Lauren Coombe, Aamir Kadri, Jessica Ferrer Martinez, Vivas Tatachar, Gary Ian Gallicano
{"title":"Current approaches in regenerative medicine for the treatment of diabetes: introducing CRISPR/CAS9 technology and the case for non-embryonic stem cell therapy.","authors":"Lauren Coombe, Aamir Kadri, Jessica Ferrer Martinez, Vivas Tatachar, Gary Ian Gallicano","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Type 1 diabetes mellitus (T1DM) is an autoimmune disorder in which the body destroys its pancreatic β cells. Since these cells are responsible for insulin production, dysfunction or destruction of these cells necessitates blood glucose control through exogenous insulin shots. Curative treatment involves pancreas transplantation, but due to the incidence of transplant rejection and complications associated with immunosuppression, alternatives are being explored. Despite facing clinical challenges and issues with public perception, the field of regenerative stem cell therapy shows great promise for the treatment of diabetes. The idea of harnessing pluripotency to derive cells and tissues with characteristics of choice is astounding but feasible, and this review seeks to determine which method of stem cell derivation is preferable for diabetes treatment. In this report, we outline the methods for deriving human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs), and adult stem cells or progenitor cells to generate functional islet cells and related tissues. We discuss the specific uses and advantages of each method, and we comment on the ethics and public perceptions surrounding these methods and how they may affect the future of stem cell research. For the reasons outlined in this paper, we believe that non-embryonic stem cell lines, including iPSCs, somatic cell nuclear transfer lines, and adult tissue derived stem cells, offer the highest therapeutic potential for treating diabetes.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"7 5","pages":"104-113"},"PeriodicalIF":1.8,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334205/pdf/ajsc0007-0104.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36956279","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":"Impact of donor characteristics on the quality of bone marrow as a source of mesenchymal stromal cells.","authors":"Emilia Barreto-Durán, Claudia Camila Mejía-Cruz, Efrain Leal-García, Rafael Pérez-Núñez, Viviana Marcela Rodríguez-Pardo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In recent years, the therapeutic use of mesenchymal stromal cells (MSC) has generated a valuable number of scientific studies that delve into their biological characteristics and their potential in regenerative medicine; however, the impact of the clinical characteristics of tissue donors, from which these cells are isolated, on their potential in applied clinical research is not yet clear. The objective of this study was to evaluate the impact of the clinical characteristics of bone marrow donors on the quality of this tissue as a source of MSC for therapeutic use. Human MSC were isolated, characterized and cultured (according to ISCT criteria) from bone marrow samples from volunteer donors (n = 70) attending the Department of Orthopedics and Traumatology of the Hospital Universitario San Ignacio (Bogota, Colombia) for surgery of prosthetic hip replacement that agreed to participate voluntarily in the study. Donor data such as age, gender, weight, smoker and type of anesthesia used during the surgical procedure were recorded, and the impact of these characteristics on the volume of tissue collection, mononuclear cell count and confluence time of cells with fibroblastoid morphology was evaluated. Correlation coefficients between quantitative variables were calculated with Spearman's correlation test, and the association between qualitative and quantitative variables was evaluated with biserial correlation coefficient. A significant correlation was observed between the age of the donors and the time necessary to obtain confluent cells in vitro (r = 0.2489, P = 0.0377); similarly, the correlation between the volume of bone marrow collected and the number of mononuclear cells obtained was significant (r = 0.7101, P = 0.0001). Although a negative correlation tendency was observed between the mononuclear cell count and the confluence time, this was not significant (r = -0.2041, P = 0.0950). No significant associations were observed between gender, smoking status or type of anesthesia and the expansion characteristics of human mesenchymal stromal cells. Bone marrow donor age and the tissue collection volume impact the time of obtaining MSC in vitro and the mononuclear cell count with which the culture starts. These conditions must be considered when the bone marrow is selected as the tissue for obtaining MSC.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"7 5","pages":"114-120"},"PeriodicalIF":1.8,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334204/pdf/ajsc0007-0114.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36956281","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}
