Current Stem Cell Research & Therapy - Volume 13, Issue 8, 2018

Introduction: Rotator Cuff tears affect 15% of 60 year olds and carry a significant social and financial burden. Current operative techniques and repair adjuncts are associated with unacceptably high failure rates, stimulating investigation into novel tissue engineering and regenerative medicine (TERM) approaches in the field of rotator cuff surgery. In this review we explore the most recent advances in the field of electrospinning, focussing on proposed tissue-engineered solutions in tendon, specifically the rotator cuff. Methods: The MEDLINE/PubMed database was reviewed for English language papers and publication date within the last 5 years, using the search string “electrospinning AND tendon”. Results: Of 38 results, eighteen studies were included in the final analysis. Common themes identified included (1) drug/biological molecule delivery (2) using novel and biological materials in manufacture (3) increased mechanical strengths of materials, and, (4) techniques to improve the nanotopographical properties – of electrospun scaffolds. Human tissue was used in less than 15% of studies to determine cytocompatibility. Varying study designs were observed often employing differing outcome measures making direct comparisons and conclusions challenging. Conclusion: This review summarises the most current scientific knowledge in the study of TERM in tendon and the rotator cuff field and electrospinning techniques. We found that as knowledge of the pathology behind rotator cuff tears is furthered, specific molecules, mechanical properties and nanotopographical features are being incorporated into electrospun scaffolds.

The clustered regularly interspaced short palindromic repeats-associated protein 9 or CRISPR/Cas9 system is one of the hottest topics discussed lately due to its robustness and effectiveness in genome editing. The technology has been widely used in life science research including microbial, plant, animal, and human cell studies. Combined with the pluripotency of stem cells, the technology represents a powerful tool to generate various cell types for disease modeling, drug screening, toxicology, and targeted therapies. Generally, the CRISPR/Cas9 system has been applied in genetic modification of pluripotent or multipotent stem cells, after which the cells are differentiated into specific cell types and used for functional analysis or even clinical transplantation. Recent advancement in CRISPR/Cas9 technology has widened the scope of stem cell research and its therapeutic application. This review provides an overview of the current application and the prospect of CRISPR/Cas9 technology, particularly in stem cell research and therapy.

Background: The researchers working in the field of medical, veterinary and other biological sciences have uniformly described unique characteristic features of stem cells including selfrenewal, prolonged multiplication, immuno-modulation and multi-lineage differentiation. These characteristics of stem cells have opened new horizons in cellular therapy for the management of numerous incurable diseases in human and veterinary patients. Though the mechanisms involved in reparative processes may be similar, the indication for the stem cell therapy may be disparate in human and veterinary subjects. Objective: Among various stem cell types, currently mesenchymal stem cells (MSCs) are extensively studied in regenerative medicine owing to their readily available sources, easy harvesting and ability to differentiate both into mesodermal as well as non-mesodermal tissues under specific culture conditions with little associated ethical issues. The objective of the study was to analyze and summarize the studies and their results pertaining to the basic biology of stem cells, preclinical trials and their potential therapeutic application in veterinary medicine. Results: MSCs have been variably isolated, cultured and characterized from almost all the body tissues and fetal membranes in domestic and pet animals. The cells have been studied in numerous pre-clinical and clinical studies, in addition, to lab animal models. The results although are promising but need further extensive research studies before the cellular application becomes a clinical reality in veterinary medicine. Conclusion: The current review throws some light on different aspects of mesenchymal stem cells like sources, isolation, characterization and their potential therapeutic applications in farm and pet animals.

There is increasing evidence reporting that as a common phenomenon in MetS relative diseases, insulin resistance (IR) is regarded as an independent etiological factor and a warning indicator of MetS occurrence. Therefore, for the special group (overweight or obesity), clinical regular monitoring of IR is an important basis for the prevention and early intervention of MetS relative diseases. This surveys reveals that human umbilical cord mesenchymal stem cells (HUC-MSCs)possess a kind of potential: it may become a possible theraphy for IR in type 2 diabetes mellitus (T2DM) and related diseases. Specific emphasis is focused on evaluating the improvement IR function of HUC-MSCs under the background of development in vitro and in vivo. Next, the action mechanisms of HUC-MSCs is discussed, and some of their advantages and disadvantages in the course of clinic application are presented. The final section highlights the application of HUC-MSCs in T2DM and relative diseases at this stage. Up to now, although many questions remain unresolved, we still consider that HUC-MSCs is one of the best therapy ameliorating IR in the future.

