V. Jesús, Z. Mercedes, Mucientes Jorge, Rodríguez-Boto Gregorio, Fernández-Mateos Cecilia
{"title":"Transplantation of Autologous Bone Marrow-Derived Stromal Cells into Injured Spinal Cord Enhances Glucose Metabolism and Promotes Functional Recovery","authors":"V. Jesús, Z. Mercedes, Mucientes Jorge, Rodríguez-Boto Gregorio, Fernández-Mateos Cecilia","doi":"10.23937/2469-570x/1410057","DOIUrl":"https://doi.org/10.23937/2469-570x/1410057","url":null,"abstract":"The authors report the case of a 40-year-old man who suffered paraplegia from 2013, due to shot by firearm. In april 2017 he underwent cell therapy consisting of administration of autologous bone marrow stromal cells (BMSCs) into injured spinal cord and subarachnoid space by lumbar puncture. Throughout one year of follow-up, the patient experienced clear improvement in sensitivity, motor, and sphincter functions. After BMSCs administration, studies with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) suggested an enhancement in glucose uptake at level of injured spinal cord, at least in the course or the first 6 months after the start of cell therapy. This case supports previous observations about the improvements obtained by cell therapy with autologous BMSCs in chronic paraplegic patients, and suggests that a possible increase in tissue metabolism, mediated by the presence of BMSCs into injured spinal cord, can be one of the causes of early clinical improvements.","PeriodicalId":73481,"journal":{"name":"International journal of stem cell research and therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48765571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Contamination Rates by Delivery Method of Human Umbilical Cord Blood Samples in the United Arab Emirates and Gulf Cooperation Council Countries","authors":"M. Ibrahim, S. Aswad","doi":"10.1002/SCTM.12368","DOIUrl":"https://doi.org/10.1002/SCTM.12368","url":null,"abstract":"The use of umbilical cord blood, which is recognized as a rich source of hematopoietic stem cells, has become an alternative source to bone marrow for transplantation. Cord blood units used for transplant might be rejected due to positive bacterial microbiology. According to common cell therapy standards, a microbiology bacterial identification is required to know the type of bacterial and to determine if the bacteria are considered critical or non-critical prior to the transplant determination. This study aims to find the frequency and distribution of bacterial organisms among cord blood samples collected in the United Arab Emirates (UAE) and Gulf Cooperation Countries (GCC) and to investigate if there is a correlation with contamination rates between the delivery method, cesarean section or vaginal delivery. We employed a survey for healthcare professionals to augment the data and then employed statistical analysis to find the frequency of contamination and create best practices to avoid a high level of contamination.","PeriodicalId":73481,"journal":{"name":"International journal of stem cell research and therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SCTM.12368","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43904125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stem Cell Therapy: Recent Success and Continuing Progress in Treating Diabetes","authors":"Mathias Elton, Goveas Roveena, Rajak Manish","doi":"10.23937/2469-570X/1410053","DOIUrl":"https://doi.org/10.23937/2469-570X/1410053","url":null,"abstract":"Diabetes mellitus (DM), a cluster of metabolic diseases, resulting in high blood glucose levels, is prevalent in today’s world. The global costs of diabetes and its consequences are rising and are expected substantially increase by 2030, especially in middleand lower-income countries. Evidence-based therapies, specifically targeting the reduction of high blood glucose levels, and minimizing diabetic complications, are currently the choice of treatment. Stem cell therapy offers a promising vision to treat DM. Although challenges are still posed with this line of therapy, studies have produced regenerative beta-cells which closely resemble insulin-secreting cells. A number of sources for stem cells have been explored, ever since the proof-of-concept for cell therapy was laid down. This review summarizes stem cell therapy in the treatment of DM.","PeriodicalId":73481,"journal":{"name":"International journal of stem cell research and therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49056998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rieke Matthias, Bytyqi Afrim, Frohns Florian, G. LayerPaul
{"title":"Reconstructing Mammalian Retinal Tissue: Wnt3a Regulates Laminar Polarity in Retinal Spheroids from Neonatal Mongolian Rats, while RPE Promotes Cell Differentiation","authors":"Rieke Matthias, Bytyqi Afrim, Frohns Florian, G. LayerPaul","doi":"10.23937/2469-570X/1410051","DOIUrl":"https://doi.org/10.23937/2469-570X/1410051","url":null,"abstract":"Besides invention of iPSC technology, recent progress of stem cell-based organoids is founded on long-standing 3D-reaggregate approaches from embryonic tissues. In particular, histotypic in vitro reconstruction of avian retinal spheroids was most prolific. For instance, a complete reconstitution of all retinal layers was possible, which was supported by Wnt signalling and factors from the retinal pigmented epithelium (RPE); similar in vitro findings are still missing for mammals. Using an established