Jang Cho, Matthew D'Antuono, Michael Glicksman, Jing Wang, Jacqueline Jonklaas
{"title":"A review of clinical trials: mesenchymal stem cell transplant therapy in type 1 and type 2 diabetes mellitus.","authors":"Jang Cho, Matthew D'Antuono, Michael Glicksman, Jing Wang, Jacqueline Jonklaas","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are widely prevalent metabolic diseases with differing pathologies. T1DM manifests due to autoimmune destruction of the pancreatic beta cells, resulting in a diminished secretion of insulin. T2DM originates from a state of insulin resistance, resulting in hyperglycemia and reduction in beta cell mass. Both diseases can cause severe health consequences. Despite the globally increasing prevalence of both T1DM and T2DM there remains to be a medically defined cure for either of these diseases. Recently, mesenchymal stem cells (MSCs) have been proposed as a possible curative treatment method. In this review, we explain the molecular mechanisms underlying MSCs and their potential ability to treat T1DM and T2DM. We describe the capability of MSCs to differentiate into insulin-producing cells and regenerate pancreatic beta cells, as well as assess their role in modulating the immune system. Lastly, we evaluate the current literature focusing on the clinical application of MSC transplantation in T1DM and T2DM. Despite the favorable results, study designs and analyses cast doubt on the effectiveness of MSCs for the management of T1DM. Conversely, the positive metabolic effects consistently demonstrated in the literature offer hope for MSCs as a treatment for T2DM, at least in the short-term.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"7 4","pages":"82-93"},"PeriodicalIF":1.8,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261870/pdf/ajsc0007-0082.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36793126","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}
Mark A Pianka, Alec T McIntosh, Sahaj D Patel, Pegah R Bakhshi, Mira Jung
{"title":"Close yet so far away: a look into the management strategies of genetic imprinting disorders.","authors":"Mark A Pianka, Alec T McIntosh, Sahaj D Patel, Pegah R Bakhshi, Mira Jung","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Genetic imprinting is the process of epigenetic labelling or silencing of particular genes, based on the maternal or paternal origin of the gene, in a heritable pattern. The incidence of imprinting disorders has become a growing concern due to the potential association between these congenital syndromes and assisted reproductive technologies (ARTs). This review presents a general summary of the imprinting process as well as the current knowledge surrounding the genetic and epigenetic underpinnings of the most prevalent imprinting disorders: Beckwith-Wiedemann syndrome (BWS), Silver-Russell syndrome (SRS), Prader-Willi syndrome (PWS), and Angelman syndrome (AS). As research continues to elucidate the molecular pathways that characterize genetic imprinting, efforts have been made to establish guidelines that incorporate phenotypic manifestations as well as genetic testing to ensure safe and effective management of symptoms. While these efforts are likely to benefit future clinical management, their efficacy cannot yet be generalized to all patients diagnosed with these syndromes, as many of the genetic abnormalities and the associated phenotypic manifestations have yet to be characterized. Furthermore, future advances in the knowledge of epigenetic processes and genetic loci involved in the development of these syndromes may allow for the development of curative therapies.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"7 4","pages":"72-81"},"PeriodicalIF":1.8,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261869/pdf/ajsc0007-0072.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36793125","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}
Kyle Bruun, Erika Schermer, Anjali Sivendra, Emily Valaik, Reed B Wise, Rana Said, John R Bracht
