American journal of stem cells最新文献

{"title":"Decellularized matrices for cardiovascular tissue engineering.","authors":"Francesco Moroni, Teodelinda Mirabella","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) is one of the leading causes of death in the Western world. The replacement of damaged vessels and valves has been practiced since the 1950's. Synthetic grafts, usually made of bio-inert materials, are long-lasting and mechanically relevant, but fail when it comes to \"biointegration\". Decellularized matrices, instead, can be considered biological grafts capable of stimulating in vivo migration and proliferation of endothelial cells (ECs), recruitment and differentiation of mural cells, finally, culminating in the formation of a biointegrated tissue. Decellularization protocols employ osmotic shock, ionic and non-ionic detergents, proteolitic digestions and DNase/RNase treatments; most of them effectively eliminate the cellular component, but show limitations in preserving the native structure of the extracellular matrix (ECM). In this review, we examine the current state of the art relative to decellularization techniques and biological performance of decellularized heart, valves and big vessels. Furthermore, we focus on the relevance of ECM components, native and resulting from decellularization, in mediating in vivo host response and determining repair and regeneration, as opposed to graft corruption. </p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"3 1","pages":"1-20"},"PeriodicalIF":1.8,"publicationDate":"2014-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960753/pdf/ajsc0003-0001.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32200778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation and crosstalk between TNF family receptors in umbilical cord blood cells is not responsible for loss of engraftment capacity following culture.","authors":"Keren Mizrahi, Nadir Askenasy","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Umbilical cord blood (UCB) is a rich source of hematopoietic progenitors for transplantation. Murine and human progenitors are insensitive to apoptotic signaling mediated by the TNF family receptors, however extension of culture over 48 hours is accompanied by severe deterioration in engraftment and hematopoietic reconstituting capacity. In this study we assessed crosstalk between the Fas, TNF and TRAIL receptors, and questioned whether it contributes to increased mortality and decreased activity of UCB progenitors following extended ex vivo culture for 72 hours. The well-characterized TNF-induced expression of Fas is mediated by both TNF receptors, yet the TNF receptors determine survival rather than Fas: superior viability of TNF-R1 progenitors. Additional cross talk includes upregulation of TRAIL-R1 by Fas-ligand, mediated both by fast cycling and inductive crosstalk. These inductive interactions are not accompanied by concomitant sensitization of progenitors to receptor-mediated apoptosis during extended culture, but rather decreased fractional apoptosis in expanded progenitor subsets expressing the receptors. TRAIL upregulates both TRAIL-R1 and TRAIL-R2, accompanied by commensurate susceptibility to spontaneous apoptosis. The current data reveal inductive crosstalk between TNF family receptors, which are largely dissociated from the sensitivity of hematopoietic progenitors to apoptosis. Activation of Fas, TNF and TRAIL receptors and excessive apoptosis are not responsible for loss of engraftment and impaired reconstituting activity of UCB progenitors following extended culture. </p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"2 3","pages":"155-64"},"PeriodicalIF":1.8,"publicationDate":"2013-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875276/pdf/ajsc0002-0155.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32006404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of Pnmt+ primer cells for neuro/myocardial regeneration.","authors":"Aaron Owji,&nbsp;Namita Varudkar,&nbsp;Steven N Ebert","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Phenylethanolamine n-methyltransferase (Pnmt) catalyzes the conversion of norepinephrine into epinephrine, and thus serves as a marker of adrenergic cells. In adults, adrenergic cells are present in the adrenal medullae and the central and peripheral (sympathetic) nervous systems where they play key roles in stress responses and a variety of other functions. During early embryonic development, however, Pnmt first appears in the heart where it is associated with specialized myocytes in the pacemaking and conduction system. There is a transient surge in cardiac Pnmt expression beginning when the first myocardial contractions occur, before any nerve-like or neural crest cells appear in the heart. This early expression of Pnmt denotes a mesodermal origin of these \"Instrinsic Cardiac Adrenergic\" (ICA) cells. Interestingly, Pnmt+ cells are found in all four chambers of the developing heart, but by adult stages, are found primarily