Current Stem Cell Research & Therapy - Volume 12, Issue 6, 2017

Background: Pluripotency of stem cells is an important scientific issue and is attracting great interest for the broader community, especially for regenerative medicine field. Pluripotent stem cells (PSCs) in mammalians are defined as naive- and primed-states according to their cellular, molecular, epigenetic and functional states. Objective: Understand the correlation between DNA methylation and pluripotency of stem cells. Method: Based on published papers, we discussed the DNA methylation and corresponding functions for embryonic stem cells. We also summarized the correlation between DNA methylation and naive state maintenance, and outlook future emphasis of DNA methylation for primate naive PSCs. Results and Conclusion: DNA methylation is closely associated with cell reprogramming, functional remodeling and cell differentiation of PSCs. The pluripotency and naive characteristics of PSCs are closely associated with cell DNA methylation. However, the mechanisms, which are involved in methylation modifications of naive ground, are still one of the important scientific issues for primate naive PSCs because of lack of widely accepted culture condition.

Background: Tendon is composed of connective tissue, is able to retract with high tensile force, and plays a significant role in musculoskeletal motion. However, inappropriate physical training or accidents often result in tendon injuries. So far, the functional healing of injured tendon is still a great challenge in orthopedics. Mesenchymal stem cells (MSCs) are multilineage cells with the ability to self-renew and differentiate into a variety of cell types, including tenocytes. The plasticity of MSCs gives rise to the chance of improved healing of injured tendons and even tissue-engineered tendons. Recently, more and more works have shown that the paracrine mechanisms of MSCs also play a critical role in driving the tendon repair process. Objective: The purpose of this review is to summarize the current knowledge of the induction of tenogenic differentiation of MSCs by mechanical, chemical and mechanochemical stimulations. The role of paracrine mechanisms of MSCs during the repair of injured tendons is also discussed. Conclusion: The multilineage potential and the paracrine effects of MSCs create the chance for improved healing of injured tendons and even tissue-engineered tendons. The understanding of the regulation of the two different repair mechanisms (directed differentiation and paracrine) of MSCs has important implications for tendon repair and regeneration.

Background: Targeting the tumor microenvironment (TME) through which cancer stem cells (CSCs) crosstalk for cancer initiation and progression, may open new treatments different from those centered on the original hallmarks of cancer genetics thereby implying a new approach for suppression of TME driven activation of CSCs. Cancer is dynamic, heterogeneous, evolving with the TME and can be influenced by tissue-specific elasticity. One of the mediators and modulators of the crosstalk between CSCs and mechanical forces is miRNA, which can be developmentally regulated, in a tissue- and cellspecific manner. Objective: Here, based on our previous data, we provide a framework through which such gene expression changes in response to external mechanical forces can be understood during cancer progression. Recognizing the ways mechanical forces regulate and affect intracellular signals with applications in cancer stem cell biology. Such TME-targeted pathways shed new light on strategies for attacking cancer stem cells with fewer side effects than traditional gene-based treatments for cancer, requiring a “watch and- wait” approach. We attempt to address both normal brain microenvironment and tumor microenvironment as both works together, intertwining in pathology and physiology – a balance that needs to be maintained for the “watch-and-wait” approach to cancer. Conclusion: This review connected the subjects of tissue elasticity, tumor microenvironment, epigenetic of miRNAs, and stem-cell biology that are very relevant in cancer research and therapy. It attempts to unify apparently separate entities in a complex biological web, network, and system in a realistic and practical manner, i.e., to bridge basic research with clinical application.

