Current Stem Cell Research & Therapy - Volume 13, Issue 6, 2018

Mesenchymal stem cells or mesenchymal stromal cells (MSCs) are non-hematopoietic stromal cells that reside in many human organs and have been isolated from a variety of adult or fetal tissues such as adipose tissue, bone marrow and umbilical cord Wharton's jelly, among others. Because they are a heterogeneous population, International Society for Cellular Therapy has established 3 minimum criteria to characterize MSCs in vitro: i) adherence to plastic, ii) differentiation potential (osteogenic, chondrogenic and adipogenic lineages) and iii) expression of specific surface antigens (CD73+, CD90+, CD105+, CD34-, CD45-, CD11b-, CD14-, CD19-, CD79a-, HLA-DR-). Because of these characteristics, MSCs are useful for different applications and studies, most of them related with regenerative biomedicine. Epithelial in vitro differentiation of MSCs, for clinical use, is one of the main objectives in this field, due to, on the one hand, the difficulties to establish epithelial cell cultures and, on the other hand, the immunomodulatory capacity of MSCs that could increase the success of transplantation. According to this and the information compiled from bibliography, production of epithelial cells differentiated in vitro from MSCs is a complex procedure and a lot of techniques and culture media are necessary to explore. The objective of this review is to show the different methods of epithelial in vitro differentiation and remark the need to further study for being capable of establishing specific cell lines of epithelial cells differentiated from autogenic or allogenic MSCs.

Stem/progenitor cells for cell therapy and regenerative medicine should ideally be available in large numbers, after having been isolated using minimally invasive or non-invasive methodologies. Also, they should exhibit wide differentiation potential into multiple lineages, as well as capability to be used successfully in autologous or allogeneic transplantation, and all this in accordance with the applicable guidelines of good manufacturing practice. Thus, the identification and characterization of alternative sources of mesenchymal stem cells (MSCs) is of great importance. The human uterus emerges as an interesting source of MSCs. Both endometrial MSCs (eMSCs) and human uterine cervical stem cells (hUCESCs) were easily obtained with minimal morbidity. Both eMSCs and hUCESCs show a high proliferation rate, which allows for the harvesting of high amounts of these cells, both for research studies and potential therapeutic uses. It has been demonstrated that eMSCs have wide capability of differentiation into many cellular lineages, as well as potential therapeutic effects in several pathological processes. Similarly, hUCESCs'secretome (conditioned medium) shows potent antiinflammatory, anti-tumor, anti-bacterial and regenerative properties.

Background: Multipotent Mesenchymal Stromal Cells (MSCs) are the most common type of stem cell used in the regeneration of skeletal tissue. These cells have multipotent, angiogenic, paracrine, anti-fibrotic and immunological properties. They are readily available, easily isolated and have many therapeutic applications. The ageing population is on the increase and with this comes an upsurge in medical conditions that may benefit from novel stem cell-based therapies to treat ageingassociated diseases. Given that autologous implantations have shown to be beneficial in these targeted therapies, questions are raised regarding the effect of ageing and gender on the efficacy of stem cells. Objective: In this review, we look at the ageing process and look at the effects of ageing and gender on the characterization, proliferation and differentiation of mesenchymal stem cells. We also discuss future therapeutic strategies that may be used to overcome these effects and cell senescence. Conclusion: Advancements in modern technology and experimental techniques have provided an insight into how ageing affects properties of MSCs. However, it is evident that further work needs to be conducted due to many mixed reviews and conflicting data. Given that the human life expectancy is expected to increase the topic of cell ageing and therapeutic applications will remain a hot topic in years to come.

Endothelial progenitor cells are circulating blood cells derived from various sources like bone marrow, spleen, umbilical cord, liver, kidney and other sources that play a vital role in the regeneration of the endothelial lining of blood vessels and wound repair. There are two types of EPCs, early EPCs and late EPCs. EPCs are believed to originate from hematopoietic stem cells and mesenchymal stem cells. The mobilization of progenitor cells from bone marrow to the peripheral circulation is highly regulated under both normal physiological conditions and stress. EPCs contribute to neovascularization and tissue repair in the musculoskeletal, neural tissues and the bone which are mobilized and recruited to the injured tissue. Cell-based therapies of endothelial progenitor cells are time-consuming and expensive for performing in-vitro cell expansion procedures. New therapeutic approaches are being developed using animal models based on the specific functions of EPC in in-vitro and in-vivo experiments which have revealed the importance of various signalling pathways. It has been clear that the activation state of EPCs is critical to the vessel repair process and the role has not been completely understood.