{"title":"Therapeutic applications of adipose-derived stem cells in cardiovascular disease.","authors":"Kyle Bruun, Erika Schermer, Anjali Sivendra, Emily Valaik, Reed B Wise, Rana Said, John R Bracht","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) is the number one cause of death globally, and new therapeutic techniques outside of traditional pharmaceutical and surgical interventions are currently being developed. At the forefront is stem cell-centered therapy, with adipose derived stem cells (ADSCs), an adult stem population, providing significant clinical promise. When introduced into damaged heart tissue, ADSCs promote cardiac regeneration by a variety of mechanisms including differentiation into new cardiomyocytes and secretion of paracrine factors acting on endogenous cardiac cells. We discuss the application of ADSCs, their biochemical capabilities, availability, ease of extraction, clinical trial results, and areas of concern. The multipotent capacity of ADSCs along with their ability to secrete factors promoting cell survival and regeneration, along with their immunosuppressive capacity, make them an extremely promising approach in the field of CVD therapy.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"7 4","pages":"94-103"},"PeriodicalIF":1.8,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261868/pdf/ajsc0007-0094.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36793127","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}
Durai Murugan, A. Devasia, G. Tharion, Sanjay Kumar
{"title":"Human Urothelial Cells Isolation, In Vitro Expansion and Characterization for Evaluating Bio-Engineering Potentials","authors":"Durai Murugan, A. Devasia, G. Tharion, Sanjay Kumar","doi":"10.28967/jscrt.2018.01.18001","DOIUrl":"https://doi.org/10.28967/jscrt.2018.01.18001","url":null,"abstract":"","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"1 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2018-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69316791","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}
Nurdan Kokturk, Fatma Yıldırım, Pınar Yıldız Gülhan, Yeon Mok Oh
{"title":"Stem cell therapy in chronic obstructive pulmonary disease. How far is it to the clinic?","authors":"Nurdan Kokturk, Fatma Yıldırım, Pınar Yıldız Gülhan, Yeon Mok Oh","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a respiratory disease that has a major impact worldwide. The currently-available drugs mainly focus on relieving the symptoms of COPD patients. However, in the latter stages of the disease, the airways become largely obstructed and lung parenchyma becomes destructed due to underlying inflammation. The inappropriate repair of lung tissue after injury may contribute to the development of disease. Novel regenerative therapeutic approaches have been investigated with the aim of repairing or replacing the injured functional structures of the respiratory system. Endogenous and exogenous sources of stem cells are available for the treatment of many diseases. Stem cell therapy is newly introduced to the field of COPD. Currently the research is in its infancy; however, the field is profoundly growing. Previous studies suggest that cell-based therapies and novel bioengineering approaches may be potential therapeutic strategies for lung repair and remodelling. In this paper, we review the current evidence of stem cell therapy in COPD.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"7 3","pages":"56-71"},"PeriodicalIF":1.8,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146161/pdf/ajsc0007-0056.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36514139","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}
Maria Teresa González-Garza, Delia E Cruz-Vega, Alejandro Cárdenas-Lopez, Rosa Maria de la Rosa, Jorge E Moreno-Cuevas
{"title":"Comparing stemness gene expression between stem cell subpopulations from peripheral blood and adipose tissue.","authors":"Maria Teresa González-Garza, Delia E Cruz-Vega, Alejandro Cárdenas-Lopez, Rosa Maria de la Rosa, Jorge E Moreno-Cuevas","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cell therapy presents a promising alternative for the treatment of degenerative diseases. The main sources of adult stem cells are bone marrow, adipose tissue and peripheral blood. Within those tissues, there are cell subpopulations that share pluripotential characteristics. Nevertheless, there is insufficient data to determine which of these stem cell subtypes would have a better possibility to differentiate to a specific tissue. The objective of this research was to analyze and compare the stemness genes expression from peripheral blood and adipose tissue of plastic adherent cells, and those immune-selected by the CD133<sup>+</sup> and CD271<sup>+</sup> membrane markers. On all cell subpopulation groups, self-renew capacity, the membranes markers CD73, CD90 and CD105, as well as the stemness genes <i>NANOG, OCT4, SOX2, REX1, NOTCH1</i> and, <i>NESTIN</i> expression were analyzed. Results showed that all samples presented the minimal criteria to define them as human stem cells. All cell subpopulation were capable of self-renewal. Nevertheless, the subpopulation cell types showed differences on the time needed to reach confluence. The slowest doubling times were for those cells bearing the CD133 marker from both sources. Surface markers determined by flow cytometry were positive for CD73, CD90 and, CD105, and