{"title":"Therapeutic potential of Pnmt+ primer cells for neuro/myocardial regeneration.","authors":"Aaron Owji, Namita Varudkar, 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}
Faith R Kreitzer, Nathan Salomonis, Alice Sheehan, Miller Huang, Jason S Park, Matthew J Spindler, Paweena Lizarraga, William A Weiss, Po-Lin So, Bruce R Conklin
{"title":"A robust method to derive functional neural crest cells from human pluripotent stem cells.","authors":"Faith R Kreitzer, Nathan Salomonis, Alice Sheehan, Miller Huang, Jason S Park, Matthew J Spindler, Paweena Lizarraga, William A Weiss, Po-Lin So, 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}
Farhard Khimani, Ryan Livengood, Olukemi Esan, Jeffrey A Vos, Vivek Abhyankar, Ludwig Gutmann, William Tse
{"title":"Pancytopenia related to dental adhesive in a young patient.","authors":"Farhard Khimani, Ryan Livengood, Olukemi Esan, Jeffrey A Vos, Vivek Abhyankar, Ludwig Gutmann, 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, O Raabe, S Wenisch, 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}
Jameson P Holloman, Calvin C Ho, Arushi Hukki, Jennifer L Huntley, G Ian Gallicano
{"title":"The development of hematopoietic and mesenchymal stem cell transplantation as an effective treatment for multiple sclerosis.","authors":"Jameson P Holloman, Calvin C Ho, Arushi Hukki, Jennifer L Huntley, 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}
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
{"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, Gudrun Göhring, 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}
{"title":"Mesenchymal stem cell and regenerative medicine: regeneration versus immunomodulatory challenges.","authors":"Sujata Law, Samaresh Chaudhuri","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mesenchymal Stem cells (MSC) are now presented with the opportunities of multifunctional therapeutic approaches. Several reports are in support of their self-renewal, capacity for multipotent differentiation, and immunomodulatory properties. They are unique to contribute to the regeneration of mesenchymal tissues such as bone, cartilage, muscle, ligament, tendon, and adipose. In addition to promising trials in regenerative medicine, such as in the treatment of major bone defects and myocardial infarction, MSC has shown a therapeutic effect other than direct hematopoiesis support in hematopoietic reconstruction. MSCs are identified by the expression of many molecules including CD105 (SH2) and CD73(SH3/4) and are negative for the hematopoietic markers CD34, CD45, and CD14. Manufacturing of MSC for clinical trials is also an important aspect as their differentiation, homing and Immunomodulatory properties may differ. Their suppressive effects on immune cells, including T cells, B cells, NK cells and DC cells, suggest MSCs as a novel therapy for GVHD and other autoimmune disorders. Since the cells by themselves are non-immunogenic, tissue matching between MSC donor and recipient is not essential and, MSC may be the first cell type able to be used as an \"off-the-shelf\" therapeutic product. Following a successful transplantation, the migration of MSC to the site of injury refers to the involvement of chemokines and chemokine receptors of respective specificity. It has been demonstrated that cultured MSCs have the ability to engraft into healthy as well as injured tissue and can differentiate into several cell types in vivo, which facilitates MSC to be an ideal tool for regenerative therapy in different disease types. However, some observations have raised questions about the limitations for proper use of MSC considering some critical factors that warn regular clinical use.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"2 1","pages":"22-38"},"PeriodicalIF":1.8,"publicationDate":"2013-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636724/pdf/ajsc0002-0022.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31429924","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}
O Raabe, K Shell, A Goessl, C Crispens, Y Delhasse, A Eva, G Scheiner-Bobis, S Wenisch, S Arnhold
{"title":"Effect of extracorporeal shock wave on proliferation and differentiation of equine adipose tissue-derived mesenchymal stem cells in vitro.","authors":"O Raabe, K Shell, A Goessl, C Crispens, Y Delhasse, A Eva, G Scheiner-Bobis, S Wenisch, S Arnhold","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mesenchymal stem cells are regarded as common cellular precursors of the musculoskeletal tissue and are responsible for tissue regeneration in the course of musculoskeletal disorders. In equine veterinary medicine extracorporeal shock wave therapy (ESWT) is used to optimize healing processes of bone, tendon and cartilage. Nevertheless, little is known about the effects of the shock waves on cells and tissues. Thus, the aim of this study was to investigate the influence of focused ESWT on the viability, proliferation, and differentiation capacity of adipose tissue-derived mesenchymal stem cells (ASCs) and to explore its effects on gap junctional communication and the activation of signalling cascades associated with cell proliferation and differentiation. ASCs were treated with different pulses of focused ESWT. Treated cells showed increased proliferation and expression of Cx43, as detected by means of qRT-PCR, histological staining, immunocytochemistry and western blot. At the same time, cells responded to ESWT by significant activation (phosphorylation) of Erk1/2, detected in western blots. No significant effects on the differentiation potential of the ASCs were evident. Taken together, the present results show significant effects of shock waves on stem cells in vitro.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"2 1","pages":"62-73"},"PeriodicalIF":1.8,"publicationDate":"2013-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636727/pdf/ajsc0002-0062.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31429928","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}
Luis Riera Del Moral, Carlota Largo Aramburu, José Ramón Ramírez García, Luis Riera de Cubas, Damián García-Olmo, Mariano García-Arranz
{"title":"Experimental model for coadjuvant treatment with mesenchymal stem cells for aortic aneurysm.","authors":"Luis Riera Del Moral, Carlota Largo Aramburu, José Ramón Ramírez García, Luis Riera de Cubas, Damián García-Olmo, Mariano García-Arranz","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Unlabelled: </strong>Many factors are possibly involved in the inflammatory process which causes the degeneration of the arterial wall in the formation of Abdominal Aortic Aneurysms. During the last years different experimental models have been published to treat this fault of the arterial walls. Parallel the clinical treatment has evolved. With this work we have tried to develop an animal model basing on the clinical current treatment. Finally, we propose a treatment based on mesenchymal cells to disable local immune response, preventing excessive fibrosis, apoptosis, and inducing intrinsic cellular progenitors.</p><p><strong>Objective: </strong>To present a reproducible superior animal model of experimentation, intending to show that mesenchymal stem cells inserted in the sac of an artificial aneurysm are able to survive, so that they can be made accountable for a subsequent beneficial effect upon this condition.</p><p><strong>Methods: </strong>Six Landrace-White pigs, weighing around 25Kg. We generate 2 aneurysms of abdominal aorta (2x1cm) with Dacron's patches. Later we treat the aneurysms endoscopic with a covered endograft. Finally, in one of the aneurysmal sac we introduce 1cc fibrin sealant and in another 1 cc of fibrin sealant with 10 million MSC. Animals were sacrificed at 24 hs and 1, 3, 5, 7 and 9 weeks. Samples of aneurysms were processed histologically (H&E and Masson). The injected cells were located by immunofluorescence (GFP market).</p><p><strong>Results: </strong>The surgical technique is reproducible and similar to those conducted in common clinical practice. Histological cross-section samples of cases treated with MSC and analyzed by a blind researcher present a lower inflammation reaction, or with longer evolution time than in controls. Immunofluorescence studies have detected cells marked with GFP up to three weeks after treatment.</p><p><strong>Conclusion: </strong>This reproducible animal model is similar to common clinical treatment. MSC can stand alive at least for three weeks since their implantation within an aneurysm sac. This may improve the results of conventional endovascular treatment by the stabilization of the aneurysmal sac.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"1 3","pages":"174-81"},"PeriodicalIF":1.8,"publicationDate":"2012-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636731/pdf/ajsc0001-0174.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31428393","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}