD-mediated degeneration. We also discuss whether olfactory bulb dopaminergic neurons derived from adult SVZ neural stem cells are a suitable source for cell replacement strategies. PMID:24574954

  5. Stem Cell Replacement Improves Expression of SMP30 in db/db Mice

    PubMed Central

    Li, Ming; Guo, Kequan; Taketani, Shigeru; Adachi, Yasushi; Ikehara, Susumu

    2015-01-01

    We have previously reported that replacing bone marrow stem cells may improve hyperglycemia and oxidative stress in db/db mice, a type 2 diabetic mouse model. Senescence marker protein 30 (SMP30) is an antioxidant protein that decreases with aging. However, it has not been clear whether SMP30 decreases in the livers of obese mice, and whether stem cell replacement would improve SMP30 expression in the liver. Bone marrow stem cells of db/db mice were replaced with the bone marrow stem cells of C57BL/6 mice. Plasma cytokine and insulin levels were measured, and glycogen content, expression of SMP30, and fibrosis in the liver were assessed. Our results showed that stem cell replacement increased the expression of SMP30 in the liver, resulting from decreased plasma inflammation cytokines and hyperinsulinemia in db/db mice. This is the first report that stem cell replacement increased the expression of SMP30 in the liver, and may help prevent fibrosis in the liver of db/db mice. PMID:26694363

  6. Stem cells for cell replacement therapy: a therapeutic strategy for HD?

    PubMed

    Rosser, Anne; Svendsen, Clive N

    2014-09-15

    Much interest has been expressed over the last couple of decades in the potential application of stem cells to medicine, both for research and diagnostic tools and as a source of donor cells for therapeutic purposes. Potential therapeutic applications include replacement of cells in many body organs where the capacity for intrinsic repair is limited, including the pancreas, heart, and brain. A key challenge is to generate the relevant donor cell types, and this is particularly challenging in the brain where the number of different neuronal subtypes is so great. Although dopamine neuron replacement in Parkinson's disease has been the focus of most clinical studies, great interest has been shown in this approach for other disorders, including Huntington's disease. Replacing complete neural circuits in the adult brain is clearly challenging, and there are many other complexities with regard to both donor cells and host. This article presents the pros and cons of taking a cell therapy approach in Huntington's disease. It considers the implantation both of cells that are already of the same neural subtype as those lost in the disease process (ie, primary fetal cells derived from the developing striatum) and those derived from stem cells, which require "directing" toward that phenotype. PMID:25216372

  7. Phenotypic Evolutionary Models in Stem Cell Biology: Replacement, Quiescence, and Variability

    PubMed Central

    Mangel, Marc; Bonsall, Michael B.

    2008-01-01

    Phenotypic evolutionary models have been used with great success in many areas of biology, but thus far have not been applied to the study of stem cells except for investigations of cancer. We develop a framework that allows such modeling techniques to be applied to stem cells more generally. The fundamental modeling structure is the stochastic kinetics of stem cells in their niche and of transit amplifying and fully differentiated cells elsewhere in the organism, with positive and negative feedback. This formulation allows graded signals to be turned into all or nothing responses, and shows the importance of looking beyond the niche for understanding how stem cells behave. Using the deterministic version of this framework, we show how competition between different stem cell lines can be analyzed, and under what circumstances stem cells in a niche will be replaced by other stem cells with different phenotypic characteristics. Using the stochastic version of our framework and state dependent life history theory, we show that the optimal behavior of a focal stem cell will involve long periods of quiescence and that a population of identical stem cells will show great variability in the times at which activity occurs; we compare our results with classic ones on quiescence and variability in the hematopoietic system. PMID:18270578

  8. Stem cell-based organ replacements-airway and lung tissue engineering.

    PubMed

    Fishman, Jonathan M; Lowdell, Mark; Birchall, Martin A

    2014-06-01

    Tissue engineering requires the use of cells seeded onto scaffolds, often in conjunction with bioactive molecules, to regenerate or replace tissues. Significant advances have been made in recent years within the fields of stem cell biology and biomaterials, leading to some exciting developments in airway tissue engineering, including the first use of stem cell-based tissue-engineered tracheal replacements in humans. In addition, recent advances within the fields of scaffold biology and decellularization offer the potential to transplant patients without the use of immunosuppression. PMID:24994525

  9. Potential application of induced pluripotent stem cells in cell replacement therapy for Parkinson's disease.

    PubMed

    Chen, L W; Kuang, F; Wei, L C; Ding, Y X; Yung, K K L; Chan, Y S

    2011-06-01

    Parkinson's disease (PD), a common degenerative disease in humans, is known to result from loss of dopamine neurons in the substantia nigra and is characterized by severe motor symptoms of tremor, rigidity, bradykinsia and postural instability. Although levodopa administration, surgical neural lesion, and deep brain stimulation have been shown to be effective in improving parkinsonian symptoms, cell replacement therapy such as transplantation of dopamine neurons or neural stem cells has shed new light on an alternative treatment strategy for PD. While the difficulty in securing donor dopamine neurons and the immuno-rejection of neural transplants largely hinder application of neural transplants in clinical treatment, induced pluripotent stem cells (iPS cells) derived from somatic cells may represent a powerful tool for studying the pathogenesis of PD and provide a source for replacement therapies in this neurodegenerative disease. Yamanaka et al. [2006, 2007] first succeeded in generating iPS cells by reprogramming fibroblasts with four transcription factors, Oct4, Sox2, Klf4, and c-Myc in both mouse and human. Animal studies have further shown that iPS cells from fibroblasts could be induced into dopamine neurons and transplantation of these cells within the central nervous system improved motor symptoms in the 6-OHDA model of PD. More interestingly, neural stem cells or fibroblasts from patients can be efficiently reprogrammed and subsequently differentiated into dopamine neurons. Derivation of patient-specific iPS cells and subsequent differentiation into dopamine neurons would provide a disease-specific in vitro model for disease pathology, drug screening and personalized stem cell therapy for PD. This review summarizes current methods and modifications in producing iPS cells from somatic cells as well as safety concerns of reprogramming procedures. Novel reprogramming strategies that deter abnormal permanent genetic and epigenetic alterations are essential for propagating clinically-qualified iPS cells. Future investigations into cell transforming and reprogramming processes are needed to generate the disease-specific iPS cells for personalized regeneration medicine of PD patients by disclosing detailed reprogramming mechanisms. PMID:21495962

  10. Identification of putative dental epithelial stem cells in a lizard with life-long tooth replacement.

    PubMed

    Handrigan, Gregory R; Leung, Kelvin J; Richman, Joy M

    2010-11-01

    Most dentate vertebrates, including humans, replace their teeth and yet the process is poorly understood. Here, we investigate whether dental epithelial stem cells exist in a polyphyodont species, the leopard gecko (Eublepharis macularius). Since the gecko dental epithelium lacks a histologically distinct site for stem cells analogous to the mammalian hair follicle bulge, we performed a pulse-chase experiment on juvenile geckos to identify label-retaining cells (LRCs). We detected LRCs exclusively on the lingual side of the dental lamina, which exhibits low proliferation rates and is not involved in tooth morphogenesis. Lingual LRCs were organized into pockets of high density close to the successional lamina. A subset of the LRCs expresses Lgr5 and other genes that are markers of adult stem cells in mammals. Also similar to mammalian stem cells, the LRCs appear to proliferate in response to gain of function of the canonical Wnt pathway. We suggest that the LRCs in the lingual dental lamina represent a population of stem cells, the immediate descendents of which form the successional lamina and, ultimately, the replacement teeth in the gecko. Furthermore, their location on the non-tooth-forming side of the dental lamina implies that dental stem cells are sequestered from signals that might otherwise induce them to differentiate. PMID:20876646

  11. Induced pluripotent stem cells in Alzheimer's disease: applications for disease modeling and cell-replacement therapy.

    PubMed

    Yang, Juan; Li, Song; He, Xi-Biao; Cheng, Cheng; Le, Weidong

    2016-01-01

    Alzheimer's disease (AD) is the most common cause of dementia in those over the age of 65. While a numerous of disease-causing genes and risk factors have been identified, the exact etiological mechanisms of AD are not yet completely understood, due to the inability to test theoretical hypotheses on non-postmortem and patient-specific research systems. The use of recently developed and optimized induced pluripotent stem cells (iPSCs) technology may provide a promising platform to create reliable models, not only for better understanding the etiopathological process of AD, but also for efficient anti-AD drugs screening. More importantly, human-sourced iPSCs may also provide a beneficial tool for cell-replacement therapy against AD. Although considerable progress has been achieved, a number of key challenges still require to be addressed in iPSCs research, including the identification of robust disease phenotypes in AD modeling and the clinical availabilities of iPSCs-based cell-replacement therapy in human. In this review, we highlight recent progresses of iPSCs research and discuss the translational challenges of AD patients-derived iPSCs in disease modeling and cell-replacement therapy. PMID:27184028

  12. “Global” cell replacement is feasible via neural stem cell transplantation: Evidence from the dysmyelinated shiverer mouse brain

    PubMed Central

    Yandava, Booma D.; Billinghurst, Lori L.; Snyder, Evan Y.

    1999-01-01

    Many diseases of the central nervous system (CNS), particularly those of genetic, metabolic, or infectious/inflammatory etiology, are characterized by “global” neural degeneration or dysfunction. Therapy might require widespread neural cell replacement, a challenge not regarded conventionally as amenable to neural transplantation. Mouse mutants characterized by CNS-wide white matter disease provide ideal models for testing the hypothesis that neural stem cell transplantation might compensate for defective neural cell types in neuropathologies requiring cell replacement throughout the brain. The oligodendrocytes of the dysmyelinated shiverer (shi) mouse are “globally” dysfunctional because they lack myelin basic protein (MBP) essential for effective myelination. Therapy, therefore, requires widespread replacement with MBP-expressing oligodendrocytes. Clonal neural stem cells transplanted at birth—using a simple intracerebroventricular implantation technique—resulted in widespread engraftment throughout the shi brain with repletion of MBP. Accordingly, of the many donor cells that differentiated into oligodendroglia—there appeared to be a shift in the fate of these multipotent cells toward an oligodendroglial fate—a subgroup myelinated up to 52% (mean = ≈40%) of host neuronal processes with better compacted myelin of a thickness and periodicity more closely approximating normal. A number of recipient animals evinced decrement in their symptomatic tremor. Therefore, “global” neural cell replacement seems feasible for some CNS pathologies if cells with stem-like features are used. PMID:10359833

  13. Short stem shoulder replacement

    PubMed Central

    Bell, Simon N.; Coghlan, Jennifer A.

    2014-01-01

    Context: It is agreed that it is important to anatomically reproduce the proximal humeral anatomy when performing a prosthetic shoulder replacement. This can be difficult with a long stemmed prosthesis, in particular if there is little relationship of the metaphysis to the humeral shaft. The ‘short stem’ prosthesis can deal with this problem. Aims: A prospective study assessed the results of total shoulder arthroplasty using a short stem humeral prosthesis, a ceramic humeral head, and a pegged cemented polyethylene glenoid. Materials and methods: Patients with primary shoulder osteoarthritis were recruited into this prospective trial and pre-operatively had the ASES, Constant, SPADI, and DASH scores recorded. The patients were clinically reviewed at the two weeks, eight weeks, one year, and two year mark with completion of a data form. Radiological evaluation was at the eight week, one year and two year follow-up. At the one and two year follow-up the satisfaction rating, the range of passive and active motion, Constant, ASES, SPADI, DASH and pain results were recorded and analysed with SPPS 20. Results: During the study period 97 short stem, ceramic head total shoulder replacements were carried out. At the time of follow-up 12 were two years from operation and 38 one year from operation. Active elevation was overall mean 160 degrees. Constant scores were 76 at 1 year, and 86 at 2 years, ASES 88 and 93, and satisfaction 96% and 98% respectively at one and 2 year follow up. There were no problems during insertion of the humeral prosthesis, or any radiolucent lines or movement of the prosthesis on later radiographs. Conclusion: The short stem prosthesis had no complications, and on follow up radiographs good bone fixation. These fairly short term clinical results were overall good. PMID:25258497

  14. Directing Human Induced Pluripotent Stem Cells into a Neurosensory Lineage for Auditory Neuron Replacement

    PubMed Central

    Gunewardene, Niliksha; Bergen, Nicole Van; Crombie, Duncan; Needham, Karina; Dottori, Mirella

    2014-01-01

    Abstract Emerging therapies for sensorineural hearing loss include replacing damaged auditory neurons (ANs) using stem cells. Ultimately, it is important that these replacement cells can be patient-matched to avoid immunorejection. As human induced pluripotent stem cells (hiPSCs) can be obtained directly from the patient, they offer an opportunity to generate patient-matched neurons for transplantation. Here, we used an established neural induction protocol to differentiate two hiPSC lines (iPS1 and iPS2) and one human embryonic stem cell line (hESC; H9) toward a neurosensory lineage in vitro. Immunocytochemistry and qRT-PCR were used to analyze the expression of key markers involved in AN development at defined time points of differentiation. The hiPSC- and hESC-derived neurosensory progenitors expressed the dorsal hindbrain marker (PAX7), otic placodal marker (PAX2), proneurosensory marker (SOX2), ganglion neuronal markers (NEUROD1, BRN3A, ISLET1, ßIII-tubulin, Neurofilament kDa 160), and sensory AN markers (GATA3 and VGLUT1) over the time course examined. The hiPSC- and hESC-derived neurosensory progenitors had the highest expression levels of the sensory neural markers at 35 days in vitro. Furthermore, the neurons generated from this assay were found to be electrically active. While all cell lines analyzed produced functional neurosensory-like progenitors, variabilities in the levels of marker expression were observed between hiPSC lines and within samples of the same cell line, when compared with the hESC controls. Overall, these findings indicate that this neural assay was capable of differentiating hiPSCs toward a neurosensory lineage but emphasize the need for improving the consistency in the differentiation of hiPSCs into the required lineages. PMID:25126480

  15. Directing human induced pluripotent stem cells into a neurosensory lineage for auditory neuron replacement.

    PubMed

    Gunewardene, Niliksha; Bergen, Nicole Van; Crombie, Duncan; Needham, Karina; Dottori, Mirella; Nayagam, Bryony A

    2014-08-01

    Emerging therapies for sensorineural hearing loss include replacing damaged auditory neurons (ANs) using stem cells. Ultimately, it is important that these replacement cells can be patient-matched to avoid immunorejection. As human induced pluripotent stem cells (hiPSCs) can be obtained directly from the patient, they offer an opportunity to generate patient-matched neurons for transplantation. Here, we used an established neural induction protocol to differentiate two hiPSC lines (iPS1 and iPS2) and one human embryonic stem cell line (hESC; H9) toward a neurosensory lineage in vitro. Immunocytochemistry and qRT-PCR were used to analyze the expression of key markers involved in AN development at defined time points of differentiation. The hiPSC- and hESC-derived neurosensory progenitors expressed the dorsal hindbrain marker (PAX7), otic placodal marker (PAX2), proneurosensory marker (SOX2), ganglion neuronal markers (NEUROD1, BRN3A, ISLET1, ßIII-tubulin, Neurofilament kDa 160), and sensory AN markers (GATA3 and VGLUT1) over the time course examined. The hiPSC- and hESC-derived neurosensory progenitors had the highest expression levels of the sensory neural markers at 35 days in vitro. Furthermore, the neurons generated from this assay were found to be electrically active. While all cell lines analyzed produced functional neurosensory-like progenitors, variabilities in the levels of marker expression were observed between hiPSC lines and within samples of the same cell line, when compared with the hESC controls. Overall, these findings indicate that this neural assay was capable of differentiating hiPSCs toward a neurosensory lineage but emphasize the need for improving the consistency in the differentiation of hiPSCs into the required lineages. PMID:25126480

  16. Wnt5a-treated midbrain neural stem cells improve dopamine cell replacement therapy in parkinsonian mice.

    PubMed

    Parish, Clare L; Castelo-Branco, Gonçalo; Rawal, Nina; Tonnesen, Jan; Sorensen, Andreas Toft; Salto, Carmen; Kokaia, Merab; Lindvall, Olle; Arenas, Ernest

    2008-01-01

    Dopamine (DA) cell replacement therapy in Parkinson disease (PD) can be achieved using human fetal mesencephalic tissue; however, limited tissue availability has hindered further developments. Embryonic stem cells provide a promising alternative, but poor survival and risk of teratoma formation have prevented their clinical application. We present here a method for generating large numbers of DA neurons based on expanding and differentiating ventral midbrain (VM) neural stem cells/progenitors in the presence of key signals necessary for VM DA neuron development. Mouse VM neurospheres (VMNs) expanded with FGF2, differentiated with sonic hedgehog and FGF8, and transfected with Wnt5a (VMN-Wnt5a) generated 10-fold more DA neurons than did conventional FGF2-treated VMNs. VMN-Wnt5a cells exhibited the transcriptional and biochemical profiles and intrinsic electrophysiological properties of midbrain DA cells. Transplantation of these cells into parkinsonian mice resulted in significant cellular and functional recovery. Importantly, no tumors were detected and only a few transplanted grafts contained sporadic nestin-expressing progenitors. Our findings show that Wnt5a improves the differentiation and functional integration of stem cell-derived DA neurons in vivo and define Wnt5a-treated neural stem cells as an efficient and safe source of DA neurons for cell replacement therapy in PD. PMID:18060047

  17. Stem Cells

    MedlinePlus

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

  18. Autologous adipose stem cells and polylactide discs in the replacement of the rabbit temporomandibular joint disc

    PubMed Central

    Ahtiainen, Katja; Mauno, Jari; Ellä, Ville; Hagström, Jaana; Lindqvist, Christian; Miettinen, Susanna; Ylikomi, Timo; Kellomäki, Minna; Seppänen, Riitta

    2013-01-01

    The temporomandibular joint (TMJ) disc lacks functional replacement after discectomy. We investigated tissue-engineered bilayer polylactide (PLA) discs and autologous adipose stem cells (ASCs) as a potential replacement for the TMJ disc. These ASC discs were pre-cultured either in control or in differentiation medium, including transforming growth factor (TGF)-β1 for one week. Prior to implantation, expression of fibrocartilaginous genes was measured by qRT-PCR. The control and differentiated ASC discs were implanted, respectively, in the right and left TMJs of rabbits for six (n = 5) and 12 months (n = 5). Thereafter, the excised TMJ areas were examined with cone beam computed tomography (CBCT) and histology. No signs of infection, inflammation or foreign body reactions were detected at histology, whereas chronic arthrosis and considerable condylar hypertrophy were observed in all operated joints at CBCT. The left condyle treated with the differentiated ASC discs appeared consistently smoother and more sclerotic than the right condyle. The ASC disc replacement resulted in dislocation and morphological changes in the rabbit TMJ. The ASC discs pre-treated with TGF-β1 enhanced the condylar integrity. While adverse tissue reactions were not shown, the authors suggest that with improved attachment and design, the PLA disc and biomaterial itself would hold potential for TMJ disc replacement. PMID:23720535

  19. Mitochondrial gene replacement in human pluripotent stem cell-derived neural progenitors.

    PubMed

    Iyer, S; Xiao, E; Alsayegh, K; Eroshenko, N; Riggs, M J; Bennett, J P; Rao, R R

    2012-05-01

    Human pluripotent stem cell-derived neural progenitor (hNP) cells are an excellent resource for understanding early neural development and neurodegenerative disorders. Given that many neurodegenerative disorders can be correlated with defects in the mitochondrial genome, optimal utilization of hNP cells requires an ability to manipulate and monitor changes in the mitochondria. Here, we describe a novel approach that uses recombinant human mitochondrial transcription factor A (rhTFAM) protein to transfect and express a pathogenic mitochondrial genome (mtDNA) carrying the G11778A mutation associated with Leber's hereditary optic neuropathy (LHON) disease, into dideoxycytidine (ddC)-treated hNPs. Treatment with ddC reduced endogenous mtDNA and gene expression, without loss of hNP phenotypic markers. Entry of G11778A mtDNA complexed with the rhTFAM was observed in mitochondria of ddC-hNPs. Expression of the pathogenic RNA was confirmed by restriction enzyme analysis of the SfaN1-digested cDNA. On the basis of the expression of neuron-specific class III beta-tubulin, neuronal differentiation occurred. Our results show for the first time that pathogenic mtDNA can be introduced and expressed into hNPs without loss of phenotype or neuronal differentiation potential. This mitochondrial gene replacement technology allows for creation of in vitro stem cell-based models useful for understanding neuronal development and treatment of neurodegenerative disorders. PMID:21918550

  20. Multi-kilobase homozygous targeted gene replacement in human induced pluripotent stem cells

    PubMed Central

    Byrne, Susan M.; Ortiz, Luis; Mali, Prashant; Aach, John; Church, George M.

    2015-01-01

    Sequence-specific nucleases such as TALEN and the CRISPR/Cas9 system have so far been used to disrupt, correct or insert transgenes at precise locations in mammalian genomes. We demonstrate efficient ‘knock-in’ targeted replacement of multi-kilobase genes in human induced pluripotent stem cells (iPSC). Using a model system replacing endogenous human genes with their mouse counterpart, we performed a comprehensive study of targeting vector design parameters for homologous recombination. A 2.7 kilobase (kb) homozygous gene replacement was achieved in up to 11% of iPSC without selection. The optimal homology arm length was around 2 kb, with homology length being especially critical on the arm not adjacent to the cut site. Homologous sequence inside the cut sites was detrimental to targeting efficiency, consistent with a synthesis-dependent strand annealing (SDSA) mechanism. Using two nuclease sites, we observed a high degree of gene excisions and inversions, which sometimes occurred more frequently than indel mutations. While homozygous deletions of 86 kb were achieved with up to 8% frequency, deletion frequencies were not solely a function of nuclease activity and deletion size. Our results analyzing the optimal parameters for targeting vector design will inform future gene targeting efforts involving multi-kilobase gene segments, particularly in human iPSC. PMID:25414332

  1. Current applications of mesenchymal stem cells for tissue replacement in otolaryngology-head and neck surgery

    PubMed Central

    King, Suzanne N; Hanson, Summer E; Hematti, Peiman; Thibeault, Susan L

    2012-01-01

    Cellular therapy utilizing adult mesenchymal stromal/stem cells (MSCs) may very well revolutionize the treatment of a variety of head and neck diseases through the restoration of normal structure and function. Transplanting allogeneic or autologous MSCs into damaged tissues can serve multiple regenerative functions through their self-renewal, differentiation capacity, immune modulation and secretion of bioactive molecules. Further, trophic factors expressed by MSCs have been shown to influence their microenvironment through the promotion of extracellular matrix remodeling, angiogenesis and wound healing needed to regenerate or replace injured tissues. Although clinical applications of MSC based therapies in Otolaryngology-Head and Neck Surgery are still in their infancy, efforts are being made to understand and exploit MSCs for tissue repair as well as engineering strategies. In this review, we highlight pre clinical and clinical investigations employing MSC based therapies for the reconstruction of bone, cartilage, soft tissue and vocal fold defects. PMID:23671810

  2. Ionizing radiation leads to the replacement and de novo production of colonic Lgr5(+) stem cells.

    PubMed

    Otsuka, Kensuke; Hamada, Nobuyuki; Magae, Junji; Matsumoto, Hideki; Hoshi, Yuko; Iwasaki, Toshiyasu

    2013-06-01

    Tissue stem cells have self-renewal capability throughout their whole life, which is high enough to lead to the accumulation of DNA damage in a stem cell pool. Whether radiation-induced damage accumulates in tissue stem cells remains unknown, but could be investigated if the fate of tissue stem cells could be followed after irradiation. To realize this goal, we used an Lgr5-dependent lineage tracing system that allows the conditional in vivo labeling of Lgr5(+) intestinal stem cells and their progeny. We found that radiation induced loss of Lgr5(+) stem cells in the colon, but not in the duodenum. Interestingly, the loss of colonic Lgr5(+) cells was compensated by de novo production of Lgr5(+) cells, which increased after irradiation. These findings show that ionizing radiation effectively stimulates the turnover of colonic Lgr5(+) stem cells, implying that radiation-induced damage does not accumulate in the colonic Lgr5(+) stem cells by this mechanism. PMID:23627781

  3. Use of Differentiated Pluripotent Stem Cells in Replacement Therapy for Treating Disease

    PubMed Central

    Fox, Ira J.; Daley, George Q.; Goldman, Steven A.; Huard, Johnny; Kamp, Timothy J.; Trucco, Massimo

    2015-01-01

    Patient-derived pluripotent stem cells (PSC) directed to various cell fates holds promise as source material for treating numerous disorders. The availability of precisely differentiated PSC-derived cells will dramatically impact blood component and hematopoietic stem cell therapies, and should facilitate treatment of diabetes, some forms of liver disease and neurologic disorders, retinal diseases, and possibly heart disease. Although an unlimited supply of specific cell types are needed, other barriers must be overcome. This review of the state of cell therapies highlights important challenges. Successful cell transplantation will require optimizing the best cell type and site for engraftment, overcoming limitations to cell migration and tissue integration, and occasionally needing to control immunologic reactivity. Collaboration among scientists, clinicians, and industry is critical for generating new stem cell-based therapies. PMID:25146295

  4. Human Neural Stem Cell Replacement Therapy for Amyotrophic Lateral Sclerosis by Spinal Transplantation

    PubMed Central

    Hefferan, Michael P.; Galik, Jan; Kakinohana, Osamu; Sekerkova, Gabriela; Santucci, Camila; Marsala, Silvia; Navarro, Roman; Hruska-Plochan, Marian; Johe, Karl; Feldman, Eva; Cleveland, Don W.; Marsala, Martin

    2012-01-01

    Background Mutation in the ubiquitously expressed cytoplasmic superoxide dismutase (SOD1) causes an inherited form of Amyotrophic Lateral Sclerosis (ALS). Mutant synthesis in motor neurons drives disease onset and early disease progression. Previous experimental studies have shown that spinal grafting of human fetal spinal neural stem cells (hNSCs) into the lumbar spinal cord of SOD1G93A rats leads to a moderate therapeutical effect as evidenced by local α-motoneuron sparing and extension of lifespan. The aim of the present study was to analyze the degree of therapeutical effect of hNSCs once grafted into the lumbar spinal ventral horn in presymptomatic immunosuppressed SOD1G93A rats and to assess the presence and functional integrity of the descending motor system in symptomatic SOD1G93A animals. Methods/Principal Findings Presymptomatic SOD1G93A rats (60–65 days old) received spinal lumbar injections of hNSCs. After cell grafting, disease onset, disease progression and lifespan were analyzed. In separate symptomatic SOD1G93A rats, the presence and functional conductivity of descending motor tracts (corticospinal and rubrospinal) was analyzed by spinal surface recording electrodes after electrical stimulation of the motor cortex. Silver impregnation of lumbar spinal cord sections and descending motor axon counting in plastic spinal cord sections were used to validate morphologically the integrity of descending motor tracts. Grafting of hNSCs into the lumbar spinal cord of SOD1G93A rats protected α-motoneurons in the vicinity of grafted cells, provided transient functional improvement, but offered no protection to α-motoneuron pools distant from grafted lumbar segments. Analysis of motor-evoked potentials recorded from the thoracic spinal cord of symptomatic SOD1G93A rats showed a near complete loss of descending motor tract conduction, corresponding to a significant (50–65%) loss of large caliber descending motor axons. Conclusions/Significance These data demonstrate that in order to achieve a more clinically-adequate treatment, cell-replacement/gene therapy strategies will likely require both spinal and supraspinal targets. PMID:22916141

  5. A Distinct Subpopulation of Bone Marrow Mesenchymal Stem Cells, Muse Cells, Directly Commit to the Replacement of Liver Components.

    PubMed

    Katagiri, H; Kushida, Y; Nojima, M; Kuroda, Y; Wakao, S; Ishida, K; Endo, F; Kume, K; Takahara, T; Nitta, H; Tsuda, H; Dezawa, M; Nishizuka, S S

    2016-02-01

    Genotyping graft livers by short tandem repeats after human living-donor liver transplantation (n = 20) revealed the presence of recipient or chimeric genotype cases in hepatocytes (6 of 17, 35.3%), sinusoidal cells (18 of 18, 100%), cholangiocytes (15 of 17, 88.2%) and cells in the periportal areas (7 of 8, 87.5%), suggesting extrahepatic cell involvement in liver regeneration. Regarding extrahepatic origin, bone marrow mesenchymal stem cells (BM-MSCs) have been suggested to contribute to liver regeneration but compose a heterogeneous population. We focused on a more specific subpopulation (1-2% of BM-MSCs), called multilineage-differentiating stress-enduring (Muse) cells, for their ability to differentiate into liver-lineage cells and repair tissue. We generated a physical partial hepatectomy model in immunodeficient mice and injected green fluorescent protein (GFP)-labeled human BM-MSC Muse cells intravenously (n = 20). Immunohistochemistry, fluorescence in situ hybridization and species-specific polymerase chain reaction revealed that they integrated into regenerating areas and expressed liver progenitor markers during the early phase and then differentiated spontaneously into major liver components, including hepatocytes (≈74.3% of GFP-positive integrated Muse cells), cholangiocytes (≈17.7%), sinusoidal endothelial cells (≈2.0%), and Kupffer cells (≈6.0%). In contrast, the remaining cells in the BM-MSCs were not detected in the liver for up to 4 weeks. These results suggest that Muse cells are the predominant population of BM-MSCs that are capable of replacing major liver components during liver regeneration. PMID:26663569

  6. Anatomic Mesenchymal Stem Cell-Based Engineered Cartilage Constructs for Biologic Total Joint Replacement.

    PubMed

    Saxena, Vishal; Kim, Minwook; Keah, Niobra M; Neuwirth, Alexander L; Stoeckl, Brendan D; Bickard, Kevin; Restle, David J; Salowe, Rebecca; Wang, Margaret Ye; Steinberg, David R; Mauck, Robert L

    2016-02-01

    Cartilage has a poor healing response, and few viable options exist for repair of extensive damage. Hyaluronic acid (HA) hydrogels seeded with mesenchymal stem cells (MSCs) polymerized through UV crosslinking can generate functional tissue, but this crosslinking is not compatible with indirect rapid prototyping utilizing opaque anatomic molds. Methacrylate-modified polymers can also be chemically crosslinked in a cytocompatible manner using ammonium persulfate (APS) and N,N,N',N'-tetramethylethylenediamine (TEMED). The objectives of this study were to (1) compare APS/TEMED crosslinking with UV crosslinking in terms of functional maturation of MSC-seeded HA hydrogels; (2) generate an anatomic mold of a complex joint surface through rapid prototyping; and (3) grow anatomic MSC-seeded HA hydrogel constructs using this alternative crosslinking method. Juvenile bovine MSCs were suspended in methacrylated HA (MeHA) and crosslinked either through UV polymerization or chemically with APS/TEMED to generate cylindrical constructs. Minipig porcine femoral heads were imaged using microCT, and anatomic negative molds were generated by three-dimensional printing using fused deposition modeling. Molded HA constructs were produced using the APS/TEMED method. All constructs were cultured for up to 12 weeks in a chemically defined medium supplemented with TGF-β3 and characterized by mechanical testing, biochemical assays, and histologic analysis. Both UV- and APS/TEMED-polymerized constructs showed increasing mechanical properties and robust proteoglycan and collagen deposition over time. At 12 weeks, APS/TEMED-polymerized constructs had higher equilibrium and dynamic moduli than UV-polymerized constructs, with no differences in proteoglycan or collagen content. Molded HA constructs retained their hemispherical shape in culture and demonstrated increasing mechanical properties and proteoglycan and collagen deposition, especially at the edges compared to the center of these larger constructs. Immunohistochemistry showed abundant collagen type II staining and little collagen type I staining. APS/TEMED crosslinking can be used to produce MSC-seeded HA-based neocartilage and can be used in combination with rapid prototyping techniques to generate anatomic MSC-seeded HA constructs for use in filling large and anatomically complex chondral defects or for biologic joint replacement. PMID:26871863

  7. Impact of enzyme replacement therapy and hematopoietic stem cell transplantation in patients with Morquio A syndrome

    PubMed Central

    Tomatsu, Shunji; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J; Shimada, Tsutomu; Bober, Michael B; Chinen, Yasutsugu; Yabe, Hiromasa; Montaño, Adriana M; Giugliani, Roberto; Kubaski, Francyne; Yasuda, Eriko; Rodríguez-López, Alexander; Espejo-Mojica, Angela J; Sánchez, Oscar F; Mason, Robert W; Barrera, Luis A; Mackenzie, William G; Orii, Tadao

    2015-01-01

    Patients with mucopolysaccharidosis IVA (MPS IVA) can present with systemic skeletal dysplasia, leading to a need for multiple orthopedic surgical procedures, and often become wheelchair bound in their teenage years. Studies on patients with MPS IVA treated by enzyme replacement therapy (ERT) showed a sharp reduction on urinary keratan sulfate, but only modest improvement based on a 6-minute walk test and no significant improvement on a 3-minute climb-up test and lung function test compared with the placebo group, at least in the short-term. Surgical remnants from ERT-treated patients did not show reduction of storage materials in chondrocytes. The impact of ERT on bone lesions in patients with MPS IVA remains limited. ERT seems to be enhanced in a mouse model of MPS IVA by a novel form of the enzyme tagged with a bone-targeting moiety. The tagged enzyme remained in the circulation much longer than untagged native enzyme and was delivered to and retained in bone. Three-month-old MPS IVA mice treated with 23 weekly infusions of tagged enzyme showed marked clearance of the storage materials in bone, bone marrow, and heart valves. When treatment was initiated at birth, reduction of storage materials in tissues was even greater. These findings indicate that specific targeting of the enzyme to bone at an early stage may improve efficacy of ERT for MPS IVA. Recombinant N-acetylgalactosamine-6-sulfate sulfatase (GALNS) in Escherichia coli BL21 (DE3) (erGALNS) and in the methylotrophic yeast Pichia pastoris (prGALNS) has been produced as an alternative to the conventional production in Chinese hamster ovary cells. Recombinant GALNS produced in microorganisms may help to reduce the high cost of ERT and the introduction of modifications to enhance targeting. Although only a limited number of patients with MPS IVA have been treated with hematopoietic stem cell transplantation (HSCT), beneficial effects have been reported. A wheelchair-bound patient with a severe form of MPS IVA was treated with HSCT at 15 years of age and followed up for 10 years. Radiographs showed that the figures of major and minor trochanter appeared. Loud snoring and apnea disappeared. In all, 1 year after bone marrow transplantation, bone mineral density at L2–L4 was increased from 0.372 g/cm2 to 0.548 g/cm2 and was maintained at a level of 0.48±0.054 for the following 9 years. Pulmonary vital capacity increased approximately 20% from a baseline of 1.08 L to around 1.31 L over the first 2 years and was maintained thereafter. Activity of daily living was improved similar to the normal control group. After bilateral osteotomies, a patient can walk over 400 m using hip–knee–ankle–foot orthoses. This long-term observation of a patient shows that this treatment can produce clinical improvements although bone deformity remained unchanged. In conclusion, ERT is a therapeutic option for MPS IVA patients, and there are some indications that HSCT may be an alternative to treat this disease. However, as neither seems to be a curative therapy, at least for the skeletal dysplasia in MPS IVA patients, new approaches are investigated to enhance efficacy and reduce costs to benefit MPS IVA patients. PMID:25897204

  8. Enzyme replacement therapy prior to haematopoietic stem cell transplantation in Mucopolysaccharidosis Type I: 10year combined experience of 2 centres.

    PubMed

    Ghosh, Arunabha; Miller, Weston; Orchard, Paul J; Jones, Simon A; Mercer, Jean; Church, Heather J; Tylee, Karen; Lund, Troy; Bigger, Brian W; Tolar, Jakub; Wynn, Robert F

    2016-03-01

    Haematopoietic stem cell transplantation is the treatment of choice for the severe form of Mucopolysaccharidosis Type I, or Hurler syndrome. In many centres standard practice is to deliver enzyme replacement therapy alongside haematopoietic stem cell transplantation to improve the condition of the patient prior to transplant. We report the combined 10year experience of this approach in two paediatric metabolic and transplant centres. Of 81 patients who underwent a first transplant procedure for Hurler, 88% (71/81) survived and 81% (66/81) were alive and engrafted at a median follow-up of 46months (range 3-124months). The incidence of grade II-IV acute and any chronic graft versus host disease was 17% and 11% respectively. Urinary glycosaminoglycans were significantly reduced after a period of enzyme replacement therapy, and further reductions were seen at 13-24months and 25+months after transplantation. In several individuals with decreased cardiac contractility, an improvement of their condition during enzyme replacement therapy enabled them to undergo transplantation, with one individual receiving full intensity conditioning. PMID:26832957

  9. Types of Stem Cells

    MedlinePlus

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

  10. Tracking of iron-labeled human neural stem cells by magnetic resonance imaging in cell replacement therapy for Parkinson's disease

    PubMed Central

    Ramos-Gómez, Milagros; Martínez-Serrano, Alberto

    2016-01-01

    Human neural stem cells (hNSCs) derived from the ventral mesencephalon are powerful research tools and candidates for cell therapies in Parkinson's disease. However, their clinical translation has not been fully realized due, in part, to the limited ability to track stem cell regional localization and survival over long periods of time after in vivo transplantation. Magnetic resonance imaging provides an excellent non-invasive method to study the fate of transplanted cells in vivo. For magnetic resonance imaging cell tracking, cells need to be labeled with a contrast agent, such as magnetic nanoparticles, at a concentration high enough to be easily detected by magnetic resonance imaging. Grafting of human neural stem cells labeled with magnetic nanoparticles allows cell tracking by magnetic resonance imaging without impairment of cell survival, proliferation, self-renewal, and multipotency. However, the results reviewed here suggest that in long term grafting, activated microglia and macrophages could contribute to magnetic resonance imaging signal by engulfing dead labeled cells or iron nanoparticles dispersed freely in the brain parenchyma over time. PMID:26981077

  11. Human foetal brain tissue as quality control when developing stem cells towards cell replacement therapy for neurological diseases.

    PubMed

    Nelander, Jenny; Grealish, Shane; Parmar, Malin

    2013-12-18

    Human foetal brain tissue has been used in experimental and clinical trials to develop cell replacement therapy in neurodegenerative disorders such as Parkinson's disease and Huntington's disease. These pioneering clinical studies have shown proof of principle that cell replacement therapy can be effective and is worthwhile to develop as a therapeutic strategy for repairing the damaged brain. However, because of the limited availability of foetal brain material, and difficulties in producing standardized and quality-tested cell preparations from this source, there have been extensive efforts in investigating the potential use of alternative cell sources for generating a large number of transplantable, authentic neural progenitors and neurons. In this review, we highlight the value of using human foetal tissue as a reference material for quality control of acquired cell fate of in vitro generated neurons before and after transplantation. PMID:24257249

  12. Learn About Stem Cells

    MedlinePlus

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

  13. Optimizing stem cell culture

    PubMed Central

    Van Der Sanden, Boudewijn; Dhobb, Mehdi; Berger, François; Wion, Didier

    2010-01-01

    Stem cells always balance between self-renewal and differentiation. Hence, stem cell culture parameters are critical and need to be continuously refined according to progress in our stem cell biology understanding and the latest technological developments. This led to the progressive replacement of ill-defined additives such as serum or feeder cell layers by recombinant cytokines or growth factors. Another example is the control of the oxygen pressure. For many years cell cultures have been done under atmospheric oxygen pressure which is much higher than the one experienced by stem cells in vivo. A consequence of cell metabolism is that cell culture conditions are constantly changing. Therefore, the development of high sensitive monitoring processes and control algorithms is required for ensuring cell culture medium homeostasis. Stem cells also sense the physical constraints of their microenvironment. Rigidity, stiffness and geometry of the culture substrate influence stem cell fate. Hence, nanotopography is probably as important as medium formulation in the optimization of stem cell culture conditions. Recent advances include the development of synthetic bioinformative substrates designed at the micro- and nanoscale level. On going research in many different fields including stem cell biology, nanotechnology, and bioengineering suggest that our current way to culture cells in Petri dish or flasks will soon be outdated as flying across the Atlantic Ocean in the Lindbergh’s plane. PMID:20803548

  14. Stem Cell Basics

    MedlinePlus

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

  15. Stem Cell Basics

    MedlinePlus

    ... General Information Stem Cell Basics Stem Cell Basics Stem Cell Information General Information Clinical Trials Funding Information Current Research Policy Glossary Site Map Stem Cell Basics This primer on stem cells is intended ...

  16. Tissue engineering of replacement skin: the crossroads of biomaterials, wound healing, embryonic development, stem cells and regeneration.

    PubMed

    Metcalfe, Anthony D; Ferguson, Mark W J

    2007-06-22

    Advanced therapies combating acute and chronic skin wounds are likely to be brought about using our knowledge of regenerative medicine coupled with appropriately tissue-engineered skin substitutes. At the present time, there are no models of an artificial skin that completely replicate normal uninjured skin. Natural biopolymers such as collagen and fibronectin have been investigated as potential sources of biomaterial to which cells can attach. The first generation of degradable polymers used in tissue engineering were adapted from other surgical uses and have drawbacks in terms of mechanical and degradation properties. This has led to the development of synthetic degradable gels primarily as a way to deliver cells and/or molecules in situ, the so-called smart matrix technology. Tissue or organ repair is usually accompanied by fibrotic reactions that result in the production of a scar. Certain mammalian tissues, however, have a capacity for complete regeneration without scarring; good examples include embryonic or foetal skin and the ear of the MRL/MpJ mouse. Investigations of these model systems reveal that in order to achieve such complete regeneration, the inflammatory response is altered such that the extent of fibrosis and scarring is diminished. From studies on the limited examples of mammalian regeneration, it may also be possible to exploit such models to further clarify the regenerative process. The challenge is to identify the factors and cytokines expressed during regeneration and incorporate them to create a smart matrix for use in a skin equivalent. Recent advances in the use of DNA microarray and proteomic technology are likely to aid the identification of such molecules. This, coupled with recent advances in non-viral gene delivery and stem cell technologies, may also contribute to novel approaches that would generate a skin replacement whose materials technology was based not only upon intelligent design, but also upon the molecules involved in the process of regeneration. PMID:17251138

  17. Notch pathway activation can replace the requirement for Wnt4 and Wnt9b in mesenchymal-to-epithelial transition of nephron stem cells

    PubMed Central

    Boyle, Scott C.; Kim, Mijin; Valerius, M. Todd; McMahon, Andrew P.; Kopan, Raphael

    2011-01-01

    The primary excretory organ in vertebrates is the kidney, which is responsible for blood filtration, solute homeostasis and pH balance. These functions are carried out by specialized epithelial cells organized into tubules called nephrons. Each of these cell types arise during embryonic development from a mesenchymal stem cell pool through a process of mesenchymal-to-epithelial transition (MET) that requires sequential action of specific Wnt signals. Induction by Wnt9b directs cells to exit the stem cell niche and express Wnt4, which is both necessary and sufficient for the formation of epithelia. Without either factor, MET fails, nephrons do not form and newborn mice die owing to kidney failure. Ectopic Notch activation in stem cells induces mass differentiation and exhaustion of the stem cell pool. To investigate whether this reflected an interaction between Notch and Wnt, we employed a novel gene manipulation strategy in cultured embryonic kidneys. We show that Notch activation is capable of inducing MET in the absence of both Wnt4 and Wnt9b. Following MET, the presence of Notch directs cells primarily to the proximal tubule fate. Only nephron stem cells have the ability to undergo MET in response to Wnt or Notch, as activation in the closely related stromal mesenchyme has no inductive effect. These data demonstrate that stem cells for renal epithelia are uniquely poised to undergo MET, and that Notch activation can replace key inductive Wnt signals in this process. After MET, Notch provides an instructive signal directing cells towards the proximal tubule lineage at the expense of other renal epithelial fates. PMID:21852398

  18. Activities of Daily Living in patients with Hunter syndrome: Impact of enzyme replacement therapy and hematopoietic stem cell transplantation

    PubMed Central

    Tanjuakio, Julian; Suzuki, Yasuyuki; Patel, Pravin; Yasuda, Eriko; Kubaski, Francyne; Tanaka, Akemi; Yabe, Hiromasa; Mason, Robert W.; Montaño, Adriana M.; Orii, Kenji E.; Orii, Koji O.; Fukao, Toshiyuki; Orii, Tadao; Tomatsu, Shunji

    2014-01-01

    The aim of this study was to assess the Activities of Daily Living (ADL) in patients with Hunter syndrome (mucopolysaccharidosis II; MPS II) using a newly designed ADL questionnaire. We applied the questionnaire to evaluate clinical phenotypes and therapeutic efficacies of enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT). We also explored early signs and symptoms to make early diagnosis feasible. We devised a new ADL questionnaire with three domains: “Movement,” “Movement with Cognition,” and “Cognition.” Each domain has four subcategories rated on a 5-point scale based on level of assistance. We also scored signs and symptoms unique to MPS by 12 subcategories (five points per category), providing 60 points in total. The questionnaire was first administered to 138 healthy Japanese controls (0.33 – 50 years), and successively, to 74 Japanese patients with Hunter syndrome (4 – 49 years). The patient cohort consisted of 51 severe and 23 attenuated phenotypes; 20 patients treated with HSCT, 23 patients treated early with ERT (≤ 8 years), and 25 patients treated late with ERT (> 8 years), and 4 untreated patients. Among 18 severe phenotypic patients treated by HSCT, 10 were designated as early HSCT (≤ 5 years), while 8 were designated as late HSCT (> 5 years). Scores from patients with severe phenotypes were lower than controls and attenuated phenotypes in all categories. Among patients with severe phenotypes, there was a trend that HSCT provides a higher ADL score than early ERT, and there was a significant difference in ADL scores between late ERT and HSCT groups. Early ERT and early HSCT provided a higher score than late ERT and late HSCT, respectively. In conclusion, we have evaluated the feasibility of a new questionnaire in control population and patients with Hunter syndrome, leading to a novel evaluation method for clinical phenotypes and therapeutic efficacy. Early treatment with HSCT provides a better consequence in ADL of patients. PMID:25468646

  19. Stem Cells and Diseases

    MedlinePlus

    ... Home General Information Can Stem Cells Help Me? Stem Cell Information General Information Clinical Trials Funding Information Current Research Policy Glossary Site Map Can Stem Cells Help Me? The International Society for Stem Cell ...