Background: Today, coronary artery disease is still one of the most important causes of mortality despite advanced surgical methods, pharmacotherapies and organ transplantation. These treatment modalities are intended to prevent further progression of myocardial infarction and do not involve the repair of the damaged part. Therefore, stem cell therapy has emerged as a new approach for the treatment of coronary artery disease. However, there are some restrictions that limit the use of these cells for desired repair. The leading limitation is that newly formed cardiomyocytes do not provide electrical integrity with local cells. Objective: In this paper, we review the difficulties that limit the use of stem cell therapy in cardiac repair and emphasize the importance of the integration of stem cell with tissue scaffolds with conductivity. Furthermore, significance of using graphene scaffolds in cardiac tissue engineering is highlighted due to its conductivity features. Result: Recently, the fabrication of tissue scaffoldings has made it possible to create a biomimetic cellular environment while providing a new approach to solving these problems in treatment. Especially, the integration of stem cell therapy with graphene-based tissue scaffolds with electrical conductivity, is one of the promising new strategies to turn the success of two approaches of tissue engineering into synergistic effect in cardiac repair. Conclusion: Literature analysis has demonstrated that there are some limitations in use of stem cell therapy for successful treatment of cardiac repair and graphene-based tissue engineering approaches which are promising to solve these problems in the near future.

Background: The urinary bladder and urethra comprise the lower urinary tracts. Pathological conditions that affect both structures necessitate reconstructive urological intervention with autologous tissue sources that cause neuromechanical and metabolic complications. Stem-cell therapies may offer an attractive alternative as they can replicate important host derived cellular functions such as mitosis, proliferation, differentiation and apoptosis. Objective: To provide an overview on the application of stem cell therapies for regenerating the lower urinary tracts and to discuss factors that need to be addressed before stem-cells can be reliably introduced into clinical urological practice. Results: Advantages of stem cells in reconstructive urology are their ability to self-renew and their durability. Mesenchymal stem cells (MSCs), embryonic stem cells (ESCs) and adult stem cells (ASCs) demonstrate excellent urological regenerative properties. Repairing defective lower urinary tract structures with various stem-cell derived therapies has been widely reported with encouraging results in vitro and in pre-clinical in vivo trials. Ethical considerations, cost, regulation, manufacturing and reimbursement need to be fully transparent before stem-cells are routinely applied to urological patients. International collaboration with consensus guidelines should be considered to facilitate standards that allow safe use of stem-cell therapies in urology. Conclusion: Stem cells therapies in urology are developing rapidly with many important achievements to date. Despite promising in vitro and pre-clinical data; implementation of stem cells into daily urological practice is not imminent. Further investigation is required to determine whether stem-cells will provide better clinical outcomes than current urological tissue replacement strategies.

Background: Obesity is an increasing global health problem, but its treatment is not yet optimal, especially in the long term. For this reason, preclinical studies have been conducted relating to a new therapeutic strategy for obesity based on adipose-derived mesenchymal stem cells (AD-MSCs). The aim of our systematic review is to summarize these findings deriving from the animal model in order to establish whether there is sufficient evidence to justify going forward to clinical studies. Methods: Literature searches, study selection, methods and quality appraisal were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were collated using a narrative approach. Results: Of the 578 articles retrieved, seven studies met the inclusion criteria, and their analysis revealed several main findings. There was a strong evidence of the positive effect of AD-MSCs in obesity treatment in terms of body weight, glucose metabolism homeostasis, lipid profiles, non-alcoholic fatty liver disease and systemic inflammation. Moreover, there was recent evidence from a few studies for a significant effect of AD-MSCs transplantation on the improvement of obesity-related hormonal status, (i.e., leptin) and body composition patterns, though these investigations may need further replication. Conclusion: The effects of AD-MSCs transplantation on obesity, in terms of weight loss and obesityrelated diseases, are promising in animal models. In the future, further well-designed studies should be performed to understand the mechanism of action and to overcome some methodological limitations such as the small sample sizes and risk of bias evidenced in our systematic review, before moving forward to assess AD-MSCs as a potential strategy for human obesity management.

Objective: To compile and analyze the published studies on cell therapy for type 2 diabetes mellitus (T2DM) to obtain a better insight into management of T2DM that involved stem cell therapy. Methods: We searched all published studies in Pubmed/Medline, and Cochrane library, using keywords: ‘stem cell’ AND ‘therapy’ AND ‘diabetes type 2’. Inclusion criteria: original articles on the use of stem cells in humans with T2DM. Exclusion criteria: articles in the non-English literature, studies on T2DM complications that did not assess both adverse events and any of the common diabetes study outcomes. Data collection: type of study, number of cases, and all data that were related to outcome and adverse events. Data were analyzed descriptively to conclude the possible cause of adverse reactions, and which protocols gave a satisfactory outcome. Results: We collected 25 original articles, out of which 17 studies did not have controls and were classified as case reports, while there were 8 studies that were controlled clinical trials. Most studies used autologous bone marrow mononuclear cells (BM-MNCs) or autologous or allogeneic mesenchymal stem cells (MSCs) from various sources. Adverse events were mild and mostly intervention related. Efficacy of autologous BM-MNCs that were given via interventional route was comparable to Wharton jelly or umbilical cord MSCs that were given via intravenous (IV), Intra muscular (IM), or subcutaneous (SC) route. Conclusion: Further controlled studies that compare BM-MNCs to BM-MSCs or WJ-MSCs or UCSCs are recommended to prove their comparable efficacy. In addition, studies that compare various routes of administration (IV, IM or SC) versus the more invasive interventional routes are needed.