Current Stem Cell Research & Therapy - Volume 13, Issue 5, 2018

Cancer immunotherapy, a new weapon against cancers by harnessing the patient's own immune system, potentiates an extended remission and possibly a cure for cancer. T cells genetically engineered with chimeric antigen receptor (CAR) vectors can specifically target the surface antigen of cancer cells and kill them in an MHC-independent manner. CD19 is extensively expressed on cancerous cells in B cell malignancies. To target this antigen, CAR T cells have gained great success in treating patients with B cell leukemia and lymphoma. Currently, the data from clinical trials on CAR T cells in solid tumors are limited; thus, CAR T cells targeting GD2, HER2, EGFRvIII, CSPG4, DNAX, mesothelin, and other molecules are under active investigation for solid tumors. In this review, we summarize the clinical results for CAR T cells in the case of hematologic and solid tumors, along with the current developments in CAR T cell immunotherapy.

MicroRNAs are small non-coding RNAs that can modulate gene expression at posttranscriptional level, and they participate in almost all important biological processes. Immune system is elaborately regulated to maintain the equilibrium between immunity and tolerance. Recent studies have revealed significant functions of microRNAs in the maintenance of immune homeostasis using both cell and transgenic mouse models. In collaboration with various transcriptional factors and cytokines, microRNAs constitute an effective and flexible regulatory network governing the development and activation of immune cells; as well as maintenance of immune tolerance. In this review, microRNAs involved in T cell development, proliferation, and lineage differentiation will be summarized. Based on current knowledge, the function of microRNAs in establishing and maintaining immune tolerance will also be discussed in relation to determining the outcome of allograft transplantation.

Background: Autoimmune disease is a refractory disease. Accumulating Evidence has revealed that the manipulation of mesenchymal stem cells may have the potential to control or even treat autoimmune diseases. Human gingiva-derived mesenchymal stem cells (GMSCs) are emerging as a new line of mesenchymal stem cells that have displayed some potential advantages in controlling and treating autoimmune diseases. Objective: In this review, we briefly update the current understanding on the biology of GMSCs and their effects on preventing and treating autoimmune diseases. Conclusion: The availability of gingival mesenchymal stem cells (GMSCs), together with their potent capacity of multi-directional differentiation and inflammatory modulation, making GMSCs an ideal subtype of MSCs in treating autoimmune disease. Our and other studies have launched the earliest appraisal on GMSCs and carried out a lot of biological researches. The clinical trial of GMSCs on patients with autoimmune diseases will further approve their therapeutic effects, as well as its cellular and molecular mechanisms.

Acquired severe aplastic anemia (SAA) is a rare and life-threatening bone marrow failure syndrome characterized by cytotoxic T-cells excessive activity, hematopoietic precursors decrease and peripheral blood (PB) pancytopenia. Patients with severe aplastic anemia (SAA) die 1 to 2 years after diagnosis due to fatal infections and/or hemorrhagic complications if they do not undergo any effective treatment. Nowadays, Immunosuppressive therapy (IST) and allogeneic hematopoietic stem cell transplantation (HSCT) are still the standard treatment for SAA. For patients younger than 40 years old, allogeneic HSCT is often the best choice. Recently, outcomes of matched unrelated donor and haploidentical donor transplantation have significantly improved, notably in some cases which are comparable to the result of matched related donor transplantation. Mixed chimerism status is more common in SAA post-transplantation patients, which is effected by conditioning regimen used in transplantation and is closely relevant to donor cells rejection and secondary graft failure. In this article, we briefly have reviewed the current state and future directions for SAA HSCT, and have shared our SAA data and transplant experience of the recent decade. We have analyzed the impact of conditioning regimen on engraftment and chimerism status in SAA transplantation, and have compiled our findings in this report.

Background: Adult stem cells are somatic stem cells distributed all over the body. They represent a promising future for regenerative medicine because of their multiple advantages as they are widely available, accessible, easily stored and manipulated to a wide range of cells and with minimal invasive extraction. Objective: This review describes three examples of adult stem cells: oral mucosal epithelial stem cells, human immature dental pulp stem cells and hair follicle bulge stem cells that show an ability to correct limbal stem cell deficiency, their isolation and cultivation methods, feeder layers, carriers, markers expressed, successfulness to regenerate the ocular surface and mimic the corneal function in LSCD. Conclusion: Although hair follicle bulge stem cells and human immature dental pulp stem cells are a promising adult stem cell source to correct limbal stem cell deficiency, but the published research evaluating this ability is limited. Therefore, this article emphasize further research in this area.