  20. Stem cell glycolipids.

    PubMed

    Yanagisawa, Makoto

    2011-09-01

    Glycolipids are compounds containing one or more monosaccharide residues bound by a glycosidic linkage to a hydrophobic moiety. Because of their expression patterns and the intracellular localization patterns, glycolipids, including stage-specific embryonic antigens (SSEA-3, SSEA-4, and possibly SSEA-1) and gangliosides (e.g., GD3, GD2, and A2B5 antigens), have been used as marker molecules of stem cells. In this review, I will introduce glycolipids expressed in pluripotent stem cells (embryonic stem cells, induced pluripotent stem cells, very small embryonic-like stem cells, amniotic stem cells, and multilineage-differentiating stress enduring cells), multipotent stem cells (neural stem cells, mesenchymal stem cells, fetal liver multipotent progenitor cells, and hematopoietic stem cells), and cancer stem cells (brain cancer stem cells and breast cancer stem cells), and discuss their availability as biomarkers for identifying and isolating stem cells. PMID:21161592

  1. Replacing cells in multiple sclerosis.

    PubMed

    Duncan, Ian D

    2008-02-15

    Cell transplantation is emerging as a major potential therapeutic approach in the treatment of otherwise untreatable neurodegenerative diseases. In multiple sclerosis (MS), a major direction of current research is to devise strategies that will remyelinate axons and protect them against subsequent ongoing degeneration. Ongoing loss of axons will lead to chronic disability. Oligodendrocytes and their progenitors are lost during multiple relapses in the course of MS and either needs to be replaced from an exogenous source or the remaining progenitors stimulated to differentiate and remyelinate. The successful isolation and purification of human oligodendrocytes from neural or embryonic stem cells offer hope that a source of sufficient cells for translational application might be achievable in the future. Focal repair of strategic lesions followed by more disseminated delivery of exogenous cells will be the short and long-term goals. PMID:17585942

  2. Dynamic stem cell heterogeneity.

    PubMed

    Krieger, Teresa; Simons, Benjamin D

    2015-04-15

    Recent lineage-tracing studies based on inducible genetic labelling have emphasized a crucial role for stochasticity in the maintenance and regeneration of cycling adult tissues. These studies have revealed that stem cells are frequently lost through differentiation and that this is compensated for by the duplication of neighbours, leading to the consolidation of clonal diversity. Through the combination of long-term lineage-tracing assays with short-term in vivo live imaging, the cellular basis of this stochastic stem cell loss and replacement has begun to be resolved. With a focus on mammalian spermatogenesis, intestinal maintenance and the hair cycle, we review the role of dynamic heterogeneity in the regulation of adult stem cell populations. PMID:25852198

  3. Replacing and safeguarding pancreatic β cells for diabetes.

    PubMed

    Bruin, Jennifer E; Rezania, Alireza; Kieffer, Timothy J

    2015-12-01

    Pluripotent stem cells are a scalable source of pancreatic cells for transplantation into patients with diabetes. Here, we describe how the field is gaining momentum toward a β cell replacement therapy. PMID:26631630

  4. Stem cells and cardiovascular disease.

    PubMed

    Abbott, J Dawn; Giordano, Frank J

    2003-01-01

    Several recent discoveries have shifted the paradigm that there is no potential for myocardial regeneration and have fueled enthusiasm for a new frontier in the treatment of cardiovascular disease-stem cells. Fundamental to this emerging field is the cumulative evidence that adult bone marrow stem cells can differentiate into a wide variety of cell types, including cardiac myocytes and endothelial cells. This phenomenon has been termed stem cell plasticity and is the basis for the explosive recent interest in stem cell-based therapies. Directed to cardiovascular disease, stem cell therapy holds the promise of replacing lost heart muscle and enhancing cardiovascular revascularization. Early evidence of the feasibility of stem cell therapy for cardiovascular disease came from a series of animal experiments demonstrating that adult stem cells could become cardiac muscle cells (myogenesis) and participate in the formation of new blood vessels (angiogenesis and vasculogenesis) in the heart after myocardial infarction. These findings have been rapidly translated to ongoing human trials, but many questions remain. This review focuses on the use of adult bone marrow-derived stem cells for the treatment of ischemic cardiovascular disease and will contrast how far we have come in a short time with how far we still need to go before stem cell therapy becomes routine in cardiovascular medicine. PMID:12900745

  5. Stem cell treatment of degenerative eye disease☆

    PubMed Central

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

    2015-01-01

    Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs) and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE) cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs) has so far been reliant on mesenchymal stem cells (MSC). Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs), MSC derived from bone marrow (BMSC), adipose tissues (ADSC) and dental pulp (DPSC), together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment. PMID:25752437

  6. Stem cell treatment of degenerative eye disease.

    PubMed

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

    2015-05-01

    Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs) and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE) cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs) has so far been reliant on mesenchymal stem cells (MSC). Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs), MSC derived from bone marrow (BMSC), adipose tissues (ADSC) and dental pulp (DPSC), together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment. PMID:25752437

  7. Embryonic stem cells. Stem cell programs.

    PubMed

    Zerhouni, Elias

    2003-05-01

    The availability of human embryonic stem cell lines provides an important tool for scientists to explore the fundamental mechanisms that regulate differentiation into specific cell types. When more is known about the mechanisms that govern these processes, human embryonic stem cells may be clinically useful in generating cell types that have been damaged or depleted by a variety of human diseases. The NIH is actively pursuing a variety of initiatives to promote this developing research field, while continuing and expanding its long-standing investment in adult stem cells and research. PMID:12738840

  8. Cancer Stem Cell Consortium

    Cancer.gov

    Mission The Cancer Stem Cell Consortium is a self-assembled organization of intramural scientists at all levels of training with an interest in fundamental questions concerning stem cells, developmental biology, and cancer. We host scientific exchanges, w

  9. Putative intestinal stem cells

    PubMed Central

    Pirvulet, V

    2015-01-01

    A heterogeneous set of intestinal stem cells markers has been described in intestinal glands but the ultrastructural identity of intestinal stem cells remains unknown. By using electron microscopy, this study demonstrated the presence of cells with stem morphology in the intestinal glands of mice of different ages. These putative intestinal stem cells have large, euchromatic, irregular shaped nucleus, large, visible nucleolus, few ER cisternae and mitochondria. Their morphology is distinct from the morphology of any other intestinal gland cell. Stem cells located at the base of intestinal glands undergo mitosis. This study enhances the hypothesis of a gland (crypt) base columnar cell that gives rise to all the intestinal lineages. PMID:26366225

  10. Stem cells assessed.

    PubMed

    Blanpain, Cdric; Daley, George Q; Hochedlinger, Konrad; Passegu, Emmanuelle; Rossant, Janet; Yamanaka, Shinya

    2012-07-01

    The increasing momentum of stem cell research continues, with the better characterization of induced pluripotent stem (iPS) cells, the conversion of differentiated cells into different cell types and the use of pluripotent stem cells to generate whole tissues, among other advances. Here, six experts in the field of stem cell research compare different stem cell models and highlight the importance of pursuing complementary experimental approaches for a better understanding of pluripotency and differentiation and an informed approach to medical applications. PMID:22678486

  11. Pancreatic Stem Cells Remain Unresolved

    PubMed Central

    Morahan, Grant

    2014-01-01

    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. PMID:25132582

  12. 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. PMID:23257690

  13. Editorial: Stem Cell Engineering.

    PubMed

    Cabral, Joaquim M S; Palecek, Sean P

    2015-10-01

    In recent years, the promise of stem cells as tools for basic research, in vitro diagnostics, and in vivo therapeutics is increasingly being realized. This Special issue of Biotechnology Journal explores recent advances in the emerging field of stem cell engineering, with a focus on applying engineering approaches to understanding stem cell biology and enabling translation of stem cells to commercial and clinical products. PMID:26447639

  14. Information on Stem Cell Research

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS Information on Stem Cell Research Research @ NINDS Stem Cell Highlights Submit a ... found here: Human Induced Pluripotent Stem Cells NINDS Stem Cell Research on Campus The Intramural Research Program of ...

  15. 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

  16. Cell replacement therapy for Parkinson's disease.

    PubMed

    Wijeyekoon, Ruwani; Barker, Roger A

    2009-07-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the degeneration of dopaminergic neurons projecting from the substantia nigra to the striatum is a key pathological feature of the disease. Although pharmacological dopamine replacement is generally very effective in early disease, it is only a symptomatic therapy and can have significant side effects with long term use. One of the key strategies in a more restorative approach to PD therapy involves replacement of this degenerating nigro-striatal dopaminergic network with cells and several possible cell sources are being explored. While much experience and some success have been gained with fetal ventral mesencephalic (FVM) tissue transplants, the rapidly advancing stem cell field is providing attractive alternative options which circumvent many of the ethical and practical problems inherent in trials with FVM tissue. Of these embryonic stem cells and induced pluripotent stem cells seem the most promising. However further development and optimisation of the safety and efficacy of the techniques involved in generating and manipulating these, as well as other, cell sources will be essential before any further clinical trials are carried out. PMID:19007882

  17. Stem Cells and Calcium Signaling

    PubMed Central

    Tonelli, Fernanda M.P.; Santos, Anderson K.; Gomes, Dawidson A.; da Silva, Saulo L.; Gomes, Katia N.; Ladeira, Luiz O.

    2014-01-01

    The increasing interest in stem cell research is linked to the promise of developing treatments for many lifethreatening, debilitating diseases, and for cell replacement therapies. However, performing these therapeutic innovations with safety will only be possible when an accurate knowledge about the molecular signals that promote the desired cell fate is reached. Among these signals are transient changes in intracellular Ca2+ concentration [Ca2+]i. Acting as an intracellular messenger, Ca2+ has a key role in cell signaling pathways in various differentiation stages of stem cells. The aim of this chapter is to present a broad overview of various moments in which Ca2+-mediated signaling is essential for the maintenance of stem cells and for promoting their development and differentiation, also focusing on their therapeutic potential. PMID:22453975

  18. Embryonic stem cell therapy.

    PubMed

    Goswami, Joydeep; Rao, Mahendra

    2007-10-01

    Stem cell therapies, particularly those using embryonic stem cells, offer a novel approach to treating disease. There is an ongoing effort to develop tools and reagents to assist in understanding stem cells at a research level. In addition to these research tools, making stem cell therapy a reality requires the development of tools that enable the translation of research into viable therapies. Three sets of tools are discussed in this article: tools enabling stem cell scale-up and manufacture to GMP standards, tools addressing the behavior of cells in animal models, and tools to assess transplanted cells in early clinical trials. The development of such tools will address many of the safety and efficacy questions that are likely to arise as stem cell therapies move from bench to bedside. PMID:17899490

  19. Stem cells versus plasticity in liver and pancreas regeneration.

    PubMed

    Kopp, Janel L; Grompe, Markus; Sander, Maike

    2016-02-25

    Cell replacement in adult organs can be achieved through stem cell differentiation or the replication or transdifferentiation of existing cells. In the adult liver and pancreas, stem cells have been proposed to replace tissue cells, particularly following injury. Here we review how specialized cell types are produced in the adult liver and pancreas. Based on current evidence, we propose that the plasticity of differentiated cells, rather than stem cells, accounts for tissue repair in both organs. PMID:26911907

  20. Scientists Find Stem Cells That Might Repair Skull, Face Bones

    MedlinePlus

    ... gov/medlineplus/news/fullstory_157041.html Scientists Find Stem Cells That Might Repair Skull, Face Bones Discovery made ... they may be one step closer to using stem cells to replace damaged skull and facial bones in ...

  1. 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

  2. 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

  3. Stress and stem cells

    PubMed Central

    Tower, John

    2013-01-01

    The unique properties and functions of stem cells make them particularly susceptible to stresses and also lead to their regulation by stress. Stem cell division must respond to the demand to replenish cells during normal tissue turnover as well as in response to damage. Oxidative stress, mechanical stress, growth factors, and cytokines signal stem cell division and differentiation. Many of the conserved pathways regulating stem cell self-renewal and differentiation are also stress-response pathways. The long life span and division potential of stem cells create a propensity for transformation (cancer) and specific stress responses such as apoptosis and senescence act as antitumor mechanisms. Quiescence regulated by CDK inhibitors and a hypoxic niche regulated by FOXO transcription factor function to reduce stress for several types of stem cells to facilitate long-term maintenance. Aging is a particularly relevant stress for stem cells, because repeated demands on stem cell function over the life span can have cumulative cell-autonomous effects including epigenetic dysregulation, mutations, and telomere erosion. In addition, aging of the organism impairs function of the stem cell niche and systemic signals, including chronic inflammation and oxidative stress. PMID:23799624

  4. Toward beta cell replacement for diabetes.

    PubMed

    Johannesson, Bjarki; Sui, Lina; Freytes, Donald O; Creusot, Remi J; Egli, Dieter

    2015-04-01

    The discovery of insulin more than 90 years ago introduced a life-saving treatment for patients with type 1 diabetes, and since then, significant progress has been made in clinical care for all forms of diabetes. However, no method of insulin delivery matches the ability of the human pancreas to reliably and automatically maintain glucose levels within a tight range. Transplantation of human islets or of an intact pancreas can in principle cure diabetes, but this approach is generally reserved for cases with simultaneous transplantation of a kidney, where immunosuppression is already a requirement. Recent advances in cell reprogramming and beta cell differentiation now allow the generation of personalized stem cells, providing an unlimited source of beta cells for research and for developing autologous cell therapies. In this review, we will discuss the utility of stem cell-derived beta cells to investigate the mechanisms of beta cell failure in diabetes, and the challenges to develop beta cell replacement therapies. These challenges include appropriate quality controls of the cells being used, the ability to generate beta cell grafts of stable cellular composition, and in the case of type 1 diabetes, protecting implanted cells from autoimmune destruction without compromising other aspects of the immune system or the functionality of the graft. Such novel treatments will need to match or exceed the relative safety and efficacy of available care for diabetes. PMID:25733347

  5. Toward beta cell replacement for diabetes

    PubMed Central

    Johannesson, Bjarki; Sui, Lina; Freytes, Donald O; Creusot, Remi J; Egli, Dieter

    2015-01-01

    The discovery of insulin more than 90 years ago introduced a life-saving treatment for patients with type 1 diabetes, and since then, significant progress has been made in clinical care for all forms of diabetes. However, no method of insulin delivery matches the ability of the human pancreas to reliably and automatically maintain glucose levels within a tight range. Transplantation of human islets or of an intact pancreas can in principle cure diabetes, but this approach is generally reserved for cases with simultaneous transplantation of a kidney, where immunosuppression is already a requirement. Recent advances in cell reprogramming and beta cell differentiation now allow the generation of personalized stem cells, providing an unlimited source of beta cells for research and for developing autologous cell therapies. In this review, we will discuss the utility of stem cell-derived beta cells to investigate the mechanisms of beta cell failure in diabetes, and the challenges to develop beta cell replacement therapies. These challenges include appropriate quality controls of the cells being used, the ability to generate beta cell grafts of stable cellular composition, and in the case of type 1 diabetes, protecting implanted cells from autoimmune destruction without compromising other aspects of the immune system or the functionality of the graft. Such novel treatments will need to match or exceed the relative safety and efficacy of available care for diabetes. PMID:25733347

  6. Preservation of stem cells

    PubMed Central

    Hanna, Jacob

    2009-01-01

    Adult stem cells (hematopoietic and mesenchymal) have demonstrated tremendous human therapeutic potential. Currently, human embryonic stem cells are used principally for understanding development and disease progression but also hold tremendous therapeutic potential. The ability to preserve stem cells is critical for their use in clinical and research applications. Preservation of cells permits the transportation of cells between sites, as well as completion of safety and quality control testing. Preservation also permits the development of a ‘manufacturing paradigm’ for cell therapies, thereby maximizing the number of products that can be produced at a given facility. in this article, we will review modes of preservation and the current status of preservation of hematopoietic, mesenchymal and human embryonic stem cells. Current and emerging issues in the area of stem cell preservation will also be described. PMID:20046676

  7. 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

  8. The leukemic stem cell

    PubMed Central

    Jordan, Craig T.

    2007-01-01

    Malignant stem cells have recently been described as the source of several types of human cancer. These unique cell types are typically rare and possess properties that are distinct from most other tumor cells. The properties of leukemic stem cells indicate that current chemotherapy drugs will not be effective. The use of current cytotoxic agents is not effective in leukemia because the agents target both the leukemic and normal stem cell populations. Consequently, new strategies are required that specifically and preferentially target the malignant stem cell population, while sparing normal stem cells. Several well known agents are lethal for the leukemic stem cell in preclinical testing. They include parthenolide, commonly known as feverfew, and TDZD-8. They have undergone various levels of preclinical development, but have not been used in patients as yet in the cancer setting. These drugs and combinations of existing therapies that target the leukemic stem cell population may provide a cure in this disease. This article summarizes recent findings in the leukemic stem cell field and discusses new directions for therapy. PMID:17336250

  9. 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 ...

  10. Donating Peripheral Blood Stem Cells

    MedlinePlus

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

  11. [Human pluripotent stems cells I].

    PubMed

    López Moratalla, N; González de la Tajada, I

    2003-01-01

    In the last few years, the great progress of certain fields, such as molecular biology and development, has allowed a detailed knowledge of mechanisms implicated in cellular programing. This has permitted a rapid and unexpected advance in therapeutic cellular strategies. Thus, it has been possible to discover mechanisms involved in cellular differentiation and therefore has opened possibilities for human cellular manipulation and function replacement of damaged cells. Embryonic stem cells, have been obtained from the embryoblast. A lot of types of cellular lineages that include neurons, glial cells, pancreatic islets cells, hepatic cells, osteoblast and adipocytes, have been derived from mouse embryonic stem cells. In the same way, cellular lineages have been obtained by nuclear transference techniques capable of generating embryonic clones. Some scientist intend to evade by this approach, the bioethic reproval for human cloning, emphasizing that this is a "therapeutic cloning". In the present work, we propose to analyze mechanisms that permit stem cells to be pluripotential and discuss the ethical use of embryos as a source for stem cells with therapeutic potential. PMID:14727573

  12. Hematopoietic stem cell transplantation

    PubMed Central

    Hatzimichael, Eleftheria; Tuthill, Mark

    2010-01-01

    More than 25,000 hematopoietic stem cell transplantations (HSCTs) are performed each year for the treatment of lymphoma, leukemia, immune-deficiency illnesses, congenital metabolic defects, hemoglobinopathies, and myelodysplastic and myeloproliferative syndromes. Before transplantation, patients receive intensive myeloablative chemoradiotherapy followed by stem cell “rescue.” Autologous HSCT is performed using the patient’s own hematopoietic stem cells, which are harvested before transplantation and reinfused after myeloablation. Allogeneic HSCT uses human leukocyte antigen (HLA)-matched stem cells derived from a donor. Survival after allogeneic transplantation depends on donor–recipient matching, the graft-versus-host response, and the development of a graft versus leukemia effect. This article reviews the biology of stem cells, clinical efficacy of HSCT, transplantation procedures, and potential complications. PMID:24198516

  13. Lung Stem cell biology

    PubMed Central

    Ardhanareeswaran, Karthikeyan; Mirotsou, Maria

    2013-01-01

    Over the past few years new insights have been added to the study of stem cells in the adult lung. The exploration of the endogenous lung progenitors as well as the study of exogenously delivered stem cell populations holds promise for advancing our understanding of the biology of lung repair mechanisms. Moreover, it opens new possibilities for the use of stem cell therapy for the development of regenerative medicine approaches for the treatment of lung disease. Here, we discuss the main types of lung epithelial progenitor populations; the potential of endothelial progenitors, mesenchymal stem cells and embryonic stem cells for lung therapy; as well as summarize the cellular mechanisms involved. The de it provides novel insights for the development of regenerative medicine approaches for the treatment of lung disease. PMID:23406722

  14. Stem Cell Information: Glossary

    MedlinePlus

    ... blood stem cells Culture medium Differentiation Directed differentiation DNA Ectoderm Embryo Embryoid bodies Embryonic germ cells Embryonic ... mitosis and meiosis . Chromosome —A structure consisting of DNA and regulatory proteins found in the nucleus of ...

  15. Out of Eden: Stem Cells and Their Niches

    NASA Astrophysics Data System (ADS)

    Watt, Fiona M.; Hogan, Brigid L. M.

    2000-02-01

    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. Both intrinsic and extrinsic signals regulate stem cell fate and some of these signals have now been identified. Certain aspects of the stem cell microenvironment, or niche, are conserved between tissues, and this can be exploited in the application of stem cells to tissue replacement therapy.

  16. 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

  17. Harnessing stem cells and dendritic cells for novel therapies.

    PubMed

    Markowicz, Sergiusz

    2008-01-01

    This review presents the latest achievements in basic studies on stem-cell biology and on approaches aimed to design therapies based on stem cells and dendritic cells. Studies on stem-cell homeostasis are aimed to delineate the accessibility of these cells for therapeutic purposes. Hematopoietic stem cell transplantation has become a routine application of stem cells in the treatment of patients with cancer and with hematologic disorders. Perspectives of application of the mesenchymal stem cells for regenerative medicine and for tolerance induction following allogeneic transplantation are being extensively explored. Reprogramming of adult somatic cells to an undifferentiated pluripotent state in vitro by a transduction with just four genes encoding transcription factors opened the way for the generation of patient-specific pluripotent stem cells. Such induced pluripotent stem cells hold a great promise for replacement therapies of various so far incurable disorders. However, because of the tumorigenic potential of the retroviral vector transduction-induced pluripotent stem cells, before these cells become useful for clinical application, appropriate, safe methods of stem cell generation, selection, proliferation and differentiation need to be elaborated. There is a great potential for further developments of cancer immunotherapies and for controlling of post-transplantational reactions, if current basic studies on stem cells and on immunostimulatory and tolerogenic dendritic cells would be successfully translated to the clinic. PMID:19172843

  18. 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

  19. Cell replacement therapy for central nervous system diseases

    PubMed Central

    Tso, Danju; McKinnon, Randall D.

    2015-01-01

    The brain and spinal cord can not replace neurons or supporting glia that are lost through traumatic injury or disease. In pre-clinical studies, however, neural stem and progenitor cell transplants can promote functional recovery. Thus the central nervous system is repair competent but lacks endogenous stem cell resources. To make transplants clinically feasible, this field needs a source of histocompatible, ethically acceptable and non-tumorgenic cells. One strategy to generate patient-specific replacement cells is to reprogram autologous cells such as fibroblasts into pluripotent stem cells which can then be differentiated into the required cell grafts. However, the utility of pluripotent cell derived grafts is limited since they can retain founder cells with intrinsic neoplastic potential. A recent extension of this technology directly reprograms fibroblasts into the final graftable cells without an induced pluripotent stem cell intermediate, avoiding the pluripotent caveat. For both types of reprogramming the conversion efficiency is very low resulting in the need to amplify the cells in culture which can lead to chromosomal instability and neoplasia. Thus to make reprogramming biology clinically feasible, we must improve the efficiency. The ultimate source of replacement cells may reside in directly reprogramming accessible cells within the brain. PMID:26604878

  20. Cardiac Stem Cell Niches

    PubMed Central

    Leri, Annarosa; Rota, Marcello; Hosoda, Toru; Goichberg, Polina; Anversa, Piero

    2014-01-01

    The critical role that stem cell niches have in cardiac homeostasis and myocardial repair following injury is the focus of this review. Cardiac niches represent specialized microdomains where the quiescent and activated state of resident stem cells is regulated. Alterations in niche function with aging and cardiac diseases result in abnormal sites of cardiomyogenesis and inadequate myocyte formation. The relevance of Notch 1 signaling, gap-junction formation, HIF-1? and metabolic state in the regulation of stem cell growth and differentiation within the cardiac niches are discussed. PMID:25267073

  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. Interventional stem cell therapy.

    PubMed

    Prologo, J D; Hawkins, M; Gilliland, C; Chinnadurai, R; Harkey, P; Chadid, T; Lee, Z; Brewster, Luke

    2016-04-01

    The ability to deliver cells in appropriate doses to their targeted site of action is a well-known obstacle to optimising stem cell therapy. Systemic administration of cells results in pulmonary "trapping," which significantly decreases the number of available circulating cells to impact underlying disorders. Directed delivery of stem cells in interventional radiology may provide an additional option for bypassing the lungs, as well as introduce novel potential avenues for decreasing doses required to effect cellular therapy, efficiently obtain local paracrine effects, and/or to simplify targeting strategies. PMID:26874660

  3. Pre-stem cell transplantation enzyme replacement therapy in Hurler syndrome does not lead to significant antibody formation or delayed recovery of the endogenous enzyme post-transplant: a case report.

    PubMed

    Soni, Sandeep; Hente, Monica; Breslin, Nancy; Hersh, Joseph; Whitley, Chester; Cheerva, Alexandra; Bertolone, Salvatore

    2007-08-01

    Combined enzyme replacement therapy (ERT) and stem cell transplant (SCT) were done for a two year old boy with severe Hurler syndrome(HS) with the aim to decrease transplant related complications. He tolerated both the procedures well without any major complications. Urine glycosaminoglycans (GAGs) decreased post-transplant and child has improved clinically and neurologically. Insignificant titers of the anti-iduronidase antibodies which developed post-transplant did not affect the transplant outcome or the endogenous recovery of the alpha-L-iduronidase enzyme. PMID:17631030

  4. Melanoma stem cells.

    PubMed

    Roesch, Alexander

    2015-02-01

    The cancer stem cell concept significantly broadens our understanding of melanoma biology. However, this concept should be regarded as an integral part of a holistic cancer model that also includes the genetic evolution of tumor cells and the variability of cell phenotypes within a dynamic tumor microenvironment. The biologic complexity and methodological difficulties in identifying cancer stem cells and their biomarkers are currently impeding the direct translation of experimental findings into clinical practice. Nevertheless, it is these methodological shortcomings that provide a new perspective on the phenotypic heterogeneity and plasticity of melanoma with important consequences for future therapies. The development of new combination treatment strategies, particularly with regard to overcoming treatment resistance, could significantly benefit from targeted elimination of cell subpopulations with cancer stem cell properties. PMID:25631128

  5. 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

  6. Hematopoietic stem cells.

    PubMed

    Trigg, Michael E

    2004-04-01

    The hematopoietic system of the young child acquires, through time, the ability to cope with exposure to a number of environmental toxins and infectious agents. Occasionally, severe aplastic anemia occurs secondary to exposure to some of these toxins or infectious agents. The occurrence of severe aplastic anemia provides an opportunity to study the maturation of the hematopoietic system because often the immune system is partially intact. Hematopoietic stem cell transplants permit the study of the complete reconstitution of the hematopoietic and immunologic system. Stem cell transplants are often used to treat severe aplastic anemia or, alternatively, may be part of the treatment for an underlying malignant disease or a genetic disease. Sources of stem cells and the age of the recipient and donor have an impact on the success of the stem cell transplant. A stem cell transplantation provides a window of opportunity to study and observe the normal maturation of the immune system and the sensitivity. Very clearly, children recover from severe aplastic anemia and stem cell transplantations more readily with fewer problems and complications than adults. The environmental risks that a child who received a stem cell transplantation faces are related primarily to the deficiencies of the hematopoietic system and immune system during the recovery phase. Therefore, diminished resistance to infectious agents, primarily viruses and other opportunistic organisms, are the primary risk that children who are recovering from these transplantations face. There are few data on the susceptibility of these children to the toxic effects of other environmental toxicants during the recovery period, which may take years before complete recovery. PMID:15060199

  7. 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

  8. 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.

  9. Stem cells: a minireview.

    PubMed

    Jackson, Kathyjo A; Majka, Susan M; Wulf, Gerald G; Goodell, Margaret A

    2002-01-01

    The identification of adult-derived stem cells which maintain plasticity throughout the course of a lifetime, has transformed the field of stem cell biology. Bone marrow derived hematopoietic stem cells (HSC) are the most well-characterized population of these multipotential cells. First identified for their ability to reconstitute blood lineages and rescue lethally irradiated hosts, these cells have also been shown to differentiate and integrate into skeletal muscle, cardiac myocytes, vascular endothelium, liver, and brain tissue. Various populations of HSC are being studied, exploiting cell surface marker expression, such as Sca-1, c-kit, CD34, and lin; as well as the abilityto efflux the vital dye Hoecsht 33342. Detection of engrafted donor derived cells into various tissue types in vivo is a laborious process and may involve detection of beta-galactosidase via colorimetric reaction or antibody labeling or green fluorescent protein (GFP) via fluorescence microscopy, as well as in situ hybridization to detect the Y-chromosome. Using these techniques, the search has begun for tissue specific stem cells capable of host tissue regeneration, self renewal, and transdifferentiation. Caution is urged when interpreting these types of experiments because although they are stimulating, limitations of the technologies may provide misleading results. PMID:12046843

  10. Placental stem cells.

    PubMed

    Antoniadou, Eleni; David, Anna L

    2016-02-01

    The placenta represents a reservoir of progenitor, stem cells and epithelial cells that have been shown to differentiate into various types, including adipogenic, osteogenic, myogenic, hepatogenic, cardiac, pancreatic, endothelial, pulmonary and neurogenic lineages. This review focuses on the properties of placenta-derived cells, and it evaluates their current therapeutic applications in regenerative medicine and cell transplantations. Ongoing clinical and preclinical studies are investigating the safety and efficacy of the human amniotic epithelial cells (hAECs), human amniotic mesenchymal stromal cells (hAMSCs) and chorionic mesenchymal stromal cells (hCMSCs). The establishment of biobanks for placental stem cells will enable the translation of scientific research into the clinic. The advantage of the placenta as a cellular source is that it contains different cell lineages, such as the haematopoietic lineage that originates from the chorion, allantois and yolk sac, and the mesenchymal lineage that originates from the chorion and amnion. In this review, we address advances in placental stem cell characterization, and we explore their possible uses in cell therapy. PMID:26547389

  11. 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

  12. State of the Art in Stem Cell Research: Human Embryonic Stem Cells, Induced Pluripotent Stem Cells, and Transdifferentiation

    PubMed Central

    de Peppo, Giuseppe Maria; Marolt, Darja

    2012-01-01

    Stem cells divide by asymmetric division and display different degrees of potency, or ability to differentiate into various specialized cell types. Owing to their unique regenerative capacity, stem cells have generated great enthusiasm worldwide and represent an invaluable tool with unprecedented potential for biomedical research and therapeutic applications. Stem cells play a central role in the understanding of molecular mechanisms regulating tissue development and regeneration in normal and pathological conditions and open large possibilities for the discovery of innovative pharmaceuticals to treat the most devastating diseases of our time. Not least, their intrinsic characteristics allow the engineering of functional tissues for replacement therapies that promise to revolutionize the medical practice in the near future. In this paper, the authors present the characteristics of pluripotent stem cells and new developments of transdifferentiation technologies and explore some of the biomedical applications that this emerging technology is expected to empower. PMID:24089646

  13. Stem cell therapy for the spinal cord

    PubMed Central

    2012-01-01

    Injury and disease of the spinal cord are generally met with a poor prognosis. This poor prognosis is due not only to the characteristics of the diseases but also to our poor ability to deliver therapeutics to the spinal cord. The spinal cord is extremely sensitive to direct manipulation, and delivery of therapeutics has proven a challenge for both scientists and physicians. Recent advances in stem cell technologies have opened up a new avenue for the treatment of spinal cord disease and injury. Stem cells have proven beneficial in rodent models of spinal cord disease and injury. In these animal models, stem cells have been shown to produce their effect by the dual action of cell replacement and the trophic support of the factors secreted by these cells. In this review we look at the main clinical trials involving stem cell transplant into the spinal cord, focusing on motor neuron diseases and spinal cord injury. We will also discuss the major hurdles in optimizing stem cell delivery methods into the spinal cord. We shall examine current techniques such as functional magnetic resonance imaging guidance and cell labeling and will look at the current research striving to improve these techniques. With all caveats and future research taken into account, this is a very exciting time for stem cell transplant into the spinal cord. We are only beginning to realize the huge potential of stem cells in a central nervous system setting to provide cell replacement and trophic support. Many more trials will need to be undertaken before we can fully exploit the attributes of stem cells. PMID:22776143

  14. Stem Cell Transplants (For Parents)

    MedlinePlus

    ... Caring for Your Child All About Food Allergies Stem Cell Transplants KidsHealth > For Parents > Stem Cell Transplants Print A A A Text Size What's ... Recovery Coping en español Trasplantes de células madre Stem cells are cells in the body that have the ...

  15. From Beta Cell Replacement to Beta Cell Regeneration

    PubMed Central

    Liu, Chengcheng

    2014-01-01

    Diabetes is affecting more than 25.8 million people in the United States, causing huge burden on the health care system and economy. Insulin injection, which is the predominant treatment for diabetes, is incapable of replenishing the lost insulin-producing beta cell in patients. Restoring beta cell mass through replacement therapy such as islet transplantation or beta cell regeneration through in vitro and in vivo strategies has attracted particular attentions in the field due to its potential to cure diabetes. In the aspect of islet transplantation, gene therapy, stem cell therapy, and more biocompatible immunosuppressive drugs have been tested in various preclinical animal models to improve the longevity and function of human islets against the posttransplantation challenges. In the islet regeneration aspect, insulin-producing cells have been generated through in vitro transdifferentiation of stem cells and other types of cells and demonstrated to be capable of glycemic control. Moreover, several biomarkers including cell-surface receptors, soluble factors, and transcriptional factors have been identified or rediscovered in mediating the process of beta cell proliferation in rodents. This review summarizes the current progress and hurdles in the preclinical efforts in resurrecting beta cells. It may provide some useful insights into the future drug discovery for antidiabetic purposes. PMID:25355714

  16. Heart repair and stem cells

    PubMed Central

    van Laake, Linda W; Hassink, Rutger; Doevendans, Pieter A; Mummery, Christine

    2006-01-01

    Of the medical conditions currently being discussed in the context of possible treatments based on cell transplantation therapy, few have received more attention than the heart. Much focus has been on the potential application of bone marrow-derived cell preparations, which have already been introduced into double-blind, placebo-controlled clinical trials. The consensus is that bone marrow may have therapeutic benefit but that this is not based on the ability of bone marrow cells to transdifferentiate into cardiac myocytes. Are there potential stem cell sources of cardiac myocytes that may be useful in replacing those lost or dysfunctional after myocardial infarction? Here, this question is addressed with a review of the recent literature. PMID:17008381

  17. Stem cell therapy for diabetes.

    PubMed

    Lee, K O; Gan, S U; Calne, R Y

    2012-12-01

    Stem cell therapy holds immense promise for the treatment of patients with diabetes mellitus. Research on the ability of human embryonic stem cells to differentiate into islet cells has defined the developmental stages and transcription factors involved in this process. However, the clinical applications of human embryonic stem cells are limited by ethical concerns, as well as the potential for teratoma formation. As a consequence, alternative forms of stem cell therapies, such as induced pluripotent stem cells, umbilical cord stem cells and bone marrow-derived mesenchymal stem cells, have become an area of intense study. Recent advances in stem cell therapy may turn this into a realistic treatment for diabetes in the near future. PMID:23565384

  18. 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.

  19. Stem cells and healthy aging.

    PubMed

    Goodell, Margaret A; Rando, Thomas A

    2015-12-01

    Research into stem cells and aging aims to understand how stem cells maintain tissue health, what mechanisms ultimately lead to decline in stem cell function with age, and how the regenerative capacity of somatic stem cells can be enhanced to promote healthy aging. Here, we explore the effects of aging on stem cells in different tissues. Recent research has focused on the ways that genetic mutations, epigenetic changes, and the extrinsic environmental milieu influence stem cell functionality over time. We describe each of these three factors, the ways in which they interact, and how these interactions decrease stem cell health over time. We are optimistic that a better understanding of these changes will uncover potential strategies to enhance stem cell function and increase tissue resiliency into old age. PMID:26785478

  20. Stem Cells and Female Reproduction

    PubMed Central

    Du, Hongling; Taylor, Hugh S.

    2011-01-01

    Several recent findings in stem cell biology have resulted in new opportunities for the treatment of reproductive disease. Endometrial regeneration can be driven by bone marrow derived stem cells. This finding has potential implications for the treatment of uterine disorders. It also supports a new theory for the etiology of endometriosis. The ovaries have been shown to contain stem cells that form oocytes in adults and can be cultured in vitro to develop mature oocytes. Stem cells from the fetus have been demonstrated to lead to microchimerism in the mother and implicated in several maternal diseases. Additionally the placenta may be another source of hematopoietic stem cell. Finally endometrial derived stem cells have been demonstrated to differentiate into non-reproductive tissues. While we are just beginning to understand stem cells and many key questions remain, the potential advantages of stem cells in reproductive biology and medicine are apparent. PMID:19208782

  1. Normal and leukemic stem cells

    PubMed Central

    Pelicci, P G

    2012-01-01

    Studies on hematopoietic stem cells have provided several critical insights in the biology of stem cells in general; as mature blood cells are generally short lived, stem cells are in fact required to guarantee, throughout the life of an organism, the replenishment of differentiated blood cells by the generation of multi-lineage progenitors and precursors committed to individual hematopoietic lineages. Similarly, acute myeloid leukemia has been considered as a model system to study cancer stem cells. This presentation illustrates some recent results obtained by our group with regard to both normal and leukemic stem cells.

  2. Intestinal stem cells and inflammation.

    PubMed

    Asfaha, Samuel

    2015-12-01

    The intestinal epithelium is renewed every 3-5 days from at least two principal stem cell pools. Actively cycling crypt based columnar (CBC) Lgr5(+) cells and slower cycling Bmi1-expressing or Krt19-expressing cells maintain the small intestinal and colonic epithelium in homeostasis and injury. Following acute epithelial damage, Lgr5+ stem cells are susceptible to injury and a reserve stem cell or progenitor pool is responsible for regeneration of the epithelium. Current data suggests that intestinal stem cells respond to inflammatory signals to modulate their expansion during epithelial regeneration. Here, we review how inflammation and injury affect intestinal and colonic stem cells. PMID:26654865

  3. Characterization of Amniotic Stem Cells

    PubMed Central

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

    2014-01-01

    Abstract 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. PMID:25068631

  4. 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

  5. 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.

  6. A Simplified Method for the Aspiration of Bone Marrow from Patients Undergoing Hip and Knee Joint Replacement for Isolating Mesenchymal Stem Cells and In Vitro Chondrogenesis

    PubMed Central

    Juneja, Subhash C.; Viswanathan, Sowmya; Ganguly, Milan; Veillette, Christian

    2016-01-01

    The procedure for aspiration of bone marrow from the femur of patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA) may vary from an OR (operating room) to OR based on the surgeon's skill and may lead to varied extent of clotting of the marrow and this, in turn, presents difficulty in the isolation of mesenchymal stem cells (MSCs) from such clotted bone marrow. We present a simple detailed protocol for aspirating bone marrow from such patients, isolation, and characterization of MSCs from the aspirated bone marrow specimens and show that the bone marrow presented no clotting or exhibited minimal clotting. This represents an economical source and convenient source of MSCs from bone marrow for use in regenerative medicine. Also, we presented the detailed protocol and showed that the MSCs derived from such bone marrow specimens exhibited MSCs characteristics and generated micromass cartilages, the recipe for regenerative medicine for osteoarthritis. The protocols we presented can be used as standard operating procedures (SOPs) by researchers and clinicians. PMID:27057356

  7. Advances in Stem Cell Mobilization

    PubMed Central

    Hopman, Rusudan K.; DiPersio, John F.

    2014-01-01

    Use of granulocyte colony stimulating factor (G-CSF)–mobilized peripheral blood hematopoietic progenitor cells (HPC) has largely replaced bone marrow (BM) as a source of stem cells for both autologous and allogeneic cell transplantation. With G-CSF alone, up to 35% of patients are unable to mobilize sufficient numbers of CD34 cells/kg to ensure successful and consistent multi-lineage engraftment and sustained hematopoietic recovery. To this end, research is ongoing to identify new agents or combinations which will lead to the most effective and efficient stem cell mobilization strategies, especially in those patients who are at risk for mobilization failure. We describe both established agents and novel strategies at various stages of development. The latter include but are not limited to drugs that target the SDF-1/CXCR4 axis, S1P agonists, VCAM/VLA-4 inhibitors, parathyroid hormone, proteosome inhibitors, Groβ, and agents that stabilize HIF. While none of the novel agents have yet gained an established role in HPC mobilization in clinical practice, many early studies exploring these new pathways show promising results and warrant further investigation. PMID:24476957

  8. Human cardiac stem cells.

    PubMed

    Bearzi, Claudia; Rota, Marcello; Hosoda, Toru; Tillmanns, Jochen; Nascimbene, Angelo; De Angelis, Antonella; Yasuzawa-Amano, Saori; Trofimova, Irina; Siggins, Robert W; Lecapitaine, Nicole; Cascapera, Stefano; Beltrami, Antonio P; D'Alessandro, David A; Zias, Elias; Quaini, Federico; Urbanek, Konrad; Michler, Robert E; Bolli, Roberto; Kajstura, Jan; Leri, Annarosa; Anversa, Piero

    2007-08-28

    The identification of cardiac progenitor cells in mammals raises the possibility that the human heart contains a population of stem cells capable of generating cardiomyocytes and coronary vessels. The characterization of human cardiac stem cells (hCSCs) would have important clinical implications for the management of the failing heart. We have established the conditions for the isolation and expansion of c-kit-positive hCSCs from small samples of myocardium. Additionally, we have tested whether these cells have the ability to form functionally competent human myocardium after infarction in immunocompromised animals. Here, we report the identification in vitro of a class of human c-kit-positive cardiac cells that possess the fundamental properties of stem cells: they are self-renewing, clonogenic, and multipotent. hCSCs differentiate predominantly into cardiomyocytes and, to a lesser extent, into smooth muscle cells and endothelial cells. When locally injected in the infarcted myocardium of immunodeficient mice and immunosuppressed rats, hCSCs generate a chimeric heart, which contains human myocardium composed of myocytes, coronary resistance arterioles, and capillaries. The human myocardium is structurally and functionally integrated with the rodent myocardium and contributes to the performance of the infarcted heart. Differentiated human cardiac cells possess only one set of human sex chromosomes excluding cell fusion. The lack of cell fusion was confirmed by the Cre-lox strategy. Thus, hCSCs can be isolated and expanded in vitro for subsequent autologous regeneration of dead myocardium in patients affected by heart failure of ischemic and nonischemic origin. PMID:17709737

  9. Human cardiac stem cells

    PubMed Central

    Bearzi, Claudia; Rota, Marcello; Hosoda, Toru; Tillmanns, Jochen; Nascimbene, Angelo; De Angelis, Antonella; Yasuzawa-Amano, Saori; Trofimova, Irina; Siggins, Robert W.; LeCapitaine, Nicole; Cascapera, Stefano; Beltrami, Antonio P.; D'Alessandro, David A.; Zias, Elias; Quaini, Federico; Urbanek, Konrad; Michler, Robert E.; Bolli, Roberto; Kajstura, Jan; Leri, Annarosa; Anversa, Piero

    2007-01-01

    The identification of cardiac progenitor cells in mammals raises the possibility that the human heart contains a population of stem cells capable of generating cardiomyocytes and coronary vessels. The characterization of human cardiac stem cells (hCSCs) would have important clinical implications for the management of the failing heart. We have established the conditions for the isolation and expansion of c-kit-positive hCSCs from small samples of myocardium. Additionally, we have tested whether these cells have the ability to form functionally competent human myocardium after infarction in immunocompromised animals. Here, we report the identification in vitro of a class of human c-kit-positive cardiac cells that possess the fundamental properties of stem cells: they are self-renewing, clonogenic, and multipotent. hCSCs differentiate predominantly into cardiomyocytes and, to a lesser extent, into smooth muscle cells and endothelial cells. When locally injected in the infarcted myocardium of immunodeficient mice and immunosuppressed rats, hCSCs generate a chimeric heart, which contains human myocardium composed of myocytes, coronary resistance arterioles, and capillaries. The human myocardium is structurally and functionally integrated with the rodent myocardium and contributes to the performance of the infarcted heart. Differentiated human cardiac cells possess only one set of human sex chromosomes excluding cell fusion. The lack of cell fusion was confirmed by the Cre-lox strategy. Thus, hCSCs can be isolated and expanded in vitro for subsequent autologous regeneration of dead myocardium in patients affected by heart failure of ischemic and nonischemic origin. PMID:17709737

  10. Stem cells as therapeutics for neurodegenerative disorders?

    PubMed

    Mattson, M P

    2001-11-01

    Aging is associated with a progressive increase in the risk of several prominent neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke and amyotrophic lateral sclerosis. In each of these disorders specific populations of neurons become dysfunctional, then die and are not replaced. The adult brain and spinal cord contain populations of so-called neural stem cells (self-renewing and multipotent) and neural precursor cells (specified to a certain fate, but still mitotic) that may provide a continuing source of new neurons and glial cells during successful aging and after injury to the nervous system. Recent studies have shown that stem cells from embryos and adults can be transplanted into the nervous system, differentiate into neurons and glia and restore lost function in experimental models of neurodegenerative diseases. Embryonic stem cells may be a particularly effective donor cell type for transplantation-based therapies. Efficacy of stem cell therapies remains to be established in clinical trials in humans. Another approach is to mobilize endogenous neural stem cells. Animals studies have shown that dietary and behavioral modifications can indeed stimulate neurogenesis. Molecular and cellular mechanisms that regulate the proliferation, differentiation and survival of neural stem cells and neural precursor cells are being elucidated and are revealing novel targets for the development of pharmaceuticals that promote neurogenesis. PMID:19811037

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

    PubMed Central

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

    2012-01-01

    Melanocyte stem cells differ greatly from melanoma stem cells; the former provide pigmented cells during normal tissue homeostasis and repair, while the latter play an active role in a lethal form of cancer. These two 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 non-tumor cells. PMID:23438380

  12. Cell Replacement Therapies: Is It Time to Reprogram?

    PubMed Central

    Feund, Christian; Mummery, Christine L.; Hoeben, Rob C.

    2014-01-01

    Abstract Hematopoietic stem cell transplantations have become a very successful therapeutic approach to treat otherwise life-threatening blood disorders. It is thought that stem cell transplantation may also become a feasible treatment option for many non-blood-related diseases. So far, however, the limited availability of human leukocyte antigen-matched donors has hindered development of some cell replacement therapies. The Nobel-prize rewarded finding that pluripotency can be induced in somatic cells via expression of a few transcription factors has led to a revolution in stem cell biology. The possibility to change the fate of somatic cells by expressing key transcription factors has been used not only to generate pluripotent stem cells, but also for directly converting somatic cells into fully differentiated cells of another lineage or more committed progenitor cells. These approaches offer the prospect of generating cell types with a specific genotype de novo, which would circumvent the problems associated with allogeneic cell transplantations. This technology has generated a plethora of new disease-specific research efforts, from studying disease pathogenesis to therapeutic interventions. Here we will discuss the opportunities in this booming field of cell biology and summarize how the scientists in the Netherlands have joined efforts in one area to exploit the new technology. PMID:25141889

  13. Stem cell plasticity and carcinogenesis.

    PubMed

    Filip, S; Mokrý, J; English, D

    2006-01-01

    Presently, there is more and more talk about tumors being a disease connected with stem cells. Both stem cells and tumor cells have many similarities, and there is much evidence that microenvironment, cytokines and signal pathways control tissue specificities and have a significant role in the process of carcinogenesis. Recent experimental results show that stem cells and tumor stem cells apparently play a key role in carcinogenesis. Tumors grow up, thanks to the activity of just few stem cells that continuously produce other proliferating progenitor tumor cells. Generally, tumor elements are thought to be either undifferentiated, or dedifferentiated cells. Actually, the truth is that tumors are made of more or less differentiated cells with variable rate of differentiation. We suppose that under certain conditions tumor stem cells may participate in regeneration without giving rise to tumor formation. It is also presumed that we may reprogram tumor stem cells and progenitor cells in a certain period of time and so initiate development of normal tissue. However, till now the real relation between normal and tumor cells is not clear. Finally, we wish to remind that plasticity of tumor and normal cells cannot be separated but should be considered as individual phenomenon expressing certain condition of an organism in time. This communication is only a probe and introduction into a discussion aimed at better understanding of carcinogenesis from the view of processes at the stem cell level. Stimulation of stem cell activation may lead to prophylactic approaches for therapy and prevention in carcinogenesis. PMID:16575462

  14. 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

  15. Estrogen deficiency heterogeneously affects tissue specific stem cells in mice.

    PubMed

    Kitajima, Yuriko; Doi, Hanako; Ono, Yusuke; Urata, Yoshishige; Goto, Shinji; Kitajima, Michio; Miura, Kiyonori; Li, Tao-Sheng; Masuzaki, Hideaki

    2015-01-01

    Postmenopausal disorders are frequently observed in various organs, but their relationship with estrogen deficiency and mechanisms remain unclear. As tissue-specific stem cells have been found to express estrogen receptors, we examined the hypothesis that estrogen deficiency impairs stem cells, which consequently contributes to postmenopausal disorders. Six-week-old C57BL/6 female mice were ovariectomized, following which they received 17?-estradiol replacement or vehicle (control). Sham-operated mice were used as healthy controls. All mice were killed for evaluation 2 months after treatments. Compared with the healthy control, ovariectomy significantly decreased uterine weight, which was partially recovered by 17?-estradiol replacement. Ovariectomy significantly increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, but impaired their capacity to grow mixed cell-type colonies in vitro. Estrogen replacement further increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, without significantly affecting colony growth in vitro. The number of CD105-positive mesenchymal stem cells in bone marrow also significantly decreased after ovariectomy, but completely recovered following estrogen replacement. Otherwise, neither ovariectomy nor estrogen replacement changed the number of Pax7-positive satellite cells, which are a skeletal muscle-type stem cell. Estrogen deficiency heterogeneously affected tissue-specific stem cells, suggesting a likely and direct relationship with postmenopausal disorders. PMID:26245252

  16. Hematopoietic Stem Cells

    PubMed Central

    HAWLEY, ROBERT G.; RAMEZANI, ALI; HAWLEY, TERESA S.