model of reaggregates from dispersed retinal cells of the neonatal Gerbil [1], we show here that in contrast to supernatant from RPE (RPECM), supplementation with Wnt3a induced a correct inside-out polarity of retinal layers. XAP1+ precursors of photoreceptors (PRs) were correctly found on the external face of the sphere, but general cell differentiation remained limited. If Wnt3a was present for 4 days in vitro (div) only, the correctly polarized tissue further differentiated, e.g., more calretinin+ amacrine cells (CR+ ACs) sent out processes into an ipl-like layer and rhodopsin expression of PRs became detectable. Finally, if Wnt3a during 4 div was followed by RPECM treatment, all retinal layers with most cell types were arranged in correct order, as shown by markers including CR, Pax6, AChE, PKCá, CRALBP, and Cern901. LiCl experiments showed that the canonical Wnt/β-catenin pathway was involved. We conclude that Wnt3a conveyed a correct inside-out laminar polarity but kept cells in an undifferentiated state, while RPECM strongly promoted retinal differentiation. Both together supported a nearly complete retinal tissue reconstruction from fully dispersed cells, as never achieved before for cells from any mammalian retina.","PeriodicalId":73481,"journal":{"name":"International journal of stem cell research and therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47224885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancing research in regeneration and repair of the motor circuitry: non-human primate models and imaging scales as the missing links for successfully translating injectable therapeutics to the clinic.","authors":"Magdalini Tsintou, Kyriakos Dalamagkas, Nikos Makris","doi":"10.23937/2469-570X/1410042","DOIUrl":"https://doi.org/10.23937/2469-570X/1410042","url":null,"abstract":"<p><p>Regeneration and repair is the ultimate goal of therapeutics in trauma of the central nervous system (CNS). Stroke and spinal cord injury (SCI) are two highly prevalent CNS disorders that remain incurable, despite numerous research studies and the clinical need for effective treatments. Neural engineering is a diverse biomedical field, that addresses these diseases using new approaches. Research in the field involves principally rodent models and biologically active, biodegradable hydrogels. Promising results have been reported in preclinical studies of CNS repair, demonstrating the great potential for the development of new treatments for the brain, spinal cord and peripheral nerve injury. Several obstacles stand in the way of clinical translation of neuroregeneration research. There seems to be a key gap in the translation of research from rodent models to human applications, namely non-human primate models, which constitute a critical bridging step. Applying injectable therapeutics and multimodal neuroimaging in stroke lesions using experimental rhesus monkey models is an avenue that a few research groups have begun to embark on. Understanding and assessing the changes that the injured brain or spinal cord undergoes after an intervention with biodegradable hydrogels in non-human primates seem to represent critical preclinical research steps. Existing innovative models in non-human primates allow us to evaluate the potential of neural engineering and injectable hydrogels. The results of these preliminary studies will pave the way for translating this research into much needed clinical therapeutic approaches. Cutting edge imaging technology using Connectome scanners represents a tremendous advancement, enabling the in vivo, detailed, high-resolution evaluation of these therapeutic interventions in experimental animals. Most importantly, they also allow quantifiable and clinically meaningful correlations with humans, increasing the translatability of these innovations to the bedside.</p>","PeriodicalId":73481,"journal":{"name":"International journal of stem cell research and therapy","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870906/pdf/nihms947961.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35961874","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":"Mammary Epithelial Cell Lineage Analysis via the Lyon's Hypothesis.","authors":"Andrea L George, Gilbert H Smith","doi":"10.23937/2469-570x/1410018","DOIUrl":"https://doi.org/10.23937/2469-570x/1410018","url":null,"abstract":"<p><p>Implants of mammary glands from a single mammary fat pad in a H253 transgenic female mouse heterozygous for a lacZ-labeled X chromosome were analyzed at various time points following transplantation into the epithelium-cleared mammary fat pads of immune-compromised mice. The results show that the lacZ-marked X chromosome, demonstrated by nuclear-associated X-gal staining, was confined to a single epithelial clone that gave rise to the cap cells of all growing terminal end buds (TEB) in the expanding mammary outgrowths and also the basal cells of the elongated ducts. The nuclei of luminal cells in these ducts were uniformly negative for lacZ expression indicating that they were derived from cellular precursors that contained a silenced lac-Z marked X chromosome. This observation confirms the earlier work of Williams and Daniel, who concluded that cap cells were the precursors of the basal (myoepithelial cells) of the subtending mammary ducts.</p>","PeriodicalId":73481,"journal":{"name":"International journal of stem cell research and therapy","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34310555","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}