concentrated on the left side of the heart. This regionalized expression occurs in the left atrium and in specific regions of the left ventricle roughly corresponding to basal, mid, and apical sections. A second distinct population of Pnmt-expressing (Pnmt+) cells enters the embryonic heart from invading neural crest, and these \"Neural Crest-Derived\" (NCD) Pnmt+ cells appear to give rise to a subpopulation(s) of cardiac neurons. Pnmt expression thus serves as a marker not only for adrenergic cells, but also for precursor or \"primer\" cells destined to become specialized myocytes and neurons in the heart. This review discusses the distribution of Pnmt in the heart during development, including the types of cells where it is expressed, and their potential use for regenerative medicine therapies for cardiovascular disease. </p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"2 3","pages":"137-54"},"PeriodicalIF":1.8,"publicationDate":"2013-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875277/pdf/ajsc0002-0137.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32006401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A robust method to derive functional neural crest cells from human pluripotent stem cells.","authors":"Faith R Kreitzer,&nbsp;Nathan Salomonis,&nbsp;Alice Sheehan,&nbsp;Miller Huang,&nbsp;Jason S Park,&nbsp;Matthew J Spindler,&nbsp;Paweena Lizarraga,&nbsp;William A Weiss,&nbsp;Po-Lin So,&nbsp;Bruce R Conklin","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Neural crest (NC) cells contribute to the development of many complex tissues of all three germ layers during embryogenesis, and its abnormal development accounts for several congenital birth defects. Generating NC cells-including specific subpopulations such as cranial, cardiac, and trunk NC cells-from human pluripotent stem cells will provide a valuable model system to study human development and disease. Here, we describe a rapid and robust NC differentiation method called \"LSB-short\" that is based on dual SMAD pathway inhibition. This protocol yields high percentages of NC cell populations from multiple human induced pluripotent stem and human embryonic stem cell lines in 8 days. The resulting cells can be propagated easily, retain NC marker expression over multiple passages, and can spontaneously differentiate into several NC-derived cell lineages, including smooth muscle cells, peripheral neurons, and Schwann cells. NC cells generated by this method represent cranial, cardiac and trunk NC subpopulations based on global gene expression analyses, are similar to in vivo analogues, and express a common set of NC alternative isoforms. Functionally, they are also able to migrate appropriately in response to chemoattractants such as SDF-1, FGF8b, and Wnt3a. By yielding NC cells that likely represent all NC subpopulations in a shorter time frame than other published methods, our LSB-short method provides an ideal model system for further studies of human NC development and disease. </p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"2 2","pages":"119-31"},"PeriodicalIF":1.8,"publicationDate":"2013-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708511/pdf/ajsc0002-0119.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31230726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancytopenia related to dental adhesive in a young patient.","authors":"Farhard Khimani,&nbsp;Ryan Livengood,&nbsp;Olukemi Esan,&nbsp;Jeffrey A Vos,&nbsp;Vivek Abhyankar,&nbsp;Ludwig Gutmann,&nbsp;William Tse","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Copper deficiency resulting in hypocupremia is a rare cause of pancytopenia associated with a neurological syndrome. Hypocupremia may also occur as a consequence of excessive oral zinc consumption as described by Brewer et al and several other groups. Dental fixatives have been described as a potential source of hyperzincemia in patients. Despite the recently modified dental fixatives with safer zinc content, zinc poisoning results in hypocupremia secondary to inappropriate use of them can still happen and more likely be misdiagnosed. We describe a case of a patient with pancytopenia who was diagnosed with severe aplastic anemia and hypocellular myelodysplastic syndrome and was referred to us for consideration of bone marrow transplantation. </p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"2 2","pages":"132-6"},"PeriodicalIF":1.8,"publicationDate":"2013-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708507/pdf/ajsc0002-0132.