    2008-01-01

    Hematopoietic stem cells (HSCs) have the capacity to self-renew and the potential to differentiate into all of the mature blood cell types. The ability to prospectively identify and isolate HSCs has been the subject of extensive investigation since the first transplantation studies implying their existence almost 50 years ago. Despite significant advances in enrichment protocols, the continuous in vitro propagation of human HSCs has not yet been achieved. This chapter describes current procedures used to phenotypically and functionally characterize candidate human HSCs and initial efforts to derive permanent human HSC lines. PMID:17141055

  17. Recent advances in stem cell neurobiology.

    PubMed

    Ostenfeld, T; Svendsen, C N

    2003-01-01

    1. Neural stem cells can be cultured from the CNS of different mammalian species at many stages of development. They have an extensive capacity for self-renewal and will proliferate ex vivo in response to mitogenic growth factors or following genetic modification with immortalising oncogenes. Neural stem cells are multipotent since their differentiating progeny will give rise to the principal cellular phenotypes comprising the mature CNS: neurons, astrocytes and oligodendrocytes. 2. Neural stem cells can also be derived from more primitive embryonic stem (ES) cells cultured from the blastocyst. ES cells are considered to be pluripotent since they can give rise to the full cellular spectrum and will, therefore, contribute to all three of the embryonic germ layers: endoderm, mesoderm and ectoderm. However, pluripotent cells have also been derived from germ cells and teratocarcinomas (embryonal carcinomas) and their progeny may also give rise to the multiple cellular phenotypes contributing to the CNS. In a recent development, ES cells have also been isolated and grown from human blastocysts, thus raising the possibility of growing autologous stem cells when combined with nuclear transfer technology. 3. There is now an emerging recognition that the adult mammalian brain, including that of primates and humans, harbours stem cell populations suggesting the existence of a previously unrecognised neural plasticity to the mature CNS, and thereby raising the possibility of promoting endogenous neural reconstruction. 4. Such reports have fuelled expectations for the clinical exploitation of neural stem cells in cell replacement or recruitment strategies for the treatment of a variety of human neurological conditions including Parkinson's disease (PD), Huntington's disease, multiple sclerosis and ischaemic brain injury. Owing to their migratory capacity within the CNS, neural stem cells may also find potential clinical application as cellular vectors for widespread gene delivery and the expression of therapeutic proteins. In this regard, they may be eminently suitable for the correction of genetically-determined CNS disorders and in the management of certain tumors responsive to cytokines. Since large numbers of stem cells can be generated efficiently in culture, they may obviate some of the technical and ethical limitations associated with the use of fresh (primary) embryonic neural tissue in current transplantation strategies. 5. While considerable recent progress has been made in terms of developing new techniques allowing for the long-term culture of human stem cells, the successful clinical application of these cells is presently limited by our understanding of both (i) the intrinsic and extrinsic regulators of stem cell proliferation and (ii) those factors controlling cell lineage determination and differentiation. Although such cells may also provide accessible model systems for studying neural development, progress in the field has been further limited by the lack of suitable markers needed for the identification and selection of cells within proliferating heterogeneous populations of precursor cells. There is a further need to distinguish between the committed fate (defined during normal development) and the potential specification (implying flexibility of fate through manipulation of its environment) of stem cells undergoing differentiation. 6. With these challenges lying ahead, it is the opinion of the authors that stem-cell therapy is likely to remain within the experimental arena for the foreseeable future. In this regard, few (if any) of the in vivo studies employing neural stem cell grafts have shown convincingly that behavioural recovery can be achieved in the various model paradigms. Moreover, issues relating to the quality control of cultured cells and their safety following transplantation have only begun to be addressed. 7. While on the one hand cell biotechnologists have been quick to realise the potential commercial value, human stem cell research and its clinical applications has been the subject of intense ethical and legislative considerations. The present chapter aims to review some recent aspects of stem cell research applicable to developmental neurobiology and the potential applications in clinical neuroscience. PMID:12627808

  18. Stem Cells in Aging

    PubMed Central

    Yunis, Edmond J.; Zúñiga, Joaquin; Koka, Prasad S.; Husain, Zaheed; Romero, Viviana; Stern, Joel N.H.; Fridkis-Hareli, Masha

    2008-01-01

    Aging is a genetically programmed decline in the functional effectiveness of the organism. It is manifested by a collective group of changes in cells or organs that occur over the course of a lifespan, limiting the duration of life. Longevity usually refers to long-lived members of a population within species. Organs develop and can involute according to specific timetables. Such timetables correlate with a preordained proliferative capacity of cells mediated by cell and organ clocks. In this review, we discuss different aspects related to genetic and environmental factors that are involved in determining life span. We discuss the influence of ontogenic, genetic and environmental factors in aging. The genetic factors can be studied in embryonic stem cells (ESC) and in niches (microenvironments) of stem cells (SC) using cellular or experimental animal models. We discuss molecular mechanisms involving genes and proteins associated with death pathways, niches, or hubs, on longevity. Moreover, we also discuss genes and proteins, associated with death pathways, on longevity. Unraveling these mechanisms may further our understanding of human aging leading to development of therapeutic interventions with the potential of prolonging life. PMID:19030125

  19. Making a Hematopoietic Stem Cell

    PubMed Central

    Daniel, Michael G.; Pereira, Carlos-Filipe; Lemischka, Ihor R.; Moore, Kateri A.

    2016-01-01

    Previous attempts to either generate or expand hematopoietic stem cells (HSCs) in vitro have involved either ex vivo expansion of pre-existing patient or donor HSCs or de novo generation from pluripotent stem cells (PSCs), comprising both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). iPSCs alleviated ESC ethical issues but attempts to generate functional mature hematopoietic stem and progenitor cells (HSPCs) have been largely unsuccessful. New efforts focus on directly reprogramming somatic cells into definitive HSCs and HSPCs. To meet clinical needs and to advance drug discovery and stem cell therapy, alternative approaches are necessary. In this review, we synthesize the strategies used and the key findings made in recent years by those trying to make an HSC. PMID:26526106

  20. Making a Hematopoietic Stem Cell.

    PubMed

    Daniel, Michael G; Pereira, Carlos-Filipe; Lemischka, Ihor R; Moore, Kateri A

    2016-03-01

    Previous attempts to either generate or expand hematopoietic stem cells (HSCs) in vitro have involved either ex vivo expansion of pre-existing patient or donor HSCs or de novo generation from pluripotent stem cells (PSCs), comprising both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). iPSCs alleviated ESC ethical issues but attempts to generate functional mature hematopoietic stem and progenitor cells (HSPCs) have been largely unsuccessful. New efforts focus on directly reprogramming somatic cells into definitive HSCs and HSPCs. To meet clinical needs and to advance drug discovery and stem cell therapy, alternative approaches are necessary. In this review, we synthesize the strategies used and the key findings made in recent years by those trying to make an HSC. PMID:26526106

  1. Immunomodulation by Mesenchymal Stem Cells

    PubMed Central

    Abdi, Reza; Fiorina, Paolo; Adra, Chaker N.; Atkinson, Mark; Sayegh, Mohamed H.

    2008-01-01

    Mesenchymal stem cells (MSCs) are pluripotent stromal cells that have the potential to give rise to cells of diverse lineages. Interestingly, MSCs can be found in virtually all postnatal tissues. The main criteria currently used to characterize and identify these cells are the capacity for self-renewal and differentiation into tissues of mesodermal origin, combined with a lack in expression of certain hematopoietic molecules. Because of their developmental plasticity, the notion of MSC-based therapeutic intervention has become an emerging strategy for the replacement of injured tissues. MSCs have also been noted to possess the ability to impart profound immunomodulatory effects in vivo. Indeed, some of the initial observations regarding MSC protection from tissue injury once thought mediated by tissue regeneration may, in reality, result from immunomodulation. Whereas the exact mechanisms underlying the immunomodulatory functions of MSC remain largely unknown, these cells have been exploited in a variety of clinical trials aimed at reducing the burden of immune-mediated disease. This article focuses on recent advances that have broadened our understanding of the immunomodulatory properties of MSC and provides insight as to their potential for clinical use as a cell-based therapy for immune-mediated disorders and, in particular, type 1 diabetes. PMID:18586907

  2. 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

  3. 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

  4. Wnt Signaling in Stem Cells and Tumor Stem Cells.

    PubMed

    Kahn, Michael

    2015-09-01

    The Wnt signaling cascade is critically important in stem cell biology, both in homeostatic maintenance and repair and regeneration of tissues and organs, through their respective somatic stem cells (SSCs). However, aberrant Wnt signaling is associated with a wide array of tumor types and Wnt signaling is important in the so-termed cancer stem cell/tumor-initiating cell (CSC/TIC) population. The ability to safely therapeutically target the Wnt signaling pathway offers enormous promise. However, just like the Sword of Damocles, significant risks and concerns regarding targeting such a critical pathway in normal stem cell maintenance and tissue homeostasis remain ever present. With this in mind, we review our current understanding of the role of Wnt signaling in SSCs and CSC/TICs and the potential to pharmacologically manipulate these endogenous stem cell populations (both normal and tumor). PMID:26251120

  5. Placenta-an alternative source of stem cells

    SciTech Connect

    Matikainen, Tiina; Laine, Jarmo . E-mail: jarmo.laine@bts.redcoss.fi

    2005-09-01

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

  6. 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.

  7. Methods of Retinal Ganglion Cell Differentiation From Pluripotent Stem Cells

    PubMed Central

    Gill, Katherine P.; Hewitt, Alex W.; Davidson, Kathryn C.; Pébay, Alice; Wong, Raymond C. B.

    2014-01-01

    Glaucoma, the worldwide leading cause of irreversible blindness, is characterized by progressive degeneration of the optic nerve and loss of retinal ganglion cells. Research into glaucoma pathogenesis has been hampered by difficulties in isolating and culturing retinal ganglion cells in vitro. However, recent improvements in laboratory techniques have enabled the generation of a variety of mature cell types from pluripotent stem cells, including retinal ganglion cells. Indeed, stem cell-based approaches have the potential to revolutionize the field by providing an unlimited source of cells for replacement therapies and by enabling development of in vitro disease models for drug screening and research. Consequently, research aimed at directing pluripotent stem cells to differentiate into retinal ganglion cells has expanded dramatically during the past decade, resulting in significant advances in technique and efficiency. In this paper, we review the methodology for retinal ganglion cell differentiation from pluripotent stem cells of both mouse and human origin and summarize how these techniques have opened up new avenues for modelling glaucoma. Generation of stem cell–derived retinal ganglion cells will have significant translational values, providing an in vitro platform to study the mechanisms responsible for pathogenesis and for drug screening to improve treatment options, as well as for the development of cell therapies for optic neuropathies such as glaucoma. PMID:25774327

  8. Bioprinting for stem cell research.

    PubMed

    Tasoglu, Savas; Demirci, Utkan

    2013-01-01

    Recently, there has been growing interest in applying 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 biomolecules 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 cells of interest for genomic analysis. Here, we review recent achievements with bioprinting technologies in stem cell research, and identify future challenges and potential applications including tissue engineering and regenerative medicine, wound healing, and genomics. PMID:23260439

  9. 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

  10. Stem cells for spine surgery

    PubMed Central

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

    2015-01-01

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

  11. 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. PMID:25621119

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

    PubMed Central

    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

  13. 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

  14. Stem cell mitochondria during aging.

    PubMed

    Min-Wen, Jason Chua; Jun-Hao, Elwin Tan; Shyh-Chang, Ng

    2016-04-01

    Mitochondria are the central hubs of cellular metabolism, equipped with their own mitochondrial DNA (mtDNA) blueprints to direct part of the programming of mitochondrial oxidative metabolism and thus reactive oxygen species (ROS) levels. In stem cells, many stem cell factors governing the intricate balance between self-renewal and differentiation have been found to directly regulate mitochondrial processes to control stem cell behaviors during tissue regeneration and aging. Moreover, numerous nutrient-sensitive signaling pathways controlling organismal longevity in an evolutionarily conserved fashion also influence stem cell-mediated tissue homeostasis during aging via regulation of stem cell mitochondria. At the genomic level, it has been demonstrated that heritable mtDNA mutations and variants affect mammalian stem cell homeostasis and influence the risk for human degenerative diseases during aging. Because such a multitude of stem cell factors and signaling pathways ultimately converge on the mitochondria as the primary mechanism to modulate cellular and organismal longevity, it would be most efficacious to develop technologies to therapeutically target and direct mitochondrial repair in stem cells, as a unified strategy to combat aging-related degenerative diseases in the future. PMID:26851627

  15. When stem cells meet immunoregulation.

    PubMed

    Tasso, Roberta; Pennesi, Giuseppina

    2009-05-01

    The clinical use of stem cells to prevent tissue injury or reconstruct damaged organs is constrained by different ethical and biological issues. Whereas the use of adult stem cells isolated from differentiated tissues is advantageous from the ethical point of view, the immune response of a host to implants of either embryonic or adult stem cells remains a critical problem. Embryonic stem cells can be rejected by an immunocompetent recipient as well as some types of adult stem cells. There is, however, a population of adult stem cells able to differentiate into the three mesenchymal lineages, osteocytes, chondrocytes, adipocytes that have the additional capacity of modulating the immune response by the activation of disparate mechanisms, among which the generation of antigen-specific CD4(+)CD25(+)FoxP3(+) regulatory T lymphocytes. This short review will focus on the immunological properties of embryonic and adult stem cells are, with particular emphasis on the immunomodulatory function of mesenchymal stem cells and their interactions with regulatory T lymphocytes. PMID:19539568

  16. Blood and Marrow Stem Cell Transplant

    MedlinePlus

    ... on Twitter. What Is a Blood and Marrow Stem Cell Transplant? A blood and marrow stem cell transplant ... NEXT >> Updated: November 15, 2011 Blood and Marrow Stem Cell Transplant in the News May 19, 2015 New ...

  17. What's It Like to Donate Stem Cells?

    MedlinePlus

    ... To learn more What’s it like to donate stem cells? People usually volunteer to donate stem cells for ... an autologous transplant. If you want to donate stem cells for someone else People who want to donate ...

  18. Generating cartilage repair from pluripotent stem cells.

    PubMed

    Cheng, Aixin; Hardingham, Timothy E; Kimber, Susan J

    2014-08-01

    The treatment of degeneration and injury of articular cartilage has been very challenging for scientists and surgeons. As an avascular and hypocellular tissue, cartilage has a very limited capacity for self-repair. Chondrocytes are the only cell type in cartilage, in which they are surrounded by the extracellular matrix that they secrete and assemble. Autologous chondrocyte implantation for cartilage defects has achieved good results, but the limited resources and complexity of the procedure have hindered wider application. Stem cells form an alternative to chondrocytes as a source of chondrogenic cells due to their ability to proliferate extensively while retaining the potential for differentiation. Adult stem cells such as mesenchymal stem cells have been differentiated into chondrocytes, but the limitations in their proliferative ability and the heterogeneous cell population hinder their adoption as a prime alternative source for generating chondrocytes. Human embryonic stem cells (hESCs) are attractive as candidates for cell replacement therapy because of their unlimited self-renewal and ability for differentiation into mesodermal derivatives as well as other lineages. In this review, we focus on current protocols for chondrogenic differentiation of ESCs, in particular the chemically defined culture system developed in our lab that could potentially be adapted for clinical application. PMID:23957872

  19. 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

  20. Stem cell mechanics: Auxetic nuclei

    NASA Astrophysics Data System (ADS)

    Wang, Ning

    2014-06-01

    The nuclei of naive mouse embryonic stem cells that are transitioning towards differentiation expand when the cells are stretched and contract when they are compressed. What drives this auxetic phenotype is, however, unclear.

  1. Metabolic circuits in neural stem cells

    PubMed Central

    Kim, Do-Yeon; Rhee, Inmoo

    2015-01-01

    Metabolic activity indicative of cellular demand is emerging as a key player in cell fate decision. Numerous studies have demonstrated that diverse metabolic pathways have a critical role in the control of the proliferation, differentiation and quiescence of stem cells. The identification of neural stem/progenitor cells (NSPCs) and the characterization of their development and fate decision process have provided insight into the regenerative potential of the adult brain. As a result, the potential of NSPCs in cell replacement therapies for neurological diseases is rapidly growing. The aim of this review is to discuss the recent findings on the crosstalk among key regulators of NSPC development and the metabolic regulation crucial for the function and cell fate decisions of NSPCs. Fundamental understanding of the metabolic circuits in NSPCs may help to provide novel approaches for reactivating neurogenesis to treat degenerative brain conditions and cognitive decline. PMID:25037158

  2. Stem cell sources for cardiac regeneration.

    PubMed

    Roccio, M; Goumans, M J; Sluijter, J P G; Doevendans, P A

    2008-03-01

    Cell-based cardiac repair has the ambitious aim to replace the malfunctioning cardiac muscle developed after myocardial infarction, with new contractile cardiomyocytes and vessels. Different stem cell populations have been intensively studied in the last decade as a potential source of new cardiomyocytes to ameliorate the injured myocardium, compensate for the loss of ventricular mass and contractility and eventually restore cardiac function. An array of cell types has been explored in this respect, including skeletal muscle, bone marrow derived stem cells, embryonic stem cells (ESC) and more recently cardiac progenitor cells. The best-studied cell types are mouse and human ESC cells, which have undisputedly been demonstrated to differentiate into cardiomyocyte and vascular lineages and have been of great help to understand the differentiation process of pluripotent cells. However, due to their immunogenicity, risk of tumor development and the ethical challenge arising from their embryonic origin, they do not provide a suitable cell source for a regenerative therapy approach. A better option, overcoming ethical and allogenicity problems, seems to be provided by bone marrow derived cells and by the recently identified cardiac precursors. This report will overview current knowledge on these different cell types and their application in cardiac regeneration and address issues like implementation of delivery methods, including tissue engineering approaches that need to be developed alongside. PMID:18427385

  3. Twenty-five years of peripheral blood stem cell transplantation.

    PubMed

    Körbling, Martin; Freireich, Emil J

    2011-06-16

    Peripheral blood stem cell transplantation (PBSCT) is the most common transplantation procedure performed in medicine. Its clinical introduction in 1986 replaced BM as a stem-cell source to approximately 100% in the autologous and to approximately 75% in the allogeneic transplantation setting. This historical overview provides a brief insight into the discovery of circulating hematopoietic stem cells in the early 1960s, the development of apheresis technology, the discovery of hematopoietic growth factors and small molecule CXCR4 antagonist for stem- cell mobilization, and in vivo experimental transplantation studies that eventually led to clinical PBSCT. Also mentioned are the controversies surrounding the engraftment potential of circulating stem cells before acceptance as a clinical modality. Clinical trials comparing the outcome of PBSCT with BM transplantation, registry data analyses, and the role of the National Marrow Donor Program (NMDP) in promoting unrelated blood stem-cell donation are addressed. PMID:21460243

  4. Stem cells in burn eschar.

    PubMed

    van der Veen, Vincent C; Vlig, Marcel; van Milligen, Florine J; de Vries, Sharon I; Middelkoop, Esther; Ulrich, Magda M W

    2012-01-01

    This study compares mesenchymal cells isolated from excised burn wound eschar with adipose-derived stem cells (ASCs) and dermal fibroblasts in their ability to conform to the requirements for multipotent mesenchymal stem cells (MSCs). A population of multipotent stem cells in burn eschar could be an interesting resource for tissue engineering approaches to heal burn wounds. Cells from burn eschar, dermis, and adipose tissue were assessed for relevant CD marker profiles using flow cytometry and for their trilineage differentiation ability in adipogenic, osteogenic, and chondrogenic conditions. Although the different cell types did not differ significantly in their CD marker expression, the eschar-derived cells and ASCs readily differentiated into adipocytes, osteoblasts, and chondrocytes, while dermal fibroblasts only exhibited some chondrogenic potential. We conclude that the eschar-derived mesenchymal cells represent a population of multipotent stem cells. The origin of the cells from burn eschar remains unclear, but it is likely they represent a population of adult stem cells mobilized from other parts of the body in response to the burn injury. Their resemblance to ASCs could also be cause for speculation that in deep burns the subcutaneous adipose tissue might be an important stem cell source for the healing wound. PMID:21944933

  5. 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

  6. Stem cells for tooth engineering.

    PubMed

    Bluteau, G; Luder, H U; De Bari, C; Mitsiadis, T A

    2008-01-01

    Tooth development results from sequential and reciprocal interactions between the oral epithelium and the underlying neural crest-derived mesenchyme. The generation of dental structures and/or entire teeth in the laboratory depends upon the manipulation of stem cells and requires a synergy of all cellular and molecular events that finally lead to the formation of tooth-specific hard tissues, dentin and enamel. Although mesenchymal stem cells from different origins have been extensively studied in their capacity to form dentin in vitro, information is not yet available concerning the use of epithelial stem cells. The odontogenic potential resides in the oral epithelium and thus epithelial stem cells are necessary for both the initiation of tooth formation and enamel matrix production. This review focuses on the different sources of stem cells that have been used for making teeth in vitro and their relative efficiency. Embryonic, post-natal or even adult stem cells were assessed and proved to possess an enormous regenerative potential, but their application in dental practice is still problematic and limited due to various parameters that are not yet under control such as the high risk of rejection, cell behaviour, long tooth eruption period, appropriate crown morphology and suitable colour. Nevertheless, the development of biological approaches for dental reconstruction using stem cells is promising and remains one of the greatest challenges in the dental field for the years to come. PMID:18671204

  7. Targeting Breast Cancer Stem Cells

    PubMed Central

    Liu, Suling; Wicha, Max S.

    2010-01-01

    There is increasing evidence that many cancers, including breast cancer, contain populations of cells that display stem-cell properties. These breast cancer stem cells, by virtue of their relative resistance to radiation and cytotoxic chemotherapy, may contribute to treatment resistance and relapse. The elucidation of pathways that regulate these cells has led to the identification of potential therapeutic targets. A number of agents capable of targeting breast cancer stem cells in preclinical models are currently entering clinical trials. Assessment of the efficacy of the agents will require development of innovative clinical trial designs with appropriate biologic and clinical end points. The effective targeting of breast cancer stem cells has the potential to significantly improve outcome for women with both early-stage and advanced breast cancer. PMID:20498387

  8. Human skeletal muscle-derived stem cells retain stem cell properties after expansion in myosphere culture

    SciTech Connect

    Wei, Yan; Department of Otolaryngology, Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guang Zhou ; Li, Yuan; Chen, Chao; Stoelzel, Katharina; Kaufmann, Andreas M.

    2011-04-15

    Human skeletal muscle contains an accessible adult stem-cell compartment in which differentiated myofibers are maintained and replaced by a self-renewing stem cell pool. Previously, studies using mouse models have established a critical role for resident stem cells in skeletal muscle, but little is known about this paradigm in human muscle. Here, we report the reproducible isolation of a population of cells from human skeletal muscle that is able to proliferate for extended periods of time as floating clusters of rounded cells, termed 'myospheres' or myosphere-derived progenitor cells (MDPCs). The phenotypic characteristics and functional properties of these cells were determined using reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry and immunocytochemistry. Our results showed that these cells are clonogenic, express skeletal progenitor cell markers Pax7, ALDH1, Myod, and Desmin and the stem cell markers Nanog, Sox2, and Oct3/4 significantly elevated over controls. They could be maintained proliferatively active in vitro for more than 20 weeks and passaged at least 18 times, despite an average donor-age of 63 years. Individual clones (4.2%) derived from single cells were successfully expanded showing clonogenic potential and sustained proliferation of a subpopulation in the myospheres. Myosphere-derived cells were capable of spontaneous differentiation into myotubes in differentiation media and into other mesodermal cell lineages in induction media. We demonstrate here that direct culture and expansion of stem cells from human skeletal muscle is straightforward and reproducible with the appropriate technique. These cells may provide a viable resource of adult stem cells for future therapies of disease affecting skeletal muscle or mesenchymal lineage derived cell types.

  9. Dental pulp stem cell (DPSC) isolation, characterization, and differentiation.

    PubMed

    Ferro, Federico; Spelat, Renza; Baheney, Chelsea S

    2014-01-01

    Dental pulp stem cells (DPSC) have been proposed as an alternative to pluripotent stem cells to study multilineage differentiation in vitro and for therapeutic application. Standard culture media for isolation and expansion of stem cells includes animal sera or animal-derived matrix components (e.g., Matrigel(®)). However, animal-derived reagents raise significant concerns with respect to the translational ability of these cells due to the possibility of infection and/or severe immune reaction. For these reasons clinical grade substitutes to animal components are needed in order for stem cells to reach their full therapeutic potential. In this chapter we detail a method for isolation and proliferation of DPSC in a chemically defined medium containing a low percentage of human serum. We demonstrate that in this defined culture medium a 1.25 % human serum component sufficiently replaces fetal bovine serum. This method allows for isolation of a morphologically and phenotypically uniform population of DPSCs from dental pulp tissue. DPSCs represent a rapidly proliferating cell population that readily differentiates into the osteoblastic, neuronal, myocytic, and hepatocytic lineages. This multilineage capacity of these DPSCs suggests that they may have a more broad therapeutic application than lineage-restricted adult stem cell populations such as mesenchymal stem cells. Further the culture protocol presented here makes these cells more amenable to human application than current expansion techniques for other pluripotent stem cells (embryonic stem cell lines or induced pluripotent stem cells). PMID:25173163

  10. 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

  11. Dispelling Stem-Cell Ideology.

    PubMed

    Shrader-Frechette, Kristin

    2016-05-01

    Week-old embryos are considered the richest source of stem cells usable in medical treatments. Because the embryos are destroyed when the stem cells are removed, the debate over the embryo's legal, moral, political, and scientific status has exploded. In this debate, Sheldon Krimsky's Stem Cell Dialogues: A Philosophical and Scientific Inquiry into Medical Frontiers (Columbia UP, 2015) is the single best book. Evenhanded, eminently readable, up to date, educational, scientifically precise, powerfully researched, and very entertaining, Krimsky's slim volume is one that no scientist, policy-maker, ethicist, or intelligent reader should miss. PMID:27150419

  12. 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

  13. Sources of Stem Cells for Transplant

    MedlinePlus

    ... Topic Donor matching for allogeneic transplant Sources of stem cells for transplant There are 3 possible sources of ... cord blood transplants are being actively studied. Which stem cell source is best? All 3 sources of stem ...

  14. Understanding the cancer stem cell

    PubMed Central

    Bomken, S; Fier, K; Heidenreich, O; Vormoor, J

    2010-01-01

    The last 15 years has seen an explosion of interest in the cancer stem cell (CSC). Although it was initially believed that only a rare population of stem cells are able to undergo self-renewing divisions and differentiate to form all populations within a malignancy, a recent work has shown that these cells may not be as rare as thought first, at least in some malignancies. Improved experimental models are beginning to uncover a less rigid structure to CSC biology, in which the concepts of functional plasticity and clonal evolution must be incorporated into the traditional models. Slowly the genetic programmes and biological processes underlying stem cell biology are being elucidated, opening the door to the development of drugs targeting the CSC. The aim of ongoing research to understand CSCs is to develop novel stem cell-directed treatments, which will reduce therapy resistance, relapse and the toxicity associated with current, non-selective agents. PMID:20664590

  15. Stem cells-the hidden treasure: A strategic review.

    PubMed

    Chopra, Hitesh; Hans, Manoj Kumar; Shetty, Shashit

    2013-07-01

    In today's scenario, medical and dental professionals face a mammoth task while treating perplexing medical situations like organ failure or tissue loss. Though, different strategies exist to replace them, but ideal one is the same natural tissue or organ. In this aspect, stem cells have emerged in a promising way to provide an ideal replacement. There are different types of stem cells starting from the embryonic stage referred to as human embryonic stem cells to adult stem cells. Though in dentistry stem cell research is lagging as compared to the medical field but still a lot progress has been achieved in recent years. The stem cells have been isolated from dental pulp, human exfoliated deciduous teeth, and apical papilla and so on. These stem cells have provided exciting results like dentin-pulp regeneration, periodontal regeneration but ambiguity still prevails. As a result, much has to be further researched before its clinical application becomes a reality. Hence, these stem cells opened a new avenue in the field of regenerative dentistry. PMID:24130574

  16. Stem cell population asymmetry can reduce rate of replicative aging.

    PubMed

    Hormoz, Sahand

    2013-08-21

    Cycling tissues such as the intestinal epithelium, germ line, and hair follicles, require a constant flux of differentiated cells. These tissues are maintained by a population of stem cells, which generate differentiated progenies and self-renew. Asymmetric division of each stem cell into one stem cell and one differentiated cell can accomplish both tasks. However, in mammalian cycling tissues, some stem cells divide symmetrically into two differentiated cells and are replaced by a neighbor that divides symmetrically into two stem cells. Besides this heterogeneity in fate (population asymmetry), stem cells also exhibit heterogenous proliferation-rates; in the long run, however, all stem cells proliferate at the same average rate (equipotency). We construct and simulate a mathematical model based on these experimental observations. We show that the complex steady-state dynamics of population-asymmetric stem cells reduces the rate of replicative aging of the tissue-potentially lowering the incidence of somatic mutations and genetics diseases such as cancer. Essentially, slow-dividing stem cells proliferate and purge the population of the fast-dividing - older - cells which had undertaken the majority of the tissue-generation burden. As the number of slow-dividing cells grows, their cycling-rate increases, eventually turning them into fast-dividers, which are themselves replaced by newly emerging slow-dividers. Going beyond current experiments, we propose a mechanism for equipotency that can potentially halve the rate of replicative aging. Our results highlight the importance of a population-level understanding of stem cells, and may explain the prevalence of population asymmetry in a wide variety of cycling tissues. PMID:23623948

  17. Once Upon a Stem Cell

    MedlinePlus

    ... of nutrients and proteins that spurred human embryonic stem cells to become heart progenitor cells, or adult heart cells in their beginning stages. Those cells then grew into the three different types that make up functioning heart muscle. This work advances our understanding of how the ...

  18. Diabetes and Stem Cell Function

    PubMed Central

    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. PMID:26075247

  19. Donating Peripheral Blood Stem Cells

    MedlinePlus

    ... and recovery with PBSC donation Jeff, peripheral blood stem cell (PBSC) donor, explains the donation process. You may experience headaches, or bone or muscle aches, for several days before PBSC donation. These ...

  20. Human embryonic stem cells and cardiac repair.

    PubMed

    Zhu, Wei-Zhong; Hauch, Kip D; Xu, Chunhui; Laflamme, Michael A

    2009-01-01

    The muscle lost after a myocardial infarction is replaced with noncontractile scar tissue, often initiating heart failure. Whole-organ cardiac transplantation is the only currently available clinical means of replacing the lost muscle, but this option is limited by the inadequate supply of donor hearts. Thus, cell-based cardiac repair has attracted considerable interest as an alternative means of ameliorating cardiac injury. Because of their tremendous capacity for expansion and unquestioned cardiac potential, pluripotent human embryonic stem cells (hESCs) represent an attractive candidate cell source for obtaining cardiomyocytes and other useful mesenchymal cell types for such therapies. Human embryonic stem cell-derived cardiomyocytes exhibit a committed cardiac phenotype and robust proliferative capacity, and recent testing in rodent infarct models indicates that they can partially remuscularize injured hearts and improve contractile function. Although the latter successes give good reason for optimism, considerable challenges remain in the successful application of hESCs to cardiac repair, including the need for preparations of high cardiac purity, improved methods of delivery, and approaches to overcome immune rejection and other causes of graft cell death. This review will describe the phenotype of hESC-derived cardiomyocytes and preclinical experience with these cells and will consider strategies to overcoming the aforementioned challenges. PMID:18657407

  1. Immunotargeting of cancer stem cells

    PubMed Central

    Gąbka-Buszek, Agnieszka; Jankowski, Jakub; Mackiewicz, Andrzej

    2015-01-01

    Cancer stem cells (CSCs) represent a distinctive population of tumour cells that control tumour initiation, progression, and maintenance. Their influence is great enough to risk the statement that successful therapeutic strategy must target CSCs in order to eradicate the disease. Because cancer stem cells are highly resistant to chemo- and radiotherapy, new tools to fight against cancer have to be developed. Expression of antigens such as ALDH, CD44, EpCAM, or CD133, which distinguish CSCs from normal cells, together with CSC immunogenicity and relatively low toxicity of immunotherapies, makes immune targeting of CSCs a promising approach for cancer treatment. This review will present immunotherapeutic approaches using dendritic cells, T cells, pluripotent stem cells, and monoclonal antibodies to target and eliminate CSCs. PMID:25691822

  2. Tracking stem cells in the cardiovascular system.

    PubMed

    Chemaly, Elie R; Yoneyama, Ryuichi; Frangioni, John V; Hajjar, Roger J

    2005-11-01

    Stem cells are a promising approach to cardiovascular therapeutics. Animal experiments have assessed the fate of injected stem cells through ex vivo methods on sacrificed animals. Approaches are needed for in vivo tracking of stem cells. Various imaging techniques and contrast agents for stem cell tracking will be reviewed. PMID:16297767

  3. Immune Modulation of Stem Cells and Regeneration

    PubMed Central

    Aurora, Arin B.; Olson, Eric N.

    2014-01-01

    The immune system, best known as the first line of defense against invading pathogens, is integral to tissue development, homeostasis and wound repair. In recent years, there has been a growing appreciation that cellular and humoral components of the immune system also contribute to regeneration of damaged tissues, including limbs, skeletal muscle, heart and the nervous system. Here, we discuss key findings that implicate inflammatory cells and their secreted factors in tissue replacement following injury via stem cells and other reparative mechanisms. We highlight clinical conditions that are amenable to immune-mediated regeneration and suggest immune targeting strategies for tissue regeneration. PMID:24996166

  4. Plasticity of spermatogonial stem cells.

    PubMed

    Cooke, Paul S; Simon, Liz; Nanjappa, Manjunatha K; Medrano, Theresa I; Berry, Suzanne E

    2015-01-01

    There have been significant breakthroughs over the past decade in the development and use of pluripotent stem cells as a potential source of cells for applications in regenerative medicine. It is likely that this methodology will begin to play an important role in human clinical medicine in the years to come. This review describes the plasticity of one type of pluripotent cell, spermatogonial stem cells (SSCs), and their potential therapeutic applications in regenerative medicine and male infertility. Normally, SSCs give rise to sperm when in the testis. However, both human and murine SSCs can give rise to cells with embryonic stem (ES) cell-like characteristics that can be directed to differentiate into tissues of all three embryonic germ layers when placed in an appropriate inductive microenvironment, which is in contrast to other postnatal stem cells. Previous studies have reported that SSCs expressed an intermediate pluripotent phenotype before differentiating into a specific cell type and that extended culture was necessary for this to occur. However, recent studies from our group using a tissue recombination model demonstrated that SSCs differentiated rapidly into another tissue, in this case, prostatic epithelium, without expression of pluripotent ES cell markers before differentiation. These results suggest that SSCs are capable of directly differentiating into other cell types without going through an intermediate ES cell-like stage. Because SSCs do not require reprogramming to achieve a pluripotent state, they are an attractive source of pluripotent cells for use in regenerative medicine. PMID:25677134

  5. Plasticity of spermatogonial stem cells

    PubMed Central

    Cooke, Paul S; Simon, Liz; Nanjappa, Manjunatha K; Medrano, Theresa I; Berry, Suzanne E

    2015-01-01

    There have been significant breakthroughs over the past decade in the development and use of pluripotent stem cells as a potential source of cells for applications in regenerative medicine. It is likely that this methodology will begin to play an important role in human clinical medicine in the years to come. This review describes the plasticity of one type of pluripotent cell, spermatogonial stem cells (SSCs), and their potential therapeutic applications in regenerative medicine and male infertility. Normally, SSCs give rise to sperm when in the testis. However, both human and murine SSCs can give rise to cells with embryonic stem (ES) cell-like characteristics that can be directed to differentiate into tissues of all three embryonic germ layers when placed in an appropriate inductive microenvironment, which is in contrast to other postnatal stem cells. Previous studies have reported that SSCs expressed an intermediate pluripotent phenotype before differentiating into a specific cell type and that extended culture was necessary for this to occur. However, recent studies from our group using a tissue recombination model demonstrated that SSCs differentiated rapidly into another tissue, in this case, prostatic epithelium, without expression of pluripotent ES cell markers before differentiation. These results suggest that SSCs are capable of directly differentiating into other cell types without going through an intermediate ES cell-like stage. Because SSCs do not require reprogramming to achieve a pluripotent state, they are an attractive source of pluripotent cells for use in regenerative medicine. PMID:25677134

  6. Pluripotent stem cells in mice.

    PubMed

    Schmidt, Rainer; Scheubert, Lena; Lustrek, Mitja; Repsilber, Dirk; Fuellen, Georg

    2012-01-01

    Pluripotent stem cells are able to self-renew and to differentiate into all adult cell types. Many studies report data describing these cells and characterize them in molecular terms. Gene expression data of pluripotent and non-pluripotent cells from mouse were assembled. Machine learning was applied to classify samples into pluripotent and non-pluripotent cells. To identify minimal sets of best biomarkers, three methods were used: information gain, random forests, and genetic algorithm. PMID:22874386

  7. Lost in translation: pluripotent stem cell-derived hematopoiesis.

    PubMed

    Ackermann, Mania; Liebhaber, Steffi; Klusmann, Jan-Henning; Lachmann, Nico

    2015-11-01

    Pluripotent stem cells (PSCs) such as embryonic stem cells or induced pluripotent stem cells represent a promising cell type to gain novel insights into human biology. Understanding the differentiation process of PSCs in vitro may allow for the identification of cell extrinsic/intrinsic factors, driving the specification process toward all cell types of the three germ layers, which may be similar to the human in vivo scenario. This would not only lay the ground for an improved understanding of human embryonic development but would also contribute toward the generation of novel cell types used in cell replacement therapies. In this line, especially the developmental process of mesodermal cells toward the hematopoietic lineage is of great interest. Therefore, this review highlights recent progress in the field of hematopoietic specification of pluripotent stem cell sources. In addition, we would like to shed light on emerging factors controlling primitive and definitive hematopoietic development and to highlight recent approaches to improve the differentiation potential of PSC sources toward hematopoietic stem/progenitor cells. While the generation of fully defined hematopoietic stem cells from PSCs remains challenging in vitro, we here underline the instructive role of cell extrinsic factors such as cytokines for the generation of PSC-derived mature hematopoietic cells. Thus, we have comprehensively examined the role of cytokines for the derivation of mature hematopoietic cell types such as macrophages, granulocytes, megakaryocytes, erythrocytes, dendritic cells, and cells of the B- and T-cell lineage. PMID:26174486

  8. Lost in translation: pluripotent stem cell-derived hematopoiesis

    PubMed Central

    Ackermann, Mania; Liebhaber, Steffi; Klusmann, Jan-Henning; Lachmann, Nico

    2015-01-01

    Pluripotent stem cells (PSCs) such as embryonic stem cells or induced pluripotent stem cells represent a promising cell type to gain novel insights into human biology. Understanding the differentiation process of PSCs in vitro may allow for the identification of cell extrinsic/intrinsic factors, driving the specification process toward all cell types of the three germ layers, which may be similar to the human in vivo scenario. This would not only lay the ground for an improved understanding of human embryonic development but would also contribute toward the generation of novel cell types used in cell replacement therapies. In this line, especially the developmental process of mesodermal cells toward the hematopoietic lineage is of great interest. Therefore, this review highlights recent progress in the field of hematopoietic specification of pluripotent stem cell sources. In addition, we would like to shed light on emerging factors controlling primitive and definitive hematopoietic development and to highlight recent approaches to improve the differentiation potential of PSC sources toward hematopoietic stem/progenitor cells. While the generation of fully defined hematopoietic stem cells from PSCs remains challenging in vitro, we here underline the instructive role of cell extrinsic factors such as cytokines for the generation of PSC-derived mature hematopoietic cells. Thus, we have comprehensively examined the role of cytokines for the derivation of mature hematopoietic cell types such as macrophages, granulocytes, megakaryocytes, erythrocytes, dendritic cells, and cells of the B- and T-cell lineage. PMID:26174486

  9. Cell replacement and visual restoration by retinal sheet transplants

    PubMed Central

    Seiler, Magdalene J.; Aramant, Robert B.

    2012-01-01

    Retinal diseases such as age-related macular degeneration (ARMD) and retinitis pigmentosa (RP) affect millions of people. Replacing lost cells with new cells that connect with the still functional part of the host retina might repair a degenerating retina and restore eyesight to an unknown extent. A unique model, subretinal transplantation of freshly dissected sheets of fetal-derived retinal progenitor cells, combined with its retinal pigment epithelium (RPE), has demonstrated successful results in both animals and humans. Most other approaches are restricted to rescue endogenous retinal cells of the recipient in earlier disease stages by a ‘nursing’ role of the implanted cells and are not aimed at neural retinal cell replacement. Sheet transplants restore lost visual responses in several retinal degeneration models in the superior colliculus (SC) corresponding to the location of the transplant in the retina. They do not simply preserve visual performance – they increase visual responsiveness to light. Restoration of visual responses in the SC can be directly traced to neural cells in the transplant, demonstrating that synaptic connections between transplant and host contribute to the visual improvement. Transplant processes invade the inner plexiform layer of the host retina and form synapses with presumable host cells. In a Phase II trial of RP and ARMD patients, transplants of retina together with its RPE improved visual acuity. In summary, retinal progenitor sheet transplantation provides an excellent model to answer questions about how to repair and restore function of a degenerating retina. Supply of fetal donor tissue will always be limited but the model can set a standard and provide an informative base for optimal cell replacement therapies such as embryonic stem cell (ESC)-derived therapy. PMID:22771454

  10. Adult stem cell-based apexogenesis

    PubMed Central

    Li, Yao; Shu, Li-Hong; Yan, Ming; Dai, Wen-Yong; Li, Jun-Jun; Zhang, Guang-Dong; Yu, Jin-Hua

    2014-01-01

    Generally, the dental pulp needs to be removed when it is infected, and root canal therapy (RCT) is usually required in which infected dental pulp is replaced with inorganic materials (paste and gutta percha). This treatment approach ultimately brings about a dead tooth. However, pulp vitality is extremely important to the tooth itself, since it provides nutrition and acts as a biosensor to detect the potential pathogenic stimuli. Despite the reported clinical success rate, RCT-treated teeth are destined to be devitalized, brittle and susceptible to postoperative fracture. Recently, the advances and achievements in the field of stem cell biology and regenerative medicine have inspired novel biological approaches to apexogenesis in young patients suffering from pulpitis or periapical periodontitis. This review mainly focuses on the benchtop and clinical regeneration of root apex mediated by adult stem cells. Moreover, current strategies for infected pulp therapy are also discussed here. PMID:25332909

  11. 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

  12. 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

  13. 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

  14. Biomaterial Approaches for Stem Cell-Based Myocardial Tissue Engineering

    PubMed Central

    Cutts, Josh; Nikkhah, Mehdi; Brafman, David A

    2015-01-01

    Adult and pluripotent stem cells represent a ready supply of cellular raw materials that can be used to generate the functionally mature cells needed to replace damaged or diseased heart tissue. However, the use of stem cells for cardiac regenerative therapies is limited by the low efficiency by which stem cells are differentiated in vitro to cardiac lineages as well as the inability to effectively deliver stem cells and their derivatives to regions of damaged myocardium. In this review, we discuss the various biomaterial-based approaches that are being implemented to direct stem cell fate both in vitro and in vivo. First, we discuss the stem cell types available for cardiac repair and the engineering of naturally and synthetically derived biomaterials to direct their in vitro differentiation to the cell types that comprise heart tissue. Next, we describe biomaterial-based approaches that are being implemented to enhance the in vivo integration and differentiation of stem cells delivered to areas of cardiac damage. Finally, we present emerging trends of using stem cell-based biomaterial approaches to deliver pro-survival factors and fully vascularized tissue to the damaged and diseased cardiac tissue. PMID:26052226

  15. Induced stem cells as a novel multiple sclerosis therapy

    PubMed Central

    Xie, Chong; Liu, Yan-qun; Guan, Yang-tai; Zhang, Guang-Xian

    2016-01-01

    Stem cell replacement is providing hope for many degenerative diseases that lack effective therapeutic methods including multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. Transplantation of neural stem cells or mesenchymal stem cells is a potential therapy for MS thanks to their capacity for cell repopulation as well as for their immunomodulatory and neurotrophic properties. Induced pluripotent stem cell (iPSC), an emerging cell source in regenerative medicine, is also being tested for the treatment of MS. Remarkable improvement in mobility and robust remyelination have been observed after transplantation of iPSC-derived neural cells into demyelinated models. Direct reprogramming of somatic cells into induced neural cells, such as induced neural stem cells (iNSCs) and induced oligodendrocyte progenitor cells (iOPCs), without passing through the pluripotency stage, is an alternative for transplantation that has been proved effective in the congenital hypomyelination model. iPSC technology is rapidly progressing as efforts are being made to increase the efficiency of iPSC therapy and reduce its potential side effects. In this review, we discuss the recent advances in application of stem cells, with particular focus on induced stem/progenitor cells (iPSCs, iNSC, iOPCs), which are promising in the treatment of MS. PMID:25732737

  16. [The hematopoietic stem cell niche].

    PubMed

    Kunisaki, Yuya

    2015-10-01

    Somatic stem cells self-renew to maintain tissue homeostasis for the lifetime of organisms through tightly controlled proliferation and differentiation. Hematopoietic stem cells (HSCs) are essentially required for hematopoietic homeostasis. Therefore, they not only ensure lifelong replenishment of all blood lineages, but also maintain a constant pool. Cell cycle quiescence is a critical feature contributing to stem cell maintenance. Recent studies have highlighted the importance of bone marrow (BM) microenvironments that regulate HSC functions (HSC niches). In the HSC field, there has been considerable interest and debate regarding whether or not quiescence and proliferation of HSCs is regulated by distinct niches. Previous reports suggest that quiescent HSCs reside near osteoblasts in the BM whereas actively cycling HSCs are found near sinusoids. However, this popular concept has not been supported by rigorous analyses. To gain more insight into the spatial localization of HSCs, we have developed a whole-mount staining technique that allows precise measurements of 3D distances of HSCs from structures and allows computational simulation to define the significance of these interactions. This novel approach has allowed us to uncover two distinct types of vessels associated with quiescent and proliferating HSCs and to underscore the importance of arteriolar vessels for stem cell quiescence. We will discuss the crosstalk between the two hematopoietic and mesenchymal stem cells with a review of the recent literature. PMID:26458426

  17. [Human pluripotent stem cell and neural differentiation].

    PubMed

    Wataya, Takafumi; Muguruma, Keiko; Sasai, Yoshiki

    2008-10-01

    Recovery of lost brain function is an important issue in medical studies because neurons of the central nervous system (CNS) have poor potential for regeneration. Since few CNS diseases can be treated completely by medicines, regenerative therapy by using stem cells should be studied as a new type of therapeutic intervention. The efficacy of cell replacement therapy in Parkinson's disease has been well investigated. Several studies on fetal tissue transplantation have revealed that quantity and purity of transplanted cells are necessary for recovery of symptoms. SFEB (Serum-free floating culture of embryoid body-like aggregates) method is capable of inducing multi-potential CNS progenitors that can be steered to differentiate into region-specific tissues. On the basis of the existing knowledge of embryology, we have succeeded in the generating of various types of neurons such as telencephalic, cerebeller (Purkinje and granule cells), retinal (photoreceptor cells) and hypothalamic neurons. Application of this culture method to human ES (hES) cells is necessary for clinical purpose: however, poor survival of hES cells in SFEB culture might limit the possibility of using these cells for future medical applications. We found that a selective Rho-associated kinase (ROCK) inhibitor, Y-27632, markedly diminished the dissociation-induced apoptosis of hES cells and enabled the cells to form aggregates in SFEB culture. For both mouse and human ES cells, SFEB culture is a favorable method that can generate large amounts of region-specific neurons. However, stem cell-based therapy continues to face several obstacles. It is important that researchers in the basic sciences and clinical medicine should discuss these problems together to overcome both scientific and ethical issues related to stem cells. PMID:18975604

  18. [Therapeutic use of stem cells].