Osteoporosis is a common age-related disorder characterized by low bone mass and deterioration in bone microarchitecture, leading to increased skeletal fragility and fracture risk. The pathophysiology of osteoporosis is multifactorial. It is related to the imbalance between osteoblasts and osteoclasts; reduced bone mass and increased adipogenesis in the bone marrow. Moreover, angiogenesis, inflammatory process and miRNAs have shown effects in the formation of osteoporosis. In the recent years, mesenchymal stem cells (MSCs) have been regarded as an excellent choice for cell-based tissue engineering therapy of osteoporosis. Growing evidence showed that paracrine effect has been considered as the predominant mechanism for the role of MSCs in tissue repair. Recently, many studies have proposed that MSCs-derived exosomes are effective for a variety of diseases like cancer, cardiovascular diseases, etc. However, whether the MSCs-derived exosomes could serve as a novel therapeutic tool for osteoporosis has not clearly described. In this review, we summarize the MSCs-derived exosomes and the relationship with osteogenesis, osteoclast differentiation, angiogenesis, immune processes and miRNAs. Finally, we suggest that MSCs-derived exosomes might be a promising therapeutic method for osteoporosis in the future.

With the ageing population, musculoskeletal conditions are becoming more inherent. Delayed union is defined as a slower than normal fracture healing response, with no healing after 4 to 6 months; however, the union is anticipated given sufficient time. In the context of delayed/non-union, fragility fractures in osteoporotic populations carry significant patient morbidity and socioeconomic costs. Multiple mechanisms hinder fracture healing in osteoporotic patients, imbalanced bone remodelling leads to impaired bone microarchitecture due to reduced osteoblast number and activity and as such, callus formation is diminished. Since stem cells can self-renew and differentiate into various tissue lineages, they are becoming very popular in tissue regeneration in musculoskeletal conditions. In this review, we discuss the role of stem cells in physiological fracture healing and their potential therapeutic use following a fracture. We explore the potential of stem cells, the release of chemokines and cytokines to reduce fracture risk in osteoporosis.

Background: Mesenchymal stem cells (MSC) are unique in their ability to self-renew and differentiate into one of many lineage possibilities. It is therefore integral to preserve these qualities to prevent the far reaching effects of a defective stem cell. Human mesenchymal stem cells (hMSC) are precursors for and can differentiate into osteoblasts, adipocytes and chondrocytes. They were originally found in the bone marrow, but have also been located in the umbilical cord, adipose tissue and muscle. Few studies have been conducted into the in vivo effects of age on these cells. This contribution reviews current knowledge surrounding the effects of age on the characteriation and differentiation of human mesenchymal stem cells. Method: 471 articles were found using a combination of Online published articles from January 1983 to January 2016 were searched using the Cochrane Library, PubMed, Medline, Scopus, Web of Science and Science Direct databases. There were no existing systematic reviews on this research topic. Results: Nine studies were identified that met the predefined selection criteria. Three studies were used to assess the effects of ageing on characterisation of hMSC with no conclusive results. The cumulative results of these studies show that the effect of ageing on characterisation of hMSC remains inconclusive. Seven studies were used to assess the differentiation potentials of hMSC showing that age either decreased or altered lineage preference in hMSC differentiation. Conclusion: There is indication that ageing affects hMSC characterisation and differentiation, however it is not conclusive. There are not enough high quality controlled clinical trials to make reliable conclusions.

Mesenchymal Stem Cells (MSCs) are an attractive option for the development of treatment for musculoskeletal pathologies due to their wide availability, clinical safety and multiple techniques available. Understanding the control of MSC differentiation into skeletal muscle is vital for developing protocols and therapeutic applications that are safe and effective. This paper therefore aims to review the current understanding of factors that regulate the differentiation of MSCs into skeletal muscle. Medline, Embase, Pubmed and Web of Science were searched for December 2015 using the terms *differentia*, skeletal*, skeleton*, myocyt*, myogen* and mesenchym* stem-cell*. This returned a total of 1215 results. 48 papers were included in the review. Forty-eight studies were reviewed. Eight related to external signalling molecules, sixteen related to local environmental factors and twenty-four related to intracellular signalling pathways. Uniaxial strain, medium stiffness of the extracellular matrix and submicron grooved topography were identified as promoting myogenesis. TGF-β was identified as a main inhibitor of myogenesis. Smad and Pax signalling were identified as important intracellular pathways and the relationship of menin, Setdb1, GEFT, PAX3-FOXO1, IGF-II, TAZ and PRDM2 with MyoD and MyoG was explored. Further research into the effect of the inflammatory response on skeletal muscle differentiation is suggested. Clarification of the mechanism of action of TGF-β, the role of submicron grooves and cyclic uniaxial strain, and two important factors in the development of tissue scaffolds.