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31586621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amniotic fluid derived stem cells give rise to neuron-like cells without a further differentiation potential into retina-like cells.","authors":"K Hartmann,&nbsp;O Raabe,&nbsp;S Wenisch,&nbsp;S Arnhold","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Amniotic fluid contains heterogeneous cell types and has become an interesting source for obtaining fetal stem cells. These stem cells have a high proliferative capacity and a good differentiation potential and may thus be suitable for regenerative medicine. As there is increasing evidence, that these stem cells are also able to be directed into the neural lineage, in our study we investigated the neuronal and glial differentiation potential of these cells, so that they may also be applied to cure degenerative diseases of the retina. Mesenchymal stem cells were isolated from routine prenatal amniocentesis at 15 to 18 weeks of pregnancy of human amniotic fluid and expanded in the cell culture. Cells were cultivated according to standard procedures for mesenchymal stem cells and were differentiated along the neural lineage using various protocols. Furthermore, it was also tried to direct them into cell types of the retina as well as into endothelial cells. Cells of more than 72 amniotic fluid samples were collected and characterized. While after induction neural-like phenotypes could actually be detected, which was confirmed using neural marker proteins such as GFAP and ßIII tubulina further differentiation into retinal like cells could not reliably be shown. These data suggest that amniotic fluid derived cells are an interesting cell source, which may also give rise to neural-like cells. However, a more specific differentiation into neuronal and glial cells could not unequivocally be shown, so that further investigations have to becarried out. </p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"2 2","pages":"108-18"},"PeriodicalIF":1.8,"publicationDate":"2013-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708508/pdf/ajsc0002-0108.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31230725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On becoming neural: what the embryo can tell us about differentiating neural stem cells.","authors":"Sally A Moody,&nbsp;Steven L Klein,&nbsp;Beverley A Karpinski,&nbsp;Thomas M Maynard,&nbsp;Anthony-Samuel Lamantia","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>THE EARLIEST STEPS OF EMBRYONIC NEURAL DEVELOPMENT ARE ORCHESTRATED BY SETS OF TRANSCRIPTION FACTORS THAT CONTROL AT LEAST THREE PROCESSES: the maintenance of proliferative, pluripotent precursors that expand the neural ectoderm; their transition to neurally committed stem cells comprising the neural plate; and the onset of differentiation of neural progenitors. The transition from one step to the next requires the sequential activation of each gene set and then its down-regulation at the correct developmental times. Herein, we review how these gene sets interact in a transcriptional network to regulate these early steps in neural development. A key gene in this regulatory network is FoxD4L1, a member of the forkhead box (Fox) family of transcription factors. Knock-down experiments in Xenopus embryos show that FoxD4L1 is required for the expression of the other neural transcription factors, whereas increased FoxD4L1 levels have three different effects on these genes: up-regulation of neural ectoderm precursor genes; transient down-regulation of neural plate stem cell genes; and down-regulation of neural progenitor differentiation genes. These different effects indicate that FoxD4L1 maintains neural ectodermal precursors in an immature, proliferative state, and counteracts premature neural stem cell and neural progenitor differentiation. Because it both up-regulates and down-regulates genes, we characterized the regions of the FoxD4L1 protein that are specifically involved in these transcriptional functions. We identified a transcriptional activation domain in the N-terminus and at least two domains in the C-terminus that are required for transcriptional repression. These functional domains are highly conserved in the mouse and human homologues. Preliminary studies of the related FoxD4 gene in cultured mouse embryonic stem cells indicate that it has a similar role in promoting immature neural ectodermal precursors and delaying neural progenitor differentiation. These studies in Xenopus embryos and mouse embryonic stem cells indicate that FoxD4L1/FoxD4 has the important function of regulating the balance between the genes that expand neural ectodermal precursors and those that promote neural stem/progenitor differentiation. Thus, regulating the level of expression of FoxD4 may be important in stem cell protocols designed to create immature neural cells for therapeutic uses. </p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"2 2","pages":"74-94"},"PeriodicalIF":1.8,"publicationDate":"2013-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708510/pdf/ajsc0002-0074.