    PubMed

    Uzan, Georges

    2004-09-15

    Stem cells display important capacities of self renewing, proliferation and differentiation. Because those present in the embryo have the more remarkable properties, their potential use in the therapy of until now incurable degenerative diseases have been envisioned. Embryonic stem (ES) cells are located in the inner mass of the balstocyst at early stages of the development. Even in long-term cultures they still retain their undifferentiated features. Under specific culture conditions, ES cells can be committed into a variety of differentiation pathways, giving rise to large amounts of cells corresponding to different tissues (neurones, cardiomyocytes, skeletal muscle, etc.). However, producing these tissues from already established ES cell lines would lead to immune rejection when transplanted to patients. To prevent this pitfall and using the expertise accumulated by animal cloning by nucleus transfer, it has been proposed to adapt this technique to human ES cells. The therapeutic cloning consists in transferring the nucleus of somatic stem cells isolated from the patient into an enucleated oocyte, to allow blastocyst development from which ES cells will be derived. From these stem cells, compatible tissues will be then produced. The problem is that it is in theoretically possible to reimplant the cloned blastocyst into a surrogate mother for obtaining a baby genetically identical to the donor. This is called reproductive cloning. This worrying risk raises important ethic and legal questions. PMID:15497791

  19. Characterization of pluripotent stem cells.

    PubMed

    Martí, Mercè; Mulero, Lola; Pardo, Cristina; Morera, Cristina; Carrió, Meritxell; Laricchia-Robbio, Leopoldo; Esteban, Concepcion Rodriguez; Izpisua Belmonte, Juan Carlos

    2013-02-01

    Characterization of pluripotent stem cells is required for the registration of stem cell lines and allows for an impartial and objective comparison of the results obtained when generating multiple lines. It is therefore crucial to establish specific, fast and reliable protocols to detect the hallmarks of pluripotency. Such protocols should include immunocytochemistry (takes 2 d), identification of the three germ layers in in vitro-derived embryoid bodies by immunocytochemistry (immunodetection takes 3 d) and detection of differentiation markers in in vivo-generated teratomas by immunohistochemistry (differentiation marker detection takes 4 d). Standardization of the immunodetection protocols used ensures minimum variations owing to the source, the animal species, the endogenous fluorescence or the inability to collect large amounts of cells, thereby yielding results as fast as possible without loss of quality. This protocol provides a description of all the immunodetection procedures necessary to characterize mouse and human stem cell lines in different circumstances. PMID:23306458

  20. Stem cells and periodontal regeneration.

    PubMed

    Lin, N-H; Gronthos, S; Bartold, P M

    2008-06-01

    Periodontitis is an inflammatory disease which manifests clinically as loss of supporting periodontal tissues including periodontal ligament and alveolar bone. For decades periodontists have sought ways to repair the damage which occurs during periodontitis. This has included the use of a range of surgical procedures, the use of a variety of grafting materials and growth factors, and the use of barrier membranes. To date periodontal regeneration is considered to be biologically possible but clinically unpredictable. Recently, reports have begun to emerge demonstrating that populations of adult stem cells reside in the periodontal ligament of humans and other animals. This opens the way for new cell-based therapies for periodontal regeneration. For this to become a reality a thorough understanding of adult human stem cells is needed. This review provides an overview of adult human stem cells and their potential use in periodontal regeneration. PMID:18494965

  1. Storage of hemopoietic stem cells

    PubMed Central

    Pamphilon, Derwood; Mijovic, Aleksandar

    2007-01-01

    Background: Autologous, and in some cases allogeneic, hemopoietic stem cells (HSC) are stored for varying periods of time prior to infusion. For periods of greater than 48 h, storage requires cryopreservation. It is essential to optimize cell storage and ensure the quality of the product for subsequent reinfusion. Methods: A number of important variables may affect the subsequent quality of infused HSC and therapeutic cells (TC). This review discusses these and also reviews the regulatory framework that now aims to ensure the quality of stem cells and TC for transplantation. Results: Important variables included cell concentration, temperature, interval from collection to cryopreservation, manipulations performed. They also included rate of freezing and whether controlled-rate freezing was employed. Parameters studied were type of cryoprotectant utilized [dimethyl sulphoxide (DMSO) is most commonly used, sometimes in combination with hydroxyethyl starch (HES)]; and storage conditions. It is also important to assess the quality of stored stem cells. Measurements employed included the total cell count (TNC), mononuclear cell count (MNC), CD34+ cells and colony-forming units - granulocyte macrophage (CFU-GM). Of these, TNC and CD34+ are the most useful. However, the best measure of the quality of stored stem cells is their subsequent engraftment. The quality systems used in stem cell laboratories are described in the guidance of the Joint Accreditation Committee of ISCT (Europe) and the EBMT (JACIE) and the EU Directive on Tissues and Cells plus its supporting commission directives. Inspections of facilities are carried out by the appropriate national agencies and JACIE. Conclusion: For high-quality storage of HSC and TC, processing facilities should use validated procedures that take into account critical variables. The quality of all products must be assessed before and after storage. PMID:21938237

  2. Tenascins in stem cell niches.

    PubMed

    Chiquet-Ehrismann, Ruth; Orend, Gertraud; Chiquet, Matthias; Tucker, Richard P; Midwood, Kim S

    2014-07-01

    Tenascins are extracellular matrix proteins with distinct spatial and temporal expression during development, tissue homeostasis and disease. Based on their expression patterns and knockout phenotypes an important role of tenascins in tissue formation, cell adhesion modulation, regulation of proliferation and differentiation has been demonstrated. All of these features are of importance in stem cell niches where a precise regulation of growth versus differentiation has to be guaranteed. In this review we summarize the expression and possible functions of tenascins in neural, epithelial and osteogenic stem cell niches during normal development and organ turnover, in the hematopoietic and pro-inflammatory niche as well as in the metastatic niche during cancer progression. PMID:24472737

  3. Reconstructing the stem cell debate.

    PubMed

    Sitko, Bradley J

    2002-01-01

    Human embryonic stem cells have been a major topic in science, medicine, and religion since their discovery in 1998. However, due to the complex discourse and rhetoric of scientific language, debate has remained within the professional realm via "expert bioethics." Using the tenets of pragmatism, the author examines the need to move the debate to society as a whole and disentangle the stem cell debate from the ideologies of the human cloning and abortion debates. Opening this issue to a societal debate will advance societal growth, resulting in informed decisions on moral issues, funding, or regulation associated with hES cell research. PMID:12755109

  4. Stem Cells for Periodontal Regeneration

    PubMed Central

    Pejcic, A; Kojovic, D; Mirkovic, D; Minic, I

    Periodontal regeneration is considered to be biologically possible but clinically unpredictable. In periodontitis, inflammation manifests clinically as loss of supporting periodontal tissues and regeneration of damaged tissue is the main goal of treatment. For decades, periodontists have sought to repair the damage through a variety of surgical procedures, and use of grafting materials and growth factors, and of barrier membranes. Reports have emerged that demonstrate which populations of adult stem cells reside in the periodontal ligaments of humans and other animals. This opens the way for new cell-based therapies for periodontal regeneration. This review provides an overview of adult human stem cells and their potential use in periodontal regeneration. PMID:24265588

  5. Stem cells for periodontal regeneration.

    PubMed

    Pejcic, A; Kojovic, D; Mirkovic, D; Minic, I

    2013-06-01

    Periodontal regeneration is considered to be biologically possible but clinically unpredictable. In periodontitis, inflammation manifests clinically as loss of supporting periodontal tissues and regeneration of damaged tissue is the main goal of treatment. For decades, periodontists have sought to repair the damage through a variety of surgical procedures, and use of grafting materials and growth factors, and of barrier membranes. Reports have emerged that demonstrate which populations of adult stem cells reside in the periodontal ligaments of humans and other animals. This opens the way for new cell-based therapies for periodontal regeneration. This review provides an overview of adult human stem cells and their potential use in periodontal regeneration. PMID:24265588

  6. Hematopoietic stem cells: multiparameter regulation.

    PubMed

    Song, Kedong; Li, Liying; Wang, Yiwei; Liu, Tianqing

    2016-04-01

    Hematopoietic stem cells (HSCs) are capable to self-renew with multi-potency which generated much excitement in clinical therapy. However, the main obstacle of HSCs in clinical application was insufficient number of HSCs which were derived from either bone marrow, peripheral blood or umbilical cord blood. This review briefly discusses the indispensable utility of growth factors and cytokines, stromal cells, extracellular matrix, bionic scaffold and microenvironment aiming to control the hematopoiesis in all directions and provide a better and comprehensive understanding for in vitro expansion of hematopoietic stem cells. PMID:26883144

  7. Neural stem cells: from neurobiology to clinical applications.

    PubMed

    Andressen, Christian

    2013-01-01

    In spite of increasing numbers of publications about cell replacement therapies in various neurodegenerative diseases, reports on therapeutic benefits are still rare due to the huge array of parameters affecting the clinically relevant outcome. Limiting conditions can be attributed to origin and number of cells used for transplantation, their in vitro storage, propagation and/or predifferentiation. In addition, the ability of these cells for a site directed differentiation and functional integration in sufficient numbers is known to depend on extrinsic factors including intracerebral position of graft(s). Thus, obstacles to the use of cells in replacement therapies of neurological disorders reflect the molecular as well as cellular complexity of affected functional systems. This review will highlight central aspects of cell replacement strategies that are currently regarded as the most limiting issues in respect to survival, cell identity and site directed differentiation as well as functional integration of grafts. Special attention will be paid to neural stem cells, derived from either fetal or adult central nervous tissue. Unravelling the molecular biology of these proliferating cells in combination with instructive environmental cues for their site directed differentiation will pave the way to high reproducibility in collection, propagation, and predifferentiation of transplantable cells in vitro. In addition, this knowledge of intrinsic and extrinsic cues for a site directed neural differentiation during development will broaden the perspective for any pluripotent stem cell, namely embryonic stem and induced pluripotent stem cells, as an alternate source for a cell based therapy of neurodegenerative diseases. PMID:23092257

  8. Endometrial stem cell transplantation in MPTP- exposed primates: an alternative cell source for treatment of Parkinson's disease.

    PubMed

    Wolff, Erin F; Mutlu, Levent; Massasa, Efi E; Elsworth, John D; Eugene Redmond, D; Taylor, Hugh S

    2015-01-01

    Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. Cell-replacement therapies have emerged as a promising strategy to slow down or replace neuronal loss. Compared to other stem cell types, endometrium-derived stem cells (EDSCs) are an attractive source of stem cells for cellular therapies because of their ease of collection and vast differentiation potential. Here we demonstrate that endometrium-derived stem cells may be transplanted into an MPTP exposed monkey model of PD. After injection into the striatum, endometrium-derived stem cells engrafted, exhibited neuron-like morphology, expressed tyrosine hydroxylase (TH) and increased the numbers of TH positive cells on the transplanted side and dopamine metabolite concentrations in vivo. Our results suggest that endometrium-derived stem cells may provide a therapeutic benefit in the primate model of PD and may be used in stem cell based therapies. PMID:25283241

  9. Stem cell-based therapy for Huntington's disease.

    PubMed

    Maucksch, Christof; Vazey, Elena M; Gordon, Renee J; Connor, Bronwen

    2013-04-01

    Huntington's disease (HD) is a late-onset neurodegenerative disease characterized by a progressive loss of medium spiny neurons in the basal ganglia. The development of stem cell-based therapies for HD aims to replace lost neurons and/or to prevent cell death. This review will discuss pre-clinical studies which have utilized stem or progenitor cells for transplantation therapy using HD animal models. In several studies, neural stem and progenitor cells used as allotransplants and xenografts have been shown to be capable of surviving transplantation and differentiating into mature GABAergic neurons, resulting in behavioral improvements. Beneficial effects have also been reported for transplantation of stem cells derived from non-neural tissue, for example, mesenchymal- and adipose-derived stem cells, which have mainly been attributed to their secretion of growth and neurotrophic factors. Finally, we review studies using stem cells genetically engineered to over-express defined neurotrophic factors. While these studies prove the potential of stem cells for transplantation therapy in HD, it also becomes clear that technical and ethical issues regarding the availability of stem cells must be solved before human trials can be conducted. PMID:23097329

  10. Derivation of porcine pluripotent stem cells for biomedical research.

    PubMed

    Shiue, Yow-Ling; Yang, Jenn-Rong; Liao, Yu-Jing; Kuo, Ting-Yung; Liao, Chia-Hsin; Kang, Ching-Hsun; Tai, Chein; Anderson, Gary B; Chen, Lih-Ren

    2016-07-01

    Pluripotent stem cells including embryonic stem cells (ESCs), embryonic germ cells (EGCs), and induced pluripotent stem cells (iPSCs) are capable of self-renew and limitlessly proliferating in vitro with undifferentiated characteristics. They are able to differentiate in vitro, spontaneously or responding to suitable signals, into cells of all three primary germ layers. Consequently, these pluripotent stem cells will be valuable sources for cell replacement therapy in numerous disorders. However, the promise of human ESCs and EGCs is cramped by the ethical argument about destroying embryos and fetuses for cell line creation. Moreover, there are still carcinogenic risks existing toward the goal of clinical application for human ESCs, EGCs, and iPSCs. Therefore, a suitable animal model for stem cell research will benefit the further development of human stem cell technology. The pigs, on the basis of their similarity in anatomy, immunology, physiology, and biochemical properties, have been wide used as model animals in the study of various human diseases. The development of porcine pluripotent stem cell lines will hold the opportunity to provide an excellent material for human counterpart to the transplantation in biomedical research and further development of cell-based therapeutic strategy. PMID:27158128

  11. Learning about Cancer by Studying Stem Cells

    MedlinePlus

    ... Science Home Page Learning About Cancer by Studying Stem Cells By Sharon Reynolds Posted January 8, 2014 Normally, ... of them are exploring the process by studying stem cells. Modeling Early Pancreatic Cancer Pancreatic cancer cells grown ...

  12. Stem cell differentiation: Sticky mechanical memory

    NASA Astrophysics Data System (ADS)

    Eyckmans, Jeroen; Chen, Christopher S.

    2014-06-01

    Physical cues from the extracellular environment influence the lineage commitment of stem cells. Now, experiments on human mesenchymal stem cells cultured on photodegradable hydrogels show that the cells' fate can also be determined by past physical environments.

  13. Glioblastoma stem cells and stem cell-targeting immunotherapies.

    PubMed

    Esparza, Rogelio; Azad, Tej D; Feroze, Abdullah H; Mitra, Siddhartha S; Cheshier, Samuel H

    2015-07-01

    Advancements in immunotherapeutics promise new possibilities for the creation of glioblastoma (GBM) treatment options. Ongoing work in cancer stem cell biology has progressively elucidated the role of this tumor sub-population in oncogenesis and has distinguished them as prime therapeutic targets. Current clinical trials take a multifaceted approach with the intention of harnessing the intrinsic cytotoxic capabilities of the immune system to directly target glioblastoma cancer stem cells (gCSC) or indirectly disrupt their stromal microenvironment. Monoclonal antibodies (mAbs), dendritic cell (DC) vaccines, and chimeric antigen receptor (CAR) T cell therapies have emerged as the most common approaches, with particular iterations incorporating cancer stem cell antigenic markers in their treatment designs. Ongoing work to determine the comprehensive antigenic profile of the gCSC in conjunction with efforts to counter the immunosuppressive tumor microenvironment holds much promise in future immunotherapeutic strategies against GBM. Given recent advancements in these fields, we believe there is tremendous potential to improve outcomes of GBM patients in the continuing evolution of immunotherapies targeted to cancer stem cell populations in GBM. PMID:25682090

  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. DNA methylation and hydroxymethylation in stem cells

    PubMed Central

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

    2015-01-01

    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. PMID:25776144

  16. 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. PMID:25776144

  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. Human Retinal Pigment Epithelium Stem Cell (RPESC).

    PubMed

    Saini, Janmeet S; Temple, Sally; Stern, Jeffrey H

    2016-01-01

    The retinal pigment epithelium (RPE) is a pigmented cellular monolayer that supports photoreceptor cells located in the overlying neural retina. The RPE is critical for vision and its dysfunction results in numerous pathologies, several with limited available disease-altering strategies. Regeneration of the retina from RPE is robust in lower vertebrates, but is not normally exhibited in mammals. We recently found that a subpopulation of human RPE cells can be stimulated in culture to generate multipotent self-renewing cells-the RPE stem cell (RPESC). RPESC can be expanded to generate RPE progeny that are a potential source for cell replacement therapy. Alternatively, RPESC can produce mesenchymal progeny which serve as a disease model of epiretinal membrane formation. Yet another potential application of RPESCs is activation within the eye to awaken dormant endogenous repair. PMID:26427459

  19. Stem cell-based cell therapy in neurological diseases: a review.

    PubMed

    Kim, Seung U; de Vellis, Jean

    2009-08-01

    Human neurological disorders such as Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), Alzheimer's disease, multiple sclerosis (MS), stroke, and spinal cord injury are caused by a loss of neurons and glial cells in the brain or spinal cord. Cell replacement therapy and gene transfer to the diseased or injured brain have provided the basis for the development of potentially powerful new therapeutic strategies for a broad spectrum of human neurological diseases. However, the paucity of suitable cell types for cell replacement therapy in patients suffering from neurological disorders has hampered the development of this promising therapeutic approach. In recent years, neurons and glial cells have successfully been generated from stem cells such as embryonic stem cells, mesenchymal stem cells, and neural stem cells, and extensive efforts by investigators to develop stem cell-based brain transplantation therapies have been carried out. We review here notable experimental and preclinical studies previously published involving stem cell-based cell and gene therapies for Parkinson's disease, Huntington's disease, ALS, Alzheimer's disease, MS, stroke, spinal cord injury, brain tumor, and lysosomal storage diseases and discuss the future prospects for stem cell therapy of neurological disorders in the clinical setting. There are still many obstacles to be overcome before clinical application of cell therapy in neurological disease patients is adopted: 1) it is still uncertain what kind of stem cells would be an ideal source for cellular grafts, and 2) the mechanism by which transplantation of stem cells leads to an enhanced functional recovery and structural reorganization must to be better understood. Steady and solid progress in stem cell research in both basic and preclinical settings should support the hope for development of stem cell-based cell therapies for neurological diseases. PMID:19301431

  20. Neural stem and progenitor cells in health and disease

    PubMed Central

    Ladran, Ian; Tran, Ngoc; Topol, Aaron; Brennand, Kristen J.

    2014-01-01

    Neural stem/progenitor cells (NSPCs) have the potential to differentiate into neurons, astrocytes, and/or oligodendrocytes. Because these cells can be expanded in culture, they represent a vast source of neural cells. With the recent discovery that patient fibroblasts can be reprogrammed directly into induced NSPCs, the regulation of NSPC fate and function, in the context of cell-based disease models and patient-specific cell-replacement therapies, warrants review. PMID:24068527

  1. Isolation, Characterization, and Differentiation of Stem Cells for Cartilage Regeneration

    PubMed Central

    Beane, Olivia S.; Darling, Eric M.

    2012-01-01

    The goal of tissue engineering is to create a functional replacement for tissues damaged by injury or disease. In many cases, impaired tissues cannot provide viable cells, leading to the investigation of stem cells as a possible alternative. Cartilage, in particular, may benefit from the use of stem cells since the tissue has low cellularity and cannot effectively repair itself. To address this need, researchers are investigating the chondrogenic capabilities of several multipotent stem cell sources, including adult and extra-embryonic mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Comparative studies indicate that each cell type has advantages and disadvantages, and while direct comparisons are difficult to make, published data suggest some sources may be more promising for cartilage regeneration than others. In this review, we identify current approaches for isolating and chondrogenically differentiating MSCs from bone marrow, fat, synovium, muscle, and peripheral blood, as well as cells from extra-embyronic tissues, ESCs, and iPSCs. Additionally, we assess chondrogenic induction with growth factors, identifying standard cocktails used for each stem cell type. Cell-only (pellet) and scaffold-based studies are also included, as is a discussion of in vivo results. PMID:22907257

  2. Searching for oligodendrocyte precursors for cell replacement therapies.

    PubMed

    Sypecka, Joanna

    2011-01-01

    Inherited or acquired oligodendrocyte deficiency or abnormalities usually lead to severe neurological disorders, common in humans and animals. The wide spectrum of diseases to be treated, their frequency and lack of effective treatments result in an urgent need to elaborate alternative options such as cell replacement therapies. Elaborating the protocols for the efficient oligodendrocyte progenitor cell (OPC) generation for neurorestrative purposes still meets the essential obstacles. Searching for the most convenient, accessible and rich sources of stem-like cells is the first of them. The immunological barrier is another problem, which could however be solved by usage of either the allo- or the autografts and the pure, xeno-free compounds for the cell propagation. The third criterion is the efficiency of the progenitor derivation, proliferation and purification. The effective cellular replacement experiments carried on animal models of congenital and acquired neurodegenerative disease approached their translation into clinical practice. Notwithstanding due to urgent need for treatment of a broad spectrum of traumas and neurodegenerative disorders accompanied by hypo/demyelination, different cell sources and alternative strategies should necessarily be tested to expand the treatment options. PMID:21499330

  3. Stem Cell Transplantation for Neuroprotection in Stroke

    PubMed Central

    Shinozuka, Kazutaka; Dailey, Travis; Tajiri, Naoki; Ishikawa, Hiroto; Kaneko, Yuji; Borlongan, Cesar V.

    2013-01-01

    Stem cell-based therapies for stroke have expanded substantially over the last decade. The diversity of embryonic and adult tissue sources provides researchers with the ability to harvest an ample supply of stem cells. However, the optimal conditions of stem cell use are still being determined. Along this line of the need for optimization studies, we discuss studies that demonstrate effective dose, timing, and route of stem cells. We recognize that stem cell derivations also provide uniquely individual difficulties and limitations in their therapeutic applications. This review will outline the current knowledge, including benefits and challenges, of the many current sources of stem cells for stroke therapy. PMID:24147217

  4. Chemical approaches to studying stem cell biology

    PubMed Central

    Li, Wenlin; Jiang, Kai; Wei, Wanguo; Shi, Yan; Ding, Sheng

    2013-01-01

    Stem cells, including both pluripotent stem cells and multipotent somatic stem cells, hold great potential for interrogating the mechanisms of tissue development, homeostasis and pathology, and for treating numerous devastating diseases. Establishment of in vitro platforms to faithfully maintain and precisely manipulate stem cell fates is essential to understand the basic mechanisms of stem cell biology, and to translate stem cells into regenerative medicine. Chemical approaches have recently provided a number of small molecules that can be used to control cell self-renewal, lineage differentiation, reprogramming and regeneration. These chemical modulators have been proven to be versatile tools for probing stem cell biology and manipulating cell fates toward desired outcomes. Ultimately, this strategy is promising to be a new frontier for drug development aimed at endogenous stem cell modulation. PMID:23266890

  5. Stem cell therapy of cataract

    PubMed Central

    Maleki, Masoud

    2015-01-01

    Introduction: Cataract is recognized as a disease of the lens resulting in many blindness cases, while the only therapeutic procedure is surgery. Thus, to tackle this disease, alternative methods are required. Stem cell therapy is one of the alternative treatment modalities. Paired lens’ epithelial pieces induced by vitreous body were shown to produce lens-like structures. Here, Wharton’s jelly derived stem cells are suggested as the best candidates for this purpose, as these cells have potency for the differentiation into the lens fiber cells. Hypothesis: It is hypothesized that Wharton’s jelly derived stem cells could be used as a novel and appropriate source for the treatment of cataract. Evaluation of Hypothesis: To attain this aim, lens of an animal model of cataract can be removed. Then, the human Wharton’s jelly stem cells (hWJSCs) are injected into a capsule. Finally, the expression of crystalline proteins and vision function are analyzed. Conclusion: It is hypothesized that the lens capsule could act as a natural scaffold and hWJSCs could be used to restore the lens structure in the empty capsule. PMID:26929919

  6. 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.

  7. Stem Cells in the Limbal Stroma.

    PubMed

    Funderburgh, James L; Funderburgh, Martha L; Du, Yiqin

    2016-04-01

    The corneal stroma contains a population of mesenchymal cells subjacent to the limbal basement membrane with characteristics of adult stem cells. These 'niche cells' support limbal epithelial stem cell viability. In culture by themselves, the niche cells display a phenotype typical of mesenchymal stem cells. These stromal stem cells exhibit a potential to differentiate to multiple cell types, including keratocytes, thus providing an abundant source of these rare cells for experimental and bioengineering applications. Stromal stem cells have also shown the ability to remodel pathological stromal tissue, suppressing inflammation and restoring transparency. Because stromal stem cells can be obtained by biopsy, they offer a potential for autologous stem cell treatment for stromal opacities. This review provides an overview of the status of work on this interesting cell population. PMID:26804252

  8. Production of neural stem cells from human pluripotent stem cells.

    PubMed

    Wen, Yu; Jin, Sha

    2014-10-20

    Despite significant advances in commercially available media and kits and the differentiation approaches for human neural stem cell (NSC) generation, NSC production from the differentiation of human pluripotent stem cell (hPSC) is complicated by its time-consuming procedure, complex medium composition, and purification step. In this study, we developed a convenient and simplified NSC production protocol to meet the demand of NSC production. We demonstrated that NSCs can be generated efficiently without requirement of specific small molecules or embryoid body formation stage. Our experimental results suggest that a short suspension culture period may facilitate ectoderm lineage specification rather than endoderm or mesoderm lineage specification from hPSCs. The method developed in this study shortens the turnaround time of NSC production from both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) differentiation. It provides a straightforward and useful strategy for generating NSCs that can benefit a wide range of research applications for human brain research. PMID:25150215

  9. Leydig cells: From stem cells to aging

    PubMed Central

    Chen, Haolin; Ge, Ren-Shan; Zirkin, Barry R.

    2009-01-01

    Leydig cells are the testosterone-producing cells of the testis. The adult Leydig cell population ultimately develops from undifferentiated mesenchymal-like stem cells present in the interstitial compartment of the neonatal testis. Four distinct stages of adult Leydig cell development have been identified and characterized: stem Leydig cells, progenitor Leydig cells, immature Leydig cells and adult Leydig cells. The stem Leydig cells are undifferentiated cells that are capable of indefinite self-renewal, differentiation, and replenishment of the Leydig cell niche. Progenitor Leydig cells are derived from the stem Leydig cells. These spindle-shaped cells are luteinizing hormone (LH) receptor positive, have high mitotic activity, and produce little testosterone but rather testosterone metabolites. The progenitor Leydig cells give rise to immature Leydig cells which are round, contain large amounts of smooth endoplasmic reticulum, and produce some testosterone but also very high levels of testosterone metabolites. A single division of these cells produces adult Leydig cells, which are terminally differentiated cells that produce high levels of testosterone. As men age, serum testosterone levels decline, and this is associated with alterations in body composition, energy level, muscle strength, physical, sexual and cognitive functions, and mood. In the Brown Norway rat, used extensively as a model for male reproductive aging, age-related reductions in serum testosterone result from significant decline in the ability of aged Leydig cells to produce testosterone in response to LH stimulation. This review describes Leydig cell development and aging. Additionally, the molecular mechanisms by which testosterone synthesis declines with aging are discussed. PMID:19481681

  10. Epigenetic regulation of mammalian stem cells.

    PubMed

    Li, Xuekun; Zhao, Xinyu

    2008-12-01

    Two critical properties of stem cells are self-renewal and multipotency. The maintenance of their "stemness" state and commitment to differentiation are therefore tightly controlled by intricate molecular networks. Epigenetic mechanisms, including DNA methylation, chromatin remodeling and the noncoding RNA-mediated process, have profound regulatory roles in mammalian gene expression. Recent studies have shown that epigenetic regulators are key players in stem cell biology and their dysfunction can result in human diseases such as cancer and neurodevelopmental disorders. Here, we review the recent evidences that advance our knowledge in epigenetic regulations of mammalian stem cells, with focus on embryonic stem cells and neural stem cells. PMID:18393635

  11. The Impact of Mesenchymal Stem Cells on Differentiation of Hematopoietic Stem Cells

    PubMed Central

    Saleh, Mahshid; Shamsasanjan, karim; Movassaghpourakbari, Aliakbar; Akbarzadehlaleh, Parvin; Molaeipour, Zahra

    2015-01-01

    Bone marrow microenvironment contains cellular and acellular compartments. The cellular compartment includes hematopoietic stem cells, mesenchymal stem cells and some other stromal cell types, while the acellular compartment is composed of scaffold proteins known as the extra cellular matrix. Direct cell-cell contact as well as cytokines secreted by mesenchymal stem cells during coculture of hematopoietic stem cells and mesenchymal stem cells play a critical role in hematopoiesis, and determines the fate of hematopoietic stem cells. Several studies have demonstrated the impact of mesenchymal stem cells on self-renewal, expansion, proliferation and differentiation of hematopoietic stem cells in vitro, which have shown different and contradictory results. In this paper, we will investigate the effect of mesenchymal stem cells on differentiation of hematopoietic stem cells in vitro. PMID:26504750

  12. 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.

  13. 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

  14. Stem cells in gastric cancer

    PubMed Central

    Zhao, Yue; Feng, Fei; Zhou, Yong-Ning

    2015-01-01

    Gastric cancer (GC) is one of the leading causes of cancer-related mortality worldwide. Cancer stem cells (CSCs), which were first identified in acute myeloid leukemia and subsequently in a large array of solid tumors, play important roles in cancer initiation, dissemination and recurrence. CSCs are often transformed tissue-specific stem cells or de-differentiated transit amplifying progenitor cells. Several populations of multipotent gastric stem cells (GSCs) that reside in the stomach have been determined to regulate physiological tissue renewal and injury repair. These populations include the Villin+ and Lgr5+ GSCs in the antrum, the Troy+ chief cells in the corpus, and the Sox2+ GSCs that are found in both the antrum and the corpus. The disruption of tumor suppressors in Villin+ or Lgr5+ GSCs leads to GC in mouse models. In addition to residing GSCs, bone marrow-derived cells can initiate GC in a mouse model of chronic Helicobacter infection. Furthermore, expression of the cell surface markers CD133 or CD44 defines gastric CSCs in mouse models and in human primary GC tissues and cell lines. Targeted elimination of CSCs effectively reduces tumor size and grade in mouse models. In summary, the recent identification of normal GSCs and gastric CSCs has greatly improved our understanding of the molecular and cellular etiology of GC and will aid in the development of effective therapies to treat patients. PMID:25574084

  15. Stem cells in breast epithelia.

    PubMed

    Li, P; Barraclough, R; Fernig, D G; Smith, J A; Rudland, P S

    1998-08-01

    The rodent and human nonpregnant mammary glands contain epithelial, intermediate and myoepithelial cells which have all been isolated as cell lines in vitro. Transforming growth factor-alpha (TGF alpha) and basic fibroblast growth factor (bFGF) are produced by myoepithelial cells and can stimulate the growth of intermediate stem cells in vitro. Epithelial and intermediate cells behave like stem cells in vitro, since they can differentiate into alveolar-like an myoepithelial cells. The myoepithelial differentiation pathway is associated with the early expression of a calcium-binding regulatory protein called p9Ka and the protease, Cathepsin D. Myoepithelial cells are also present in benign lesions but not in malignant mammary carcinomas of rats or humans, whose resultant cell lines fail to differentiate completely along the myoepithelial cell pathway. Loss of the myoepithelial cell in some invasive carcinomas may be compensated, at least in part, by changes in malignant cells. Over-expression of TGF alpha and/or erbB receptors may reduce the requirement for TGF alpha, whilst ectopic production of bFGF and its receptors and p9Ka/Cathespin D may assist in tumorigenesis and in metastasis, respectively. Thus compensation for, or retention of, molecules potentially involved in the differentiation of mammary cells may be a mechanism by which malignancy progresses in some human invasive carcinomas. PMID:9797716

  16. 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.

  17. FDA Warns About Stem Cell Claims

    MedlinePlus

    ... are stem cells? How are they regulated? Health Fraud Scams Related Consumer Updates Adult Stem Cell Research Shows Promise Don't Be Fooled By Health Fraud Scams FDA 101: Health Fraud Awareness Cord Blood: ...

  18. 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 ...

  19. Blood-Forming Stem Cell Transplants

    MedlinePlus

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

  20. Becoming a Blood Stem Cell Donor

    MedlinePlus

    ... total__ Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Subscribe Subscribed Unsubscribe 361 361 Loading... ... Ever considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  1. Bioengineered stem cells as an alternative for islet cell transplantation

    PubMed Central

    Moore, Sarah J; Gala-Lopez, Boris L; Pepper, Andrew R; Pawlick, Rena L; Shapiro, AM James

    2015-01-01

    Type 1 diabetes is an autoimmune and increasingly prevalent condition caused by immunological destruction of beta cells. Insulin remains the mainstay of therapy. Endeavours in islet transplantation have clearly demonstrated that type 1 diabetes is treatable by cellular replacement. Many challenges remain with this approach. The opportunity to use bioengineered embryonic or adult pluripotential stem cells, or islets derived from porcine xenograft sources could address future demands, but are still associated with considerable challenges. This detailed review outlines current progress in clinical islet transplantation, and places this in perspective for the remarkable scientific advances now occurring in stem cell and regenerative medicine approaches in the treatment of future curative treatment of diabetes. PMID:25815266

  2. Modeling Stem Cell Induction Processes

    PubMed Central

    Grácio, Filipe; Cabral, Joaquim; Tidor, Bruce

    2013-01-01

    Technology for converting human cells to pluripotent stem cell using induction processes has the potential to revolutionize regenerative medicine. However, the production of these so called iPS cells is still quite inefficient and may be dominated by stochastic effects. In this work we build mass-action models of the core regulatory elements controlling stem cell induction and maintenance. The models include not only the network of transcription factors NANOG, OCT4, SOX2, but also important epigenetic regulatory features of DNA methylation and histone modification. We show that the network topology reported in the literature is consistent with the observed experimental behavior of bistability and inducibility. Based on simulations of stem cell generation protocols, and in particular focusing on changes in epigenetic cellular states, we show that cooperative and independent reaction mechanisms have experimentally identifiable differences in the dynamics of reprogramming, and we analyze such differences and their biological basis. It had been argued that stochastic and elite models of stem cell generation represent distinct fundamental mechanisms. Work presented here suggests an alternative possibility that they represent differences in the amount of information we have about the distribution of cellular states before and during reprogramming protocols. We show further that unpredictability and variation in reprogramming decreases as the cell progresses along the induction process, and that identifiable groups of cells with elite-seeming behavior can come about by a stochastic process. Finally we show how different mechanisms and kinetic properties impact the prospects of improving the efficiency of iPS cell generation protocols. PMID:23667423

  3. Current focus of stem cell application in retinal repair.

    PubMed

    Alonso-Alonso, María L; Srivastava, Girish K

    2015-04-26

    The relevance of retinal diseases, both in society's economy and in the quality of people's life who suffer with them, has made stem cell therapy an interesting topic for research. Embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adipose derived mesenchymal stem cells (ADMSCs) are the focus in current endeavors as a source of different retinal cells, such as photoreceptors and retinal pigment epithelial cells. The aim is to apply them for cell replacement as an option for treating retinal diseases which so far are untreatable in their advanced stage. ESCs, despite the great potential for differentiation, have the dangerous risk of teratoma formation as well as ethical issues, which must be resolved before starting a clinical trial. iPSCs, like ESCs, are able to differentiate in to several types of retinal cells. However, the process to get them for personalized cell therapy has a high cost in terms of time and money. Researchers are working to resolve this since iPSCs seem to be a realistic option for treating retinal diseases. ADMSCs have the advantage that the procedures to obtain them are easier. Despite advancements in stem cell application, there are still several challenges that need to be overcome before transferring the research results to clinical application. This paper reviews recent research achievements of the applications of these three types of stem cells as well as clinical trials currently based on them. PMID:25914770

  4. Stem Cells for Heart Cell Therapies

    PubMed Central

    Jing, Donghui; Parikh, Abhirath; Canty, John M.

    2008-01-01

    Myocardial infarction–induced heart failure is a prevailing cause of death in the United States and most developed countries. The cardiac tissue has extremely limited regenerative potential, and heart transplantation for reconstituting the function of damaged heart is severely hindered mainly due to the scarcity of donor organs. To that end, stem cells with their extensive proliferative capacity and their ability to differentiate toward functional cardiomyocytes may serve as a renewable cellular source for repairing the damaged myocardium. Here, we review recent studies regarding the cardiogenic potential of adult progenitor cells and embryonic stem cells. Although large strides have been made toward the engineering of cardiac tissues using stem cells, important issues remain to be addressed to enable the translation of such technologies to the clinical setting. PMID:18821841

  5. Human Embryonic Stem Cells and Cardiac Repair

    PubMed Central

    Zhu, Wei-Zhong; Hauch, Kip; Xu, Chunhui; Laflamme, Michael A.

    2008-01-01

    The muscle lost after a myocardial infarction is replaced with non-contractile scar tissue, often initiating heart failure. Whole-organ cardiac transplantation is the only currently available clinical means of replacing the lost muscle, but this option is limited by the inadequate supply of donor hearts. Thus, cell-based cardiac repair has attracted considerable interest as an alternative means of ameliorating cardiac injury. Because of their tremendous capacity for expansion and unquestioned cardiac potential, pluripotent human embryonic stem cells (hESCs) represent an attractive candidate cell source for obtaining cardiomyocytes and other useful mesenchymal cell types for such therapies. hESC-derived cardiomyocytes (hESC-CMs) exhibit a committed cardiac phenotype and robust proliferative capacity, and recent testing in rodent infarct models indicates that they can partially remuscularize injured hearts and improve contractile function. Although the latter successes give good reason for optimism, considerable challenges remain to the successful application of hESCs to cardiac repair, including the need for preparations of high cardiac purity, improved methods of delivery, and approaches to overcome immune rejection and other causes of graft cell death. This review will describe the phenotype of hESC-CMs and preclinical experience with these cells and will consider strategies to overcoming the aforementioned challenges. PMID:18657407

  6. Nine Things to Know About Stem Cell Treatments

    MedlinePlus

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

  7. 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…

  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. Monitoring of beta cell replacement outcomes.

    PubMed

    Chang, Charles A; Haque, Waqas Z; Yoshimatsu, Gumpei; Balajii, Prathab S; Lawrence, Michael C; Naziruddin, Bashoo

    2016-03-01

    Pancreatic islet transplantation is a promising beta cell replacement treatment for patients with "brittle" type 1 diabetes (T1D) or intractable chronic pancreatitis to restore or preserve pancreatic endocrine function. Early after transplant, a significant islet mass is lost due to an innate inflammatory response, and further loss of the islet graft occurs over time due to immune response, drug toxicity, or metabolic exhaustion. Thus, clinically feasible techniques are essential to monitor islet graft function and survival to maintain appropriate therapy. Currently, islet graft function is monitored using blood glucose levels, insulin and C-peptide levels, and islet imaging. However, these tests are influenced by physiological changes, including beta cell stimulation. Biomarkers that are independent of metabolic stimuli would be more accurate and reliable in detecting islet damage. Antibodies against islet autoantigens are useful but not reliable markers of islet injury due to their presence during the pretransplant period. Several islet-specific proteins such as Glutamate decarboxylase-65, doublecortin, protein phosphatase 1, regulatory (inhibitor) subunit 1A, ubiquitin C-terminal hydrolase-L1, and the high-mobility group box-1 protein have been proposed as candidates to monitor islet damage, but these biomarkers have short half-lives and unreliable detection. Unmethylated insulin DNA has been studied in T1D patients and has been documented as a highly correlative and selective biomarker for beta cell death. More recently, microRNAs (miRNAs) that are selectively expressed in islets have been shown to provide sensitive and accurate quantification of islet damage. Analysis of plasma samples from autologous and allogeneic islet transplant patients has demonstrated the value of miRNA-375 as a specific biomarker to accurately assess islet damage. Use of selective, sensitive, and measurably reproducible biomarkers of islets will lead to effective monitoring of beta cell replacement therapy and may also lead to development of preventative and interventional treatment strategies to improve outcomes. PMID:26763742

  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. 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

  12. Neural stem cells could serve as a therapeutic material for age-related neurodegenerative diseases

    PubMed Central

    Suksuphew, Sarawut; Noisa, Parinya

    2015-01-01

    Progressively loss of neural and glial cells is the key event that leads to nervous system dysfunctions and diseases. Several neurodegenerative diseases, for instance Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, are associated to aging and suggested to be a consequence of deficiency of neural stem cell pool in the affected brain regions. Endogenous neural stem cells exist throughout life and are found in specific niches of human brain. These neural stem cells are responsible for the regeneration of new neurons to restore, in the normal circumstance, the functions of the brain. Endogenous neural stem cells can be isolated, propagated, and, notably, differentiated to most cell types of the brain. On the other hand, other types of stem cells, such as mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells can also serve as a source for neural stem cell production, that hold a great promise for regeneration of the brain. The replacement of neural stem cells, either endogenous or stem cell-derived neural stem cells, into impaired brain is highly expected as a possible therapeutic mean for neurodegenerative diseases. In this review, clinical features and current routinely treatments of age-related neurodegenerative diseases are documented. Noteworthy, we presented the promising evidence of neural stem cells and their derivatives in curing such diseases, together with the remaining challenges to achieve the best outcome for patients. PMID:25815135

  13. Laser printing of skin cells and human stem cells.

    PubMed

    Koch, Lothar; Kuhn, Stefanie; Sorg, Heiko; Gruene, Martin; Schlie, Sabrina; Gaebel, Ralf; Polchow, Bianca; Reimers, Kerstin; Stoelting, Stephanie; Ma, Nan; Vogt, Peter M; Steinhoff, Gustav; Chichkov, Boris

    2010-10-01

    Laser printing based on laser-induced forward transfer (LIFT) is a new biofabrication technique for the arrangement of biological materials or living cells in well-defined patterns. In the current study, skin cell lines (fibroblasts/keratinocytes) and human mesenchymal stem cells (hMSC) were chosen for laser printing experiments due to their high potential in regeneration of human skin and new application possibilities of stem cell therapy. To evaluate the influence of LIFT on the cells, their survival rate, their proliferation and apoptotic activity, and the DNA damages and modifications of their cell surface markers were assessed and statistically evaluated over several days. The cells survived the transfer procedure with a rate of 98%  +/- 1% standard error of the mean (skin cells) and 90%  +/- 10% (hMSC), respectively. All used cell types maintain their ability to proliferate after LIFT. Further, skin cells and hMSC did not show an increase of apoptosis or DNA fragmentation. In addition, the hMSC keep their phenotype as proven by fluorescence activated cell sorting (FACS) analysis. This study demonstrates LIFT as a suitable technique for unharmed computer-controlled positioning of different cell types and a promising tool for future applications in the ex vivo generation of tissue replacements. PMID:19883209

  14. Retinal stem cells and potential cell transplantation treatments.

    PubMed

    Lin, Tai-Chi; Hsu, Chih-Chien; Chien, Ke-Hung; Hung, Kuo-Hsuan; Peng, Chi-Hsien; Chen, Shih-Jen

    2014-11-01

    The retina, histologically composed of ten delicate layers, is responsible for light perception and relaying electrochemical signals to the secondary neurons and visual cortex. Retinal disease is one of the leading clinical causes of severe vision loss, including age-related macular degeneration, Stargardt's disease, and retinitis pigmentosa. As a result of the discovery of various somatic stem cells, advances in exploring the identities of embryonic stem cells, and the development of induced pluripotent stem cells, cell transplantation treatment for retinal diseases is currently attracting much attention. The sources of stem cells for retinal regeneration include endogenous retinal stem cells (e.g., neuronal stem cells, Müller cells, and retinal stem cells from the ciliary marginal zone) and exogenous stem cells (e.g., bone mesenchymal stem cells, adipose-derived stem cells, embryonic stem cells, and induced pluripotent stem cells). The success of cell transplantation treatment depends mainly on the cell source, the timing of cell harvesting, the protocol of cell induction/transplantation, and the microenvironment of the recipient's retina. This review summarizes the different sources of stem cells for regeneration treatment in retinal diseases and surveys the more recent achievements in animal studies and clinical trials. Future directions and challenges in stem cell transplantation are also discussed. PMID:25238708

  15. Human Foetal Mesenchymal Stem Cells.

    PubMed

    Gtherstrm, Cecilia

    2016-02-01

    Finding suitable cell sources is one of the main challenges in regenerative medicine. In addition to improving the dysfunctional tissue requiring reconstruction, low immunogenicity is beneficial. Mesenchymal stem cells (MSCs) are immune-privileged multipotent stromal cells that can easily multiply and differentiate along many lineages with a minimal oncogenic risk. MSCs derived from foetal tissues present characteristics that suggest an even stronger cell therapeutic potential in comparison to adult MSCs. Due to these characteristics, they have been and are currently being tested in clinical trials for a diverse variety of disorders. PMID:26725704

  16. Neural repair with pluripotent stem cells.

    PubMed

    Döbrössy, Máté; Pruszak, Jan

    2013-01-01

    The nervous system is characterized by its complex network of highly specialized cells that enable us to perceive stimuli from the outside world and react accordingly. The computational integration enabled by these networks remains to be elucidated, but appropriate sensory input, processing, and motor control are certainly essential for survival. Consequently, loss of nervous tissue due to injury or disease represents a considerable biomedical challenge. Stem cell research offers the promise to provide cells for nervous system repair to replace lost and damaged neural tissue and alleviate disease. We provide a protocol-based chapter on fundamental principles and procedures of pluripotent stem cell (PSC) differentiation and neural transplantation. Rather than detailed methodological step-by-step descriptions of these procedures, we provide an overview and highlight the most critical aspects and key steps of PSC neural induction, subtype specification in different in vitro systems, as well as neural cell transplantation to the central nervous system. We conclude with a summary of suitable readout methods including in vitro phenotypic analysis, histology, and functional analysis in vivo. PMID:24029933

  17. 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.

  18. Chromatin structure of pluripotent stem cells and induced pluripotent stem cells

    PubMed Central

    Recillas-Targa, Flix

    2011-01-01

    Pluripotent embryonic stem (ES) cells are specialized cells with a dynamic chromatin structure, which is intimately connected with their pluripotency and physiology. In recent years somatic cells have been reprogrammed to a pluripotent state through over-expression of a defined set of transcription factors. These cells, known as induced pluripotent stem (iPS) cells, recapitulate ES cell properties and can be differentiated to apparently all cell lineages, making iPS cells a suitable replacement for ES cells in future regenerative medicine. Chromatin modifiers play a key function in establishing and maintaining pluripotency, therefore, elucidating the mechanisms controlling chromatin structure in both ES and iPS cells is of utmost importance to understanding their properties and harnessing their therapeutic potential. In this review, we discuss recent studies that provide a genome-wide view of the chromatin structure signature in ES cells and iPS cells and that highlight the central role of histone modifiers and chromatin remodelers in pluripotency maintenance and induction. PMID:21325400

  19. 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. PMID:26542929

  20. Establishing procedures for institutional oversight of stem cell research.

    PubMed

    Zettler, Patricia; Wolf, Leslie E; Lo, Bernard

    2007-01-01

    Academic health centers (AHCs), which are at the forefront of stem cell research, need to establish institutional stem cell research oversight committees (SCROs) to comply with 2005 National Academy of Sciences (NAS) recommendations and to establish public trust in this sensitive research. Institutional review boards (IRBs) typically lack the expertise and time to adequately review the specific ethical issues raised by stem cell research. To assure careful, timely, and coordinated review of the science and ethics of stem cell protocols, AHCs need to address many practical procedural issues, such as SCRO membership, quorum, conflicts of interest, and procedures for protocol review. The SCRO committee at the University of California San Francisco (UCSF), established in 2003, has developed detailed policies and procedures on these issues. The UCSF SCRO has broad scientific expertise and uses ad hoc reviewers to strengthen the review process. Studies receiving full SCRO review have three lead reviewers: a scientist, a reviewer with ethics expertise, and a public representative. Studies introducing human stem cells into nonhuman blastocysts receive full review, even if the stem cells are anonymized. Some protocols are eligible for expedited review. The SCRO neither replaces nor duplicates review by the IRB and institutional animal care and use committees. Other AHCs can draw on the UCSF experience when developing their own policies and procedures for stem cell research oversight. PMID:17198282

  1. Stem Cell Research in Pakistan; Past, Present and Future

    PubMed Central

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

    2015-01-01

    Background and Objectives Stem cells have proved to have great therapeutic potential as stem cell treatment is replacing traditional ways of treatment in different disorders like cancer, aplastic anemia, stroke, heart disorders. The developed and developing countries are investing differently in this area of research so research output and clinical translation of research greatly vary among developed and developing countries. Present study was done to investigate the current status of stem cells research in Pakistan and ways to improve it. Results Many advanced countries (USA, UK and Canada etc.) are investing heavily in stem cell research and treatment. Different developing countries like Iran, Turkey and India are also following the developed countries and investing a lot in stem cells research. Pakistan is also making efforts in establishing this field to get desired benefits but unfortunately the progress is at very low pace. If Government plays an active role along with private sector, stem cell research in Pakistan can be boosted up. The numbers of publications from Pakistan are very less compared to developed and neighboring countries and Pakistan also has very less number of institutes working in this area of research. Conclusions Stem cells research is at its initial stages in Pakistan and there is great need to bring Government, academia and industry together so they could make serious efforts to promote research in this very important field. This will help millions of patients suffering from incurable disorders and will also reduce economic loss. PMID:26019749

  2. Development of stem cell-based therapy for Parkinson's disease.

    PubMed

    Han, Fabin; Baremberg, Deborah; Gao, Junyu; Duan, Jing; Lu, Xianjie; Zhang, Nan; Chen, Qingfa

    2015-01-01

    Parkinson's disease (PD) is one of the most common neurodegenerative disorders of aging, characterized by the degeneration of dopamine neurons (DA neurons) in the substantial nigra, leading to the advent of both motor symptoms and non-motor symptoms. Current treatments include electrical stimulation of the affected brain areas and dopamine replacement therapy. Even though both categories are effective in treating PD patients, the disease progression cannot be stopped. The research advance into cell therapies provides exciting potential for the treatment of PD. Current cell sources include neural stem cells (NSCs) from fetal brain tissues, human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs) and directly induced dopamine neurons (iDA neurons). Here, we evaluate the research progress in different cell sources with a focus on using iPSCs as a valuable source and propose key challenges for developing cells suitable for large-scale clinical applications in the treatment of PD. PMID:26339485

  3. Cell motion predicts human epidermal stemness.

    PubMed

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

    2015-04-27

    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

  4. 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

  5. Cancer Stem Cell Consortium

    Cancer.gov

    Chair Kathleen Kelly, Cell and Cancer Biology Branch, CCR, NCI Members Snorri Thorgeirsson, Laboratory of Experimental Carcinogenesis, CCR, NCI Mike Alley, Developmental Therapeutics Program, NCI Jesper Andersen, Laboratory of Experimental Carcinogenesis,

  6. Microengineered synthetic cellular microenvironment for stem cells

    PubMed Central

    Sun, Yubing; Weng, Shinuo

    2014-01-01

    Stem cells possess the ability of self-renewal and differentiation into specific cell types. Therefore, stem cells have great potentials in fundamental biology studies and clinical applications. The most urgent desire for stem cell research is to generate appropriate artificial stem cell culture system, which can mimic the dynamic complexity and precise regulation of the in vivo biochemical and biomechanical signals, to regulate and direct stem cell behaviors. Precise control and regulation of the biochemical and biomechanical stimuli to stem cells have been successfully achieved using emerging micro/nanoengineering techniques. This review provides insights into how these micro/nanoengineering approaches, particularly microcontact printing and elastomeric micropost array, are applied to create dynamic and complex environment for stem cells culture. PMID:22639443

  7. Dislodgement of a cemented exeter femoral stem during closed manipulative reduction of a dislocated total hip replacement

    PubMed Central

    Rajeev, Aysha; Mohamed, Abdalla; Shaikh, Mazharuddin; Banaszkiewicz, Paul

    2016-01-01

    Introduction The incidence of cemented femoral stem migration and dislodgement even though has been described is extremely unusual. There is a high chance of polished femoral stem displacement happening while trying to reduce a dislocated total hip replacement by closed measures. Presentation of the case A 73 year old lady who had an Exeter cemented total hip replacement about two weeks back was admitted from Accident and Emergency with a dislocation. During the closed manipulative reduction under general anaesthesia it was noted that the femoral stem has dislodged from the canal. She underwent revision of the total hip replacement with good outcome. Discussion Femoral stem dislodgement occurs in total hip replacement if polished stem or inadequate cementing of the collar is carried out. Conclusion Gentle manipulative reduction under general anaesthesia of dislocated total hip replacement should be carried out if the polished femoral stem is used. PMID:27060643

  8. Autophagic response to cell culture stress in pluripotent stem cells.

    PubMed

    Gregory, Siân; Swamy, Sushma; Hewitt, Zoe; Wood, Andrew; Weightman, Richard; Moore, Harry

    2016-05-01

    Autophagy is an important conserved cellular process, both constitutively as a recycling pathway for long lived proteins and as an upregulated stress response. Recent findings suggest a fundamental role for autophagic processes in the maintenance of pluripotent stem cell function. In human embryonic stem cells (hESCS), autophagy was investigated by transfection of LC3-GFP to visualize autophagosomes and with an antibody to LC3B protein. The presence of the primary cilium (PC) in hESCs as the site of recruitment of autophagy-related proteins was also assessed. HESCs (mShef11) in vitro displayed basal autophagy which was upregulated in response to deprivation of culture medium replacement. Significantly higher levels of autophagy were exhibited on spontaneous differentiation of hESCs in vitro. The PC was confirmed to be present in hESCs and therefore may serve to coordinate autophagy function. PMID:26385182

  9. Adipose Tissue Stem Cells.

    PubMed

    Müller, Sebastian; Kulenkampff, Elisabeth; Wolfrum, Christian

    2016-01-01

    Adipose tissue is the major storage sites of energy deposition which can be recruited in times of need to provide fuel for other organs (reviewed in Gunawardana 2014). When normalized to volume, adipose tissue is mainly composed of so-called mature adipocytes which are cells that have the capacity to store energy in the form of triacylglycerols (TAGs) in lipid droplets. When normalized to cell number, only 20-30% of the adipose tissue is made up from mature adipocytes; the other 70-80% are composed of the so-called stromal vascular fraction (SVF), which consists of fibroblasts, adipocyte precursors, endothelial cells, and immune cells (Rosenwald et al. 2013; Wang et al. 2013). This cell heterogeneity clearly demonstrates that adipose tissue is a complex organ with various different functions in the regulation of whole body metabolism. In line with this, over the past several years, our understanding of adipose tissue has changed. Only 20 years ago adipose tissue was considered to be an inert energy storage organ, while nowadays it is accepted that besides its role in energy storage and dissipation, adipose tissue serves as a key organ for the regulation of whole body energy metabolism by cross talk with other organs through the secretion of adipokines, such as tumor necrosis factor α, (TNF-α), interleukin-6 (IL-6), adiponectin, leptin, and resistin, just to mention a few (Bluher and Mantzoros 2015). PMID:25912015

  10. Stem Cells in Teeth and Craniofacial Bones.

    PubMed

    Zhao, H; Chai, Y

    2015-11-01

    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

  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. Induced pluripotent stem cells and Parkinson's disease: modelling and treatment.