Backgrounds: Pharmacotherapy and surgery constitute the mainstay of treatment for inflammatory bowel disease (IBD). But post-treatment relapsing and recurrence persist as concerns in patients with IBD. Stem cell therapy (SCT) has emerged as a promising treatment strategy in inflammatory bowel disease (IBD), including hematopoietic stem cells (HST), mensenchymal stem cells (MSCs). However, severe complications limit the clinical use of SCT in IBD. Therefore, this review aims to summarize SCT-associated complications, and illustrate possible prevention strategies. Methods: We searched Pubmed for studies which reported the use of SCT to treat patients with IBD. Searching terms included ‘IBD’ or ‘Inflammatory bowel disease’ or ‘CD’ or ‘Crohn’s disease’ and ‘stem cell therapy’ or ‘stem cell transplantation’. Results: HSCT can restore the immune tolerance following chemotherapy-induced immune ablation, and MSCs could affect immune cells or secret trophic factors to treat IBD. However, severe complications limit the clinical use of SCT in IBD. Dominant SCT-associated complications include infection, ectopic tissues, and graft-versus-host disease (GVHD), especially for auto-HSCT. As for infection, bacteremia and virus infection were found after SCT treatment, and the use of anti-microbial regimens could reduce incidences of infection. Ectopic tissue formation in the recipient was observed after treatment with HSCT or MSC. Homing and tissue integration might be the possible mechanisms for not forming ectopic tissues. In addition, GVHD was also observed in allogeneic HSCT. Therefore, autologous HSCT and MSCs transplantation were recommended to avoid GVHD. Conclusions: MSCs with their low immunogenicity property eliminate the need for chemotherapy, and are over HSCT in reducing the risk of severe complications. For better application of SCT in IBD, antimicrobial prophylaxis should be used combined with SCT.

Background: The strategy to expand CD34+ hematopoietic stem cells (HSCs) is being increasingly practiced to meet the demand for a higher cell dose. This is for hematopoietic reconstitution in patients with higher body weights. Interestingly, literature reports show that CD34- (CD34 negative) cell population also possesses the potential to reconstitute the bone marrow & in a certain phase, converts them into CD34+ phenotype. The current practice of positive selection of CD34+ HSCs by eliminating rest of the (CD34-) population for expansion could probably pose a risk of losing valuable HSCs with good reconstitution potentials. MSCs (Mesenchymal Stem Cells) hold great promise for use in various regenerative medicine applications. International Society for Cellular Therapy (ISCT) defined MSCs to be CD34 negative; tissue resident MSCs and peripheral blood-derived MSCs express CD34 on their surface even in vitro, though up to limited passages. This interesting observation of CD34 positive expression displayed in vivo by non-hematopoietic cell types such as MSCs was intriguing, thus prompting a detailed review of its significance, if any. Objective: Based on an extensive review, we strongly believe that CD34 expression in MSCs has some significant role in hematopoietic reconstitution & in regeneration of degenerated tissues. The concept of poor CD34 expression or stunted expression by certain MSCs should not be ignored. Several interesting research findings are in agreement with our assumption. However, it still leaves behind several unanswered questions that can only be addressed through detailed studies of phenotypic developmental pathways of MSCs.

Background: Since the discovery and isolation of a mesenchymal stem cell population from within the stromal vascular fraction (SVF) of adipose tissue, there has been a concerted effort to discover the characteristics of these cells. Particular attention has been paid to their morphology, selfrenewal capacity, multi-lineage differentiation capabilities and, as is of greatest interest in this instance, their cell surface profile. Objectives: The purpose of this study is to analyze and summarize the available literature that pertains to the cell surface characterization of adipose-derived stem cells (ASCs). The identification of a common set of positive and negative cell surface markers would allow for a much more consistent and reliable method of identifying this stem cell population both in vitro and in vivo. Search Methods: The keywords “adipose-derived stem cells; stromal cells; surface markers” were searched in the following electronic databases: Medline, PubMed, ZETOC, Web of Knowledge, AMED, EMBASE, Ovid in process & other non-indexed citations and PsychINFO. Results: The most commonly reported positive markers were found to be CD90, CD44, CD29, CD105, CD13, CD34, CD73, CD166, CD10, CD49e and CD59, while the most commonly found negative markers were CD31, CD45, CD14, CD11b, CD34, CD19, CD56 and CD146. In addition, a number of other markers appeared in the literature including HLA-ABC, HLA-DR, SH2, SH3, STRO-1, VEGF2, vWF, ABCG2, SSEA-1 (CD15), PDGFR, alpha- SMA, c-Kit (CD117), OCT4+ and CCR5X (CD195). Conclusion: A minimum panel of positive and negative markers for identifying ASCs can be recommended. The following markers should be positive: CD90, CD44, CD29, CD105, CD13, CD34, CD73, CD166, CD10, CD49e and CD59. The following markers should be negative: CD31, CD45, CD14, CD11b, CD19, CD56 and CD146. In addition to this, the positive expression of HLA- ABC and STRO- 1 should be seen along with the negative expression on HLA-DR. This review, however, has also found that there are a number of disagreements over the expression and existence of various markers, namely CD31, CD34, c- Kit (CD117) and STRO-1.