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31230723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The development of hematopoietic and mesenchymal stem cell transplantation as an effective treatment for multiple sclerosis.","authors":"Jameson P Holloman,&nbsp;Calvin C Ho,&nbsp;Arushi Hukki,&nbsp;Jennifer L Huntley,&nbsp;G Ian Gallicano","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This article examines the current use and future implications of stem cell therapy in treating Multiple Sclerosis (MS). MS is the most common neurological disease in young adults, affecting approximately two million people worldwide. Currently there is no cure for MS. The standard treatment of MS involves disease-modifying drugs, which work to alleviate the symptoms of MS. However, these drugs carry adverse side effects and are ineffective in preventing disease progression in many MS patients. Hematopoietic stem cell transplantation (HSCT) was first used in 1995 to treat patients with severe rapidly progressing MS. The HSCT treatment protocol has evolved into a less intense conditioning regimen that is currently demonstrating efficacy in treating patients with variable disease severity-with best results in early-stage rapidly progressing MS patients with active CNS inflammation. Mesenchymal stem cell therapy (MSCT) is an experimental stem cell therapy currently undergoing clinical trials. Animal models and early clinical trials have shown promise that MSCT might be a low risk treatment to precipitate neuroregeneration and immunomodulation in MS patients. Specifically, neuroprogenitor and placental-derived mesenchymal stem cells offer the best hope for a practical treatment for MS. Stem cell therapy, and perhaps a combinatorial therapeutic approach, holds promise for a better treatment for MS. </p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"2 2","pages":"95-107"},"PeriodicalIF":1.8,"publicationDate":"2013-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708509/pdf/ajsc0002-0095.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31230724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BMP9 signaling in stem cell differentiation and osteogenesis.","authors":"Joseph D Lamplot, Jiaqiang Qin, Guoxin Nan, Jinhua Wang, Xing Liu, Liangjun Yin, Justin Tomal, Ruidong Li, Wei Shui, Hongyu Zhang, Stephanie H Kim, Wenwen Zhang, Jiye Zhang, Yuhan Kong, Sahitya Denduluri, Mary Rose Rogers, Abdullah Pratt, Rex C Haydon, Hue H Luu, Jovito Angeles, Lewis L Shi, Tong-Chuan He","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily and play a critical role in skeletal development, bone formation and stem cell differentiation. Disruptions in BMP signaling result in a variety of skeletal and extraskeletal anomalies. BMP9 is a poorly characterized member of the BMP family and is among the most osteogenic BMPs, promoting osteoblastic differentiation of mesenchymal stem cells (MSCs) both in vitro and in vivo. Recent findings from various in vivo and molecular studies strongly suggest that the mechanisms governing BMP9-mediated osteoinduction differ from other osteogenic BMPs. Many signaling pathways with diverse functions have been found to play a role in BMP9-mediated osteogenesis. Several of these pathways are also critical in the differentiation of other cell lineages, including adipocytes and chondrocytes. While BMP9 is known to be a potent osteogenic factor, it also influences several other pathways including cancer development, angiogenesis and myogenesis. Although BMP9 has been demonstrated as one of the most osteogenic BMPs, relatively little is known about the specific mechanisms responsible for these effects. BMP9 has demonstrated efficacy in promoting spinal fusion and bony non-union repair in animal models, demonstrating great translational promise. This review aims to summarize our current knowledge of BMP9-mediated osteogenesis by presenting recently completed work which may help us to further elucidate these pathways.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"2 1","pages":"1-21"},"PeriodicalIF":1.8,"publicationDate":"2013-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636726/pdf/ajsc0002-0001.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31429925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic instability of modified stem cells - a first step towards malignant transformation?","authors":"Doris Steinemann,&nbsp;Gudrun Göhring,&nbsp;Brigitte Schlegelberger","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Induced pluripotent stem cells (iPSC) are important tools in regenerative medicine. Yet, it is becoming increasingly clear that the reprogramming process, including retroviral transduction with potent oncogenes like c-Myc and long-term cultivation, may induce genetic instability. Genetically altered iPS cells can grow out and dominate the cell culture. This review intends to comprehensively summarize the current knowledge on genetic instability of embryonic and iPSCs, with an emphasis on cytogenetic alterations, and compares these data with what is known from tumorigenesis.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"2 1","pages":"39-51"},"PeriodicalIF":1.8,"publicationDate":"2013-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636728/pdf/ajsc0002-0039.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31429926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}