    PubMed

    Xu, Xiaoyun; Huang, Jinsha; Li, Jie; Liu, Ling; Han, Chao; Shen, Yan; Zhang, Guoxin; Jiang, Haiyang; Lin, Zhicheng; Xiong, Nian; Wang, Tao

    2016-02-01

    Many neurodegenerative disorders, such as Parkinson's disease (PD), are characterized by progressive neuronal loss in different regions of the central nervous system, contributing to brain dysfunction in the relevant patients. Stem cell therapy holds great promise for PD patients, including with foetal ventral mesencephalic cells, human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Moreover, stem cells can be used to model neurodegenerative diseases in order to screen potential medication and explore their mechanisms of disease. However, related ethical issues, immunological rejection and lack of canonical grafting protocols limit common clinical use of stem cells. iPSCs, derived from reprogrammed somatic cells, provide new hope for cell replacement therapy. In this review, recent development in stem cell treatment for PD, using hiPSCs, as well as the potential value of hiPSCs in modelling for PD, have been summarized for application of iPSCs technology to clinical translation for PD treatment. PMID:26748765

  14. Potential feasibility of dental stem cells for regenerative therapies: stem cell transplantation and whole-tooth engineering.

    PubMed

    Nakahara, Taka

    2011-07-01

    Multipotent mesenchymal stem cells from bone marrow are expected to be a somatic stem cell source for the development of new cell-based therapy in regenerative medicine. However, dental clinicians are unlikely to carry out autologous cell/tissue collection from patients (i.e., marrow aspiration) as a routine procedure in their clinics; hence, the utilization of bone marrow stem cells seems impractical in the dental field. Dental tissues harvested from extracted human teeth are well known to contain highly proliferative and multipotent stem cell compartments and are considered to be an alternative autologous cell source in cell-based medicine. This article provides a short overview of the ongoing studies for the potential application of dental stem cells and suggests the utilization of 2 concepts in future regenerative medicine: (1) dental stem cell-based therapy for hepatic and other systemic diseases and (2) tooth replacement therapy using the bioengineered human whole tooth, called the "test-tube dental implant." Regenerative therapies will bring new insights and benefits to the fields of clinical medicine and dentistry. PMID:21805289

  15. Genome Editing in Human Pluripotent Stem Cells.

    PubMed

    Smith, Cory; Ye, Zhaohui; Cheng, Linzhao

    2016-01-01

    Pluripotent stem cells (PSCs), defined by their capacity for self-renewal and differentiation into all cell types, are an integral tool for basic biological research and disease modeling. However, full use of PSCs for research and regenerative medicine requires the ability to precisely edit their DNA to correct disease-causing mutations and for functional analysis of genetic variations. Recent advances in DNA editing of human stem cells (including PSCs) have benefited from the use of designer nucleases capable of making double-strand breaks (DSBs) at specific sequences that stimulate endogenous DNA repair. The clustered, regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has become the preferred designer nuclease for genome editing in human PSCs and other cell types. Here we describe the principles for designing a single guide RNA to uniquely target a gene of interest and describe strategies for disrupting, inserting, or replacing a specific DNA sequence in human PSCs. The improvements in efficiency and ease provided by these techniques allow individuals to precisely engineer PSCs in a way previously limited to large institutes and core facilities. PMID:27037079

  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. Recent progressions in stem cell research: breakthroughs achieved and challenges faced.

    PubMed

    Tani, Jowy; Umbas, Rainy

    2009-01-01

    Stem cell studies have been conducted to study characteristics of stem cells, to develop better techniques for patient-specific stem cell lines generation, and to explore the therapeutic potential of stem cells. Techniques that enable efficient generation of new stem cell lines would facilitate research and allow generation of patient-specific stem cell lines for transplantation therapy. Somatic-Cell Nuclear Transfer (SCNT), which involves injection of donor cell nucleus into enucleated ovum, is the standard technique for new embryonic stem (ES) cell lines generation; presently its efficiency is low. A newer technique, pluripotent stem cell induction, reprograms somatic cells into induced pluripotent stem (iPS) cells by introducing certain factors into somatic cells. While certain adult stem cell treatments have been investigated on human participants, most ES cell or iPS cell treatments were still experimented on animal models. Recently, therapeutic potential of stem cell for several disorders was demonstrated. Researchers demonstrated stem cell's potential for treating hematologic disorders by correcting sickle cell anemia in rat model with iPS cells. Its potential role in treating cardiovascular disorder was demonstrated as injection of damaged rat heart with human ES cells derived cardiomyocyte plus "prosurvival" cocktail improved heart function. It might also treat nervous system disorders; injected into brain, ES cells derived neurons replace some loss cells in stroke rats and iPS cells derived neurons improved Parkinsonian syndrome in rats. Progress was also seen in other aspects of regenerative medicine. To overcome controversies caused by embryo destruction for obtaining ES cells, single blastomer stem cell derivation, Cdx2-inactivation, and parthenogenesis were proposed. All ES cell, iPS cell, and adult stem cell research should be continued with support from all sides. PMID:19258678

  18. Insights into kidney stem cell development and regeneration using zebrafish.

    PubMed

    Drummond, Bridgette E; Wingert, Rebecca A

    2016-02-26

    Kidney disease is an escalating global health problem, for which the formulation of therapeutic approaches using stem cells has received increasing research attention. The complexity of kidney anatomy and function, which includes the diversity of renal cell types, poses formidable challenges in the identification of methods to generate replacement structures. Recent work using the zebrafish has revealed their high capacity to regenerate the integral working units of the kidney, known as nephrons, following acute injury. Here, we discuss these findings and explore the ways that zebrafish can be further utilized to gain a deeper molecular appreciation of renal stem cell biology, which may uncover important clues for regenerative medicine. PMID:26981168

  19. Insights into kidney stem cell development and regeneration using zebrafish

    PubMed Central

    Drummond, Bridgette E; Wingert, Rebecca A

    2016-01-01

    Kidney disease is an escalating global health problem, for which the formulation of therapeutic approaches using stem cells has received increasing research attention. The complexity of kidney anatomy and function, which includes the diversity of renal cell types, poses formidable challenges in the identification of methods to generate replacement structures. Recent work using the zebrafish has revealed their high capacity to regenerate the integral working units of the kidney, known as nephrons, following acute injury. Here, we discuss these findings and explore the ways that zebrafish can be further utilized to gain a deeper molecular appreciation of renal stem cell biology, which may uncover important clues for regenerative medicine. PMID:26981168

  20. Stem cell paracrine actions and tissue regeneration

    PubMed Central

    Baraniak, Priya R; McDevitt, Todd C

    2010-01-01

    Stem cells have emerged as a key element of regenerative medicine therapies due to their inherent ability to differentiate into a variety of cell phenotypes, thereby providing numerous potential cell therapies to treat an array of degenerative diseases and traumatic injuries. A recent paradigm shift has emerged suggesting that the beneficial effects of stem cells may not be restricted to cell restoration alone, but also due to their transient paracrine actions. Stem cells can secrete potent combinations of trophic factors that modulate the molecular composition of the environment to evoke responses from resident cells. Based on this new insight, current research directions include efforts to elucidate, augment and harness stem cell paracrine mechanisms for tissue regeneration. This article discusses the existing studies on stem/progenitor cell trophic factor production, implications for tissue regeneration and cancer therapies, and development of novel strategies to use stem cell paracrine delivery for regenerative medicine. PMID:20017699

  1. 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

  2. Mesenchymal stem cells for retinal diseases.

    PubMed

    Xu, Wei; Xu, Guo-Xing

    2011-01-01

    Retinal diseases are featured with the common result of retinal cell apoptosis that will cause irreversible vision loss. Various attempts have been made for the solution against cell death. However, few approaches turn out to be effective. With the progress in mesenchymal stem cells (MSCs) research, MSCs were considered as a promising source for cell replacement or neuroprotection in retinal disorders. MSCs have the property of self-renewal and are multipotent cells derived from various mesenchymal tissues, which were demonstrated being capable of differentiating into multilineage tissue cells. Some works were also done to differentiate MSCs into retinal cells. MSCs could be induced to express retinal cell markers under certain stimuli. Recent studies also suggest that MSCs should be an ideal source for neuroprotection via the secretion of a variety of neurotrophins. Engineered MSCs were also used as vehicles for continuous delivery of neurotrophins against retinal degeneration with encouraging results. Since there are still barriers on the differentiation of MSCs into functional retinal cells, the use of MSCs for neuroprotection in retinal diseases seems to be a more practicable approach and worthy of further investigations. PMID:22553693

  3. Generation and Purification of Definitive Endoderm Cells Generated from Pluripotent Stem Cells.

    PubMed

    Diekmann, Ulf; Naujok, Ortwin

    2016-01-01

    Differentiation of pluripotent stem cells into cells of the definitive endoderm requires an in vitro gastrulation event. Differentiated somatic cells derived from this germ layer may then be used for cell replacement therapies of degenerative diseases of the liver, lung, and pancreas. Here we describe an endoderm differentiation protocol, which initiates the differentiation from a defined cell number of dispersed single cells and reliably yields in >70-80 % endoderm-committed cells in a short 5-day treatment regimen. PMID:25762297

  4. 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

  5. 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

  6. 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…

  7. Regenerative Endodontics in light of the stem cell paradigm

    PubMed Central

    Rosa, Vinicius; Botero, Tatiana M.; Nör, Jacques E.

    2013-01-01

    Stem cells play a critical role in development and in tissue regeneration. The dental pulp contains a small sub-population of stem cells that are involved in the response of the pulp to caries progression. Specifically, stem cells replace odontoblasts that have undergone cell death as a consequence of the cariogenic challenge. Stem cells also secrete factors that have the potential to enhance pulp vascularization and provide the oxygen and nutrients required for the dentinogenic response that is typically observed in teeth with deep caries. However, the same angiogenic factors that are required for dentin regeneration may ultimately contribute to the demise of the pulp by enhancing vascular permeability and interstitial pressure. Recent studies focused on the biology of dental pulp stem cells revealed that the multipotency and angiogenic capacity of these cells could be exploited therapeutically in dental pulp tissue engineering. Collectively, these findings suggest new treatment paradigms in the field of Endodontics. The goal of this review is to discuss the potential impact of dental pulp stem cells to Regenerative Endodontics. PMID:21726222

  8. Electrophysiological recordings from neuroepithelial stem cells.

    PubMed

    Yamashita, Masayuki

    2015-01-01

    During embryonic development, neuroepithelial cells act as neural stem cells by renewing themselves. These cells are tightly interconnected and make contact with the basement membrane of the neuroepithelium. Under such circumstances, intracellular recording with a fine-tipped microelectrode is a successful method to study the electrophysiological properties of the neuroepithelial stem cell. This chapter describes the detailed techniques of intracellular recording from neuroepithelial stem cells. PMID:25063504

  9. Stem cells for liver regeneration.

    PubMed

    Than, N N; Newsome, P N

    2014-06-01

    The liver has a unique capacity to repair following injury, which is largely achieved by proliferation of hepatocytes. However, in situations of chronic or overwhelming liver injury, additional repair mechanisms, namely liver progenitor or oval cells, are activated. These cells, located in the canals of Hering, express markers for both hepatocytes and biliary cells and have the capacity to differentiate down both hepatocyte and biliary lineages. Previous work has suggested that the administration of autologous or allogeneic cell therapies such as haematopoietic or mesenchymal stem cells can augment liver repair by either stimulating endogenous repair mechanisms or by suppressing ongoing damage. A better understanding of how cell therapies can promote liver regeneration will lead to the refinement of these therapeutic approaches and also develop new pharmacological agents for liver repair. PMID:24453286

  10. 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.

  11. 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

  12. Stem cells - biological update and cell therapy progress

    PubMed Central

    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. PMID:26609255

  13. 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. PMID:26609255

  14. Chemically Induced Reprogramming of Somatic Cells to Pluripotent Stem Cells and Neural Cells

    PubMed Central

    Biswas, Dhruba; Jiang, Peng

    2016-01-01

    The ability to generate transplantable neural cells in a large quantity in the laboratory is a critical step in the field of developing stem cell regenerative medicine for neural repair. During the last few years, groundbreaking studies have shown that cell fate of adult somatic cells can be reprogrammed through lineage specific expression of transcription factors (TFs)-and defined culture conditions. This key concept has been used to identify a number of potent small molecules that could enhance the efficiency of reprogramming with TFs. Recently, a growing number of studies have shown that small molecules targeting specific epigenetic and signaling pathways can replace all of the reprogramming TFs. Here, we provide a detailed review of the studies reporting the generation of chemically induced pluripotent stem cells (ciPSCs), neural stem cells (ciNSCs), and neurons (ciN). We also discuss the main mechanisms of actions and the pathways that the small molecules regulate during chemical reprogramming. PMID:26861316

  15. Transcriptome sequencing of hematopoietic stem cells and chronic myelgenous leukemia stem cells.

    PubMed

    Kim, Junil; Kim, Seong-Jin; Naka, Kazuhito

    2016-03-01

    Dipeptide species are accumulated in the chronic myelogenous leukemia (CML) stem cells [1]. To investigate the molecular mechanisms of the accumulation of dipeptide species in CML stem cells, we performed transcriptome sequencing of long-term stem cells, short-term stem cells, progenitor cells from healthy control and CML-affected mice (GSE70031). The transcriptome data revealed that the expression of a dipeptide transporter (solute carrier family 15, member 2 (SLC15A2)) was elevated only in the CML stem cells. This result indicates that dipeptide species accumulates in CML stem cells through a dipeptide transporter SLC15A2. PMID:26981360

  16. Transcriptome sequencing of hematopoietic stem cells and chronic myelgenous leukemia stem cells

    PubMed Central

    Kim, Junil; Kim, Seong-Jin; Naka, Kazuhito

    2015-01-01

    Dipeptide species are accumulated in the chronic myelogenous leukemia (CML) stem cells [1]. To investigate the molecular mechanisms of the accumulation of dipeptide species in CML stem cells, we performed transcriptome sequencing of long-term stem cells, short-term stem cells, progenitor cells from healthy control and CML-affected mice (GSE70031). The transcriptome data revealed that the expression of a dipeptide transporter (solute carrier family 15, member 2 (SLC15A2)) was elevated only in the CML stem cells. This result indicates that dipeptide species accumulates in CML stem cells through a dipeptide transporter SLC15A2. PMID:26981360

  17. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    PubMed Central

    Feng, Xuezhu; Zhang, Jiuchun; Smuga-Otto, Kimberly; Tian, Shulan; Yu, Junying; Stewart, Ron; Thomson, James A.

    2012-01-01

    Unlike mouse embryonic stem cells (ESCs), which are closely related to the inner cell mass, human ESCs appear to be more closely related to the later primitive ectoderm. For example, human ESCs and primitive ectoderm share a common epithelial morphology, growth factor requirements, and the potential to differentiate to all three embryonic germ layers. However, it has previously been shown that human ESCs can also differentiate to cells expressing markers of trophoblast, an extraembryonic lineage formed before the formation of primitive ectoderm. Here, we show that phorbol ester 12-O-tetradecanoylphorbol 13-acetate causes human ESCs to undergo an epithelial mesenchymal transition and to differentiate into cells expressing markers of parietal endoderm, another extraembryonic lineage. We further confirmed that this differentiation is through the activation of protein kinase C (PKC) pathway and demonstrated that a particular PKC subtype, PKC-δ, is most responsible for this transition. PMID:22213079

  18. Intestinal stem cells and celiac disease.

    PubMed

    Piscaglia, Anna Chiara

    2014-04-26

    Stem cells (SCs) are the key to tissue genesis and regeneration. Given their central role in homeostasis, dysfunctions of the SC compartment play a pivotal role in the development of cancers, degenerative disorders, chronic inflammatory pathologies and organ failure. The gastrointestinal tract is constantly exposed to harsh mechanical and chemical conditions and most of the epithelial cells are replaced every 3 to 5 d. According to the so-called Unitarian hypothesis, this renewal is driven by a common intestinal stem cell (ISC) residing within the crypt base at the origin of the crypt-to-villus hierarchical migratory pattern. Celiac disease (CD) can be defined as a chronic immune-mediated disease that is triggered and maintained by dietary proteins (gluten) in genetically predisposed individuals. Many advances have been achieved over the last years in understanding of the pathogenic interactions among genetic, immunological and environmental factors in CD, with a particular emphasis on intestinal barrier and gut microbiota. Conversely, little is known about ISC modulation and deregulation in active celiac disease and upon a gluten-free diet. Nonetheless, bone marrow-derived SC transplantation has become an option for celiac patients with complicated or refractory disease. This manuscript summarizes the "state of the art" regarding CD and ISCs, their niche and potential role in the development and treatment of the disease. PMID:24772248

  19. Intestinal stem cells and celiac disease

    PubMed Central

    Piscaglia, Anna Chiara

    2014-01-01

    Stem cells (SCs) are the key to tissue genesis and regeneration. Given their central role in homeostasis, dysfunctions of the SC compartment play a pivotal role in the development of cancers, degenerative disorders, chronic inflammatory pathologies and organ failure. The gastrointestinal tract is constantly exposed to harsh mechanical and chemical conditions and most of the epithelial cells are replaced every 3 to 5 d. According to the so-called Unitarian hypothesis, this renewal is driven by a common intestinal stem cell (ISC) residing within the crypt base at the origin of the crypt-to-villus hierarchical migratory pattern. Celiac disease (CD) can be defined as a chronic immune-mediated disease that is triggered and maintained by dietary proteins (gluten) in genetically predisposed individuals. Many advances have been achieved over the last years in understanding of the pathogenic interactions among genetic, immunological and environmental factors in CD, with a particular emphasis on intestinal barrier and gut microbiota. Conversely, little is known about ISC modulation and deregulation in active celiac disease and upon a gluten-free diet. Nonetheless, bone marrow-derived SC transplantation has become an option for celiac patients with complicated or refractory disease. This manuscript summarizes the “state of the art” regarding CD and ISCs, their niche and potential role in the development and treatment of the disease. PMID:24772248

  20. Stem Cell-Based Therapy in Idiopathic Pulmonary Fibrosis.

    PubMed

    Barczyk, Marek; Schmidt, Matthias; Mattoli, Sabrina

    2015-08-01

    Idiopathic pulmonary fibrosis is a progressive fibrosing disorder for which there is no cure and no pharmacological treatment capable of increasing in a meaningful way the survival rate. Lung transplantation remains the only possible treatment for patients with advanced disease, although the increase in 5-year survival is only 45 %. Some preclinical studies have generated promising results about the therapeutic potential of exogenous stem cells. However, two initial clinical trials involving the endobronchial or systemic delivery of autologous adipose tissue-derived or unrelated-donor, placenta-derived mesenchymal stem cells have not convincingly demonstrated that these treatments are acceptably safe. The results of other ongoing clinical trials may help to identify the best source and delivery route of mesenchymal stem cells and to estimate the risk of unwanted effects related to the mesenchymal nature of the transplanted cells. Considering that most of the therapeutic potential of these cells has been ascribed to paracrine signaling, the use of mesenchymal stem cell-derived secretome as an alternative to the transplantation of single cell suspension may circumvent many regulatory and clinical problems. Technical and safety concerns still limit the possibility of clinical applications of other promising interventions that are based on the use of human amnion stem cells, embryonic stem cells or induced pluripotent stem cells to replace or regenerate the dysfunctional alveolar epithelium. We summarize the current status of the field and identify major challenges and opportunities for the possible future integration of stem cell-based treatments into the currently recommended clinical management strategy for idiopathic pulmonary fibrosis. PMID:25896401

  1. Long-term maintenance of human induced pluripotent stem cells by automated cell culture system

    PubMed Central

    Konagaya, Shuhei; Ando, Takeshi; Yamauchi, Toshiaki; Suemori, Hirofumi; Iwata, Hiroo

    2015-01-01

    Pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem (iPS) cells, are regarded as new sources for cell replacement therapy. These cells can unlimitedly expand under undifferentiated conditions and be differentiated into multiple cell types. Automated culture systems enable the large-scale production of cells. In addition to reducing the time and effort of researchers, an automated culture system improves the reproducibility of cell cultures. In the present study, we newly designed a fully automated cell culture system for human iPS maintenance. Using an automated culture system, hiPS cells maintained their undifferentiated state for 60 days. Automatically prepared hiPS cells had a potency of differentiation into three germ layer cells including dopaminergic neurons and pancreatic cells. PMID:26573336

  2. 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. PMID:24800720

  3. 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

  4. 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. PMID:25772134

  5. The therapeutic potential of stem cells

    PubMed Central

    Watt, Fiona M.; Driskell, Ryan R.

    2010-01-01

    In recent years, there has been an explosion of interest in stem cells, not just within the scientific and medical communities but also among politicians, religious groups and ethicists. Here, we summarize the different types of stem cells that have been described: their origins in embryonic and adult tissues and their differentiation potential in vivo and in culture. We review some current clinical applications of stem cells, highlighting the problems encountered when going from proof-of-principle in the laboratory to widespread clinical practice. While some of the key genetic and epigenetic factors that determine stem cell properties have been identified, there is still much to be learned about how these factors interact. There is a growing realization of the importance of environmental factors in regulating stem cell behaviour and this is being explored by imaging stem cells in vivo and recreating artificial niches in vitro. New therapies, based on stem cell transplantation or endogenous stem cells, are emerging areas, as is drug discovery based on patient-specific pluripotent cells and cancer stem cells. What makes stem cell research so exciting is its tremendous potential to benefit human health and the opportunities for interdisciplinary research that it presents. PMID:20008393

  6. 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.

  7. 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

  8. Epigenetic regulation of stem cell differentiation.

    PubMed

    Wu, Hao; Sun, Yi Eve

    2006-04-01

    Stem cells undergo extensive self-renewal and have the capacity to differentiate along multiple cell lineages. Progression from stem cells into differentiated progeny requires long-lasting changes in gene expression. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA-mediated regulatory events, are essential to controlling the heritable cellular memory of gene expression during development. Recent studies on cell fate specification of embryonic and adult stem cells/progenitors have highlighted a general and critical role for dynamic epigenetic regulation in stem cell self-renewal and differentiation. PMID:16549544

  9. Adult Stem Cell Responses to Nanostimuli.

    PubMed

    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

  10. Stem Cells for Augmenting Tendon Repair

    PubMed Central

    Gulotta, Lawrence V.; Chaudhury, Salma; Wiznia, Daniel

    2012-01-01

    Tendon healing is fraught with complications such as reruptures and adhesion formation due to the formation of scar tissue at the injury site as opposed to the regeneration of native tissue. Stem cells are an attractive option in developing cell-based therapies to improve tendon healing. However, several questions remain to be answered before stem cells can be used clinically. Specifically, the type of stem cell, the amount of cells, and the proper combination of growth factors or mechanical stimuli to induce differentiation all remain to be seen. This paper outlines the current literature on the use of stem cells for tendon augmentation. PMID:22190960

  11. Endothelial potential of human embryonic stem cells

    PubMed Central

    Zoldan, Janet; Basevitch, Yaara; Langer, Robert

    2007-01-01

    Growing interest in using endothelial cells for therapeutic purposes has led to exploring human embryonic stem cells as a potential source for endothelial progenitor cells. Embryonic stem cells are advantageous when compared with other endothelial cell origins, due to their high proliferation capability, pluripotency, and low immunogenity. However, there are many challenges and obstacles to overcome before the vision of using embryonic endothelial progenitor cells in the clinic can be realized. Among these obstacles is the development of a productive method of isolating endothelial cells from human embryonic stem cells and elucidating their differentiation pathway. This review will focus on the endothelial potential of human embryonic stem cells that is described in current studies, with respect to the differentiation of human embryonic stem cells to endothelial cells, their isolation, and their characterization. PMID:17412888

  12. 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. PMID:23517628

  13. Melanocyte stem cells: Biology and current aspects

    PubMed Central

    Gola, Monika; Czajkowski, Rafa?; Bajek, Anna; Dura, Aleksander; Drewa, Tomasz

    2012-01-01

    Summary Epidermal stem cells have become an object of intensive research. The epidermis constitutes one of the main sources of stem cells and is a tissue of choice for use in exploring their biology. Stratified squamous epithelium (epidermis) possesses the capacity for self-renewal and repair due to the presence of epidermal stem cells (ESC). They have been identified within basal layer of the interfollicular epidermis (IFE), in the bulge of the hair follicles of rodents, and also in the human follicular bulge. Melanocyte stem cells (MSC) from hair follicles (precisely from the bulge region, which also contains epidermal stem cells) provide an attractive model for the study of stem cells and their regulation at the niche. This review summarizes the rapidly developing field of epidermal stem cell research and their application in regenerative medicine, paying particular attention to melanocyte stem cells, their biology and some of the processes that occur during hair graying and regeneration of the pigmentary system, as well as discussing how aged-associated changes in the melanocyte stem cells compartment impact hair graying. This review also includes differentiation of human skin stem cells into functional epidermal melanocytes. PMID:23018363

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

    PubMed Central

    Otsu, Masahiro; Nakayama, Takashi; Inoue, Nobuo

    2014-01-01

    Basic research on pluripotent stem cells is designed to enhance understanding of embryogenesis, whereas applied research is designed to develop novel therapies and prevent diseases. Attainment of these goals has been enhanced by the establishment of embryonic stem cell lines, the technological development of genomic reprogramming to generate induced-pluripotent stem cells, and improvements in vitro techniques to manipulate stem cells. This review summarizes the techniques required to generate neural cells from pluripotent stem cells. In particular, this review describes current research applications of a simple neural differentiation method, the neural stem sphere method, which we developed. PMID:25426263

  15. Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantations suitable for treatment of Parkinson's disease?★

    PubMed Central

    Yoon, Hyung Ho; Min, Joongkee; Shin, Nari; Kim, Yong Hwan; Kim, Jin-Mo; Hwang, Yu-Shik; Suh, Jun-Kyo Francis; Hwang, Onyou; Jeon, Sang Ryong

    2013-01-01

    Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson's disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups (PBS injection) demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase (dopaminergic neuronal marker) staining and G protein-activated inward rectifier potassium channel 2 (A9 dopaminergic neuronal marker) were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stem cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine. PMID:25206413

  16. [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. PMID:26483336

  17. Stem cell applications for pathologies of the urinary bladder

    PubMed Central

    Mousa, Noha A; Abou-Taleb, Hisham A; Orabi, Hazem

    2015-01-01

    New stem cell based therapies are undergoing intense research and are widely investigated in clinical fields including the urinary system. The urinary bladder performs critical complex functions that rely on its highly coordinated anatomical composition and multiplex of regulatory mechanisms. Bladder pathologies resulting in severe dysfunction are common clinical encounter and often cause significant impairment of patient’s quality of life. Current surgical and medical interventions to correct urinary dysfunction or to replace an absent or defective bladder are sub-optimal and are associated with notable complications. As a result, stem cell based therapies for the urinary bladder are hoped to offer new venues that could make up for limitations of existing therapies. In this article, we review research efforts that describe the use of different types of stem cells in bladder reconstruction, urinary incontinence and retention disorders. In particular, stress urinary incontinence has been a popular target for stem cell based therapies in reported clinical trials. Furthermore, we discuss the relevance of the cancer stem cell hypothesis to the development of bladder cancer. A key subject that should not be overlooked is the safety and quality of stem cell based therapies introduced to human subjects either in a research or a clinical context. PMID:26131312

  18. Equine Induced Pluripotent Stem Cells have a Reduced Tendon Differentiation Capacity Compared to Embryonic Stem Cells

    PubMed Central

    Bavin, Emma P.; Smith, Olivia; Baird, Arabella E. G.; Smith, Lawrence C.; Guest, Deborah J.

    2015-01-01

    Tendon injuries occur commonly in horses and their repair through scar tissue formation predisposes horses to a high rate of re-injury. Pluripotent stem cells may provide a cell replacement therapy to improve tendon tissue regeneration and lower the frequency of re-injury. We have previously demonstrated that equine embryonic stem cells (ESCs) differentiate into the tendon cell lineage upon injection into the damaged horse tendon and can differentiate into functional tendon cells in vitro to generate artificial tendons. Induced pluripotent stem cells (iPSCs) have now been derived from horses but, to date, there are no reports on their ability to differentiate into tendon cells. As iPSCs can be produced from adult cell types, they provide a more accessible source of cells than ESCs, which require the use of horse embryos. The aim of this study was to compare tendon differentiation by ESCs and iPSCs produced through two independent methods. In two-dimensional differentiation assays, the iPSCs expressed tendon-associated genes and proteins, which were enhanced by the presence of transforming growth factor-β3. However, in three-dimensional (3D) differentiation assays, the iPSCs failed to differentiate into functional tendon cells and generate artificial tendons. These results demonstrate the utility of the 3D in vitro tendon assay for measuring tendon differentiation and the need for more detailed studies to be performed on equine iPSCs to identify and understand their epigenetic differences from pluripotent ESCs prior to their clinical application. PMID:26664982

  19. Derivation, characterization and retinal differentiation of induced pluripotent stem cells.

    PubMed

    Mekala, Subba Rao; Vauhini, Vasundhara; Nagarajan, Usha; Maddileti, Savitri; Gaddipati, Subhash; Mariappan, Indumathi

    2013-03-01

    Millions of people world over suffer visual disability due to retinal dystrophies which can be age-related or a genetic disorder resulting in gradual degeneration of the retinal pigmented epithelial (RPE) cells and photoreceptors. Therefore, cell replacement therapy offers a great promise in treating such diseases. Since the adult retina does not harbour any stem cells, alternative stem cell sources like the embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) offer a great promise for generating different cell types of the retina. Here, we report the derivation of four iPSC lines from mouse embryonic fibroblasts (MEFs) using a cocktail of recombinant retroviruses carrying the genes for Oct4, Sox2, Klf4 and cMyc. The iPS clone MEF-4F3 was further characterized for stemness marker expression and stable reprogramming by immunocytochemistry, FACS and RT-PCR analysis. Methylation analysis of the nanog promoter confirmed the reprogrammed epigenetic state. Pluripotency was confirmed by embryoid body (EB) formation and lineage-specific marker expression. Also, upon retinal differentiation, patches of pigmented cells with typical cobble-stone phenotype similar to RPE cells are generated within 6 weeks and they expressed ZO-1 (tight junction protein), RPE65 and bestrophin (mature RPE markers) and showed phagocytic activity by the uptake of fluorescent latex beads. PMID:23385820

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

    PubMed

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

    2014-11-01

    In response to recurrent exposure to environmental insults such as allergens, pollution, irritants, smoke and viral/bacterial infection, the epithelium of the lung is continually damaged. Homeostasis of the lung requires a balance between immune regulation and promotion of tissue regeneration, which requires the co-ordinated proliferation and differentiation of stem and progenitor cells. In this review we reflect on the current understanding of lung epithelial stem and progenitor cells and advocate a model hierarchy in which self-renewing multipotent lung epithelial stem cells give rise to lineage restricted progenitor cells that repopulate airway and alveolar epithelial cell lineages during homeostasis and repair. We also discuss the role of mesenchymal progenitor cells in maintaining the structural integrity of the lung and propose a model in which mesenchymal cells act as the quintessential architects of lung regeneration by providing molecular signals, such as FGF-10, to regulate the fate and specificity of epithelial stem and progenitor cells. Moreover, we discuss the current status and future prospects for translating lung stem cell therapies to the clinic to replace, repair, or regenerate diseased lung tissue. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation. PMID:25450456

  1. 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

  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. PMID:23157178

  3. Mammary stem cells have myoepithelial cell properties.

    PubMed

    Prater, Michael D; Petit, Valérie; Alasdair Russell, I; Giraddi, Rajshekhar R; 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

    2014-10-01

    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 actin-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 two independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage-tracing approach we follow the progeny of myoepithelial cells that express α-smooth muscle actin and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy. PMID:25173976

  4. 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

  5. Induction of Trabecular Meshwork Cells From Induced Pluripotent Stem Cells

    PubMed Central

    Ding, Qiong J.; Zhu, Wei; Cook, Amy C.; Anfinson, Kristin R.; Tucker, Budd A.; Kuehn, Markus H.

    2014-01-01

    Purpose. Loss or dysfunction of trabecular meshwork (TM) cells has been associated with the development of pathologically elevated IOP, and it is conceivable that replacement of damaged TM cells could restore function to the TM. We propose that the use of TM-like cells derived from induced pluripotent stem cells (iPSCs) created from a patient's own dermal fibroblasts offers the best solution to this challenge. Here we demonstrate that mouse iPSCs can be induced to differentiate into TM-like cells suitable for autologous transplantation. Methods. Directed induction of stem cell differentiation was achieved through coculture of mouse iPSCs with human TM cells for up to 21 days. The resultant TM-like cells (iPSC-TM) were characterized morphologically, immunohistochemically, and functionally. Results. The iPSC-TM cells closely resembled cultured human TM cells morphologically and began to express many markers of TM cells while ceasing to express pluripotency markers such as Nanog, Oct4, and Sox2. Functionally, these cells developed the ability to phagocytose particles. Finally, exposure to dexamethasone or phorbol 12-myristate acetate caused a distinct increase in the production and secretion of myocilin and matrix metalloproteinase-3, respectively, behavior characteristic of TM cells. Conclusions. Our data demonstrate that iPSCs can be induced to assume a phenotype that resembles native TM cells in many important aspects. Not only do these cells represent a valuable research tool, but transplantation into glaucomatous eyes with elevated IOP may also restore function to the TM, resulting in re-establishment of IOP. PMID:25298418

  6. Epithelial stem cells in adult skin.

    PubMed

    Tadeu, Ana Mafalda Baptista; Horsley, Valerie

    2014-01-01

    The skin is the first line of defense against dehydration and external environmental aggressions. It constantly renews itself throughout adult life mainly due to the activity of tissue-specific stem cells. In this review, we discuss fundamental characteristics of different stem cell populations within the skin and how they are able to contribute to normal skin homeostasis. We also examine the most recent results regarding the cell-intrinsic and -extrinsic components of the stem cell niche within the adult skin epithelium. Finally, we address the recent efforts to understand how abnormal regulation of stem cell activity contributes to the initiation and progression of skin-associated cancers. PMID:24439804

  7. Tendon Regeneration and Repair with Stem Cells

    PubMed Central

    MacLean, S.; Khan, W. S.; Malik, A. A.; Snow, M.; Anand, S.

    2012-01-01

    The use of stems cells in tendon repair is of particular interest given the frequency of tendon injuries worldwide together with the technical difficulty often encountered when repairing or augmenting tendons. Stems cells have the capability to differentiate into a variety of different cell types including osteocytes and tenocytes, and if normal architecture of damaged tendon (either macroscopic or microscopic) could be restored, this would significantly improve the management of patients with these injuries. There is already encouraging research on the use of stems cells clinically although considerable further work is required to improve knowledge and clinical applications of stem cells in tissue engineering. PMID:25098364

  8. Extrafollicular Dermal Melanocyte Stem Cells and Melanoma

    PubMed Central

    Hoerter, James D.; Bradley, Patrick; Casillas, Alexandria; Chambers, Danielle; Denholm, Carli; Johnson, Kimberly; Weiswasser, Brandon

    2012-01-01

    Recent studies suggest that extrafollicular dermal melanocyte stem cells (MSCs) persist after birth in the superficial nerve sheath of peripheral nerves and give rise to migratory melanocyte precursors when replacements for epidermal melanocytes are needed on the basal epidermal layer of the skin. If a damaged MSC or melanocyte precursor can be shown to be the primary origin of melanoma, targeted identification and eradication of it by antibody-based therapies will be the best method to treat melanoma and a very effective way to prevent its recurrence. Transcription factors and signaling pathways involved in MSC self-renewal, expansion and differentiation are reviewed. A model is presented to show how the detrimental effects of long-term UVA/UVB radiation on DNA and repair mechanisms in MSCs convert them to melanoma stem cells. Zebrafish have many advantages for investigating the role of MSCs in the development of melanoma. The signaling pathways regulating the development of MSCs in zebrafish are very similar to those found in humans and mice. The ability to easily manipulate the MSC population makes zebrafish an excellent model for studying how damage to MSCs may lead to melanoma. PMID:22666269

  9. The short stem GHEs in total hip replacement experience after 380 implantations

    PubMed Central

    Ghanem, Mohamed; Farag, M.; Schneider, P.; Hitzler, P.; Gulow, J.; Freiherr von Salis-Soglio, G

    2013-01-01

    Introduction: Standard straight stems have been recognized as a gold standard implant in the field of hip replacement surgery. However, lately uncemented bone-preserving short stems started to gain more and more popularity. This was reflected in the increasing variety of available models. Up till now, short and mid-term results are available. Patients and methods: In 2002, the cementless short stemmed GHEs was introduced. 380 patients were included in our study between 2002 and 2008. Only GHEs short stems were implanted. The clinical and radiological evaluations were performed in the Orthopaedic Department, Leipzig University Hospitals, on the average of 24 months (3 to 60 months) postoperatively. Results: 365 primary implantations and 15 revision implantations were carried out. Average age 60 years. Favourable clinical and radiological outcome was seen in 361/380 patients (95%). Postoperative complications were seen in 19/380 patients (5%): 8 fissures/fractures (2.1%), 5 infections (1.3%), 4 aseptic loosenings (1.1%), 2 dislocations (0.5%). Conclusions: Short stem implants, including our own experience with GHEs model, are satisfying and promising. They represent a valuable supplementation of the treatment modalities in hip replacement surgery. However, long term results are still awaited. PMID:26504707

  10. Mesenchymal Stem Cell-Based Tissue Engineering for Chondrogenesis

    PubMed Central

    Seo, Seogjin; Na, Kun

    2011-01-01

    In tissue engineering fields, recent interest has been focused on stem cell therapy to replace or repair damaged or worn-out tissues due to congenital abnormalities, disease, or injury. In particular, the repair of articular cartilage degeneration by stem cell-based tissue engineering could be of enormous therapeutic and economic benefit for an aging population. Bone marrow-derived mesenchymal stem cells (MSCs) that can induce chondrogenic differentiation would provide an appropriate cell source to repair damaged cartilage tissues; however, we must first understand the optimal environmental conditions for chondrogenic differentiation. In this review, we will focus on identifying the best combination of MSCs and functional extracellular matrices that provides the most successful chondrogenesis. PMID:22007146

  11. Dopaminergic differentiation using pluripotent stem cells.

    PubMed

    Mom?ilovi?, Olga; Montoya-Sack, Justine; Zeng, Xianmin

    2012-12-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder. The motor symptoms of PD are caused by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta of mesencephalon. The causes for death of DA neurons are not well understood, but the strongest risk factor is increasing age. There is no cure currently available for PD, and treatment is limited to management of PD symptoms in patients. Primary DA neurons are virtually unobtainable from living patients and animal studies have proven inadequate for studying the mechanism of PD development. Pluripotent stem cells (PSC) are primary self-renewing cells capable of differentiating into all cell types of an organism, including DA neurons. PSCs represent an abundant source of cells that can be genetically modified or isolated from patients with complex diseases, enabling the production of large quantities of DA neurons for disease modeling, drug screening, and gene function studies. Furthermore, since PD arises as a result of deterioration of DA neurons in a specific brain region, it has been suggested that a relatively small number of cells could restore normal function. PSCs could provide a source of DA neurons for cell replacement therapy. In this Prospects article, we focus on the development and in vitro derivation of DA neurons from PSCs, as well as current applications of the technological advances, with the emphasis on future directions and efforts in the field. PMID:22807388

  12. 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. PMID:25893594

  13. 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.

  14. 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.

  15. 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

  16. Telomere biology in stem cells and reprogramming.

    PubMed

    Batista, Luis F Z

    2014-01-01

    Telomerase expression in humans is restricted to different populations of stem and progenitor cells, being silenced in most somatic tissues. Efficient telomere homeostasis is essential for embryonic and adult stem cell function and therefore essential for tissue homeostasis throughout organismal life. Accordingly, the mutations in telomerase culminate in reduced stem cell function both in vivo and in vitro and have been associated with tissue dysfunction in human patients. Despite the importance of telomerase for stem cell biology, the mechanisms behind telomerase regulation during development are still poorly understood, mostly due to difficulties in acquiring and maintaining pluripotent stem cell populations in culture. In this chapter, we will analyze recent developments in this field, including the importance of efficient telomere homeostasis in different stem cell types and the role of telomerase in different techniques used for cellular reprogramming. PMID:24993698

  17. Potential antitumor therapeutic strategies of human amniotic membrane and amniotic fluid-derived stem cells.

    PubMed

    Kang, N-H; Hwang, K-A; Kim, S U; Kim, Y-B; Hyun, S-H; Jeung, E-B; Choi, K-C

    2012-08-01

    As stem cells are capable of self-renewal and can generate differentiated progenies for organ development, they are considered as potential source for regenerative medicine and tissue replacement after injury or disease. Along with this capacity, stem cells have the therapeutic potential for treating human diseases including cancers. According to the origins, stem cells are broadly classified into two types: embryonic stem cells (ESCs) and adult stem cells. In terms of differentiation potential, ESCs are pluripotent and adult stem cells are multipotent. Amnion, which is a membranous sac that contains the fetus and amniotic fluid and functions in protecting the developing embryo during gestation, is another stem cell source. Amnion-derived stem cells are classified as human amniotic membrane-derived epithelial stem cells, human amniotic membrane-derived mesenchymal stem cells and human amniotic fluid-derived stem cells. They are in an intermediate stage between pluripotent ESCs and lineage-restricted adult stem cells, non-tumorigenic, and contribute to low immunogenicity and anti-inflammation. Furthermore, they are easily available and do not cause any controversial issues in their recovery and applications. Not only are amnion-derived stem cells applicable in regenerative medicine, they have anticancer capacity. In non-engineered stem cells transplantation strategies, amnion-derived stem cells effectively target the tumor and suppressed the tumor growth by expressing cytotoxic cytokines. Additionally, they also have a potential as novel delivery vehicles transferring therapeutic genes to the cancer formation sites in gene-directed enzyme/prodrug combination therapy. Owing to their own advantageous properties, amnion-derived stem cells are emerging as a new candidate in anticancer therapy. PMID:22653384

  18. 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. PMID:25990836

  19. [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. PMID:24448860

  20. Preclinical Assessment of Stem Cell Therapies for Neurological Diseases

    PubMed Central

    Joers, Valerie L.; Emborg, Marina E.

    2010-01-01

    Stem cells, as subjects of study for use in treating neurological diseases, are envisioned as a replacement for lost neurons and glia, a means of trophic support, a therapeutic vehicle, and, more recently, a tool for in vitro modeling to understand disease and to screen and personalize treatments. In this review we analyze the requirements of stem cell–based therapy for clinical translation, advances in stem cell research toward clinical application for neurological disorders, and different animal models used for analysis of these potential therapies. We focus on Parkinson’s disease (typically defined by the progressive loss of dopaminergic nigral neurons), stroke (neurodegeneration associated with decreased blood perfusion in the brain), and multiple sclerosis (an autoimmune disorder that generates demyelination, axonal damage, astrocytic scarring, and neurodegeneration in the brain and spinal cord). We chose these disorders for their diversity and the number of people affected by them. An additional important consideration was the availability of multiple animal models in which to test stem cell applications for these diseases. We also discuss the relationship between the limited number of systematic stem cell studies performed in animals, in particular nonhuman primates and the delayed progress in advancing stem cell therapies to clinical success. PMID:20075496

  1. Stem cell-based therapies in ischemic heart diseases: a focus on aspects of microcirculation and inflammation

    PubMed Central

    Wu, Junxi; Li, Jun; Zhang, Nannan

    2011-01-01

    Stem cells possessing the potential to replace damaged myocardium with functional myocytes have drawn increasing attention in the past decade in treating ischemic heart diseases; these diseases are the leading cause of morbidity and mortality in the world. The adult heart has recently been shown to contain a few cardiac stem cells (CSCs) that, in theory, suggest cardiac repair following acute myocardial infarction is possible if the CSC titer could be increased. Stem cell-based therapies, including hematopoietic stem cells and mesenchymal stem cells, were proven to be marginal and transitional. Multiple factors and mechanisms, rather than direct cardiac regeneration are involved in stem cell-mediated cardiac functional improvement. This review will focus on (1) the interaction between inflammation and stem cells; (2) the fate of stem cells at the microcirculatory level, and their subsequent influences on stem cell-based therapies. PMID:21424917

  2. 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.

  3. Induced pluripotent stem cells from goat fibroblasts.

    PubMed

    Song, Hui; Li, Hui; Huang, Mingrui; Xu, Dan; Gu, Chenghao; Wang, Ziyu; Dong, Fulu; Wang, Feng

    2013-12-01

    Embryonic stem cells (ESCs) are a powerful model for genetic engineering, studying developmental biology, and modeling disease. To date, ESCs have been established from the mouse (Evans and Kaufman, 1981, Nature 292:154-156), non-human primates (Thomson et al., , Proc Nat Acad Sci USA 92:7844-7848), humans (Thomson et al., 1998, Science 282:1145-1147), and rats (Buehr et al., , Cell 135:1287-1298); however, the derivation of ESCs from domesticated ungulates such as goats, sheep, cattle, and pigs have not been successful. Alternatively, induced pluripotent stem cells (iPSCs) can be generated by reprogramming somatic cells with several combinations of genes encoding transcription factors (OCT3/4, SOX2, KLF4, cMYC, LIN28, and NANOG). To date, iPSCs have been isolated from various species, but only limited information is available regarding goat iPSCs (Ren et al., 2011, Cell Res 21:849-853). The objectives of this study were to generate goat iPSCs from fetal goat primary ear fibroblasts using lentiviral transduction of four human transcription factors: OCT4, SOX2, KLF4, and cMYC. The goat iPSCs were successfully generated by co-culture with mitomycin C-treated mouse embryonic fibroblasts using medium supplemented with knockout serum replacement and human basic fibroblast growth factor. The goat iPSCs colonies are flat, compact, and closely resemble human iPSCs. They have a normal karyotype; stain positive for alkaline phosphatase, OCT4, and NANOG; express endogenous pluripotency genes (OCT4, SOX2, cMYC, and NANOG); and can spontaneously differentiate into three germ layers in vitro and in vivo. PMID:24123501

  4. Germline Stem Cell Transplantation and Transgenesis

    PubMed Central

    Brinster, Ralph L.