Background: The exposure of lung to noxious agents or gasses leads to injury, which further enhances repair mechanisms by promoting the proliferation and differentiation of lung stem cells. These cells could help preserve the anatomical structure and the function of the organ. Unfortunately in many lung diseases, 'this scenario' is changed and injury progresses despite repair mechanisms or conventional treatment. Objective: This review summarizes the research on lung stem cells by giving an overview of the biology, function, niches and signaling that play role in lung stem cells and further of the regeneration of the lung. It also highlights the most common lung pathologies thought to be a result of a defective remodeling and overviews the clinical trials having results or publications, which are performed on the field. Conclusion: Though not yet approved for clinical usage, the application of stem cell therapies shown to be safe and with minimal adverse effects could be an alternative treatment to many lung diseases giving a hope for the future of severely ill patients refractory to the current therapies.

Background: Achilles tendon injuries are common, and present a challenge in the acute and chronic setting. There is significant morbidity associated with the injury and the numerous management strategies, as well as financial implications to the patient and the health service. To date, repair tissue from all methods of management fail to achieve the same functional and biomechanical properties as the native tendon. Objective: The use of tissue engineering technology may reduce morbidity, improve the biomechanical properties of repair tissue and reduce the financial burden. The goal is to produce completely integrated tendon repair tissue that has the functional and mechanical properties of the native tendon. This review evaluates the role of stem cells in tissue engineering for tendon reconstruction and the various sources for harvesting stem cells. Results: They can be obtained from the embryo, foetus or adult, and require the correct conditions for proliferation and differentiation. There remain many ethical concerns with the use of embryo or foetus harvested stem cells, thus the focus remains on adult sources, haematopoietic and non-haematopoietic. The improving knowledge of the role of growth factors is addressed, as is their effect on animal models for tendon repair. Growth factors include bone morphogenic proteins, transforming growth factor β, insulin-like growth factor and platelet derived growth factor. The role of scaffolds in human and animal models is reviewed, both naturally derived and synthetic scaffolds. Whilst numerous animal studies have reported encouraging results, further work is required. Conclusions: The ideal source of MSCs still has not been agreed upon, and little is known regarding the signalling pathways involved in tenogenesis of MSCs. Whilst current studies have shown encouraging results with regards to improved biomechanical and histological properties, further work is required to ascertain the growth factors, biomaterials and source of stem cells required for tendon regeneration.

Background: Mesenchymal stem cells (MSCs) represent a promising alternative source for cartilage tissue engineering. However, MSC culture is labor-intensive, so these cells cannot be applied immediately to regenerate cartilage for clinical purposes. Risks during the ex vivo expansion of MSCs, such as infection and immunogenicity, can be a bottleneck in their use in clinical tissue engineering. As a novel stem cell source, pericytes are generally considered to be the origin of MSCs. Pericytes do not have to undergo time-consuming ex vivo expansion because they are uncultured cells. Adipose tissue is another optimal stem cell reservoir. Because adipose tissue is well vascularized, a considerable number of pericytes are located around blood vessels in this accessible and dispensable tissue, and autologous pericytes can be applied immediately for cartilage regeneration. Objective: Thus, we suggest that adipose tissue-derived pericytes are promising seed cells for cartilage regeneration. Conclusion: Many studies have been performed to develop isolation methods for the adipose tissuederived stromal vascular fraction (AT-SVF) using lipoaspiration and sorting pericytes from AT-SVF. These methods are useful for sorting a large number of viable pericytes for clinical therapy after being combined with automatic isolation using an SVF device and automatic magnetic-activated cell sorting. These tools should help to develop one-step surgery for repairing cartilage damage. However, the use of adipose tissue-derived pericytes as a cell source for cartilage tissue engineering has not drawn sufficient attention and preclinical studies are needed to improve cell purity, to increase sorting efficiency, and to assess safety issues of clinical applications.