Leukemia is an uncontrollable growth of hematopoietic cells due to a mutation in DNA followed by cellular dysregulation and one or more chromosomal disorder that generally leads to a clonal abnormality. Theoretical and technical inability in early screening and distinguishing cancer, tumor tolerance to common treatment methods, repeated relapses of cancer after remission phase, heterogeneous chromosomal abnormality, and the side effects of current chemotherapies are some of challenges that we face with leukemia and other malignancies. Induced pluripotent stem cells (iPSC) opened a promising window to a wide range of diseases, including leukemia. Overcoming the barriers in leukemia is possible with iPSC technology. Induced hematopoietic stem cell transplantation (and gene therapy), induced cytotoxic T-lymphocytes and reprogrammed NK cells that strengthen the immune system, miRNAs, modeling approaches, and supportive cares are some aspects of the novel treatment based on iPSC technology.

Oct4 is uniformly expressed by all types of pluripotent cells and is essential for pluripotency. Oct4 is also the central reprogramming factor that is constant in most transcription factor cocktails used to generate iPS cells. This article discusses the mechanisms of regulating Oct4 expression by confluence-based Hgf and hypoxia signalling in mouse somatic cells. Stat3 is activated ligandindependently in confluent cells and triggers the formation of cell aggregates. Hgf signalling is preserved after confluence, stimulating β-catenin and Stat3 activity, which are both crucial for Oct4 transcription. Stat3 and β-catenin activities also help sustain cell survival and proliferation, resulting in the formation of cell spheres. Hypoxic conditions in spheres activate regulators of Oct4 and further induce Oct4 expression. Activation of the Oct4 gene depends on nuclear receptors Lrh1/SF1, Esrrb, and Rars. These interact synergistically to initiate Oct4 transcription through organizing a transcriptional initiation complex. cAMP signalling stimulates the production of the SF1/Lrh1 ligand. Esrrb agonist or estrogen might function in activating Esrrb, while Rars might be induced by hypoxia. Taken together, Oct4 expression is probably induced in mouse somatic cells by culturing post-confluence cells with media containing Hgf, Esrrb agonist, and cAMP agonist. Exploring confluence-related signalling to modulate the expression of Oct4 might be helpful in finding novel strategies for reprogramming somatic cells.

Background: Tissue engineering is now being used in Achilles tendon (AT) repair in animal models. There are many preclinical studies that have used different types of stem cells for AT repair. However, there are no systematic reviews that evaluate all these studies to see which type of stem cell provides the most improvement for AT repair in animal models. Sahni V et al.,(1) divided the multiple stem cell types into three broad categories; Tendon derived stem cells (TDSCs), mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs). These three categories have been used in this systematic review to group the different stem cell types together and to also see which category of stem cells provide superior enhancement of AT repair. Method: All studies that have focused on using different types of stem cells in animal models for AT repair and have also included an outcome measure to identify any improvement made with stem cells have been included in this systematic review. Online published articles from 1946 to January 2016 were searched using Ovid MEDLINE (R) and PubMed databases. Results: Of the 181 articles found and assessed for eligibility, 15 articles met predefined selection criteria and were included in this systematic review. Stem cells can either augment current methods of surgical repair or can provide an alternative route for tendon regeneration because of their unique ability of improving histological characteristics and biomechanical properties. Conclusion: This systematic review shows that stem cells can provide an improvement in AT repair in animal models. Histological analysis of the tendon tissue as well as biomechanical tests such as ultimate failure load have been used to show this improvement in AT repair. Nevertheless, we do not know which type of stem cell, from the three broad categories, provides a superior enhancement of AT regeneration in animal models. Our results underscore a need for a head-to-head comparison of the different types of stem cells used in AT repair with or without current methods of surgical repair.

Background: Knee joint trauma may result in damage of the intra-articular ligaments, with rupture of the anterior cruciate ligament (ACL) a common and troublesome injury due to poor capabilities for spontaneous regeneration. Autograft and allograft surgical reconstructions are the mainstay of treatment, but have associated risks of failure, therefore tissue-engineering techniques aiming to regenerate the native ACL are being researched as a potential alternative treatment. Objectives: This article aims to review the current evidence produced by ex vivo and in vivo studies investigating biomaterial scaffolding and mesenchymal stem cell (MSC) techniques in orthopaedic tissue engineering of ACL injuries. Methods: Databases searched were Ovid MEDLINE, Cochrane Library, Embase, Elsevier Scopus, Web of Science and NCBI PubMed, with search terms ‘ligament’, ‘scaffold’, ‘mesenchymal stem cell’ and ‘tissue engineering’. Results: 1132 articles were identified, with 19 articles suitable for review inclusion. Of the eligible studies, 10 used biologic scaffold material, 6 used synthetic constructs, and hybrid scaffolds were employed in the remaining 3 studies. Conclusions: A large amount of preclinical evidence for viability of MSC seeded biomaterial scaffolds in ACL regeneration exists. Studies show that with stimulation, MSCs adhere and proliferate well on various scaffold materials ranging from silk to engineered polymers. Hybrid scaffolds are particularly promising, and with further research, the best features from strong natural substances such as silk, and biologically inert synthetic materials could be combined. Currently, there are few plans to begin human clinical trials, but preclinical studies are moving into larger animal models.