    2016-01-01

    The recently developed testis cell transplantation method provides a powerful approach to studying the biology of the male germline stem cell and its microenvironment, the stem cell niche. The technique also is being used to examine spermatogenic defects, correct male infertility, and generate transgenic animals. PMID:12077400

  5. 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. PMID:25362798

  6. Head and Neck Cancer Stem Cells

    PubMed Central

    Krishnamurthy, S.; Nör, J.E.

    2012-01-01

    Most cancers contain a small sub-population of cells that are endowed with self-renewal, multipotency, and a unique potential for tumor initiation. These properties are considered hallmarks of cancer stem cells. Here, we provide an overview of the field of cancer stem cells with a focus on head and neck cancers. Cancer stem cells are located in the invasive fronts of head and neck squamous cell carcinomas (HNSCC) close to blood vessels (perivascular niche). Endothelial cell-initiated signaling events are critical for the survival and self-renewal of these stem cells. Markers such as aldehyde dehydrogenase (ALDH), CD133, and CD44 have been successfully used to identify highly tumorigenic cancer stem cells in HNSCC. This review briefly describes the orosphere assay, a method for in vitro culture of undifferentiated head and neck cancer stem cells under low attachment conditions. Notably, recent evidence suggests that cancer stem cells are exquisitely resistant to conventional therapy and are the “drivers” of local recurrence and metastatic spread. The emerging understanding of the role of cancer stem cells in the pathobiology of head and neck squamous cell carcinomas might have a profound impact on the treatment paradigms for this malignancy. PMID:21933937

  7. Preconditioning Stem Cells for In Vivo Delivery

    PubMed Central

    Sart, Sbastien; Ma, Teng

    2014-01-01

    Abstract Stem cells have emerged as promising tools for the treatment of incurable neural and heart diseases and tissue damage. However, the survival of transplanted stem cells is reported to be low, reducing their therapeutic effects. The major causes of poor survival of stem cells in vivo are linked to anoikis, potential immune rejection, and oxidative damage mediating apoptosis. This review investigates novel methods and potential molecular mechanisms for stem cell preconditioning in vitro to increase their retention after transplantation in damaged tissues. Microenvironmental preconditioning (e.g., hypoxia, heat shock, and exposure to oxidative stress), aggregate formation, and hydrogel encapsulation have been revealed as promising strategies to reduce cell apoptosis in vivo while maintaining biological functions of the cells. Moreover, this review seeks to identify methods of optimizing cell dose preparation to enhance stem cell survival and therapeutic function after transplantation. PMID:25126478

  8. Generation of Thyroid Follicular Cells from Pluripotent Stem Cells: Potential for Regenerative Medicine

    PubMed Central

    Sewell, Will; Lin, Reigh-Yi

    2014-01-01

    Nearly 12% of the population in the United States will be afflicted with a thyroid related disorder during their lifetime. Common treatment approaches are tailored to the specific disorder and include surgery, radioactive iodine ablation, antithyroid drugs, thyroid hormone replacement, external beam radiation, and chemotherapy. Regenerative medicine endeavors to combat disease by replacing or regenerating damaged, diseased, or dysfunctional body parts. A series of achievements in pluripotent stem cell research have transformed regenerative medicine in many ways by demonstrating repair of a number of body parts in mice, of which, the thyroid has now been inducted into this special group. Seminal work in pluripotent cells, namely embryonic stem cells and induced pluripotent stem cells, have made possible their path to becoming key tools and biological building blocks for cell-based regenerative medicine to combat the gamut of human diseases, including those affecting the thyroid. PMID:24995001

  9. Stem cell research: biology, ethics, and policy.

    PubMed

    Micielli, R

    2000-01-01

    Human stem cell research may have many promising benefits, including giving us the ability to regenerate human tissue and organs, understand the process of early human development, and provide better models to test new drugs. However, it is very controversial and in many cases presently illegal because stem cells may be derived from human embryos or from a cloning process. This paper outlines the various techniques which may be used for deriving stem cells, the ethical problems such research presents, and suggestions for creating policy for human stem cells research. PMID:11936141

  10. 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

  11. Minireview: beta-cell replacement therapy for diabetes in the 21st century: manipulation of cell fate by directed differentiation.

    PubMed

    Yechoor, Vijay; Chan, Lawrence

    2010-08-01

    Pancreatic beta-cell failure underlies type 1 diabetes; it also contributes in an essential way to type 2 diabetes. beta-Cell replacement is an important component of any cure for diabetes. The current options of islet and pancreas transplantation are not satisfactory as definitive forms of therapy. Here, we review strategies for induced de novo pancreatic beta-cell formation, which depend on the targeted differentiation of cells into pancreatic beta-cells. With this objective in mind, one can manipulate the fate of three different types of cells: 1) from terminally differentiated cells, e.g. exocrine pancreatic cells, into beta-cells; 2) from multipotent adult stem cells, e.g. hepatic oval cells, into pancreatic islets; and 3) from pluripotent stem cells, e.g. embryonic stem cells and induced pluripotent stem cells, into beta-cells. We will examine the pros and cons of each strategy as well as the hurdles that must be overcome before these approaches to generate new beta-cells will be ready for clinical application. PMID:20219891

  12. Treatment options for diabetes: potential role of stem cells.

    PubMed

    Stanekzai, Jamil; Isenovic, Esma R; Mousa, Shaker A

    2012-12-01

    There are diseases and injuries in which a patient's cells or tissues are destroyed that can only be adequately corrected by tissue or organ transplants. Stem cells may be able to generate new tissue and even cure diseases for which there is no adequate therapy. Type 1 diabetes (T1DM), an insulin-dependent diabetes, is a chronic disease affecting genetically predisposed individuals, in which insulin-secreting beta (β)-cells within pancreatic islets of Langerhans are selectively and irreversibly destroyed by autoimmune assault. Type 2 diabetes (T2DM) is characterized by a gradual decrease in insulin sensitivity in peripheral tissues and the liver (insulin resistance), followed by a gradual decline in β-cell function and insulin secretion. Successful replacing of damaged β-cells has shown considerable potential in treating T1DM, but lack of adequate donors is a barrier. The literature suggests that embryonic and adult stem cells are promising alternatives in long-term treatment of diabetes. However, any successful strategy should address both the need for β-cell replacement and controlling the autoimmune response to cells that express insulin. This review summarizes the current knowledge of options and the potential of stem cell transplantation in diabetes treatment. PMID:23020931

  13. Chemical genetics and its potential in cardiac stem cell therapy

    PubMed Central

    Vieira, Joaquim M; Riley, Paul R

    2013-01-01

    Over the last decade or so, intensive research in cardiac stem cell biology has led to significant discoveries towards a potential therapy for cardiovascular disease; the main cause of morbidity and mortality in humans. The major goal within the field of cardiovascular regenerative medicine is to replace lost or damaged cardiac muscle and coronaries following ischaemic disease. At present, de novo cardiomyocytes can be generated either in vitro, for cell transplantation or disease modelling using directed differentiation of embryonic stem cells or induced pluripotent stem cells, or in vivo via direct reprogramming of resident adult cardiac fibroblast or ectopic stimulation of resident cardiac stem or progenitor cells. A major bottleneck with all of these approaches is the low efficiency of cardiomyocyte differentiation alongside their relative functional immaturity. Chemical genetics, and the application of phenotypic screening with small molecule libraries, represent a means to enhance understanding of the molecular pathways controlling cardiovascular cell differentiation and, moreover, offer the potential for discovery of new drugs to invoke heart repair and regeneration. Here, we review the potential of chemical genetics in cardiac stem cell therapy, highlighting not only the major contributions to the field so far, but also the future challenges. LINKED ARTICLES This article is part of a themed section on Regenerative Medicine and Pharmacology: A Look to the Future. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-2 PMID:22385148

  14. Plasticity and neural stem cells in the enteric nervous system.

    PubMed

    Schäfer, Karl-Herbert; Van Ginneken, Chris; Copray, Sjef

    2009-12-01

    The enteric nervous system (ENS) is a highly organized part of the autonomic nervous system, which innervates the whole gastrointestinal tract by several interconnected neuronal networks. The ENS changes during development and keeps throughout its lifespan a significant capacity to adapt to microenvironmental influences, be it in inflammatory bowel diseases or changing dietary habits. The presence of neural stem cells in the pre-, postnatal, and adult gut might be one of the prerequisites to adapt to changing conditions. During the last decade, the ENS has increasingly come into the focus of clinical neural stem cell research, forming a considerable pool of neural crest derived stem cells, which could be used for cell therapy of dysganglionosis, that is, diseases based on the deficient or insufficient colonization of the gut by neural crest derived stem cells; in addition, the ENS could be an easily accessible neural stem cell source for cell replacement therapies for neurodegenerative disorders or traumatic lesions of the central nervous system. PMID:19943347

  15. Methods for magnetically labeling stem and other cells for detection by in vivo magnetic resonance imaging.

    PubMed

    Frank, J A; Anderson, S A; Kalsih, H; Jordan, E K; Lewis, B K; Yocum, G T; Arbab, A S

    2004-01-01

    Superparamagnetic iron oxide (SPIO) nanoparticles are being used for intracellular magnetic labeling of stem cells and other cells in order to monitor cell trafficking by magnetic resonance imaging (MRI) as part of cellular-based repair, replacement and treatment strategies. This review focuses on the various methods for magnetic labeling of stem cells and other mammalian cells and on how to translate experimental results from bench to bedside. PMID:15773025

  16. Genomic instability in induced stem cells.

    PubMed

    Pasi, C E; Dereli-Öz, A; Negrini, S; Friedli, M; Fragola, G; Lombardo, A; Van Houwe, G; Naldini, L; Casola, S; Testa, G; Trono, D; Pelicci, P G; Halazonetis, T D

    2011-05-01

    The ability to reprogram adult cells into stem cells has raised hopes for novel therapies for many human diseases. Typical stem cell reprogramming protocols involve expression of a small number of genes in differentiated somatic cells with the c-Myc and Klf4 proto-oncogenes typically included in this mix. We have previously shown that expression of oncogenes leads to DNA replication stress and genomic instability, explaining the high frequency of p53 mutations in human cancers. Consequently, we wondered whether stem cell reprogramming also leads to genomic instability. To test this hypothesis, we examined stem cells induced by a variety of protocols. The first protocol, developed specifically for this study, reprogrammed primary mouse mammary cells into mammary stem cells by expressing c-Myc. Two other previously established protocols reprogrammed mouse embryo fibroblasts into induced pluripotent stem cells by expressing either three genes, Oct4, Sox2 and Klf4, or four genes, OSK plus c-Myc. Comparative genomic hybridization analysis of stem cells derived by these protocols revealed the presence of genomic deletions and amplifications, whose signature was suggestive of oncogene-induced DNA replication stress. The genomic aberrations were to a significant degree dependent on c-Myc expression and their presence could explain why p53 inactivation facilitates stem cell reprogramming. PMID:21311564

  17. Liver Stem Cells and Hepatocellular Carcinoma

    PubMed Central

    Mishra, Lopa; Banker, Tanuj; Murray, Joseph; Byers, Stephen; Thenappan, Arun; He, Aiwu Ruth; Shetty, Kirti; Johnson, Lynt; Reddy, E. P.

    2009-01-01

    Although the existence of cancer stem cells (CSCs) was first proposed over 40 years ago, only in the past decade have these cells been identified in hematological malignancies, and more recently in solid tumors that include liver, breast, prostate, brain, and colon. Constant proliferation of stem cells is a vital component in liver tissues. In these renewing tissues, mutations will most likely result in expansion of the altered stem cells, perpetuating and increasing the chances of additional mutations and tumor progression. However, many details about hepatocellular cancer stem cells that are important for early detection remain poorly understood, including the precise cell(s) of origin, molecular genetics, and the mechanisms responsible for the highly aggressive clinical picture of hepatocellular carcinoma (HCC). Exploration of the difference between CSCs from normal stem cells is crucial not only for the understanding of tumor biology but also for the development of specific therapies that effectively target these cells in patients. These ideas have drawn attention to control of stem cell proliferation by the transforming growth factor beta (TGF-β), Notch, Wnt, and Hedgehog pathways. Recent evidence also suggests a key role for the TGF-β signaling pathway in both hepatocellular cancer suppression and endoderm formation, suggesting a dual role for this pathway in tumor suppression as well as progression of differentiation from a stem or progenitor stage. This review provides a rationale for detecting and analyzing tumor stem cells as one of the most effective ways to treat cancers such as HCC. PMID:19111019

  18. Designing Biomaterials To Direct Stem Cell Fate

    PubMed Central

    Cha, Chaenyung; Liechty, William B.; Khademhosseini, Ali; Peppas, Nicholas A.

    2012-01-01

    As stem cells are a cornerstone of regenerative medicine, research efforts have been extensively focused on controlling their self-renewal and differentiation. It is well known that stem cells are tightly regulated by a combination of physical and chemical factors from their complex extracellular surroundings; thus, conventional cell culture approaches based purely on using soluble factors to direct stem cell fate have resulted in limited success. To account for the complexities of native stem-cell niches, biomaterials are actively investigated as artificial extracellular matrices in order to mimic the natural microenvironment. This Perspective highlights important areas related to the design of biomaterials to control stem cell behavior, such as cell-responsive ligands, mechanical signals, and delivery of soluble factors. PMID:23136849

  19. Designing biomaterials to direct stem cell fate.

    PubMed

    Cha, Chaenyung; Liechty, William B; Khademhosseini, Ali; Peppas, Nicholas A

    2012-11-27

    As stem cells are a cornerstone of regenerative medicine, research efforts have been extensively focused on controlling their self-renewal and differentiation. It is well-known that stem cells are tightly regulated by a combination of physical and chemical factors from their complex extracellular surroundings; thus, conventional cell culture approaches based purely on using soluble factors to direct stem cell fate have resulted in limited success. To account for the complexities of native stem-cell niches, biomaterials are actively investigated as artificial extracellular matrices in order to mimic the natural microenvironment. This Perspective highlights important areas related to the design of biomaterials to control stem cell behavior, such as cell-responsive ligands, mechanical signals, and delivery of soluble factors. PMID:23136849

  20. Nonclinical safety strategies for stem cell therapies

    SciTech Connect

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

    2012-08-01

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

  1. Adult stem-like cells in kidney.

    PubMed

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

    2015-03-26

    Human pluripotent cells are promising for treatment for kidney diseases, but the protocols for derivation of kidney cell types are still controversial. Kidney tissue regeneration is well confirmed in several lower vertebrates such as fish, and the repair of nephrons after tubular damages is commonly observed after renal injury. Even in adult mammal kidney, renal progenitor cell or system is reportedly presents suggesting that adult stem-like cells in kidney can be practical clinical targets for kidney diseases. However, it is still unclear if kidney stem cells or stem-like cells exist or not. In general, stemness is defined by several factors such as self-renewal capacity, multi-lineage potency and characteristic gene expression profiles. The definite use of stemness may be obstacle to understand kidney regeneration, and here we describe the recent broad findings of kidney regeneration and the cells that contribute regeneration. PMID:25815133

  2. Ophthalmologic stem cell transplantation therapies

    PubMed Central

    Blenkinsop, Timothy A; Corneo, Barbara; Temple, Sally; Stern, Jeffrey H

    2013-01-01

    Vision loss is a major social issue, with more than 20 million people over the age of 18 years affected in the USA alone. Loss of vision is feared more than premature death or cardiovascular disease, according to a recent Society for Consumer Research group survey. The annual direct cost of medical care for the most prevalent eye disease, age-related macular degeneration, was estimated at US$255 billion in 2010 with an additional economic impact of US$88 billion due to lost productivity and the burden of family and community care for visual disability. With the blossoming of human stem cell research, regenerative treatments are now being developed that can help reduce this burden. Positive results from animal studies demonstrate that stem cell-based transplants can preserve and potentially improve vision. This has led to new clinical trials for several eye diseases that are yielding encouraging results. In the next few years, additional trials and longer-term results are anticipated to further develop ocular regenerative therapies, with the potential to revolutionize our approach to ophthalmic disease and damage. PMID:23210809

  3. Cancer stem cells in glioblastoma

    PubMed Central

    Lathia, Justin D.; Mack, Stephen C.; Mulkearns-Hubert, Erin E.; Valentim, Claudia L.L.; Rich, Jeremy N.

    2015-01-01

    Tissues with defined cellular hierarchies in development and homeostasis give rise to tumors with cellular hierarchies, suggesting that tumors recapitulate specific tissues and mimic their origins. Glioblastoma (GBM) is the most prevalent and malignant primary brain tumor and contains self-renewing, tumorigenic cancer stem cells (CSCs) that contribute to tumor initiation and therapeutic resistance. As normal stem and progenitor cells participate in tissue development and repair, these developmental programs re-emerge in CSCs to support the development and progressive growth of tumors. Elucidation of the molecular mechanisms that govern CSCs has informed the development of novel targeted therapeutics for GBM and other brain cancers. CSCs are not self-autonomous units; rather, they function within an ecological system, both actively remodeling the microenvironment and receiving critical maintenance cues from their niches. To fulfill the future goal of developing novel therapies to collapse CSC dynamics, drawing parallels to other normal and pathological states that are highly interactive with their microenvironments and that use developmental signaling pathways will be beneficial. PMID:26109046

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

    PubMed

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

    2012-08-01

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

  5. Mesenchymal stem cells for cardiac cell therapy.

    PubMed

    Choi, Yeong-Hoon; Kurtz, Andreas; Stamm, Christof

    2011-01-01

    Despite refinements of medical and surgical therapies, heart failure remains a fatal disease. Myocardial infarction is the most common cause of heart failure, and only palliative measures are available to relieve symptoms and prolong the patient's life span. Because mammalian cardiomyocytes irreversibly exit the cell cycle at about the time of birth, the heart has traditionally been considered to lack any regenerative capacity. This paradigm, however, is currently shifting, and the cellular composition of the myocardium is being targeted by various regeneration strategies. Adult progenitor and stem cell treatment of diseased human myocardium has been carried out for more than 10 years (Menasche et al., 2001; Stamm et al., 2003), and it has become clear that, in humans, the regenerative capacity of hematopoietic stem cells and endothelial progenitor cells, despite potent proangiogenic effects, is limited (Stamm et al., 2009). More recently, mesenchymal stem cells (MSCs) and related cell types are being evaluated in preclinical models of heart disease as well as in clinical trials (see Published Clinical Trials, below). MSCs have the capacity to self-renew and to differentiate into lineages that normally originate from the embryonic mesenchyme (connective tissues, blood vessels, blood-related organs) (Caplan, 1991; Prockop, 1997; Pittenger et al., 1999). The current definition of MSCs includes plastic adherence in cell culture, specific surface antigen expression (CD105(+)/CD90(+)/CD73(+), CD34(-)/CD45(-)/CD11b(-) or CD14(-)/CD19(-) or CD79α(-)/HLA-DR1(-)), and multilineage in vitro differentiation potential (osteogenic, chondrogenic, and adipogenic) (Dominici et al., 2006 ). If those criteria are not met completely, the term "mesenchymal stromal cells" should be used for marrow-derived adherent cells, or other terms for MSC-like cells of different origin. For the purpose of this review, MSCs and related cells are discussed in general, and cell type-specific properties are indicated when appropriate. We first summarize the preclinical data on MSCs in models of heart disease, and then appraise the clinical experience with MSCs for cardiac cell therapy. PMID:21062128

  6. Conventional and novel methods for embryonic stem cell line derivation.

    PubMed

    Kiatpongsan, Sorapop; Tannirandorn, Yuen; Numchaisrikhabsc, Pranee; Rungsiwiwut, Ruttachuk

    2006-06-01

    Cell therapy is the promising therapeutic tool for the next decade. "Regenerative Medicine" based on cell and tissue replacement therapy is proposed as a revolutionary approach to various chronic and incurable conditions. The first key step for successful cell therapy is the establishment of clinical grade human Embryonic Stem Cell (hESC) lines. This article provides a concise summary on conventional and novel methods for hESC line derivation. There is also discussion on progression, future direction and problems in hESC line development. In Thailand, more advance knowledge, skill, and technology are required to develop the first human embryonic stem cell line and step forward to make cell therapy a reality. PMID:16850695

  7. Mesenchymal stem cells: From stem cells to sarcomas.

    PubMed

    Lye, Kwan Liang; Nordin, Norshariza; Vidyadaran, Sharmili; Thilakavathy, Karuppiah

    2016-06-01

    Mesenchymal stem cells (MSCs) have garnered vast interests in clinical settings, especially in regenerative medicine due to their unique properties-they are reliably isolated and expanded from various tissue sources; they are able to differentiate into mesodermal tissues such as bones, cartilages, adipose tissues, and muscles; and they have unique immunosuppressive properties. However, there are some concerns pertaining to the role of MSCs in the human body. On one hand, they are crucial component in the regeneration and repair of the human body. On the contrary, they are shown to transform into sarcomas. Although the exact mechanisms are still unknown, many new leads have pointed to the belief that MSCs do play a role in sarcomagenesis. This review focuses on the current updates and findings of the role of MSCs in their transformation process into sarcomas. PMID:26992453

  8. Enhancing spontaneous stem cell healing (Review)

    PubMed Central

    MAGUIRE, GREG; FRIEDMAN, PETER

    2014-01-01

    Adult stem cells are distributed throughout the human body and are responsible to a great extent for the body’s ability to maintain and heal itself. Accumulating data since the 1990s regarding stem cells have demonstrated that the beneficial effects of stem cells are not restricted to their ability to differentiate and are more likely due to their ability to release a multitude of molecules. Recent studies indicated that ≤80% of the therapeutic benefit of adult stem cells is manifested by the stem cell released molecules (SRM) rather than the differentiation of the stem cells into mature tissue. Stem cells may release potent combinations of factors that modulate the molecular composition of the cellular milieu to evoke a multitude of responses from neighboring cells. A multitude of pathways are involved in cellular and tissue function and, when the body is in a state of disease or trauma, a multitude of pathways are involved in the underlying mechanisms of that disease or trauma. Therefore, stem cells represent a natural systems-based biological factory for the production and release of a multitude of molecules that interact with the system of biomolecular circuits underlying disease or tissue damage. Currently, efforts are aimed at defining, stimulating, enhancing and harnessing SRM mechanisms, in order to develop systems-based methods for tissue regeneration, develop drugs/biologics or other therapeutics and enhance the release of SRM into the body for natural healing through proper dietary, exercise and other lifestyle strategies. PMID:24649089

  9. Dedifferentiation of committed epithelial cells into stem cells in vivo.

    PubMed

    Tata, Purushothama Rao; Mou, Hongmei; Pardo-Saganta, Ana; Zhao, Rui; Prabhu, Mythili; Law, Brandon M; Vinarsky, Vladimir; Cho, Josalyn L; Breton, Sylvie; Sahay, Amar; Medoff, Benjamin D; Rajagopal, Jayaraj

    2013-11-14

    Cellular plasticity contributes to the regenerative capacity of plants, invertebrates, teleost fishes and amphibians. In vertebrates, differentiated cells are known to revert into replicating progenitors, but these cells do not persist as stable stem cells. Here we present evidence that differentiated airway epithelial cells can revert into stable and functional stem cells in vivo. After the ablation of airway stem cells, we observed a surprising increase in the proliferation of committed secretory cells. Subsequent lineage tracing demonstrated that the luminal secretory cells had dedifferentiated into basal stem cells. Dedifferentiated cells were morphologically indistinguishable from stem cells and they functioned as well as their endogenous counterparts in repairing epithelial injury. Single secretory cells clonally dedifferentiated into multipotent stem cells when they were cultured ex vivo without basal stem cells. By contrast, direct contact with a single basal stem cell was sufficient to prevent secretory cell dedifferentiation. In analogy to classical descriptions of amphibian nuclear reprogramming, the propensity of committed cells to dedifferentiate is inversely correlated to their state of maturity. This capacity of committed cells to dedifferentiate into stem cells may have a more general role in the regeneration of many tissues and in multiple disease states, notably cancer. PMID:24196716

  10. Dedifferentiation of committed epithelial cells into stem cells in vivo

    PubMed Central

    Tata, Purushothama Rao; Mou, Hongmei; Pardo-Saganta, Ana; Zhao, Rui; Prabhu, Mythili; Prabhu, Mythili; Law, Brandon M.; Vinarsky, Vladimir; Cho, Josalyn L.; Breton, Sylvie; Sahay, Amar; Medoff, Benjamin D.; Rajagopal, Jayaraj

    2014-01-01

    Summary Cellular plasticity contributes to the regenerative capacity of plants, invertebrates, teleost fishes, and amphibians. In vertebrates, differentiated cells are known to revert into replicating progenitors, but these cells do not persist as stable stem cells. We now present evidence that differentiated airway epithelial cells can revert into stable and functional stem cells in vivo. Following the ablation of airway stem cells, we observed a surprising increase in the proliferation of committed secretory cells. Subsequent lineage tracing demonstrated that the luminal secretory cells had dedifferentiated into basal stem cells. Dedifferentiated cells were morphologically indistinguishable from stem cells and they functioned as well as their endogenous counterparts to repair epithelial injury. Indeed, single secretory cells clonally dedifferentiated into multipotent stem cells when they were cultured ex vivo without basal stem cells. In contrast, direct contact with a single basal stem cell was sufficient to prevent secretory cell dedifferentiation. In analogy to classical descriptions of amphibian nuclear reprogramming, the propensity of committed cells to dedifferentiate was inversely correlated to their state of maturity. This capacity of committed cells to dedifferentiate into stem cells may play a more general role in the regeneration of many tissues and in multiple disease states, notably cancer. PMID:24196716

  11. 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

  12. Metabolic regulation of stem cell function

    PubMed Central

    Burgess, Rebecca J.; Agathocleous, Michalis; Morrison, Sean J.

    2014-01-01

    Stem cell function is regulated by intrinsic mechanisms, such as transcriptional and epigenetic regulators, as well as extrinsic mechanisms, such as short-range signals from the niche and long-range humoral signals. Interactions between these regulatory mechanisms and cellular metabolism are just beginning to be identified. In multiple systems, differentiation is accompanied by changes in glycolysis, oxidative phosphorylation, and the levels of reactive oxygen species. Indeed, metabolic pathways regulate proliferation and differentiation by regulating energy production and the generation of substrates for biosynthetic pathways. Some metabolic pathways appear to function differently in stem cells as compared with restricted progenitors and differentiated cells. They also appear to influence stem cell function by regulating signal transduction, epigenetic marks, and oxidative stress. Studies to date illustrate the importance of metabolism in the regulation of stem cell function and suggest complex cross regulation likely exists between metabolism and other stem cell regulatory mechanisms. PMID:24697828

  13. Transdifferentiation of Stem Cells: A Critical View

    NASA Astrophysics Data System (ADS)

    Gruh, Ina; Martin, Ulrich

    Recently a large amount of new data on the plasticity of stem cells of various lineages have emerged, providing new perspectives especially for the therapeutic application of adult stem cells. Previously unknown possibilities of cell differentiation beyond the known commitment of a given stem cell have been described using keywords such as "blood to liver," or "bone to brain." Controversies on the likelihood, as well as the biological significance, of these conversions almost immediately arose within this young field of stem cell biology. This chapter will concentrate on these controversies and focus on selected examples demonstrating the technical aspects of stem cell transdifferentiation and the evaluation of the tools used to analyze these events.

  14. 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

  15. Determination of Somatic and Cancer Stem Cell Self-Renewing Symmetric Division Rate Using Sphere Assays

    PubMed Central

    Deleyrolle, Loic P.; Ericksson, Geoffery; Morrison, Brian J.; Lopez, J. Alejandro; Burrage, Kevin; Burrage, Pamela; Vescovi, Angelo; Rietze, Rodney L.; Reynolds, Brent A.

    2011-01-01

    Representing a renewable source for cell replacement, neural stem cells have received substantial attention in recent years. The neurosphere assay represents a method to detect the presence of neural stem cells, however owing to a deficiency of specific and definitive markers to identify them, their quantification and the rate they expand is still indefinite. Here we propose a mathematical interpretation of the neurosphere assay allowing actual measurement of neural stem cell symmetric division frequency. The algorithm of the modeling demonstrates a direct correlation between the overall cell fold expansion over time measured in the sphere assay and the rate stem cells expand via symmetric division. The model offers a methodology to evaluate specifically the effect of diseases and treatments on neural stem cell activity and function. Not only providing new insights in the evaluation of the kinetic features of neural stem cells, our modeling further contemplates cancer biology as cancer stem-like cells have been suggested to maintain tumor growth as somatic stem cells maintain tissue homeostasis. Indeed, tumor stem cell's resistance to therapy makes these cells a necessary target for effective treatment. The neurosphere assay mathematical model presented here allows the assessment of the rate malignant stem-like cells expand via symmetric division and the evaluation of the effects of therapeutics on the self-renewal and proliferative activity of this clinically relevant population that drive tumor growth and recurrence. PMID:21246056

  16. Increased Understanding of Stem Cell Behavior in Neurodegenerative and Neuromuscular Disorders by Use of Noninvasive Cell Imaging

    PubMed Central

    Holvoet, Bryan; De Waele, Liesbeth; Quattrocelli, Mattia; Gheysens, Olivier; Sampaolesi, Maurillio; Verfaillie, Catherine M.; Deroose, Christophe M.

    2016-01-01

    Numerous neurodegenerative and neuromuscular disorders are associated with cell-specific depletion in the human body. This imbalance in tissue homeostasis is in healthy individuals repaired by the presence of endogenous stem cells that can replace the lost cell type. However, in most disorders, a genetic origin or limited presence or exhaustion of stem cells impairs correct cell replacement. During the last 30 years, methods to readily isolate and expand stem cells have been developed and this resulted in a major change in the regenerative medicine field as it generates sufficient amount of cells for human transplantation applications. Furthermore, stem cells have been shown to release cytokines with beneficial effects for several diseases. At present however, clinical stem cell transplantations studies are struggling to demonstrate clinical efficacy despite promising preclinical results. Therefore, to allow stem cell therapy to achieve its full potential, more insight in their in vivo behavior has to be achieved. Different methods to noninvasively monitor these cells have been developed and are discussed. In some cases, stem cell monitoring even reached the clinical setting. We anticipate that by further exploring these imaging possibilities and unraveling their in vivo behavior further improvement in stem cell transplantations will be achieved. PMID:26997958

  17. Tumor microenvironment for cancer stem cells.

    PubMed

    Kise, Kazuyoshi; Kinugasa-Katayama, Yumi; Takakura, Nobuyuki

    2016-04-01

    Tumor tissues consist of heterogeneous cancer cells including cancer stem cells (CSCs) that can terminally differentiate into cancer cells. Tissue-specific stem cells in normal organs maintain their stemness in a specific microenvironment, the stem cell niche; several studies have suggested that there are specific microenvironments that maintain CSCs in an immature phenotype. Cell types in a CSC niche vary from fibroblasts, to endothelial cells, immune cells, and so on; these non-cancer cells have been suggested to change their original features in the normal tissue/organ and to acquire a phenotype that protects CSCs from anticancer therapies. Therefore, to kill CSCs, we need to understand the cellular and molecular mechanisms involved in the maintenance of the immature phenotype of CSCs and in drug resistance. PMID:26362921

  18. Stem cell sources for tooth regeneration: current status and future prospects

    PubMed Central

    Otsu, Keishi; Kumakami-Sakano, Mika; Fujiwara, Naoki; Kikuchi, Kazuko; Keller, Laetitia; Lesot, Hervé; Harada, Hidemitsu

    2014-01-01

    Stem cells are capable of renewing themselves through cell division and have the remarkable ability to differentiate into many different types of cells. They therefore have the potential to become a central tool in regenerative medicine. During the last decade, advances in tissue engineering and stem cell-based tooth regeneration have provided realistic and attractive means of replacing lost or damaged teeth. Investigation of embryonic and adult (tissue) stem cells as potential cell sources for tooth regeneration has led to many promising results. However, technical and ethical issues have hindered the availability of these cells for clinical application. The recent discovery of induced pluripotent stem (iPS) cells has provided the possibility to revolutionize the field of regenerative medicine (dentistry) by offering the option of autologous transplantation. In this article, we review the current progress in the field of stem cell-based tooth regeneration and discuss the possibility of using iPS cells for this purpose. PMID:24550845

  19. Islet transplantation versus stem cells for the cell therapy of type 1 diabetes mellitus.

    PubMed

    Basta, G; Montanucci, P; Calafiore, R

    2015-12-01

    Pancreatic islet cell transplantation has represented the mainstay of cell therapy for the potential, final cure of type 1 diabetes mellitus (T1D), along the past two decades. Unfortunately, the restricted availability of cadaveric human donor pancreases coupled with heavy side effects of the recipient's general immunosuppression, have severely crippled progress of this approach into clinical trials. Only a few excellence centers, worldwide, have thus far accrued still quite marginal clinical success. In an attempt to overcome the limits of islet transplantation new technologies for use of several stem cell lineages are being under investigation, with initial experimental evidence of success. Essentially, the actual lines of research involve attempts to either activate native endogenous stem cells that replace diseased/dead cells, by a cell regeneration process, or condition other stem cells to acquire the functional properties of the targeted cells to be substituted (i.e., beta-cell-like elements associated with insulin secretory competence). A wide array of stem cells may fulfill this task, from embryonic (whose use still faces strong ethical barriers), to adult, to induced pluripotent stem cells. Mesenchymal adult stem cells, retrievable from many different sites, including adipose tissue, bone marrow and post-partum umbilical cord Wharton Jelly, seem to couple plastic to immunoregulatory properties that might greatly help progress for the disease cure. PMID:26398188

  20. Convergence of normal stem cell and cancer stem cell developmental stage: Implication for differential therapies

    PubMed Central

    Li, Shengwen Calvin; Lee, Katherine L; Luo, Jane; Zhong, Jiang F; Loudon, William G

    2011-01-01

    Increased evidence shows that normal stem cells may contribute to cancer development and progression by acting as cancer-initiating cells through their interactions with abnormal environmental elements. We postulate that normal stem cells and cancer stem cells (CSC) possess similar mechanisms of self-renewal and differentiation. CSC can be the key to the elaboration of anti-cancer-based therapy. In this article, we focus on a controversial new theme relating to CSC. Tumorigenesis may have a critical stage characterized as a therapeutic window, which can be identified by association of molecular, biochemical and biological events. Identifying such a stage can allow the production of more effective therapies (e.g. manipulated stem cells) to treat several cancers. More importantly, confirming the existence of a similar therapeutic window during the conversion of normal stem cells to malignant CSC may lead to targeted therapy specifically against CSC. This conversion information may be derived from investigating the biological behaviour of both normal stem cells and cancerous stem cells. Currently, there is little knowledge about the cellular and molecular mechanisms that govern the initiation and maintenance of CSC. Studies on co-evolution and interdependence of cancer with normal tissues may lead to a useful treatment paradigm of cancer. The crosstalk between normal stem cells and cancer formation may converge developmental stages of different types of stem cells (e.g. normal stem cells, CSC and embryonic stem cells). The differential studies of the convergence may result in novel therapies for treating cancers. PMID:22007273

  1. Stem Cell Research and Health Education

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  2. Epigenetic Targeting of Ovarian Cancer Stem Cells

    PubMed Central

    Wang, Yinu; Cardenas, Horacio; Fang, Fang; Condello, Salvatore; Taverna, Pietro; Segar, Matthew; Liu, Yunlong; Nephew, Kenneth P.; Matei, Daniela

    2014-01-01

    Emerging results indicate that cancer stem-like cells contribute to chemoresistance and poor clinical outcomes in many cancers, including ovarian cancer (OC). As epigenetic regulators play a major role in the control of normal stem cell differentiation, epigenetics may offer a useful arena to develop strategies to target cancer stem-like cells. Epigenetic aberrations, especially DNA methylation, silence tumor suppressor and differentiation-associated genes that regulate the survival of ovarian cancer stem-like cell (OCSC). In this study, we tested the hypothesis that DNA hypomethylating agents may be able to reset OCSC towards a differentiated phenotype, by evaluating the effects of the new DNA methytransferase inhibitor SGI-110 on OCSC phenotype, as defined by expression of the cancer stem-like marker aldehyde dehydrogenase (ALDH). We demonstrated that ALDH+ OC cells possess multiple stem cell characteristics, were highly chemoresistant, and were enriched in xenografts residual after platinum therapy. Low dose SGI-110 reduced the stem-like properties of ALDH+ cells, including their tumor initiating capacity, resensitized these OCSCs to platinum, and induced re-expression of differentiation-associated genes. Maintenance treatment with SGI-110 after carboplatin inhibited OCSC growth, causing global tumor hypomethylation and decreased tumor progression. Our work offers preclinical evidence that epigenome-targeting strategies have the potential to delay tumor progression by re-programming residual cancer stem-like cells. Further, the results suggest that SGI-110 might be administered in combination with platinum to prevent the development of recurrent and chemoresistant ovarian cancer. PMID:25035395

  3. 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. PMID:21905078

  4. Representations of stem cell clinics on Twitter.

    PubMed

    Kamenova, Kalina; Reshef, Amir; Caulfield, Timothy

    2014-12-01

    The practice of travelling abroad to receive unproven and unregulated stem cell treatments has become an increasingly problematic global phenomenon known as 'stem cell tourism'. In this paper, we examine representations of nine major clinics and providers of such treatments on the microblogging network Twitter. We collected and conducted a content analysis of Twitter posts (n = 363) by these establishments and by other users mentioning them, focusing specifically on marketing claims about treatment procedures and outcomes, discussions of safety and efficacy of stem cell transplants, and specific representations of patients' experiences. Our analysis has shown that there were explicit claims or suggestions of benefits associated with unproven stem cell treatments in approximately one third of the tweets and that patients' experiences, whenever referenced, were presented as invariably positive and as testimonials about the efficacy of stem cell transplants. Furthermore, the results indicated that the tone of most tweets (60.2 %) was overwhelmingly positive and there were rarely critical discussions about significant health risks associated with unproven stem cell therapies. When placed in the context of past research on the problems associated with the marketing of unproven stem cell therapies, this analysis of representations on Twitter suggests that discussions in social media have also remained largely uncritical of the stem cell tourism phenomenon, with inaccurate representations of risks and benefits for patients. PMID:24970380

  5. Stem Cell Technology for Neurodegenerative Diseases

    PubMed Central

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

    2011-01-01

    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 on the burden of these diseases on society, emphasizing the need for increased attention towards 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’s disease, Huntington’s disease, Alzheimer’s 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. PMID:21905078

  6. Chemically Induced Specification of Retinal Ganglion Cells From Human Embryonic and Induced Pluripotent Stem Cells

    PubMed Central

    Riazifar, Hamidreza; Jia, Yousheng; Chen, Jing; Lynch, Gary

    2014-01-01

    The loss of retinal ganglion cells (RGCs) is the primary pathological change for many retinal degenerative diseases. Although there is currently no effective treatment for this group of diseases, cell transplantation to replace lost RGCs holds great potential. However, for the development of cell replacement therapy, better understanding of the molecular details involved in differentiating stem cells into RGCs is essential. In this study, a novel, stepwise chemical protocol is described for the differentiation of human embryonic stem cells and induced pluripotent stem cells into functional RGCs. Briefly, stem cells were differentiated into neural rosettes, which were then cultured with the Notch inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT). The expression of neural and RGC markers (BRN3A, BRN3B, ATOH7/Math5, γ-synuclein, Islet-1, and THY-1) was examined. Approximately 30% of the cell population obtained expressed the neuronal marker TUJ1 as well the RGC markers. Moreover, the differentiated RGCs generated action potentials and exhibited both spontaneous and evoked excitatory postsynaptic currents, indicating that functional and mature RGCs were generated. In combination, these data demonstrate that a single chemical (DAPT) can induce PAX6/RX-positive stem cells to undergo differentiation into functional RGCs. PMID:24493857

  7. [Prostate cancer stem cell and drug resistance].

    PubMed

    Kosaka, Takeo; Oya, Mototsugu

    2016-01-01

    Cancer tissues are comprised of cell population including a variety of cells, such as stem cell-like cancer cells, upon which a hierarchical society is constructed. This hypothesis has been applied not only to leukemia, in which the hypothesis was first experimentally confirmed, but also to solid cancers. Recent topics shed light on the modified heterogeneity by various treatments which evolve disease progression. In prostate cancer, the identification of cancer stem cells using surface markers and the relationship with prostate origin are of current interest. This article reviews studies related to the development of prostate cancer and introduce recent progress of our project, focusing on cancer stemness and drug resistance. PMID:26793878

  8. Stem Cell Research: Unlocking the Mystery of Disease

    MedlinePlus

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

  9. Organ or Stem Cell Transplant and Your Mouth

    MedlinePlus

    ... Stem Cell Transplant and Your Mouth Organ or Stem Cell Transplant and Your Mouth Main Content Key Points​ ... Your Dentist Before Transplant Before an organ or stem cell transplant, have a dental checkup. Your mouth should ...

  10. CD44 integrates signaling in normal stem cell, cancer stem cell and (pre)metastatic niches.

    PubMed

    Williams, Karin; Motiani, Karan; Giridhar, Premkumar Vummidi; Kasper, Susan

    2013-03-01

    The stem cell niche provides a regulatory microenvironment for cells as diverse as totipotent embryonic stem cells to cancer stem cells (CSCs) which exhibit stem cell-like characteristics and have the capability of regenerating the bulk of tumor cells while maintaining self-renewal potential. The transmembrane glycoprotein CD44 is a common component of the stem cell niche and exists as a standard isoform (CD44s) and a range of variant isoforms (CD44v) generated though alternative splicing. CD44 modulates signal transduction through post-translational modifications as well as interactions with hyaluronan, extracellular matrix molecules and growth factors and their cognate receptor tyrosine kinases. While the function of CD44 in hematopoietic stem cells has been studied in considerable detail, our knowledge of CD44 function in tissue-derived stem cell niches remains limited. Here we review CD44s and CD44v in both hematopoietic and tissue-derived stem cell niches, focusing on their roles in regulating stem cell behavior including self-renewal and differentiation in addition to cell-matrix interactions and signal transduction during cell migration and tumor progression. Determining the role of CD44 and CD44v in normal stem cell, CSC and (pre)metastatic niches and elucidating their unique functions could provide tools and therapeutic strategies for treating diseases as diverse as fibrosis during injury repair to cancer progression. PMID:23598979

  11. Artificial gametes from stem cells

    PubMed Central

    Moreno, Inmaculada; Míguez-Forjan, Jose Manuel

    2015-01-01

    The generation of artificial gametes is a real challenge for the scientific community today. In vitro development of human eggs and sperm will pave the way for the understanding of the complex process of human gametogenesis and will provide with human gametes for the study of infertility and the onset of some inherited disorders. However, the great promise of artificial gametes resides in their future application on reproductive treatments for all these people wishing to have genetically related children and for which gamete donation is now their unique option of parenthood. This is the case of infertile patients devoid of suitable gametes, same sex couples, singles and those fertile couples in a high risk of transmitting serious diseases to their progeny. In the search of the best method to obtain artificial gametes, many researchers have successfully obtained human germ cell-like cells from stem cells at different stages of differentiation. In the near future, this field will evolve to new methods providing not only viable but also functional and safe artificial germ cells. These artificial sperm and eggs should be able to recapitulate all the genetic and epigenetic processes needed for the correct gametogenesis, fertilization and embryogenesis leading to the birth of a healthy and fertile newborn. PMID:26161331

  12. Artificial gametes from stem cells.

    PubMed

    Moreno, Inmaculada; Míguez-Forjan, Jose Manuel; Simón, Carlos

    2015-06-01

    The generation of artificial gametes is a real challenge for the scientific community today. In vitro development of human eggs and sperm will pave the way for the understanding of the complex process of human gametogenesis and will provide with human gametes for the study of infertility and the onset of some inherited disorders. However, the great promise of artificial gametes resides in their future application on reproductive treatments for all these people wishing to have genetically related children and for which gamete donation is now their unique option of parenthood. This is the case of infertile patients devoid of suitable gametes, same sex couples, singles and those fertile couples in a high risk of transmitting serious diseases to their progeny. In the search of the best method to obtain artificial gametes, many researchers have successfully obtained human germ cell-like cells from stem cells at different stages of differentiation. In the near future, this field will evolve to new methods providing not only viable but also functional and safe artificial germ cells. These artificial sperm and eggs should be able to recapitulate all the genetic and epigenetic processes needed for the correct gametogenesis, fertilization and embryogenesis leading to the birth of a healthy and fertile newborn. PMID:26161331

  13. Stem cells: a view from the roots.

    PubMed

    Somorjai, Ildiko M L; Lohmann, Jan U; Holstein, Thomas W; Zhao, Zhong

    2012-06-01

    In both plants and animals, regeneration requires the activation of stem cells. This is possibly related to the origin and requirements of multicellularity. Although long diverged from a common ancestry, plant and animal models such as Arabidopsis, Drosophila and mouse share considerable similarities in stem cell regulation. This includes stem cell niche organisation, epigenetic modification of DNA and histones, and the role of small RNA machinery in differentiation and pluripotency states. Dysregulation of any of these can lead to premature ageing, patterning and specification defects, as well as cancers. Moreover, emerging basal animal and plant systems are beginning to provide important clues concerning the diversity and evolutionary history of stem cell regulatory mechanisms in eukaryotes. This review provides a comparative framework, highlighting both the commonalities and differences among groups, which should promote the intelligent design of artificial stem cell systems, and thereby fuel the field of biomaterials science. PMID:22581706

  14. Overcoming Multidrug Resistance in Cancer Stem Cells

    PubMed Central

    Moitra, Karobi

    2015-01-01

    The principle mechanism of protection of stem cells is through the expression of ATP-binding cassette (ABC) transporters. These transporters serve as the guardians of the stem cell population in the body. Unfortunately these very same ABC efflux pumps afford protection to cancer stem cells in tumors, shielding them from the adverse effects of chemotherapy. A number of strategies to circumvent the function of these transporters in cancer stem cells are currently under investigation. These strategies include the development of competitive and allosteric modulators, nanoparticle mediated delivery of inhibitors, targeted transcriptional regulation of ABC transporters, miRNA mediated inhibition, and targeting of signaling pathways that modulate ABC transporters. The role of ABC transporters in cancer stem cells will be explored in this paper and strategies aimed at overcoming drug resistance caused by these particular transporters will also be discussed. PMID:26649310

  15. Adipose-derived stromal/stem cells

    PubMed Central

    Gimble, Jeffrey M.; Bunnell, Bruce A.; Frazier, Trivia; Rowan, Brian; Shah, Forum; Thomas-Porch, Caasy; Wu, Xiying

    2013-01-01

    Until recently, the complexity of adipose tissue and its physiological role was not well appreciated. This changed with the discovery of adipokines such as leptin. The cellular composition of adipose tissue is heterogeneous and changes as a function of diabetes and disease states such as diabetes. Tissue engineers view adipose tissue as a rich source of adult stromal/stem cells isolated by collagenase digestion. In vitro and in vivo studies have documented that adipose stromal/stem cells are multipotent, with the ability to differentiate along the adipocyte, chondrocyte, osteoblast and other lineage pathways. The adipose stromal/stem cells secrete a wide range of cytokines and growth factors with potential paracrine actions. Furthermore, adipose stromal/stem cells exert immunomodulatory functions when added to mixed lymphocyte reactions, suggesting that they can be transplanted allogeneically. This review article focuses on these mechanisms of adipose stromal/stem cell action and their potential utility as cellular therapeutics. PMID:23538753

  16. 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. PMID:24828515

  17. Stem cell function during plant vascular development

    PubMed Central

    Miyashima, Shunsuke; Sebastian, Jose; Lee, Ji-Young; Helariutta, Yka

    2013-01-01

    The plant vascular system, composed of xylem and phloem, evolved to connect plant organs and transport various molecules between them. During the post-embryonic growth, these conductive tissues constitutively form from cells that are derived from a lateral meristem, commonly called procambium and cambium. Procambium/cambium contains pluripotent stem cells and provides a microenvironment that maintains the stem cell population. Because vascular plants continue to form new tissues and organs throughout their life cycle, the formation and maintenance of stem cells are crucial for plant growth and development. In this decade, there has been considerable progress in understanding the molecular control of the organization and maintenance of stem cells in vascular plants. Noticeable advance has been made in elucidating the role of transcription factors and major plant hormones in stem cell maintenance and vascular tissue differentiation. These studies suggest the shared regulatory mechanisms among various types of plant stem cell pools. In this review, we focus on two aspects of stem cell function in the vascular cambium, cell proliferation and cell differentiation. PMID:23169537

  18. Engineered Microenvironments for Human Stem Cells

    PubMed Central

    Godier, Amandine F. G.; Marolt, Darja; Gerecht, Sharon; Tajnsek, Urska; Martens, Timothy P.; Vunjak-Novakovic, Gordana

    2009-01-01

    Regulation of cell differentiation and assembly remains a fundamental question in developmental biology. During development, tissues emerge from coordinated sequences of the renewal, differentiation, and assembly of stem cells. Likewise, regeneration of an adult tissue is driven by the migration and differentiation of repair cells. The fields of stem cells and regenerative medicine are starting to realize how important is the entire context of the cell environment, with the presence of other cells, three-dimensional matrices, and sequences of molecular and physical morphogens. The premise is that to unlock the full potential of stem cells, at least some aspects of the dynamic environments normally present in vivo need to be reconstructed in experimental systems used in vitro. We review here some recent work that utilized engineered environments for guiding the embryonic and adult human stem cells, and focus on vasculogenesis as a critical and universally important aspect of tissue development and regeneration. PMID:19067427

  19. 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. PMID:26635920

  20. Translational research of adult stem cell therapy

    PubMed Central

    Suzuki, Gen

    2015-01-01

    Congestive heart failure (CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell based therapies generating new cardiomyocytes and vessels have emerged as a promising treatment to reverse functional deterioration and prevent the progression to CHF. Functional efficacy of progenitor cells isolated from the bone marrow and the heart have been evaluated in preclinical large animal models. Furthermore, several clinical trials using autologous and allogeneic stem cells and progenitor cells have demonstrated their safety in humans yet their clinical relevance is inconclusive. This review will discuss the clinical therapeutic applications of three specific adult stem cells that have shown particularly promising regenerative effects in preclinical studies, bone marrow derived mesenchymal stem cell, heart derived cardiosphere-derived cell and cardiac stem cell. We will also discuss future therapeutic approaches. PMID:26635920

  1. Breast cancer stem cells and radiation

    NASA Astrophysics Data System (ADS)

    Phillips, Tiffany Marie

    2007-12-01

    The present studies explore the response of breast cancer stem cells (BCSC's) to radiation and the implications for clinical cancer treatment. Current cancer therapy eliminates bulky tumor mass but may fail to eradicate a critical tumor initiating cell population termed "cancer stem cells". These cells are potentially responsible for tumor formation, metastasis, and recurrence. Recently cancer stem cells have been prospectively identified in various malignancies, including breast cancer. The breast cancer stem cell has been identified by the surface markers CD44+/CD24 -(low). In vitro mammosphere cultures allow for the enrichment of the cancer stem cell population and were utilized in order to study differential characteristics of BCSC's. Initial studies found that BCSC's display increased radiation resistance as compared to other non-stem tumor cells. This resistance was accompanied by decreased H2AX phosphorylation, decreased reactive oxygen species formation, and increased phosphorylation of the checkpoint protein Chk1. These studies suggest differential DNA damage and repair within the BCSC population. Studies then examined the consequences of fractionated radiation on the BCSC population and found a two-fold increase in BCSC's following 5 x 3Gy. This observation begins to tie cancer stem cell self-renewal to the clinical stem cell phenomenon of accelerated repopulation. Accelerated repopulation is observed when treatment gaps increase between sequential fractions of radiotherapy and may be due to cancer stem cell symmetric self-renewal. The balance between asymmetric and symmetric stem cell division is vital for proper maintenance; deregulation is likely linked to cancer initiation and progression. The developmental Notch-1 pathway was found to regulate BCSC division. Over-expressing the constitutively active Notch-1-ICD in MCF7 cells produced an increase in the BCSC population. Additionally, radiation was observed to increase the expression of the Notch-1 ligand, Jagged-1, and this was complemented by radiation induced Notch-1 activation. Studies also linked hypoxia and BCSC renewal through Epo signaling. Treatment with rhEpo induced an increase in BCSC's, which again was due to rhEpo induced Jagged-1 expression and subsequent Notch-1 activation. This thesis suggests that radiation and rhEpo induce Jagged-1 expression in non-stem cells, which then induce Notch-1 activation in adjacent stem cells, and results in symmetric cancer stem cell self-renewal.