negative for CD45. The stemness gene expression was positive in all subpopulation. However, there were significant differences in the amount and pattern of expression among them. Those differences could be advantageous in finding the best option for their application on cell therapy. Cells with high expression of <i>OCT4</i> gene could be a better opportunity for neuron differentiation like CD133<sup>+</sup> blood cells. On the other hand, lowest expression of <i>NOTCH1</i> on CD271<sup>+</sup> cells from the same source could be a better possibility for myoblast differentiation. The observed differences could be used as an advantage to find which cell type and from the different source; this represents the best option for its application on cell therapy. Experiments focused on the best response to specific differentiation, are conducted in order to confirm those possibilities.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"7 2","pages":"38-47"},"PeriodicalIF":1.8,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013721/pdf/ajsc0007-0038.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36253119","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":"Analysis of the regulation pathways via microarray and miRNA studies: human embryonic stem cells to treat diabetes mellitus type-II.","authors":"Geeta Shroff, Rhea Shroff, Rakesh Gupta","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Diabetes mellitus occurs either due to an autoimmune destruction of β cells (Type 1) or resistance to insulin effects (Type 2). Diverse conventional medications are used for treatment of diabetes, which is associated with long term complications such as kidney failure, blindness, and stroke. We recently showed the potential of human embryonic stem cells (hESCs) in 95 patients with type 2 diabetes. In the present study, we use the microarray and miRNA studies to prove why hESCs are effective in diabetes. Three samples of hESCs were cultured and microarray technology was used for the analysis of diabetic pathways. The gene targets for miRNA were analyzed using gene ontology (GO) and DAVID database. Genes involved in the diabetic pathways were classified in accordance with GO analysis. Pathways for these genes were determined using Reactome and Panther databases. The up and down-regulation of all the genes involved were confirmed with the significant <i>p</i>-values. Pathways for insulin secretion, binding and its positive regulation were up-regulated while the pathways for negative regulation of insulin were significantly down-regulated. hESCs cultured at our facility have the capability to regenerate the pancreatic β cells after transplantation; as the insulin secretion pathways were significantly up-regulated.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"7 2","pages":"48-55"},"PeriodicalIF":1.8,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013722/pdf/ajsc0007-0048.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36253120","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}
Emily S Paffhausen, Yasir Alowais, Cara W Chao, Evan C Callihan, Karen Creswell, John R Bracht
{"title":"Discovery of a stem-like multipotent cell fate.","authors":"Emily S Paffhausen, Yasir Alowais, Cara W Chao, Evan C Callihan, Karen Creswell, John R Bracht","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Adipose derived stem cells (ASCs) can be obtained from lipoaspirates and induced <i>in vitro</i> to differentiate into bone, cartilage, and fat. Using this powerful model system we show that after <i>in vitro</i> adipose differentiation a population of cells retain stem-like qualities including multipotency. They are lipid (-), retain the ability to propagate, express two known stem cell markers, and maintain the capacity for trilineage differentiation into chondrocytes, adipocytes, and osteoblasts. However, these cells are not traditional stem cells because gene expression analysis showed an overall expression profile similar to that of adipocytes. In addition to broadening our understanding of cellular multipotency, our work may be particularly relevant to obesity-associated metabolic disorders. The adipose expandability hypothesis proposes that inability to differentiate new adipocytes is a primary cause of metabolic syndrome in obesity, including diabetes and cardiovascular disease. Here we have defined a differentiation-resistant stem-like multipotent cell population that may be involved in regulation of adipose expandability <i>in vivo</i> and may therefore play key roles in the comorbidities of obesity.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"7 2","pages":"25-37"},"PeriodicalIF":1.8,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013723/pdf/ajsc0007-0025.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36253118","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}