Current Stem Cell Research & Therapy - Volume 12, Issue 4, 2017

Cardiovascular disease remains the leading cause of death worldwide. Damage to the heart resulting from cardiovascular disease leads to gradual loss of function and reduced quality of life. Cardiac injury is particularly debilitating, more so than injury to any other organ, given our current inability to either generate new and functional cardiac tissue or to mimic the actions of the heart using external devices. Advances in the field of stem cells and genetics have paved the way for the development of a variety of novel therapies. A number of these therapies have shown great promise in regenerating cardiac tissue in non-human disease models and some have progressed towards clinical trials. Given the rapid progress and emergence of novel targets for therapy, it is perhaps timely that we assess the practicality of these techniques and their potential for translation to bedside. Hence, this review aims to outline the major therapies in development and to provide insight into the feasibility of the respective techniques with the hope that research can be steered towards developing therapies with greater potential of being employed at the bedside.

A synergy of a pre-accumulated genes with an autoimmunity advancing to slow abolition of pancreatic beta-cells causes insulin deficiency and results enrooting insulin dependent diabetes mellitus (IDDM). As per WHO data worldwide about 150 million people are diabetic and the number may rise to more than double by the year 2025. Any absolute cure for IDDM is not available yet, and one of the credible advent in the field include cell-based therapy. At this conjecture, mesenchymal stem cells (MSC) seems to have a specific and beneficial characteristics due to their in vivo as well as in vitro potential to mimic a pancreatic endocrine phenotype and immune-regulatory actions. MSC have the capacity to tweak endogenous tissue and cells of immune system. They have been proven as secure and efficacious cell-based regenerative therapy, to treat diverse autoimmune, degenerative diseases and tissue injuries. By consolidating characteristics of MSC biology, MSC-based therapy, engineering and advances in the field, MSC have a great potential to bring us notably closer to a much-needed and long-time awaited cure of IDDM. The review discusses MSC-based cellular therapeutic strategies targeting at IDDM. MSC characteristics of immunomodulation and regeneration potential when used alone or in combination with islets or in differentiated form of insulin producing cells (IPC) are taken into consideration for the review purpose.

Embryonic stem cells (ESCs) are derived from inner cell mass (ICM) and have the potency to differentiate into three germ layers (ectoderm, endoderm, and mesoderm). This potency of ESCs, called pluripotency, is critical for maintaining stemness. Transcriptional regulatory circuitry preserving stemness consists of transcription factors (TFs), epigenetic mechanisms, microRNAs (miRNAs or miRs), and long non-coding RNAs (lncRNAs). In this circuitry, components assist each other to activate essential genes for maintaining pluripotency and suppressing lineage-specific genes. TFs act directly by binding to their binding sites in the genome or indirectly by activating another gene (such as a miR), epigenetic mechanisms play their role by providing an activatory or inhibitory context for transcription, miRNAs regulate gene expression at the post-transcriptional level, and lncRNAs act as a scaffold function for epigenetic elements, regulating gene expression in ESCs. All these factors create a crossroad and collaborate to sustain stemness in the ESCs. Herein, we explain the role of each member in this circuitry and demonstrate the significance of the crossroad for keeping stemness.

Aim: The aim was to look at current evidence for treating non-unions or delayed fracture healing in regard to novel methods applying mesenchymal stem cells (MSCs) and growth factors (GF). Methods: Pre-clinical and clinical trials focusing on the use of Mesenchymal Stem Cells and Growth Factors for fracture healing were included in this review. Published articles were identified using specific search terms in Medline, Cochrane Library, PubMed, Scopus and Web of Science. Results: Of the 580 articles found, 82 met my selection criteria and were included, with 39 papers involving trials on the effects of GFs and MSCs on non-unions or bone repair. These included 11 articles on MSCs, 10 on Bone Morphogenetic Proteins, 2 on Vascular-Endothelial GF, 5 on Insulin like-GF, 4 on Transforming-GF-β, 4 on Platelet-Rich Plasma, 1 on Platelet Derived-GF and 2 on Fibroblast-GF, with the other articles included qualitatively. Overall results were positive with the addition of MSCs, Bone Morphogenetic Proteins, VEGF, IGF and TGF-β in aiding fracture healing compared to controls, with mixed results for other factors. Conclusion: Overall this review shows promising results regarding the use of MSCs and various Growth factors in the treatment of fractures and non-unions, as well as synergistic effects observed when combined together. However more research is indicated as these methods are still in the early stages of development.

Cell repair/replacing strategies for neurodegenerative diseases such as Parkinson’s disease depend on well-characterized dopaminergic neuronal candidates that are healthy and show promising effect on the rejuvenation of degenerated area of the brain. Therefore, it is imperative to develop innovative therapeutic strategies that replace damaged neurons with new/functional dopaminergic neurons. Although several research groups have reported the generation of neural precursors/neurons from human/ mouse embryonic stem cells and mesenchymal stem cells, the latter is considered to be an attractive therapeutic candidate because of its high capacity for self-renewable, no adverse effect to allogeneic versus autologous transplants, high ethical acceptance and no teratoma formation. Therefore, mesenchymal stem cells can be considered as an ideal source for replacing lost cells in degenerative diseases like Parkinson's. Hence, the use of these cells in the differentiation of dopaminergic neurons becomes significant and thrives as a therapeutic approach to treat Parkinson's disease. Here we highlight the basic biology of mesenchymal stem cells, their differentiation potential into dopaminergic neurons and potential use in the clinics.

Meniscal injury is a common problem among sportsmen and increasingly seen in the older and more active population. The traditional treatment options include a partial meniscectomy, which provides good mechanical and pain relief to the patient. However, the focus of treatment is shifting towards repairing meniscal tears where possible and replacement of the lost meniscal tissue where appropriate. Replacement can be total or partial. Total meniscal replacement using an allograft, is usually reserved for young patients, who meet certain criteria and who have undergone several subtotal meniscectomies or a single stage total meniscectomy and are still symptomatic. Partial meniscal replacement can be utilized in conjunction with a partial meniscectomy to fill the resulting space left by the resection. Collagen based implants and synthetic scaffolds have entered the European market but have demonstrated mixed results in clinical trials. Tissue engineering to create an implant that mimics the biomechanical properties holds much potential for future research.