  2. How Stem Cells Speak with Host Immune Cells in Inflammatory Brain Diseases

    PubMed Central

    Pluchino, Stefano; Cossetti, Chiara

    2014-01-01

    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. PMID:23633288

  3. Intestinal myofibroblasts: targets for stem cell therapy

    PubMed Central

    Mifflin, R. C.; Pinchuk, I. V.; Saada, J. I.

    2011-01-01

    The subepithelial intestinal myofibroblast is an important cell orchestrating many diverse functions in the intestine and is involved in growth and repair, tumorigenesis, inflammation, and fibrosis. The myofibroblast is but one of several α-smooth muscle actin-positive (α-SMA+) mesenchymal cells present within the intestinal lamina propria, including vascular pericytes, bone marrow-derived stem cells (mesenchymal stem cells or hematopoietic stem cells), muscularis mucosae, and the lymphatic pericytes (colon) and organized smooth muscle (small intestine) associated with the lymphatic lacteals. These other mesenchymal cells perform many of the functions previously attributed to subepithelial myofibroblasts. This review discusses the definition of a myofibroblast and reconsiders whether the α-SMA+ subepithelial cells in the intestine are myofibroblasts or other types of mesenchymal cells, i.e., pericytes. Current information about specific, or not so specific, molecular markers of lamina propria mesenchymal cells is reviewed, as well as the origins of intestinal myofibroblasts and pericytes in the intestinal lamina propria and their replenishment after injury. Current concepts and research on stem cell therapy for intestinal inflammation are summarized. Information about the stem cell origin of intestinal stromal cells may inform future stem cell therapies to treat human inflammatory bowel disease (IBD). PMID:21252048

  4. Stem cell therapy for heart failure: the science and current progress.

    PubMed

    Phillips, M Ian; Tang, Yao Liang; Pinkernell, Kai

    2008-05-01

    Cell therapy, particularly with stem cells, has created great interest as a solution to the fact that there are limited treatments for postischemic heart disease and none that can regenerate damaged heart cells to strengthen cardiac performance. From the first efforts with myoblasts to recent clinical trials with bone marrow-derived stem cells, early reports of cell therapy suggest improvement in cardiac performance as well as other clinical end points. Based on these exciting but tentative results, other stem cell types are being explored for their particular advantages as a source of adult stem cells. Autologous adipose-derived stem cells are multilinear and can be obtained relatively easily in large quantities from patients; cardiac-derived stem cells are highly appropriate for engraftment in their natural niche, the heart. Human umbilical cord blood cells are potentially forever young and allogenic adult mesenchymal stem cells appear not to evoke the graft versus host reaction. Human embryonic stem cells are effective and can be scaled up for supply purposes. The recent discovery of induced pluripotentcy in human adult stem cells, with only three transcription factor genes, opens a whole new approach to making autologous human pluripotent stem cells from skin or other available tissues. Despite the excitement, stem cells may have to be genetically modified with heme oxygenase, Akt or other genes to survive transplantation in a hypoxic environment. Homing factors and hormones secreted from transplanted stem cells may be more important than cells if they provide the necessary stimulus to trigger cardiac regrowth to replace scar tissue. As we await results from larger and more prolonged clinical trials, the science of stem cell therapy in cardiac disease keeps progressing. PMID:19804333

  5. Planarians as a model of aging to study the interaction between stem cells and senescent cells in vivo.

    PubMed

    Perrigue, Patrick M; Najbauer, Joseph; Jozwiak, Agnieszka A; Barciszewski, Jan; Aboody, Karen S; Barish, Michael E

    2015-01-01

    The depletion of stem cell pools and the accumulation of senescent cells in animal tissues are linked to aging. Planarians are invertebrate flatworms and are unusual in that their stem cells, called neoblasts, are constantly replacing old and dying cells. By eliminating neoblasts in worms via irradiation, the biological principles of aging are exposed in the absence of wound healing and regeneration, making planaria a powerful tool for aging research. PMID:26654402

  6. Planarians as a model of aging to study the interaction between stem cells and senescent cells in vivo

    PubMed Central

    Perrigue, Patrick M.; Najbauer, Joseph; Jozwiak, Agnieszka A.; Barciszewski, Jan; Aboody, Karen S.; Barish, Michael E.

    2015-01-01

    The depletion of stem cell pools and the accumulation of senescent cells in animal tissues are linked to aging. Planarians are invertebrate flatworms and are unusual in that their stem cells, called neoblasts, are constantly replacing old and dying cells. By eliminating neoblasts in worms via irradiation, the biological principles of aging are exposed in the absence of wound healing and regeneration, making planaria a powerful tool for aging research. PMID:26654402

  7. [Stem cells: limitations and opportunities in Peru].

    PubMed

    Amiel-Pérez, José; Casado, Fanny

    2015-10-01

    Stem cells are defined as rare cells that are characterized by asymmetric division, a process known as self-renewal, and the potential to differentiate into more than one type of terminally differentiated cell. There is a diversity of stem cells including embryonic stem cells, which exist only during the first stages of human development, and many adult stem cells depending on the specific tissues from where they derive or the ones derived from mesenchymal or stromal tissues. On the other hand, there are induced pluripotent stem cells generated by genetic engineering with similar properties to embryonic stem cells that are derived from adult tissues without the ethical and legal limitations. In all cases, there are many questions that are being addressed by research in basic sciences to better inform clinical practice. In Peru, there is much to do refining techniques and improving methodologies, which requires experience, proper facilities and highly specialized human resources. However, there are interesting efforts to place Peruvian stem cell research in the international scientific arena. PMID:26732929

  8. Concise Review: Chemical Approaches for Modulating Lineage-Specific Stem Cells and Progenitors

    PubMed Central

    Xu, Tao; Zhang, Mingliang; Laurent, Timothy; Xie, Min

    2013-01-01

    Generation and manipulation of lineage-restricted stem and progenitor cells in vitro and/or in vivo are critical for the development of stem cell-based clinical therapeutics. Lineage-restricted stem and progenitor cells have many advantageous qualities, including being able to efficiently engraft and differentiate into desirable cell types in vivo after transplantation, and they are much less tumorigenic than pluripotent cells. Generation of lineage-restricted stem and progenitor cells can be achieved by directed differentiation from pluripotent stem cells or lineage conversion from easily obtained somatic cells. Small molecules can be very helpful in these processes since they offer several important benefits. For example, the risk of tumorigenesis is greatly reduced when small molecules are used to replace integrated transcription factors, which are widely used in cell fate conversion. Furthermore, small molecules are relatively easy to apply, optimize, and manufacture, and they can more readily be developed into conventional pharmaceuticals. Alternatively, small molecules can be used to expand or selectively control the differentiation of lineage-restricted stem and progenitor cells for desirable therapeutics purposes in vitro or in vivo. Here we summarize recent progress in the use of small molecules for the expansion and generation of desirable lineage-restricted stem and progenitor cells in vitro and for selectively controlling cell fate of lineage-restricted stem and progenitor cells in vivo, thereby facilitating stem cell-based clinical applications. PMID:23580542

  9. Connecting Mitochondria, Metabolism, and Stem Cell Fate

    PubMed Central

    Wanet, Anaïs; Arnould, Thierry; Najimi, Mustapha

    2015-01-01

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

  10. Generating neurons from stem cells.

    PubMed

    Androutsellis-Theotokis, Andreas; Murase, Sachiko; Boyd, Justin D; Park, Deric M; Hoeppner, Daniel J; Ravin, Rea; McKay, Ronald D G

    2008-01-01

    Recent work shows that major developmental and clinical processes such as central nervous system regeneration and carcinogenesis involve stem cells (SCs) in the brain. In spite of this importance, the requirements of these SCs and their differentiated offspring (neurons, astrocytes, and oligodendrocytes) for survival and proper function are little understood. In vivo, the SCs themselves interact with their environment. This "SC niche" may be complex because it likely includes cells of the vascular and immune systems. The ability to maintain (1) and differentiate (1 -4) central nervous system (CNS) SCs in tissue culture where they can be pharmacologically or genetically (5) manipulated provides a powerful starting point for understanding their behavior. We present detailed information on the methods that permit CNS SCs to differentiate into functional neurons in tissue culture. Important aspects of the culture systems include (1) homogeneity, so that the input and output of a manipulation is known to involve the SC itself; (2) growth in monolayer to visualize and study individual SCs and their offspring; and (3) the use of fully defined culture components to exclude unknown factors from the culture. These conditions support the differentiation of functional, electrically active neurons. These methods allow cell growth and differentiation from normal adult and diseased tissue derived from both animal models and clinical samples. Ultimate validation of such a system comes from accurate prediction of in vivo effects, and the methods we present for CNS SC culture have also successfully predicted regenerative responses in the injured adult nervous system. PMID:18369747

  11. Differentiation of hepatocytes from pluripotent stem cells

    PubMed Central

    Mallanna, Sunil K.

    2014-01-01

    Differentiation of human embryonic stem (ES) and induced pluripotent stem (iPS) cells into hepatocyte-like cells provides a platform to study the molecular basis of human hepatocyte differentiation, to develop cell culture models of liver disease, and to potentially provide hepatocytes for treatment of end-stage liver disease. Additionally, hepatocyte-like cells generated from human pluripotent stem cells could serve as platforms for drug discovery, determination of pharmaceutical induced hepatotoxicity, and evaluation of idiosyncratic drug-drug interactions. Here, we describe a step-wise protocol previously developed in our laboratory that facilitates the highly efficient and reproducible differentiation of human pluripotent stem cells into hepatocyte-like cells. Our protocol uses defined culture conditions and closely recapitulates key developmental events that are found to occur during hepatogenesis. PMID:24510789

  12. Tissue-Derived Stem and Progenitor Cells

    PubMed Central

    Tesche, Leora J.; Gerber, David A.

    2010-01-01

    The characterization and isolation of various stem cell populations, from embryonic through tissue-derived stem cells, have led a rapid growth in the field of stem cell research. These research efforts have often been interrelated as to the markers that identify a select cell population are frequently analyzed to determine their expression in cells of distinct organs/tissues. In this review, we will expand the current state of research involving select tissue-derived stem cell populations including the liver, central nervous system, and cardiac tissues as examples of the success and challenges in this field of research. Lastly, the challenges of clinical therapies will be discussed as it applies to these unique cell populations. PMID:21048854

  13. Prepatterning in the stem cell compartment.

    PubMed

    Tonge, Peter D; Olariu, Victor; Coca, Daniel; Kadirkamanathan, Visakan; Burrell, Kelly E; Billings, Stephen A; Andrews, Peter W

    2010-01-01

    The mechanism by which an apparently uniform population of cells can generate a heterogeneous population of differentiated derivatives is a fundamental aspect of pluripotent and multipotent stem cell behaviour. One possibility is that the environment and the differentiation cues to which the cells are exposed are not uniform. An alternative, but not mutually exclusive possibility is that the observed heterogeneity arises from the stem cells themselves through the existence of different interconvertible substates that pre-exist before the cells commit to differentiate. We have tested this hypothesis in the case of apparently homogeneous pluripotent human embryonal carcinoma (EC) stem cells, which do not follow a uniform pattern of differentiation when exposed to retinoic acid. Instead, they produce differentiated progeny that include both neuronal and non-neural phenotypes. Our results suggest that pluripotent NTERA2 stem cells oscillate between functionally distinct substates that are primed to select distinct lineages when differentiation is induced. PMID:20531938

  14. Odontogenic epithelial stem cells: hidden sources.

    PubMed

    Padma Priya, Sivan; Higuchi, Akon; Abu Fanas, Salem; Pooi Ling, Mok; Kumari Neela, Vasantha; Sunil, P M; Saraswathi, T R; Murugan, Kadarkarai; Alarfaj, Abdullah A; Munusamy, Murugan A; Kumar, Suresh

    2015-12-01

    The ultimate goal of dental stem cell research is to construct a bioengineered tooth. Tooth formation occurs based on the well-organized reciprocal interaction of epithelial and mesenchymal cells. The dental mesenchymal stem cells are the best explored, but because the human odontogenic epithelium is lost after the completion of enamel formation, studies on these cells are scarce. The successful creation of a bioengineered tooth is achievable only when the odontogenic epithelium is reconstructed to produce a replica of natural enamel. This article discusses the untapped sources of odontogenic epithelial stem cells in humans, such as those present in the active dental lamina in postnatal life, in remnants of dental lamina (the gubernaculum cord), in the epithelial cell rests of Malassez, and in reduced enamel epithelium. The possible uses of these stem cells in regenerative medicine, not just for enamel formation, are discussed. PMID:26367485

  15. Stem Cell Therapies in Orthopaedic Trauma.

    PubMed

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

    2015-12-01

    Stem cells offer great promise to help understand the normal mechanisms of tissue renewal, regeneration, and repair, and also for development of cell-based therapies to treat patients after tissue injury. Most adult tissues contain stem cells and progenitor cells that contribute to homeostasis, remodeling, and repair. Multiple stem and progenitor cell populations in bone are found in the marrow, the endosteum, and the periosteum. They contribute to the fracture healing process after injury and are an important component in tissue engineering approaches for bone repair. This review focuses on current concepts in stem cell biology related to fracture healing and bone tissue regeneration, as well as current strategies and limitations for clinical cell-based therapies. PMID:26584262

  16. Brain repair how stem cells are changing neurology.

    PubMed

    Modo, Michel

    2008-01-01

    The concept that everything can die, but nothing can regenerate in the brain has been replaced with new hope that stem cells will provide avenues to repair the damaged central nervous system (CNS). The treatment of brain damage has been demonstrated preclinically using a variety of stem cell sources. The prototypical cell that gives rise to the CNS is the neural stem cell (NSC). NSCs differentiate into site-appropriate phenotypes when transplanted into the damage brain and can recover lost functions. In some cases, cells can be pre-differentiated into a particular neuronal phenotype, such as dopaminergic cells, that can then be transplanted ectopically to promote behavioural improvements in conditions like Parkinson's disease. Early clinical studies in PD have demonstrated the proof of principle that this approach can improve neurodegenerative disease. The current review will discuss the different sources of stem cells in their preclinical and clinical application, as well as providing an overview as to the issues that need to be addressed to ensure a successful translation from bench to bedside. PMID:18561598

  17. Fusion of human bone hemopoietic stem cell with esophageal carcinoma cells didn't generate esophageal cancer stem cell.

    PubMed

    Fan, H; Lu, S

    2014-01-01

    Prior studies showed that cell fusion between bone marrow-derived cell (BMDC) and somatic cell might be the origin of cancer stem cell. Our previous study suggested that cell fusion of human bone marrow-derived mesenchymal stem cell (MSC) with esophageal cancer cell did not generate cancer stem cells. But up to now, the origin of cancer stem cell is still ambiguous. In this study, we carried out the cell fusion experiment between hemopoietic stem cells (HSCs) and human esophageal cancer cells, and found that cell fusion slowed the growth speed of esophageal cancer cells and decreased the clone formation ability and tumorigenicity in NOD/SCID mice. In addition, cell fusion did not increase the ratio of side population (SP) cells and the resistance to chemotherapeutic drugs. Collectively, our data indicated that cell fusion between HSCs and esophageal cancer cells has a therapeutic effect rather than generate cells with characteristics of esophageal cancer stem cells. PMID:25030437

  18. Stem cells for spinal cord regeneration: Current status

    PubMed Central

    Sobani, Zain A.; Quadri, Syed A.; Enam, S. Ather

    2010-01-01

    Background: Nearly 11,000 cases of spinal cord injury (SCI) are reported in the United States annually. Current management options give a median survival time of 38 years; however, no rehabilitative measures are available. Stem cells have been under constant research given their ability to differentiate into neural cell lines replacing non functional tissue. Efforts have been made to establish new synapses and provide a conducive environment, by grafting cells from autologous and fetal sources; including embryonic or adult stem cells, Schwann cells, genetically modified fibroblasts, bone stromal cells, and olfactory ensheathing cells and combinations/ variants thereof. Methods: In order to discuss the underlying mechanism of SCI along with the previously mentioned sources of stem cells in context to SCI, a simple review of literature was conducted. An extensive literature search was conducted using the PubMed data base and online search engines and articles published in the last 15 years were considered along with some historical articles where a background was required. Results: Stem cell transplantation for SCI is at the forefront with animal and in vitro studies providing a solid platform to enable well-designed human studies. Olfactory ensheathing cells seem to be the most promising; whilst bone marrow stromal cells appear as strong candidates for an adjunctive role. Conclusion: The key strategy in developing the therapeutic basis of stem cell transplantation for spinal cord regeneration is to weed out the pseudo-science and opportunism. All the trials should be based on stringent scientific criteria and effort to bypass that should be strongly discouraged at the international level. PMID:21246060

  19. Update on small intestinal stem cells

    PubMed Central

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

    2013-01-01

    Among somatic stem cells, those residing in the intestine represent a fascinating and poorly explored research field. Particularly, somatic stem cells reside in the small intestine at the level of the crypt base, in a constant balance between self-renewal and differentiation. Aim of the present review is to delve into the mechanisms that regulate the delicate equilibrium through which intestinal stem cells orchestrate intestinal architecture. To this aim, special focus will be addressed to identify the integrating signals from the surrounding niche, supporting a model whereby distinct cell populations facilitate homeostatic vs injury-induced regeneration. PMID:23922464

  20. 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

  1. Stem cell technologies in regenerative medicine.

    PubMed

    Jain, Kewal K

    2002-10-01

    The IIR Life Sciences conference on stem cell technologies in regenerative medicine was held in London, UK on 11 - 12 July 2002. The conference covered not only technologies but also ethical/regulatory and financial aspects of embryonic stem (ES) cell therapy. An excellent introduction to embryonic stem cells was given by Prof. William Kridel (Ferghana Partners, London, UK). Details of basic technologies are not described as they are covered in a detailed report on cell therapy [1]. Due to limitation of space only a selected few of the seventeen presentations are reported here. PMID:12387676

  2. Speculation on the evolution of stem cells.

    PubMed

    Shostak, Stanley

    2008-01-01

    Profoundly different patterns of potency and division are exhibited by mammalian embryonic and adult stem cells. Additional confusion surrounds stem-cell surrogates, cache and reserve cells having some characteristics of stem cells and not others. Mystification may have been introduced historically with the concepts of determinate and regulative development, but, hopefully, the muddle can be resolved by tracing the evolution of stem cells in Metazoa. Blastomeres in marine sponges, cnidarians, lophotrochozoans, small ecdysozoans (e.g., Caenorhabditis elegans), and some deuterostomes (e.g., echinoderms and ascidians) exhibit determinative development. Their larval and adult cells have narrow potencies, sometimes coupled to virtually unlimited proliferation, and function in the growth, maintenance and regulation of body size. The embryos of larger arthropods and deuterostomes with well-provisioned eggs or viviparity, on the other hand, exhibit regulative development, while their larval "set-aside" or adult stem cells function in the growth, maintenance, and regulation of organ size coupled to constrained proliferation and cell turnover. Mammalian embryonic stem cells would seem adapted to rapid proliferation, functioning in part to enclose yolk or to acquire access to maternal resources. The cellular products of embryonic stem cells routinely come under global influences and give rise to the cells of germ layers and organ rudiments. Mammalian adult stem cells resemble the blastomeres of planktonic and benthic organisms with small eggs and may have evolved in mature organisms as an adaptation to the growth and maintenance of tissues via proliferation and the regulation of organ size via cell loss (e.g., terminal differentiation). Cancer stem cells, instrumental in metastasis, would seem to ignore mechanisms normally functioning in the removal of excess cells. Strategies for regenerative therapies in adult mammals, therefore, might be based on stimulating growth of adult stem cells or their surrogates in specific tissues rather than on introducing embryonic stem cells into adults. Likewise, strategies for the containment of cancer might be based on promoting normal pathways of cell loss, the basal mode for handling excess cells. PMID:19029620

  3. Biomaterials and Stem Cells for Tissue Engineering

    PubMed Central

    Zhang, Zhanpeng; Gupte, Melanie J.; Ma, Peter X.

    2013-01-01

    Importance of the field Organ failure and tissue loss are challenging health issues due to widespread injury, the lack of organs for transplantation, and limitations of conventional artificial implants. The field of tissue engineering aims to provide alternative living substitutes that restore, maintain or improve tissue function. Areas covered in this review In this paper, a wide range of porous scaffolds are reviewed, with an emphasis on phase separation techniques that generate advantageous nanofibrous 3D scaffolds for stem cell-based tissue engineering applications. In addition, methods for presentation and delivery of bioactive molecules to mimic the properties of stem cell niche are summarized. Recent progress in using these bio-instructive scaffolds to support stem cell differentiation and tissue regeneration is also presented. What the reader will gain Stem cells have great clinical potential because of their capability to differentiate into multiple cell types. Biomaterials have served as artificial extracellular environments to regulate stem cell behavior. Biomaterials with various physical, mechanical, and chemical properties can be designed to control stem cell development for regeneration. Take home message The research at the interface of stem cell biology and biomaterials has made and will continue to make exciting advances in tissue engineering. PMID:23327471

  4. Stem Cell Biomarkers in Chronic Myeloid Leukemia

    PubMed Central

    Jiang, Xiaoyan; Zhao, Yun; Forrest, Donna; Smith, Clayton; Eaves, Allen; Eaves, Connie

    2008-01-01

    Chronic myeloid leukemia (CML) is a clonal multi-step myeloproliferative disease that is initially produced and ultimately sustained by a rare subpopulation of BCR-ABL+ cells with multi-lineage stem cell properties. These BCR-ABL+ CML stem cells are phenotypically similar to normal hematopoietic stem cells which are also maintained throughout the course of the disease at varying levels in different patients. Defining the unique properties of the leukemic stem cells that produce the chronic phase of CML has therefore had to rely heavily on access to samples from rare patients in which the stem cell compartment is dominated by leukemic elements. Here we review past and ongoing approaches using such samples to identify biologically and clinically relevant biomarkers of BCR-ABL+ stem cells that explain their unusual biology and that may help to design, or at least predict, improved treatment responses in CML patients. These studies are of particular interest in light of recent evidence that chronic phase CML stem cells are not only innately resistant to imatinib mesylate and other drugs that target the BCR-ABL oncoprotein, but are also genetically unstable. PMID:18525114

  5. Stem cell applications in military medicine

    PubMed Central

    2011-01-01

    There are many similarities between health issues affecting military and civilian patient populations, with the exception of the relatively small but vital segment of active soldiers who experience high-energy blast injuries during combat. A rising incidence of major injuries from explosive devices in recent campaigns has further complicated treatment and recovery, highlighting the need for tissue regenerative options and intensifying interest in the possible role of stem cells for military medicine. In this review we outline the array of tissue-specific injuries typically seen in modern combat - as well as address a few complications unique to soldiers - and discuss the state of current stem cell research in addressing each area. Embryonic, induced-pluripotent and adult stem cell sources are defined, along with advantages and disadvantages unique to each cell type. More detailed stem cell sources are described in the context of each tissue of interest, including neural, cardiopulmonary, musculoskeletal and sensory tissues, with brief discussion of their potential role in regenerative medicine moving forward. Additional commentary is given to military stem cell applications aside from regenerative medicine, such as blood pharming, immunomodulation and drug screening, with an overview of stem cell banking and the unique opportunity provided by the military and civilian overlap of stem cell research. PMID:22011454

  6. Stem cell tracking using iron oxide nanoparticles

    PubMed Central

    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. PMID:24729700

  7. Understanding cancer stem cell heterogeneity and plasticity

    PubMed Central

    Tang, Dean G

    2012-01-01

    Heterogeneity is an omnipresent feature of mammalian cells in vitro and in vivo. It has been recently realized that even mouse and human embryonic stem cells under the best culture conditions are heterogeneous containing pluripotent as well as partially committed cells. Somatic stem cells in adult organs are also heterogeneous, containing many subpopulations of self-renewing cells with distinct regenerative capacity. The differentiated progeny of adult stem cells also retain significant developmental plasticity that can be induced by a wide variety of experimental approaches. Like normal stem cells, recent data suggest that cancer stem cells (CSCs) similarly display significant phenotypic and functional heterogeneity, and that the CSC progeny can manifest diverse plasticity. Here, I discuss CSC heterogeneity and plasticity in the context of tumor development and progression, and by comparing with normal stem cell development. Appreciation of cancer cell plasticity entails a revision to the earlier concept that only the tumorigenic subset in the tumor needs to be targeted. By understanding the interrelationship between CSCs and their differentiated progeny, we can hope to develop better therapeutic regimens that can prevent the emergence of tumor cell variants that are able to found a new tumor and distant metastases. PMID:22357481

  8. Stem cells of the beetle midgut epithelium.

    PubMed

    Nardi, James B; Bee, Charles Mark; Miller, Lou Ann

    2010-03-01

    At the completion of metamorphosis, adult insect cells have traditionally been assumed to halt cell divisions and terminally differentiate. While this model of differentiation holds for adult ectodermal epithelia that secrete cuticular specializations of exoskeletons, adult endodermal epithelia are populated by discrete three-dimensional aggregates of stem cells that continue to divide and differentiate after adult emergence. Aggregates of these presumptive adult stem cells are scattered throughout larval and pupal midgut monolayers. At the beginning of adult development (pupal-adult apolysis), the number of cells within each aggregate begins to increase rapidly. Dividing cells form three-dimensional, coherent populations that project as regenerative pouches of stem cells into the hemocoel surrounding the midgut. Stem cell pouches are regularly spaced throughout endodermal monolayers, having adopted a spacing pattern suggesting that each incipient pouch inhibits the formation of a similar pouch within a certain radius of itself-a process referred to as lateral inhibition. At completion of adult development (pupal-adult ecdysis), a distinct basal-luminal polarity has been established within each regenerative pouch. Dividing stem cells occupying the basal region are arranged in three-dimensional aggregates. As these are displaced toward the lumen, they transform into two-dimensional monolayers of differentiated epithelial cells whose apical surfaces are covered by microvilli. This organization of stem cell pouches in insect midguts closely parallels that of regenerative crypts in mammalian intestines. PMID:19909756

  9. Replacement of Diseased Mouse Liver by Hepatic Cell Transplantation

    NASA Astrophysics Data System (ADS)

    Rhim, Jonathan A.; Sandgren, Eric P.; Degen, Jay L.; Palmiter, Richard D.; Brinster, Ralph L.

    1994-02-01

    Adult liver has the unusual ability to fully regenerate after injury. Although regeneration is accomplished by the division of mature hepatocytes, the replicative potential of these cells is unknown. Here, the replicative capacity of adult liver cells and their medical usefulness as donor cells for transplantation were investigated by transfer of adult mouse liver cells into transgenic mice that display an endogenous defect in hepatic growth potential and function. The transplanted liver cell populations replaced up to 80 percent of the diseased recipient liver. These findings demonstrate the enormous growth potential of adult hepatocytes, indicating the feasibility of liver cell transplantation as a method to replace lost or diseased hepatic parenchyma.

  10. Engineering nanoscale stem cell niche: direct stem cell behavior at cell-matrix interface.

    PubMed

    Zhang, Yan; Gordon, Andrew; Qian, Weiyi; Chen, Weiqiang

    2015-09-16

    Biophysical cues on the extracellular matrix (ECM) have proven to be significant regulators of stem cell behavior and evolution. Understanding the interplay of these cells and their extracellular microenvironment is critical to future tissue engineering and regenerative medicine, both of which require a means of controlled differentiation. Research suggests that nanotopography, which mimics the local, nanoscale, topographic cues within the stem cell niche, could be a way to achieve large-scale proliferation and control of stem cells in vitro. This Progress Report reviews the history and contemporary advancements of this technology, and pays special attention to nanotopographic fabrication methods and the effect of different nanoscale patterns on stem cell response. Finally, it outlines potential intracellular mechanisms behind this response. PMID:26222885

  11. Stem cells as promising therapeutic options for neurological disorders.

    PubMed

    Yoo, Jongman; Kim, Han-Soo; Hwang, Dong-Youn

    2013-04-01

    Due to the limitations of pharmacological and other current therapeutic strategies, stem cell therapies have emerged as promising options for treating many incurable neurologic diseases. A variety of stem cells including pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells) and multipotent adult stem cells (i.e., fetal brain tissue, neural stem cells, and mesenchymal stem cells from various sources) have been explored as therapeutic options for treating many neurologic diseases, and it is becoming obvious that each type of stem cell has pros and cons as a source for cell therapy. Wise selection of stem cells with regard to the nature and status of neurologic dysfunctions is required to achieve optimal therapeutic efficacy. To this aim, the stem cell-mediated therapeutic efforts on four major neurological diseases, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke, will be introduced, and current problems and future directions will be discussed. PMID:23097262

  12. Stem cells of the suture mesenchyme in craniofacial bone development, repair and regeneration.

    PubMed

    Maruyama, Takamitsu; Jeong, Jaeim; Sheu, Tzong-Jen; Hsu, Wei

    2016-01-01

    The suture mesenchyme serves as a growth centre for calvarial morphogenesis and has been postulated to act as the niche for skeletal stem cells. Aberrant gene regulation causes suture dysmorphogenesis resulting in craniosynostosis, one of the most common craniofacial deformities. Owing to various limitations, especially the lack of suture stem cell isolation, reconstruction of large craniofacial bone defects remains highly challenging. Here we provide the first evidence for an Axin2-expressing stem cell population with long-term self-renewing, clonal expanding and differentiating abilities during calvarial development and homeostastic maintenance. These cells, which reside in the suture midline, contribute directly to injury repair and skeletal regeneration in a cell autonomous fashion. Our findings demonstrate their true identity as skeletal stem cells with innate capacities to replace the damaged skeleton in cell-based therapy, and permit further elucidation of the stem cell-mediated craniofacial skeletogenesis, leading to revealing the complex nature of congenital disease and regenerative medicine. PMID:26830436

  13. Stem cells of the suture mesenchyme in craniofacial bone development, repair and regeneration

    PubMed Central

    Maruyama, Takamitsu; Jeong, Jaeim; Sheu, Tzong-Jen; Hsu, Wei

    2016-01-01

    The suture mesenchyme serves as a growth centre for calvarial morphogenesis and has been postulated to act as the niche for skeletal stem cells. Aberrant gene regulation causes suture dysmorphogenesis resulting in craniosynostosis, one of the most common craniofacial deformities. Owing to various limitations, especially the lack of suture stem cell isolation, reconstruction of large craniofacial bone defects remains highly challenging. Here we provide the first evidence for an Axin2-expressing stem cell population with long-term self-renewing, clonal expanding and differentiating abilities during calvarial development and homeostastic maintenance. These cells, which reside in the suture midline, contribute directly to injury repair and skeletal regeneration in a cell autonomous fashion. Our findings demonstrate their true identity as skeletal stem cells with innate capacities to replace the damaged skeleton in cell-based therapy, and permit further elucidation of the stem cell-mediated craniofacial skeletogenesis, leading to revealing the complex nature of congenital disease and regenerative medicine. PMID:26830436

  14. The Effect of Laser Irradiation on Adipose Derived Stem Cell Proliferation and Differentiation

    NASA Astrophysics Data System (ADS)

    Abrahamse, H.; de Villiers, J.; Mvula, B.

    2009-06-01

    There are two fundamental types of stem cells: Embryonic Stem cells and Adult Stem cells. Adult Stem cells have a more restricted potential and can usually differentiate into a few different cell types. In the body these cells facilitate the replacement or repair of damaged or diseased cells in organs. Low intensity laser irradiation was shown to increase stem cell migration and stimulate proliferation and it is thought that treatment of these cells with laser irradiation may increase the stem cell harvest and have a positive effect on the viability and proliferation. Our research is aimed at determining the effect of laser irradiation on differentiation of Adipose Derived Stem Cells (ADSCs) into different cell types using a diode laser with a wavelength of 636 nm and at 5 J/cm2. Confirmation of stem cell characteristics and well as subsequent differentiation were assessed using Western blot analysis and cellular morphology supported by fluorescent live cell imaging. Functionality of subsequent differentiated cells was confirmed by measuring adenosine triphosphate (ATP) production and cell viability.

  15. Neural Stem Cells Injected into the Sound-Damaged Cochlea Migrate Throughout the Cochlea and Express Markers of Hair Cells, Supporting Cells, and Spiral Ganglion Cells

    PubMed Central

    Corliss, Deborah A.; Gray, Brianna; Anderson, Julia K.; Bobbin, Richard P.; Snyder, Evan Y.; Cotanche, Douglas A.

    2007-01-01

    Most cases of hearing loss are caused by the death or dysfunction of one of the many cochlear cell types. We examined whether cells from a neural stem cell line could replace cochlear cell types lost after exposure to intense noise. For this purpose, we transplanted a clonal stem cell line into the scala tympani of sound damaged mice and guinea pigs. Utilizing morphological, protein expression and genetic criteria, stem cells were found with characteristics of both neural tissues (satellite, spiral ganglion and Schwann cells) and cells of the organ of Corti (hair cells, supporting cells). Additionally, noise-exposed, stem cell-injected animals exhibited a small but significant increase in the number of satellite cells and Type I spiral ganglion neurons compared to non-injected noise-exposed animals. These results indicate that cells of this neural stem cell line migrate from the scala tympani to Rosenthal's canal and the organ of Corti. Moreover, it suggests that cells of this neural stem cell line may derive some information needed from the microenvironment of the cochlea to differentiate into replacement cells in the cochlea. PMID:17659854

  16. Adult stem cells for cardiac tissue engineering.

    PubMed

    Martinez, Eliana C; Kofidis, Theo

    2011-02-01

    Cell therapy and tissue engineering attract increasing attention as a potential approach for cardiac repair. Adult stem cells from autologous origin are a practically safe and appealing source for cell-based regenerative therapies that may hold realistic clinical potential. A plethora of interesting concepts have been introduced aiming at regenerating ischemic myocardium through adult stem cell-based bioartificial cardiac tissue supplements. Yet, current pre-clinical concepts have not reached translational applicability, and successes are only episodic. This review will provide a brief overview of the latest concepts and breakthroughs in the emerging field of cardiac adult stem cell-based tissue engineering, and discuses the challenges that this field needs to overcome to achieve realistic therapeutic translation into the clinical arena. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited". PMID:20709074

  17. 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

  18. Immunological characteristics of mesenchymal stem cells

    PubMed Central

    Machado, Cntia de Vasconcellos; Telles, Paloma Dias da Silva; Nascimento, Ivana Lucia Oliveira

    2013-01-01

    Although bone marrow is the main source, mesenchymal stem cells have already been isolated from various other tissues, such as the liver, pancreas, adipose tissue, peripheral blood and dental pulp. These plastic adherent cells are morphologically similar to fibroblasts and have a high proliferative potential. This special group of cells possesses two essential characteristics: self-renewal and differentiation, with appropriate stimuli, into various cell types. Mesenchymal stem cells are considered immunologically privileged, since they do not express costimulatory molecules, required for complete T cell activation, on their surface. Several studies have shown that these cells exert an immunosuppressive effect on cells from both innate and acquired immunity systems. Mesenchymal stem cells can regulate the immune response in vitro by inhibiting the maturation of dendritic cells, as well as by suppressing the proliferation and function of T and B lymphocytes and natural killer cells. These special properties of mesenchymal stem cells make them a promising strategy in the treatment of immune mediated disorders, such as graft-versus-host disease and autoimmune diseases, as well as in regenerative medicine. The understanding of immune regulation mechanisms of mesenchymal stem cells, and also those involved in the differentiation of these cells in various lineages is primordial for their successful and safe application in different areas of medicine. PMID:23580887

  19. Stem cell therapy for glaucoma: possibilities and practicalities

    PubMed Central

    Johnson, Thomas V; Bull, Natalie D; Martin, Keith R

    2011-01-01

    Glaucoma is a progressive, neurodegenerative, optic neuropathy in which currently available therapies cannot always prevent, and do not reverse, vision loss. Stem cell transplantation may provide a promising new avenue for treating many presently incurable degenerative conditions, including glaucoma. This article will explore the various ways in which transplantation of stem or progenitor cells may be applied for the treatment of glaucoma. We will critically discuss the translational prospects of two cell transplantation-based treatment modalities: neuroprotection and retinal ganglion cell replacement. In addition, we will identify specific questions that need to be addressed and obstacles to overcome on the path to clinical translation, and offer insight into potential strategies for approaching this goal. PMID:21686079

  20. Neural stem cells and cell death.

    PubMed

    Ceccatelli, S; Tamm, C; Sleeper, E; Orrenius, S

    2004-04-01

    Neural stem cells (NSC) undergo apoptotic cell death as an essential component of neural development. Here, we present the results of our studies on the mechanisms by which NSC undergo cell death in response to neurotoxic insults. As experimental models we used primary culture of adult NSC from the subventricular zone of the rat brain, and the neural stem cell line C17.2 initially derived from developing mouse cerebellum. NSC undergo apoptosis in response to staurosporine (0.25 microM) as well as agents inducing oxidative stress such as 2,3-dimethoxy-1,4-naphthoquinone (DMNQ). Exposed cells demonstrate an apoptotic morphology, positive TUNEL staining and phosphatidyl serine exposure as labeled with Annexin V. Using an antibody specific for cytochrome c, we found that cells exposed to staurosporine or DMNQ exhibited diffuse fluorescence throughout the cytosol, implying a release of cytochrome c from the mitochondria. In addition to positive immunoreactivity against the active fragment (p17) of caspase-3, the administration of the pan-caspase inhibitor, zVAD-fmk (40 microM), prevents apoptosis. Both NSC and C17.2 express the Fas receptor, and procaspase-8, but exposure to agonistic Fas mAb (250 ng/ml) fails to induce apoptosis. Pretreatment with cycloheximide or actinomycin D does not influence the cell response to Fas mAb, suggesting that the endogenous inhibitor of caspase-8 FLICE-inhibitory protein (FLIP) is not responsible for the inhibition of the Fas pathway. Thus, it appears that the Fas dependent cell death pathway is not operative in these cells, while the mitochondrial pathway is active and caspase-3 serves as an executioner caspase in the apoptotic machinery. It is known that Fas not only induces apoptosis, but can also deliver growth stimulatory signals through activation of the extracellular-signal regulated kinase (ERK) pathway. The Fas-induced ERK phosphorylation that we detect in C17.2 cells suggests that in NSC Fas may function as a mediator of growth rather than death. PMID:15093249

  1. Adult Stem Cells and Diseases of Aging

    PubMed Central

    Boyette, Lisa B.; Tuan, Rocky S.

    2014-01-01

    Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan. PMID:24757526

  2. 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

  3. Time to Reconsider Stem Cell Induction Strategies

    PubMed Central

    Denker, Hans-Werner

    2012-01-01

    Recent developments in stem cell research suggest that it may be time to reconsider the current focus of stem cell induction strategies. During the previous five years, approximately, the induction of pluripotency in somatic cells, i.e., the generation of so-called ‘induced pluripotent stem cells’ (iPSCs), has become the focus of ongoing research in many stem cell laboratories, because this technology promises to overcome limitations (both technical and ethical) seen in the production and use of embryonic stem cells (ESCs). A rapidly increasing number of publications suggest, however, that it is now possible to choose instead other, alternative ways of generating stem and progenitor cells bypassing pluripotency. These new strategies may offer important advantages with respect to ethics, as well as to safety considerations. The present communication discusses why these strategies may provide possibilities for an escape from the dilemma presented by pluripotent stem cells (self-organization potential, cloning by tetraploid complementation, patenting problems and tumor formation risk). PMID:24710555

  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 proposeby introducing a concept of vertical and horizontal approachthat 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. 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. PMID:19033137

  6. 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

  7. Concise review: stem cells, myocardial regeneration, and methodological artifacts.

    PubMed

    Anversa, Piero; Leri, Annarosa; Rota, Marcello; Hosoda, Toru; Bearzi, Claudia; Urbanek, Konrad; Kajstura, Jan; Bolli, Roberto

    2007-03-01

    This review discusses the current controversy about the role that endogenous and exogenous progenitor cells have in cardiac homeostasis and myocardial regeneration following injury. Although great enthusiasm was created by the possibility of reconstituting the damaged heart, the opponents of this new concept of cardiac biology have interpreted most of the findings supporting this possibility as the product of technical artifacts. This article challenges this established, static view of cardiac growth and favors the notion that the mammalian heart has the inherent ability to replace its cardiomyocytes through the activation of a pool of resident primitive cells or the administration of hematopoietic stem cells. PMID:17124006

  8. Germline Stem Cells: Origin and Destiny

    PubMed Central

    Lehmann, Ruth

    2012-01-01

    Germline stem cells are key to genome transmission to future generations. Over recent years, there have been numerous insights into the regulatory mechanisms that govern both germ cell specification and the maintenance of the germline in adults. Complex regulatory interactions with both the niche and the environment modulate germline stem cell function. This perspective highlights some examples of this regulation to illustrate the diversity and complexity of the mechanisms involved. PMID:22704513

  9. Stem cells engineering for cell-based therapy.

    PubMed

    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. PMID:17873412

  10. 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.

  11. Cancer stem cells and differentiation therapy.

    PubMed

    Sell, Stewart

    2006-01-01

    Cancers arise from stem cells in adult tissues and the cells that make up a cancer reflect the same stem cell --> progeny --> differentiation progression observed in normal tissues. All adult tissues are made up of lineages of cells consisting of tissue stem cells and their progeny (transit-amplifying cells and terminally differentiated cells); the number of new cells produced in normal tissue lineages roughly equals the number of old cells that die. Cancers result from maturation arrest of this process, resulting in continued proliferation of cells and a failure to differentiate and die. The biological behavior, morphological appearance, and clinical course of a cancer depend on the stage of maturation at which the genetic lesion is activated. This review makes a comparison of cancer cells to embryonic stem cells and to adult tis sue stem cells while addressing two basic questions: (1) Where do cancers come from?, and (2) How do cancers grow? The answers to these questions are critical to the development of approaches to the detection, prevention, and treatment of cancer. PMID:16557043

  12. Differentiation of pluripotent stem cells for regenerative medicine.

    PubMed

    Li, Ke; Kong, Yan; Zhang, Mingliang; Xie, Fei; Liu, Peng; Xu, Shaohua

    2016-02-26

    A long-standing goal in regenerative medicine is to obtain scalable functional cells on demand to replenish cells lost in various conditions, including relevant diseases, injuries, and aging. As an unlimited cell source, pluripotent stem cells (PSCs) are invaluable for regenerative medicine, because they have the potential to give rise to any cell type in an organism. For therapeutic purposes, it is important to develop specific approach to directing PSC differentiation towards desired cell types efficiently. Through directed differentiation, PSCs could give rise to scalable, clinically relevant cells for in vivo transplantation, as well as for studying diseases in vitro and discovering drugs to treat them. Over the past few years, significant progress has been made in directing differentiation of PSCs into a variety of cell types. In this review, we discuss recent progress in directed differentiation of PSCs, clinical translation of PSC-based cell replacement therapies, and remaining challenges. PMID:26851367

  13. rsPSCs: A new type of pluripotent stem cells.

    PubMed

    Weissbein, Uri; Benvenisty, Nissim

    2015-08-01

    Pluripotent stem cells capture the imagination since they can differentiate into all cell types in our body. Recent evidence suggests that in addition to embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs), a new type of region-selective pluripotent stem cells (rsPSCs) exists, possessing unique spatial and molecular characteristics. PMID:26077383

  14. Differentiation of mesenchymal stem cells into gonad and adrenal steroidogenic cells

    PubMed Central

    Yazawa, Takashi; Imamichi, Yoshitaka; Miyamoto, Kaoru; Umezawa, Akihiro; Taniguchi, Takanobu

    2014-01-01

    Hormone replacement therapy is necessary for patients with adrenal and gonadal failure. Steroid hormone treatment is also employed in aging people for sex hormone deficiency. These patients undergo such therapies, which have associated risks, for their entire life. Stem cells represent an innovative tool for tissue regeneration and the possibility of solving these problems. Among various stem cell types, mesenchymal stem cells have the potential to differentiate into steroidogenic cells both in vivo and in vitro. In particular, they can effectively be differentiated into steroidogenic cells by expressing nuclear receptor 5A subfamily proteins (steroidogenic factor-1 and liver receptor homolog-1) with the aid of cAMP. This approach will provide a source of cells for future regenerative medicine for the treatment of diseases caused by steroidogenesis deficiencies. It can also represent a useful tool for studying the molecular mechanisms of steroidogenesis and its related diseases. PMID:24772247

  15. Isolation, identification, and comparison of cartilage stem progenitor/cells from auricular cartilage and perichondrium

    PubMed Central

    Xue, Ke; Zhang, Xiaodie; Qi, Lin; Zhou, Jia; Liu, Kai

    2016-01-01

    Auricular cartilage loss or defect remains a challenge to plastic surgeons, and cartilage regenerative medicine provides a novel method to solve the problem. However, ideal seeding cells seem to be the key point in the development of cartilage regeneration. Although bone marrow-mesenchymal stem cells were considered as the ideal seeding cells in cartilage regeneration, regenerative cartilage differentiated from bone marrow-mesenchymal stem cells still faces some problems. It is reported that many tissues and organs contain a certain number of adult progenitor or stem cells that can replace cells that die or restore tissues and organs after injury. Therefore, we tried to use a fibronectin differential adhesion assay to isolate cartilage stem/progenitor cells from auricular cartilage and perichondrium. Flow cytometric analysis demonstrated the two cell populations expressed mesenchyme stem cell positive surface marker. Meanwhile, the cells differentiate into osteogenic line, chondrogenic line and adipogenic line under different induction conditions. The proliferation of cartilage stem/progenitor cells derived from perichondrium was higher than cartilage stem/progenitor cells derived from auricular cartilage. In addition, there is a difference on osteogenic differentiation, chondrogenic differentiation and adipogenic differentiation between these two cell populations. In conclusion, auricular cartilage and perichondrium both contain cartilage stem/progenitor cells, which may provide an ideal seeding cells for cartilage regeneration.

