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}
Periasamy Parikumar, Kazutoshi Haraguchi, Rajappa Senthilkumar, Samuel Jk Abraham
{"title":"Human corneal endothelial cell transplantation using nanocomposite gel sheet in bullous keratopathy.","authors":"Periasamy Parikumar, Kazutoshi Haraguchi, Rajappa Senthilkumar, Samuel Jk Abraham","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Transplantation of <i>in vitro</i> expanded human corneal endothelial precursors (HCEP) cells using a nanocomposite (D25-NC) gel sheet as supporting material in bovine's cornea has been earlier reported. Herein we report the transplantation of HCEP cells derived from a cadaver donor cornea to three patients using the NC gel sheet. In three patients with bullous keratopathy, one after cataract surgery, one after trauma and another in the corneal graft, earlier performed for congenital corneal dystrophy, not amenable to medical management HCEP cells isolated from a human cadaver donor cornea <i>in vitro</i> expanded using a thermoreversible gelation polymer (TGP) for 26 days were divided into three equal portions and 1.6 × 10<sup>5</sup> HCEP cells were injected on to the endothelium of the affected eye in each patient using the D25-NC gel sheet as a supporting material. The sheets were removed after three days. The bullae in the cornea disappeared by the 3<sup>rd</sup>-11<sup>th</sup> post-operative day in all the three patients. Visual acuity improved from Perception of light (PL)+/Projection of rays (PR)+ to Hand movements (HM)+ in one of the patients by post-operative day 3 which was maintained at 18 months follow-up. At 18 months follow-up, in another patient the visual acuity had improved from HM+ to 6/60 while in the third patient, visual acuity remained HM+ as it was prior to HCEP transplantation. There were no adverse effects during the follow-up in any of the patients.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"7 1","pages":"18-24"},"PeriodicalIF":1.8,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840311/pdf/ajsc0007-0018.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35908598","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}
Ivan Hernandez, Jonathan M Baio, Eric Tsay, Aida F Martinez, Tania I Fuentes, Leonard L Bailey, Nahidh W Hasaniya, Mary Kearns-Jonker
{"title":"Short-term hypoxia improves early cardiac progenitor cell function <i>in vitro</i>.","authors":"Ivan Hernandez, Jonathan M Baio, Eric Tsay, Aida F Martinez, Tania I Fuentes, Leonard L Bailey, Nahidh W Hasaniya, Mary Kearns-Jonker","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The use of cardiovascular progenitor cells (CPCs) to repair damaged myocardium has been the focus of intense research. Previous reports have shown that pretreatments, including hypoxia, improve cell function. However, the age-dependent effects of short-term hypoxia on CPCs, and the role of signaling in these effects, are unknown. Cloned neonatal and adult CPCs expressing Isl1, c-Kit, KDR, PDGFRA, and CXCR4, were preconditioned using hypoxia (1% O<sub>2</sub> for six hours). Intracellular signaling pathway changes were modeled using Ingenuity Pathway Analysis (IPA), while qRT-PCR, flow cytometry, and immunoblotting were used to measure pathway activation. Cellular function, including survival, cell cycle, and invasion, were evaluated using a TUNEL assay, flow cytometry, and a Transwell® invasion assay, respectively. IPA predicted, and RT-PCR and flow cytometry confirmed, that the PI3K/AKT pathway was activated following short-term hypoxia. Heat shock protein (HSP) 40 expression increased significantly in both age groups, while HSP70 expression increased only in neonatal CPCs. Neonatal CPC invasion and survival improved after hypoxia pre-treatment, while no effect was observed in cell cycling and developmental status. Prostaglandin receptor expression was enhanced in neonatal cells. Prior to transplantation, hypoxic preconditioning enhances CPC function, including invasion ability and pro-survival pathway activation.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"7 1","pages":"1-17"},"PeriodicalIF":1.8,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840310/pdf/ajsc0007-0001.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35908597","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}