Jonathan Kenyon, Gabrielle Nickel-Meester, Yulan Qing, Gabriela Santos-Guasch, Ellen Drake, PingfuFu, Shuying Sun, Xiaodong Bai, David Wald, Eric Arts, Stanton L Gerson
{"title":"Epigenetic Loss of MLH1 Expression in Normal Human Hematopoietic Stem Cell Clones is Defined by the Promoter CpG Methylation Pattern Observed by High-Throughput Methylation Specific Sequencing.","authors":"Jonathan Kenyon, Gabrielle Nickel-Meester, Yulan Qing, Gabriela Santos-Guasch, Ellen Drake, PingfuFu, Shuying Sun, Xiaodong Bai, David Wald, Eric Arts, Stanton L Gerson","doi":"10.23937/2469-570x/1410031","DOIUrl":"https://doi.org/10.23937/2469-570x/1410031","url":null,"abstract":"<p><p>Normal human hematopoietic stem and progenitor cells (HPC) lose expression of <i>MLH1</i>, an important mismatch repair (MMR) pathway gene, with age. Loss of MMR leads to replication dependent mutational events and microsatellite instability observed in secondary acute myelogenous leukemia and other hematologic malignancies. Epigenetic CpG methylation upstream of the <i>MLH1</i> promoter is a contributing factor to acquired loss of <i>MLH1</i> expression in tumors of the epithelia and proximal mucosa. Using single molecule high-throughput bisulfite sequencing we have characterized the CpG methylation landscape from -938 to -337 bp upstream of the <i>MLH1</i> transcriptional start site (position +0), from 30 hematopoietic colony forming cell clones (CFC) either expressing or not expressing <i>MLH1</i>. We identify a correlation between <i>MLH1</i> promoter methylation and loss of <i>MLH1</i> expression. Additionally, using the CpG site methylation frequencies obtained in this study we were able to generate a classification algorithm capable of sorting the expressing and non-expressing CFC. Thus, as has been previously described for many tumor cell types, we report for the first time a correlation between the loss of <i>MLH1</i> expression and increased <i>MLH1</i> promoter methylation in CFC derived from CD34<sup>+</sup> selected hematopoietic stem and progenitor cells.</p>","PeriodicalId":73481,"journal":{"name":"International journal of stem cell research and therapy","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34701958","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":"Circulating Progenitor Cells in Regenerative Technologies: A Realistic Strategy in Bone Regeneration?","authors":"Jessica B Chang, Justine C Lee","doi":"10.23937/2469-570x/1410026","DOIUrl":"https://doi.org/10.23937/2469-570x/1410026","url":null,"abstract":"<p><p>Strategies in skeletal regeneration research have been primarily focused on optimization of three components: cellular progenitors, biomaterials, and growth factors. With the increased understanding that circulating progenitor cells exist in peripheral blood, the question arises whether such cell types would allow for adequate osteogenesis and mineralization. In this review, we discuss the current literature on circulating progenitor cells in <i>in vitro</i> and <i>in vivo</i> studies on bone regeneration.</p>","PeriodicalId":73481,"journal":{"name":"International journal of stem cell research and therapy","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34601360","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}
S Tucker Price, Thomas H Beckham, Joseph C Cheng, Ping Lu, Xiang Liu, James S Norris
{"title":"Sphingosine 1-Phosphate Receptor 2 Regulates the Migration, Proliferation, and Differentiation of Mesenchymal Stem Cells.","authors":"S Tucker Price, Thomas H Beckham, Joseph C Cheng, Ping Lu, Xiang Liu, James S Norris","doi":"10.23937/2469-570x/1410014","DOIUrl":"https://doi.org/10.23937/2469-570x/1410014","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are a multipotent cell population acquired most prominently from bone marrow with the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, and others. MSCs demonstrate the capacity to home to sites of injury and contribute to tissue repair. Sphingosine 1-phosphate (S1P) is a biologically active sphingolipid impacting proliferation, apoptosis, inflammation, and angiogenesis with changes in S1P concentration providing significant implications for various disease conditions including cancer, diabetes, and cardiac disease. These functions are primarily mediated by interactions with 5 G-protein coupled S1P receptors (S1PR1-5). In this paper, we demonstrate that inhibition of S1PR2 results in increased MSC clonogenicity, migration, and proliferation; features dependent on Erk phosphorylation. Furthermore, decreased S1PR2 expression decreases the differentiation of MSCs into adipocytes and mature osteoblasts that may be the result of increased expression of MSC pluripotency factors including Nanog, Sox-9, and Oct-4. Inhibition of S1PR1 and S1PR3 in contrast does not impact MSC migration or Erk activation although increased proliferation is observed. In the study, we describe the essential role of S1PR2 in MSC differentiation pathways through modification of pluripotency factors. We propose a MAPK dependent mechanism through S1PR2 inhibition that promotes equally multipotent MSC proliferation.</p>","PeriodicalId":73481,"journal":{"name":"International journal of stem cell research and therapy","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34449000","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}