  16. [Study of recombinant stem cell factor].

    PubMed

    Wu, Jun; Gong, Xin; Chang, Shao-Hong; Zhao, Zhi-Hu; Zuo, Cong-Lin; Ma, Qing-Jun

    2003-11-01

    Stem cell factor is an important hematopoietic growth factor. In this study, the human stem cell factor was produced by recombinant E. coli, and the structure and biological activity of the recombinant stem cell factor(rhSCF) was studied. It was indicated that the rhSCF was a uncovalent dimer in phosphate buffer,and had the correct mass spectra, mass peptides spectra, composition of amino acid, N-terminal sequernce, C-terminal sequence and intrachain disulfide linkages, rhSCF alone or synergy with rhG-CSF could mobilze hematopoietic progenitors to blood in monkey. PMID:15971582

  17. [Current concepts in stem cell research].

    PubMed

    Garrido Colino, C

    2003-12-01

    In the last few years, advances in stem cell research have opened up new horizons in the treatment of human diseases and in regenerative medicine. It is not unusual to find news on stem cell research in newspapers and other media. This review describes some basic concepts in research needed to understand the medical literature on stem cells and to provide the information and bibliography necessary to be up to date in one of the subjects that has generated the greatest number of publications in the last few years. PMID:14636520

  18. 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

  19. Stem cell therapy in oral and maxillofacial region: An overview

    PubMed Central

    Sunil, PM; Manikandhan, R; Muthu, MS; Abraham, S

    2012-01-01

    Cells with unique capacity for self-renewal and potency are called stem cells. With appropriate biochemical signals stem cells can be transformed into desirable cells. The idea behind this article is to shortly review the obtained literature on stem cell with respect to their properties, types and advantages of dental stem cells. Emphasis has been given to the possibilities of stem cell therapy in the oral and maxillofacial region including regeneration of tooth and craniofacial defects. PMID:22434942

  20. Hematopoietic stem cell self-renewal.

    PubMed

    Akala, Omobolaji O; Clarke, Michael F

    2006-10-01

    Recent studies have begun to elucidate the mechanisms controlling hematopoietic stem cell (HSC) self-renewal. Self-renewal requires the integration of survival signals and proliferation controls with the maintenance of an undifferentiated state. This demands a complex crosstalk between extrinsic signals from the microenvironment and the cell-intrinsic regulators of self-renewal. The Polycomb protein Bmi1 is absolutely required for the maintenance of both adult HSCs and neural stem cells. Evidence from studies in murine and human embryonic stem cells indicates that Polycomb group proteins play a dynamic role in concert with master transcriptional regulators in actively maintaining an undifferentiated state, suggesting that this mechanism applies to multiple types of stem cell. Recently, various new players that regulate HSC maintenance (e.g. Mcl1, Tel/Etv6, Gfi1, Pten and Stat5) have been identified. In order to better understand HSC self-renewal, we need to understand how these pathways are coordinated. PMID:16919448

  1. Stem Cell Research and Health Education

    PubMed Central

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

    2009-01-01

    Stem cells are being touted as the greatest discovery for the potential treatment of a myriad of diseases in the new millennium, but there is still much research to be done before it will be known whether they can live up to this description. There is also an ethical debate over the production of one of the most valuable types of stem cell: the embryonic form. Consequently, there is public confusion over the benefits currently being derived from the use of stem cells and what can potentially be expected from their use in the future. The health educator’s role is to give an unbiased account of the current state of stem cell research. This paper provides the groundwork by discussing the types of cells currently identified, their potential use, and some of the political and ethical pitfalls resulting from such use. PMID:19672471

  2. [Effects of different culture system of isolating and passage of sheep embryonic stem-like cells].

    PubMed

    Bai, Changming; Liu, Chousheng; Wang, Zhigang; Wang, Xinzhuang

    2008-07-01

    In this research, we use mouse embryonic fibroblasts as feeder layers. To eliminate the influence of serum and mouse embryonic stem cells (ESCs) conditioned medium (ESCCM) on self-renewal of sheep embryonic stem-like cells, knockout serum replacement (KSR) was used to replace serum, then supplanted with ESCCM for the isolation and cloning of sheep embryonic stem-like cells. We found when inner cell masses (ICMs) cultured in the control group with medium supplanted with fetal bovine serum (FBS), sheep ES-like cells could not survive for more than 3 passages. However, sheep embryonic stem-like cells could remain undifferentiated for 5 passages when cultured in the medium that FBS was substituted by KSR. The result indicates that KSR culture system was more suitable for the isolation and cloning of sheep embryonic stem-like cells compared to FBS culture system. Finally we applied medium with 15% KSR as basic medium supplanted with 40% ESCCM as a new culture system to isolate sheep embryonic stem-like cells, we found one embryonic stem-like cell line still maintained undifferentiating for 8 passages, which characterized with a normal and stable karyotype and high expression of alkaline phosphatase. These results suggest that it is suitable to culture sheep ICM in the new culture system with 15% KSR as basic medium and supplanted with 40% ESCCM, which indicated that mouse ES cells might secrete factors playing important roles in promoting sheep ES-like cells' self-renewal. PMID:18837407

  3. On the Stem Cell Origin of Cancer

    PubMed Central

    Sell, Stewart

    2010-01-01

    In each major theory of the origin of cancer—field theory, chemical carcinogenesis, infection, mutation, or epigenetic change—the tissue stem cell is involved in the generation of cancer. Although the cancer type is identified by the more highly differentiated cells in the cancer cell lineage or hierarchy (transit-amplifying cells), the property of malignancy and the molecular lesion of the cancer exist in the cancer stem cell. In the case of teratocarcinomas, normal germinal stem cells have the potential to become cancers if placed in an environment that allows expression of the cancer phenotype (field theory). In cancers due to chemically induced mutations, viral infections, somatic and inherited mutations, or epigenetic changes, the molecular lesion or infection usually first occurs in the tissue stem cells. Cancer stem cells then give rise to transit-amplifying cells and terminally differentiated cells, similar to what happens in normal tissue renewal. However, the major difference between cancer growth and normal tissue renewal is that whereas normal transit amplifying cells usually differentiate and die, at various levels of differentiation, the cancer transit-amplifying cells fail to differentiate normally and instead accumulate (ie, they undergo maturation arrest), resulting in cancer growth. PMID:20431026

  4. Stem cells in human neurodegenerative disorders--time for clinical translation?

    PubMed

    Lindvall, Olle; Kokaia, Zaal

    2010-01-01

    Stem cell-based approaches have received much hype as potential treatments for neurodegenerative disorders. Indeed, transplantation of stem cells or their derivatives in animal models of neurodegenerative diseases can improve function by replacing the lost neurons and glial cells and by mediating remyelination, trophic actions, and modulation of inflammation. Endogenous neural stem cells are also potential therapeutic targets because they produce neurons and glial cells in response to injury and could be affected by the degenerative process. As we discuss here, however, significant hurdles remain before these findings can be responsibly translated to novel therapies. In particular, we need to better understand the mechanisms of action of stem cells after transplantation and learn how to control stem cell proliferation, survival, migration, and differentiation in the pathological environment. PMID:20051634

  5. Paracrine mechanisms of stem cell reparative and regenerative actions in the heart

    PubMed Central

    Mirotsou, Maria; Jayawardena, Tilanthi M; Schmeckpeper, Jeffrey; Gnecchi, Massimiliano; Dzau, Victor J

    2010-01-01

    Stem cells play an important role in restoring cardiac function in the damaged heart. In order to mediate repair, stem cells need to replace injured tissue by differentiating into specialized cardiac cell lineages and/or manipulating the cell and molecular mechanisms governing repair. Despite early reports describing engraftment and successful regeneration of cardiac tissue in animal models of heart failure, these events appear to be infrequent and yield too few new cardiomyocytes to account for the degree of improved cardiac function observed. Instead, mounting evidence suggests that stem cell mediated repair takes place via the release of paracrine factors into the surrounding tissue that subsequently direct a number of restorative processes including myocardial protection, neovascularization, cardiac remodeling, and differentiation. The potential for diverse stem cell populations to moderate many of the same processes as well as key paracrine factors and molecular pathways involved in stem cell-mediated cardiac repair will be discussed in this review. PMID:20727900

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

    PubMed Central

    Davies, Alastair H.; Zoubeidi, Amina

    2016-01-01

    The therapeutic potential of stem cells relies on dissecting the complex signaling networks that are thought to regulate their pluripotency and self-renewal. Until recently, attention has focused almost exclusively on a small set of “core” transcription factors for maintaining the stem cell state. It is now clear that stem cell regulatory networks are far more complex. In this review, we examine the role of the androgen receptor (AR) in coordinating interactions between signaling nodes that govern the balance of cell fate decisions in prostate stem cells. PMID:26880966

  7. Generation of Engraftable Hematopoietic Stem Cells From Induced Pluripotent Stem Cells by Way of Teratoma Formation

    PubMed Central

    Suzuki, Nao; Yamazaki, Satoshi; Yamaguchi, Tomoyuki; Okabe, Motohito; Masaki, Hideki; Takaki, Satoshi; Otsu, Makoto; Nakauchi, Hiromitsu

    2013-01-01

    In vitro generation of hematopoietic stem cells (HSCs) from induced pluripotent stem cells (iPSCs) has the potential to provide novel therapeutic approaches for replacing bone marrow (BM) transplantation without rejection or graft versus host disease. Hitherto, however, it has proved difficult to generate truly functional HSCs transplantable to adult host mice. Here, we demonstrate a unique in vivo differentiation system yielding engraftable HSCs from mouse and human iPSCs in teratoma-bearing animals in combination with a maneuver to facilitate hematopoiesis. In mice, we found that iPSC-derived HSCs migrate from teratomas into the BM and their intravenous injection into irradiated recipients resulted in multilineage and long-term reconstitution of the hematolymphopoietic system in serial transfers. Using this in vivo generation system, we could demonstrate that X-linked severe combined immunodeficiency (X-SCID) mice can be treated by HSCs derived from gene-corrected clonal iPSCs. It should also be noted that neither leukemia nor tumors were observed in recipients after transplantation of iPSC-derived HSCs. Taken our findings together, our system presented in this report should provide a useful tool not only for the study of HSCs, but also for practical application of iPSCs in the treatment of hematologic and immunologic diseases. PMID:23670574

  8. Fully functional hair follicle regeneration through the rearrangement of stem cells and their niches

    PubMed Central

    Toyoshima, Koh-ei; Asakawa, Kyosuke; Ishibashi, Naoko; Toki, Hiroshi; Ogawa, Miho; Hasegawa, Tomoko; Iri, Tarou; Tachikawa, Tetsuhiko; Sato, Akio; Takeda, Akira; Tsuji, Takashi

    2012-01-01

    Organ replacement regenerative therapy is purported to enable the replacement of organs damaged by disease, injury or aging in the foreseeable future. Here we demonstrate fully functional hair organ regeneration via the intracutaneous transplantation of a bioengineered pelage and vibrissa follicle germ. The pelage and vibrissae are reconstituted with embryonic skin-derived cells and adult vibrissa stem cell region-derived cells, respectively. The bioengineered hair follicle develops the correct structures and forms proper connections with surrounding host tissues such as the epidermis, arrector pili muscle and nerve fibres. The bioengineered follicles also show restored hair cycles and piloerection through the rearrangement of follicular stem cells and their niches. This study thus reveals the potential applications of adult tissue-derived follicular stem cells as a bioengineered organ replacement therapy. PMID:22510689

  9. Regeneration of the damaged central nervous system through reprogramming technology: basic concepts and potential application for cell replacement therapy.

    PubMed

    Matsui, Takeshi; Akamatsu, Wado; Nakamura, Masaya; Okano, Hideyuki

    2014-10-01

    Neural stem cell (NSC) transplantation provides a new approach for the repair of damage to the central nervous system (CNS), including that resulting from cerebral infarction and spinal cord injury (SCI). In the past, there were no reputable means of converting non-neural somatic cells into neural cells. This status was overturned by the establishment of induced pluripotent stem (iPS) cells, which have pluripotency akin to that of embryonic stem (ES) cells and can differentiate into most cells of the three germ layers. If differentiated somatic cells could be reprogrammed into iPS cells, and if these iPS cells could be induced to differentiate once again, it would be theoretically possible to obtain a large number of neural cells. However, this is not yet feasible due to the limitations of existing stem cell technology. Induction of neural cells from iPS cells is currently hindered by two distinct problems: 1) the preparation of specific types of targeted neural cells requires extensive cell culture, and 2) tumors are likely to form due to the presence of residual undifferentiated cells following transplantation of the induced cells. By contrast, direct induction methods permit the generation of target cells from somatic cells without the transitional iPS cell stage. This review outlines the present-day status of research surrounding the direct induction of NSCs from somatic cells, as well as the perspectives for the future clinical application of this technique for cell replacement therapy following CNS injury. PMID:23036600

  10. Cancer stem cells: implications for cancer therapy.

    PubMed

    Dawood, Shaheenah; Austin, Laura; Cristofanilli, Massimo

    2014-12-01

    The survival of patients with cancer has improved significantly, primarily because of multidisciplinary care, improved chemotherapeutic agents in both the adjuvant and metastatic settings, the introduction of targeted biologic agents, and the incorporation of palliative care services into the management scheme. However, despite these advances, a significant proportion of patients continue to experience recurrence after adjuvant treatment, and survival associated with stage IV solid tumors still remains low. A primary or acquired resistance to chemotherapeutic and biologic agents is responsible for the failure of many of the agents used to treat patients with a malignancy. This can be explained by the presence of intratumoral heterogeneity and the molecular complexity of many cancers. Factors contributing to intratumoral heterogeneity include genetic mutations, interactions with the microenvironment-and the presence of cancer stem cells. Cancer stem cells have been identified in a number of solid tumors, including breast cancer, brain tumors, lung cancer, colon cancer, and melanoma. Cancer stem cells have the capacity to self-renew, to give rise to progeny that are different from them, and to utilize common signaling pathways. Cancer stem cells may be the source of all the tumor cells present in a malignant tumor, the reason for the resistance to the chemotherapeutic agent used to treat the malignant tumor, and the source of cells that give rise to distant metastases. This review will focus on properties of cancer stem cells; will compare and contrast the cancer stem cell model with the clonal evolution model of tumorigenesis; will discuss the role of cancer stem cells in the development of resistance to chemotherapy; and will review the therapeutic implications and challenges of targeting cancer stem cells, with an assessment of the potential such an approach holds for improving outcomes for patients with cancer. PMID:25510809

  11. Stem cell systems and regeneration in planaria.

    PubMed

    Rink, Jochen C

    2013-03-01

    Planarians are members of the Platyhelminthes (flatworms). These animals have evolved a remarkable stem cell system. A single pluripotent adult stem cell type ("neoblast") gives rise to the entire range of cell types and organs in the planarian body plan, including a brain, digestive-, excretory-, sensory- and reproductive systems. Neoblasts are abundantly present throughout the mesenchyme and divide continuously. The resulting stream of progenitors and turnover of differentiated cells drive the rapid self-renewal of the entire animal within a matter of weeks. Planarians grow and literally de-grow ("shrink") by the food supply-dependent adjustment of organismal turnover rates, scaling body plan proportions over as much as a 50-fold size range. Their dynamic body architecture further allows astonishing regenerative abilities, including the regeneration of complete and perfectly proportioned animals even from tiny tissue remnants. Planarians as an experimental system, therefore, provide unique opportunities for addressing a spectrum of current problems in stem cell research, including the evolutionary conservation of pluripotency, the dynamic organization of differentiation lineages and the mechanisms underlying organismal stem cell homeostasis. The first part of this review focuses on the molecular biology of neoblasts as pluripotent stem cells. The second part examines the fascinating mechanistic and conceptual challenges posed by a stem cell system that epitomizes a universal design principle of biological systems: the dynamic steady state. PMID:23138344

  12. Clinical translation of human neural stem cells

    PubMed Central

    2013-01-01

    Human neural stem cell transplants have potential as therapeutic candidates to treat a vast number of disorders of the central nervous system (CNS). StemCells, Inc. has purified human neural stem cells and developed culture conditions for expansion and banking that preserve their unique biological properties. The biological activity of these human central nervous system stem cells (HuCNS-SC®) has been analyzed extensively in vitro and in vivo. When formulated for transplantation, the expanded and cryopreserved banked cells maintain their stem cell phenotype, self-renew and generate mature oligodendrocytes, neurons and astrocytes, cells normally found in the CNS. In this overview, the rationale and supporting data for pursuing neuroprotective strategies and clinical translation in the three components of the CNS (brain, spinal cord and eye) are described. A phase I trial for a rare myelin disorder and phase I/II trial for spinal cord injury are providing intriguing data relevant to the biological properties of neural stem cells, and the early clinical outcomes compel further development. PMID:23987648

  13. Cancer stem cells in multiple myeloma.

    PubMed

    Ghosh, Nilanjan; Matsui, William

    2009-05-01

    Several key observations providing evidence for the cancer stem cell hypothesis and insights into the unique biology of these cells have come from the study of multiple myeloma. These include evidence that cancer cells may be functionally heterogeneous in spite of their genetic homogeneity and that malignant progenitors share many biological features with normal adult stem cells including drug resistance and regulatory processes governing self-renewal. We review studies that have examined clonogenic cells in multiple myeloma, highlight controversies regarding the cell of origin in multiple myeloma, and discuss potential targeting strategies. PMID:18809245

  14. Engineering tissue from human embryonic stem cells

    PubMed Central

    Metallo, CM; Azarin, SM; Ji, L; De Pablo, JJ; Palecek, SP

    2008-01-01

    Abstract Recent advances in human embryonic stem cell (hESC) biology now offer an alternative cell source for tissue engineers, as these cells are capable of proliferating indefinitely and differentiating to many clinically relevant cell types. Novel culture methods capable of exerting spatial and temporal control over the stem cell microenvironment allow for more efficient expansion of hESCs, and significant advances have been made toward improving our understanding of the biophysical and biochemical cues that direct stem cell fate choices. Effective production of lineage specific progenitors or terminally differentiated cells enables researchers to incorporate hESC derivatives into engineered tissue constructs. Here, we describe current efforts using hESCs as a cell source for tissue engineering applications, highlighting potential advantages of hESCs over current practices as well as challenges which must be overcome. PMID:18194458

  15. Stem Cells for Ischemic Brain Injury: A Critical Review

    PubMed Central

    Burns, Terry C.; Verfaillie, Catherine M.; Low, Walter C.

    2014-01-01

    No effective therapy is currently available to promote recovery following ischemic stroke. Stem cells have been proposed as a potential source of new cells to replace those lost due to central nervous system injury, as well as a source of trophic molecules to minimize damage and promote recovery. We undertook a detailed review of data from recent basic science and preclinical studies to investigate the potential application of endogenous and exogenous stem cell therapies for treatment of cerebral ischemia. To date, spontaneous endogenous neurogenesis has been observed in response to ischemic injury, and can be enhanced via infusion of appropriate cytokines. Exogenous stem cells from multiple sources can generate neural cells that survive and form synaptic connections after transplantation in the stroke-injured brain. Stem cells from multiple sources cells also exhibit neuroprotective properties that may ameliorate stroke deficits. In many cases, functional benefits observed are likely independent of neural differentiation, though exact mechanisms remain poorly understood. Future studies of neuroregeneration will require the demonstration of function in endogenously born neurons following focal ischemia. Further, methods are currently lacking to definitively demonstrate the therapeutic effect of newly introduced neural cells. Increased plasticity following stroke may facilitate the functional integration of new neurons, but the loss of appropriate guidance cues and supporting architecture in the infarct cavity will likely impede the restoration of lost circuitry. As such careful investigation of the mechanisms underlying trophic benefits will be essential. Evidence to date suggest that continued development of stem cell therapies may ultimately lead to viable treatment options for ischemic brain injury. PMID:19399885

  16. Effect of isolation methodology on stem cell properties and multilineage differentiation potential of human dental pulp stem cells.

    PubMed

    Hilkens, P; Gervois, P; Fanton, Y; Vanormelingen, J; Martens, W; Struys, T; Politis, C; Lambrichts, I; Bronckaers, A

    2013-07-01

    Dental pulp stem cells (DPSCs) are an attractive alternative mesenchymal stem cell (MSC) source because of their isolation simplicity compared with the more invasive methods associated with harvesting other MSC sources. However, the isolation method to be favored for obtaining DPSC cultures remains under discussion. This study compares the stem cell properties and multilineage differentiation potential of DPSCs obtained by the two most widely adapted isolation procedures. DPSCs were isolated either by enzymatic digestion of the pulp tissue (DPSC-EZ) or by the explant method (DPSC-OG), while keeping the culture media constant throughout all experiments and in both isolation methods. Assessment of the stem cell properties of DPSC-EZ and DPSC-OG showed no significant differences between the two groups with regard to proliferation rate and colony formation. Phenotype analysis indicated that DPSC-EZ and DPSC-OG were positive for CD29, CD44, CD90, CD105, CD117 and CD146 expression without any significant differences. The multilineage differentiation potential of both stem cell types was confirmed by using standard immuno(histo/cyto)chemical staining together with an in-depth ultrastructural analysis by means of transmission electron microscopy. Our results indicate that both DPSC-EZ and DPSC-OG could be successfully differentiated into adipogenic, chrondrogenic and osteogenic cell types, although the adipogenic differentiation of both stem cell populations was incomplete. The data suggest that both the enzymatic digestion and outgrowth method can be applied to obtain a suitable autologous DPSC resource for tissue replacement therapies of both bone and cartilage. PMID:23715720

  17. Calcium signaling in human pluripotent stem cells.

    PubMed

    Apáti, Ágota; Berecz, Tünde; Sarkadi, Balázs

    2016-03-01

    Human pluripotent stem cells provide new tools for developmental and pharmacological studies as well as for regenerative medicine applications. Calcium homeostasis and ligand-dependent calcium signaling are key components of major cellular responses, including cell proliferation, differentiation or apoptosis. Interestingly, these phenomena have not been characterized in detail as yet in pluripotent human cell sates. Here we review the methods applicable for studying both short- and long-term calcium responses, focusing on the expression of fluorescent calcium indicator proteins and imaging methods as applied in pluripotent human stem cells. We discuss the potential regulatory pathways involving calcium responses in hPS cells and compare these to the implicated pathways in mouse PS cells. A recent development in the stem cell field is the recognition of so called "naïve" states, resembling the earliest potential forms of stem cells during development, as well as the "fuzzy" stem cells, which may be alternative forms of pluripotent cell types, therefore we also discuss the potential role of calcium homeostasis in these PS cell types. PMID:26922096

  18. Cancer stem cell targeted therapy: progress amid controversies

    PubMed Central

    Wang, Tao; Shigdar, Sarah; Gantier, Michael P.; Hou, Yingchun; Wang, Li; Li, Yong; Shamaileh, Hadi Al; Yin, Wang; Zhou, Shu-Feng; Zhao, Xinhan; Duan, Wei

    2015-01-01

    Although cancer stem cells have been well characterized in numerous malignancies, the fundamental characteristics of this group of cells, however, have been challenged by some recent observations: cancer stem cells may not necessary to be rare within tumors; cancer stem cells and non-cancer stem cells may undergo reversible phenotypic changes; and the cancer stem cells phenotype can vary substantially between patients. Here the current status and progresses of cancer stem cells theory is illustrated and via providing a panoramic view of cancer therapy, we addressed the recent controversies regarding the feasibility of cancer stem cells targeted anti-cancer therapy. PMID:26496035

  19. Tissue-specific designs of stem cell hierarchies.

    PubMed

    Visvader, Jane E; Clevers, Hans

    2016-04-01

    Recent work in the field of stem cell biology suggests that there is no single design for an adult tissue stem cell hierarchy, and that different tissues employ distinct strategies to meet their self-renewal and repair requirements. Stem cells may be multipotent or unipotent, and can exist in quiescent or actively dividing states. 'Professional' stem cells may also co-exist with facultative stem cells, which are more specialized daughter cells that revert to a stem cell state under specific tissue damage conditions. Here, we discuss stem cell strategies as seen in three solid mammalian tissues: the intestine, mammary gland and skeletal muscle. PMID:26999737

  20. Stem cells and bone: a historical perspective.

    PubMed

    Bianco, Paolo

    2015-01-01

    Bone physiology and stem cells were tightly intertwined with one another, both conceptually and experimentally, long before the current explosion of interest in stem cells and so-called regenerative medicine. Bone is home to the two best known and best characterized systems of postnatal stem cells, and it is the only organ in which two stem cells and their dependent lineages coordinate the overall adaptive responses of two major physiological systems. All along, the nature and the evolutionary significance of the interplay of bone and hematopoiesis have remained a major scientific challenge, but also allowed for some of the most spectacular developments in cell biology-based medicine, such as hematopoietic stem cell transplantation. This question recurs in novel forms at multiple turning points over time: today, it finds in the biology of the "niche" its popular phrasing. Entirely new avenues of investigation emerge as a new view of bone in physiology and medicine is progressively established. Looking at bone and stem cells in a historical perspective provides a unique case study to highlight the general evolution of science in biomedicine since the end of World War II to the present day. A paradigm shift in science and in its relation to society and policies occurred in the second half of the XXth century, with major implications thereof for health, industry, drug development, market and society. Current interest in stem cells in bone as in other fields is intertwined with that shift. New opportunities and also new challenges arise. This article is part of a Special Issue entitled "Stem cells and bone". PMID:25171959

  1. 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

  2. 75 FR 8085 - National Institutes of Health Guidelines for Human Stem Cell Research

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-23

    ... derived from the inner cell mass of blastocyst stage human embryos, are capable of dividing without... embryo which fails to develop to the blastocyst stage. Therefore, the NIH proposes replacing the current... stem cells (hESCs)' are pluripotent cells that are derived from ] early stage human embryos, up to...

  3. The multiple aspects of stroke and stem cell therapy.

    PubMed

    Onteniente, B

    2013-06-01

    Cumulative evidence shows that transplantation of stem cells (SC) derivatives can reduce the functional deficits induced by cerebral ischemia or hemorrhage in animals. Most SC sources have been applied to stroke models, with varying degrees of differentiation into neural derivatives and in varying number, timing and route of administration, with similar benefits on functional outcome. Pioneering clinical trials developed in parallel, and currently outnumber other applications of SC in neurological disorders. These trials reflect a paradigm shift from cell replacement therapy to disease-modeling effects, with increased used of non neural SC. This shift stems in experimental demonstration of paracrine effects of SC that attenuate inflammation, limit cell death through neurotrophic effects, and enhance endogenous recovery processes. Due to its pathogenic characteristics, stroke can uniquely benefit from this variety of actions. PMID:23642063

  4. Ethical issues in deriving stem cells from embryos and eggs.

    PubMed

    Cornwell, Glenda

    Human embryonic stem cell (ESC) research has attracted wide media coverage. It has been headline news for the past several months, revealing the complex case of Professor Hwang Woo-Suk and the scientific fraud where he purported to have created the first human patient-specific stem cell lines generated by cell nucleus replacement (CNR). To ethically obtain the raw materials (eggs, sperm and embryos) for human ESC research is an enormous challenge, yet essential if this research is to proceed in its quest to try to deliver some of the expectations placed upon it: developing treatments and possible cures for a range of serious diseases. This article examines some of the ethical issues surrounding human ESC research using the four principles frequently applied to healthcare and medical research; autonomy, beneficence, non-maleficence and justice. The author strives to ask questions throughout which will encourage debate and discussion. PMID:16835537

  5. Stem cell system in tissue regeneration in fish.

    PubMed

    Kawakami, Atsushi

    2010-01-01

    During evolution from single-cell to multi-cellular organisms, organisms developed the needed machinery by which a vast number of functionally different types of cells could be unified into an individual. To attain this goal, organisms evolved the developmental strategies that produced different cell types and unified them into complex body architecture. However, a more intriguing feature of multi-cellular organisms is that they can maintain their bodies throughout long life. For tissue maintenance, stem and/or progenitor cells in many tissues and organs are thought to play an important role; however, we know little about their control and the process of tissue reconstitution. As cells are fragile, all animals have the ability, more or less, to replace damaged or dead cells; however, there are large variations in such abilities, depending on the type of organs and the species. Though vertebrates cannot reconstitute their bodies from a small piece as do planarians, some lower vertebrates, unlike mammals, have the ability to regenerate body appendages and many internal organs. If we unveil the nature of stem cells in striking examples of such regeneration, this information can be applied to mammals and greatly benefit us. The focus in the present review is on the recent advances in our knowledge about the regeneration mechanism in fish, including the stem cells that are involved. PMID:19843152

  6. Ethical Issues in Stem Cell Research

    PubMed Central

    Lo, Bernard; Parham, Lindsay

    2009-01-01

    Stem cell research offers great promise for understanding basic mechanisms of human development and differentiation, as well as the hope for new treatments for diseases such as diabetes, spinal cord injury, Parkinson’s disease, and myocardial infarction. However, human stem cell (hSC) research also raises sharp ethical and political controversies. The derivation of pluripotent stem cell lines from oocytes and embryos is fraught with disputes about the onset of human personhood. The reprogramming of somatic cells to produce induced pluripotent stem cells avoids the ethical problems specific to embryonic stem cell research. In any hSC research, however, difficult dilemmas arise regarding sensitive downstream research, consent to donate materials for hSC research, early clinical trials of hSC therapies, and oversight of hSC research. These ethical and policy issues need to be discussed along with scientific challenges to ensure that stem cell research is carried out in an ethically appropriate manner. This article provides a critical analysis of these issues and how they are addressed in current policies. PMID:19366754

  7. WHAT CONTROLS STEM CELL DEVELOPMENT-- CELL POTENTIAL OR LOCAL ENVIRONMENT?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In H. virescens, as in M. sexta and other lepidoptera, midgut development proceeds through the sequential proliferation and differentiation of the midgut stem cells. In larvae,the stem cells repeatedly differentiatiate to goblet, columnar, and to a lesser extent endocrine cells of the midgut; a res...

  8. Stem cell transplantation: a collegial conversation.

    PubMed

    Kidson, S H; Jordaan, G

    2013-01-01

    To assist our readers in their understanding of ''Pioneer' Paarl neuro sets alarm bells ringing' in Izindaba (p. 8-9), the SAMJ sought the opinions of Professor Susan Kidson (SK), one of SA's foremost stem cell scientists. Based on her insights into the stem cell transplant undertaken on Mr Tommie Prins at the hands of neurosurgeon Dr Adriaan Liebenberg, she offered the following in relation to the stepwise production of suitable stem cells. Dr Gert Jordaan (GJ) was then approached to explain his methodology in raising the stem cells used for the transplant. Dr Jordaan's reply was received in Afrikaans, an English translation of which is supplied. We believe that the debate will continue... PMID:23237115

  9. Will embryonic stem cells change health policy?

    PubMed

    Sage, William M

    2010-01-01

    Embryonic stem cells are actively debated in political and public policy arenas. However, the connections between stem cell innovation and overall health care policy are seldom elucidated. As with many controversial aspects of medical care, the stem cell debate bridges to a variety of social conversations beyond abortion. Some issues, such as translational medicine, commercialization, patient and public safety, health care spending, physician practice, and access to insurance and health care services, are core health policy concerns. Other issues, such as economic development, technologic progress, fiscal politics, and tort reform, are only indirectly related to the health care system but are frequently seen through a health care lens. These connections will help determine whether the stem cell debate reaches a resolution, and what that resolution might be. PMID:20579256

  10. Heterochromatin components in germline stem cell maintenance

    PubMed Central

    Xing, Yalan; Li, Willis X.

    2015-01-01

    Stem cell maintenance requires expression of genes essential for stemness and repression of differentiation genes. How this is achieved remains incompletely understood. Here we investigate the requirement for central components of heterochromatin, Heterochromatin Protein 1 (HP1) and the histone H3 lys9 methyltransferase Su(var)3-9, in the Drosophila male germline stem cell (GSC) self-renewal, a paradigm for studying adult stem cell behavior. We found that mutations or RNAi knock down of HP1 or Su(var)3-9 cause loss of GSCs, accompanied by defects in cell division or survival and premature expression of the differentiation gene bag of marbles (bam). Conversely, over-expressing HP1 increases GSC number in wildtype flies and, strikingly, restores fertility to the sterile hopscotch (hop) mutant flies that lack niche signals. These results suggest that the central components of heterochromatin play roles including repressing differentiation genes in Drosophila male GSC maintenance. PMID:26626305

  11. De Novo Kidney Regeneration with Stem Cells

    PubMed Central

    Yokote, Shinya; Yamanaka, Shuichiro; Yokoo, Takashi

    2012-01-01

    Recent studies have reported on techniques to mobilize and activate endogenous stem-cells in injured kidneys or to introduce exogenous stem cells for tissue repair. Despite many recent advantages in renal regenerative therapy, chronic kidney disease (CKD) remains a major cause of morbidity and mortality and the number of CKD patients has been increasing. When the sophisticated structure of the kidneys is totally disrupted by end stage renal disease (ESRD), traditional stem cell-based therapy is unable to completely regenerate the damaged tissue. This suggests that whole organ regeneration may be a promising therapeutic approach to alleviate patients with uncured CKD. We summarize here the potential of stem-cell-based therapy for injured tissue repair and de novo whole kidney regeneration. In addition, we describe the hurdles that must be overcome and possible applications of this approach in kidney regeneration. PMID:23251079

  12. 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

  13. Immunological characteristics of human mesenchymal stem cells and multipotent adult progenitor cells.

    PubMed

    Jacobs, Sandra A; Roobrouck, Valerie D; Verfaillie, Catherine M; Van Gool, Stefaan W

    2013-01-01

    Somatic, also termed adult, stem cells are highly attractive biomedical cell candidates because of their extensive replication potential and functional multilineage differentiation capacity. They can be used for drug and toxicity screenings in preclinical studies, as in vitro model to study differentiation or for regenerative medicine to aid in the repair of tissues or replace tissues that are lost upon disease, injury or ageing. Multipotent adult progenitor cells (MAPCs) and mesenchymal stem cells (MSCs) are two types of adult stem cells derived from bone marrow that are currently being used clinically for tissue regeneration and for their immunomodulatory and trophic effects. This review will give an overview of the phenotypic and functional differences between human MAPCs and MSCs, with a strong emphasis on their immunological characteristics. Finally, we will discuss the clinical studies in which MSCs and MAPCs are already used. PMID:23295415

  14. STEM CELLS IN ENDOMETRIUM AND THEIR ROLE IN THE PATHOGENESIS OF ENDOMETRIOSIS

    PubMed Central

    Figueira, Paula Gabriela Marin; Abrão, Mauricio Simões; Krikun, Graciela; Taylor, Hugh

    2011-01-01

    The human endometrium is a dynamic tissue, which undergoes cycles of growth and regression with each menstrual cycle. Adult progenitor stem cells are likely responsible for this remarkable regenerative capacity; these same progenitor stem cells may also have an enhanced capacity to generate endometriosis if shed in a retrograde fashion. The progenitor stem cells reside in the uterus, however less committed mesenchymal stem cells may also travel from other tissues such as bone marrow to repopulate the progenitor population. Mesenchymal stem cells are also involved in the pathogenesis of endometriosis and may be the principle source of endometriosis outside of the peritoneal cavity when they differentiate into endometriosis in ectopic locations. Finally, besides progenitor stem cells, recent publications have identified multipotent stem cells in the endometrium. These multipotent stem cells are a readily available source of cells that are useful in tissue engineering and regenerative medicine. Endometrial stem cells have been used to generate chondrocytes, myocytes, neurons and adiposites in vitro as well as to replace dopiminergic neurons in a murine model of Parkinson disease. PMID:21401624

  15. Cell therapy using induced pluripotent stem cells or somatic stem cells: this is the question.

    PubMed

    Somoza, Rodrigo A; Rubio, Francisco J

    2012-05-01

    A lot of effort has been developed to bypass the use of embryonic stem cells (ES) in human therapies, because of several concerns and ethical issues. Some unsolved problems of using stem cells for human therapies, excluding the human embryonic origin, are: how to regulate cell plasticity and proliferation, immunological compatibility, potential adverse side-effects when stem cells are systemically administrated, and the in vivo signals to rule out a specific cell fate after transplantation. Currently, it is known that almost all tissues of an adult organism have somatic stem cells (SSC). Whereas ES are primary involved in the genesis of new tissues and organs, SSC are involved in regeneration processes, immuno-regulatory and homeostasis mechanisms. Although the differentiating potential of ES is higher than SSC, several studies suggest that some types of SSC, such as mesenchymal stem cells (MSC), can be induced epigenetically to differentiate into tissue-specific cells of different lineages. This unexpected pluripotency and the variety of sources that they come from, can make MSC-like cells suitable for the treatment of diverse pathologies and injuries. New hopes for cell therapy came from somatic/mature cells and the discovery that could be reprogrammed to a pluripotent stage similar to ES, thus generating induced pluripotent stem cells (iPS). For this, it is necessary to overexpress four main reprogramming factors, Sox2, Oct4, Klf4 and c-Myc. The aim of this review is to analyze the potential and requirements of cellular based tools in human therapy strategies, focusing on the advantage of using MSC over iPS. PMID:22329581

  16. Matrix elasticity directs stem cell lineage specification

    NASA Astrophysics Data System (ADS)

    Discher, Dennis

    2010-03-01

    Adhesion of stem cells - like most cells - is not just a membrane phenomenon. Most tissue cells need to adhere to a ``solid'' for viability, and over the last decade it has become increasingly clear that the physical ``elasticity'' of that solid is literally ``felt'' by cells. Here we show that Mesenchymal Stem Cells (MSCs) specify lineage and commit to phenotypes with extreme sensitivity to the elasticity typical of tissues [1]. In serum only media, soft matrices that mimic brain appear neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Inhibition of nonmuscle myosin II activity blocks all elasticity directed lineage specification, which indicates that the cytoskeleton pulls on matrix through adhesive attachments. Results have significant implications for `therapeutic' stem cells and have motivated development of a proteomic-scale method to identify mechano-responsive protein structures [2] as well as deeper physical studies of matrix physics [3] and growth factor pathways [4]. [4pt] [1] A. Engler, et al. Matrix elasticity directs stem cell lineage specification. Cell (2006).[0pt] [2] C.P. Johnson, et al. Forced unfolding of proteins within cells. Science (2007).[0pt] [3] A.E.X. Brown, et al. Multiscale mechanics of fibrin polymer: Gel stretching with protein unfolding and loss of water. Science (2009).[0pt] [4] D.E. Discher, et al. Growth factors, matrices, and forces combine and control stem cells. Science (2009).

  17. CD117+ amniotic fluid stem cells

    PubMed Central

    Cananzi, Mara; De Coppi, Paolo

    2012-01-01

    Broadly multipotent stem cells can be isolated from amniotic fluid by selection for the expression of the membrane stem cell factor receptor c-Kit, a common marker for multipotential stem cells. They have clonogenic capability and can be directed into a wide range of cell types representing the three primary embryonic lineages. Amniotic fluid stem cells maintained for over 250 population doublings retained long telomeres and a normal karyotype. Clonal human lines verified by retroviral marking were induced to differentiate into cell types representing each embryonic germ layer, including cells of adipogenic, osteogenic, myogenic, endothelial, neuronal and hepatic lineages. AFS cells could be differentiate toward cardiomyogenic lineages, when co-cultured with neonatal cardiomyocytes, and have the potential to generate myogenic and hematopoietic lineages both in vitro and in vivo. Very recently first trimester AFS cells could be reprogrammed without any genetic manipulation opening new possibilities in the field of fetal/neonatal therapy and disease modeling. In this review we are aiming to summarize the knowledge on amniotic fluid stem cells and highlight the most promising results. PMID:23037870

  18. The significance of the micropores at the stem-cement interface in total hip replacement.

    PubMed

    Zhang, H; Blunt, L; Jiang, X; Brown, L; Barrans, S

    2011-01-01

    Cemented total hip replacement has been performed worldwide to treat patients with osteoarthritis and osteonecrosis, with aseptic loosening as its primary reason for revision. It has been indicated that the stem-cement interfacial porosity may contribute to the early loosening of cemented hip prosthesis. In addition, it is generally accepted that the micropores in bone cement surface and in the bulk material are detrimental to the mechanical integrity of bone cement and act as stress concentrators, resulting in generation of fatigue cracks in the cement mantle. Furthermore, it was demonstrated that the micropores also play an important part in initiation and propagation of fretting wear on polished femoral stems. Taking this into consideration, a detailed review of the potential significance of the micropores in bone cement and the methods that could be employed to reduce porosity is given in this article. It was considered that modern cementing techniques are clinically beneficial and should be applied in surgery to further improve the survivorship of cemented total hip replacement. PMID:21144164

  19. Derivation of Insulin-Producing Beta-Cells from Human Pluripotent Stem Cells

    PubMed Central

    Schiesser, Jacqueline V.; Micallef, Suzanne J.; Hawes, Susan; Elefanty, Andrew G.; Stanley, Edouard G.

    2014-01-01

    Human embryonic stem cells have been advanced as a source of insulin-producing cells that could potentially replace cadaveric-derived islets in the treatment of type 1 diabetes. To this end, protocols have been developed that promote the formation of pancreatic progenitors and endocrine cells from human pluripotent stem cells, encompassing both embryonic stem cells and induced pluripotent stem cells. In this review, we examine these methods and place them in the context of the developmental and embryological studies upon which they are based. In particular, we outline the stepwise differentiation of cells towards definitive endoderm, pancreatic endoderm, endocrine lineages and the emergence of functional beta-cells. In doing so, we identify key factors common to many such protocols and discuss the proposed action of these factors in the context of cellular differentiation and ongoing development. We also compare strategies that entail transplantation of progenitor populations with those that seek to develop fully functional hormone expressing cells in vitro. Overall, our survey of the literature highlights the significant progress already made in the field and identifies remaining deficiencies in developing a pluripotent stem cell based treatment for type 1 diabetes. PMID:25148364

  20. Stem cells: insights into the secretome.

    PubMed

    Makridakis, Manousos; Roubelakis, Maria G; Vlahou, Antonia

    2013-11-01

    Stem cells have been considered as possible therapeutic vehicles for different health related problems such as cardiovascular and neurodegenerative diseases and cancer. Secreted molecules are key mediators in cell-cell interactions and influence the cross talk with the surrounding tissues. There is strong evidence supporting that crucial cellular functions such as proliferation, differentiation, communication and migration are strictly regulated from the cell secretome. The investigation of stem cell secretome is accumulating continuously increasing interest given the potential use of these cells in regenerative medicine. The scope of the review is to report the main findings from the investigation of stem cell secretome by the use of contemporary proteomics methods and discuss the current status of research in the field. This article is part of a Special Issue entitled: An Updated Secretome. PMID:23376432

  1. Developments in intracerebral stem cell grafts.

    PubMed

    Reyes, Stephanny; Tajiri, Naoki; Borlongan, Cesar V

    2015-04-01

    The field of stem cell therapy has emerged as a promising research area for brain repair. Optimizing the safety and efficacy of the therapy for clinical trials will require revisiting transplantation protocols. The cell delivery route stands as a key translational item that warrants careful consideration in facilitating the success of stem cell therapy in the clinic. Intracerebral administration, compared to peripheral route, requires an invasive procedure to directly implant stem cells into injured brain. Although invasive, intracerebral transplantation circumvents the prohibitive blood brain barrier in allowing grafted cells when delivered peripherally to penetrate the brain and reach the discreet damaged brain tissues. This review will highlight milestone discoveries in cell therapy for neurological disorders, with emphasis on intracerebral transplantation in relevant animal models and provide insights necessary to optimize the safety and efficacy of cell therapy for the treatment of Parkinson's disease, Huntington's disease, stroke and traumatic brain injury. PMID:25739415

  2. Development in intracerebral stem cell grafts

    PubMed Central

    Reyes, Stephanny; Tajiri, Naoki; Borlongan, Cesar V.

    2015-01-01

    The field of stem cell therapy has emerged as a promising research area for brain repair. Optimizing the safety and efficacy of the therapy for clinical trials will require revisiting transplantation protocols. The cell delivery route stands as a key translational item that warrants careful consideration in facilitating the success of stem cell therapy in the clinic. Intracerebral administration, compared to peripheral route, requires an invasive procedure to directly implant stem cells into injured brain. Although invasive, intracerebral transplantation circumvents the prohibitive blood brain barrier in allowing grafted cells when delivered peripherally to penetrate the brain and reach the discreet damaged brain tissues. This review will highlight milestone discoveries in cell therapy for neurological disorders, with emphasis on intracerebral transplantation in relevant animal models and provide insights necessary to optimize the safety and efficacy of cell therapy for the treatment of Parkinson’s disease, Huntington’s disease, stroke, and traumatic brain injury. PMID:25739415

  3. Engineering the CNS stem cell microenvironment

    PubMed Central

    Williams, Cicely A; Lavik, Erin B

    2010-01-01

    The loss of neural tissue underlies the symptomatology of several neurological insults of disparate etiology, including trauma, cerebrovascular insult and neurodegenerative disease. Restoration of damaged neural tissue through the use of exogenous or endogenous neural stem or progenitor cells is an enticing therapeutic option provided one can control their proliferation, migration and differentiation. Initial attempts at CNS tissue engineering relied on the intrinsic cellular properties of progenitor cells; however, it is now appreciated that the microenvironment surrounding the cells plays an indispensible role in regulating stem cell behavior. This article focuses on attempts to engineer the neural stem cell microenvironment by utilizing the major cellular components of the niche (endothelial cells, astrocytes and ependymal cells) and the extracellular matrix in which they are embedded. PMID:19903005

  4. Clinical grade adult stem cell banking

    PubMed Central

    Thirumala, Sreedhar; Goebel, W Scott

    2009-01-01

    There has been a great deal of scientific interest recently generated by the potential therapeutic applications of adult stem cells in human care but there are several challenges regarding quality and safety in clinical applications and a number of these challenges relate to the processing and banking of these cells ex-vivo. As the number of clinical trials and the variety of adult cells used in regenerative therapy increases, safety remains a primary concern. This has inspired many nations to formulate guidelines and standards for the quality of stem cell collection, processing, testing, banking, packaging and distribution. Clinically applicable cryopreservation and banking of adult stem cells offers unique opportunities to advance the potential uses and widespread implementation of these cells in clinical applications. Most current cryopreservation protocols include animal serum proteins and potentially toxic cryoprotectant additives (CPAs) that prevent direct use of these cells in human therapeutic applications. Long term cryopreservation of adult stem cells under good manufacturing conditions using animal product free solutions is critical to the widespread clinical implementation of ex-vivo adult stem cell therapies. Furthermore, to avoid any potential cryoprotectant related complications, reduced CPA concentrations and efficient post-thaw washing to remove CPA are also desirable. The present review focuses on the current strategies and important aspects of adult stem cell banking for clinical applications. These include current good manufacturing practices (cGMPs), animal protein free freezing solutions, cryoprotectants, freezing & thawing protocols, viability assays, packaging and distribution. The importance and benefits of banking clinical grade adult stem cells are also discussed. PMID:20046678

  5. 3 CFR - Guidelines for Human Stem Cell Research

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  6. 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. PMID:26732838

  7. Stem cells in human neurodegenerative disorders — time for clinical translation?

    PubMed Central

    Lindvall, Olle; Kokaia, Zaal

    2010-01-01

    Stem cell–based approaches have received much hype as potential treatments for neurodegenerative disorders. Indeed, transplantation of stem cells or their derivatives in animal models of neurodegenerative diseases can improve function by replacing the lost neurons and glial cells and by mediating remyelination, trophic actions, and modulation of inflammation. Endogenous neural stem cells are also potential therapeutic targets because they produce neurons and glial cells in response to injury and could be affected by the degenerative process. As we discuss here, however, significant hurdles remain before these findings can be responsibly translated to novel therapies. In particular, we need to better understand the mechanisms of action of stem cells after transplantation and learn how to control stem cell proliferation, survival, migration, and differentiation in the pathological environment. PMID:20051634

  8. Stem cells and regenerative medicine: accomplishments to date and future promise.

    PubMed

    Helmy, Karim Y; Patel, Shyam A; Silverio, Kimberly; Pliner, Lillian; Rameshwar, Pranela

    2010-11-01

    More than 50 years have passed since the first allogeneic hematopoietic stem cell transplant in patients; however, the promise of other stem cell populations for tissue replacement and repair remains unachieved. When considering cell-based interventions for personalized medicine, the factors influencing therapeutic success and safety are more complicated than for traditional small-molecule pharmacological agents and protein biologics. Failure to progress personalized stem