order Blebbistatin br Interaction between MSCs and
Interaction between MSCs and immune cells MSCs have also been shown to possess broad immunoregulatory capabilities and are capable of influencing both adaptive and innate immune responses. MSCs inhibit immune order Blebbistatin proliferation and maturation and suppress immune reactions both in vitro and in vivo in a non-MHC restricted manner . Therefore, MSCs are considered to be hypoimmunogenic, displaying low expression levels of HLA class I, no expression of HLA class Ⅱ, and no expression of costimulatory molecules, including CD40, CD80, and CD86 [28,68]. Basically, MSCs could exert widespread immunomodulatory effects on cells of both the innate and adaptive immune system. Ex-vivo expanded MSCs have also been showed to suppress the activity of a broad range of immune cells, including T cells, natural killer T (NKT) cells, dendritic cells (DCs), B cells, neutrophils, monocytes, macrophages and so on.
Therapeutic application of MSCs for immune diseases
Perspective MSCs have become a subject of clinical research interest due to their easy isolation and in vitro large scale cultivated amplification, attractive potential for multi-lineage differentiation and hematopiesis supporting, growth factors production and cytokines secretion, and potential immunomodulatory capacity. In addition, MSCs is definitely safe and well-tolerated for use in cell therapy, which provide a striking candidate for degenerative diseases and immune mediated diseases. Increased clinical evidence suggests that MSCs may have great potential in the treatment and prevention of GVHD, AA, MS, CD, SLE and some other immune mediated diseases. Nevertheless, clinical trials yielded ambiguous results on the effects of MSCs. These ambiguous findings might result from insufficient standardization during the MSCs extraction, expansion and administration procedures and interindividual MSCs donor differences. Therefore, to obtain maximal clinical benefit, lots of problems, including tissue sources, numbers of cells, the optimal passage time in culture before use, cell subpopulation and standardized process of cell production, need to be solved before MSCs as a medicine applied widely to treat patients. In addition, it is absolutely important to optimize process of treatment and be able to effectively monitor and communicate the benefits and risks of a cell therapy to a patient. Furthermore, a clear and rigorous pharmacokinetics and pharmacodynamics model of the mechanism of action of transient cell therapies is absolutely necessary. Expanding our understanding of the molecular mechanisms governing immunomodulatory properties of MSCs will enable us to greatly improve their clinical efficacy. Most importantly, further well-designed, randomized and controlled clinical trials should be designed for better understanding of the underlying biology and utilizing MSCs therapy for immune mediated disease in the future. In addition, the cell dose that was using in clinical treatment is still totally different in different group study. We suggest that we should determine the MSCs cell dose according to the biological effectiveness of the MSCs. Meanwhile, it is really urgent to develop the biological effectiveness of various MSCs biological functions.
Conflict of interst
Acknowledgments This work was supported by The National Basic Research Program of China (973 Program) (2011CB964802), National Natural Science Foundation of China (81000196 and 81330015) and Tianjin Research Program of Application Foundation and Advanced Technology (12JCZDJC25000).
Introduction The etiology of Crohn\'s disease (CD) is still not well understood. Interaction among the gut microbiota, the intestinal mucosa and the host immune system has been implicated in the pathogenesis of CD . Perianal fistula is the most notorious complication of CD, which is formidable for both patients and clinicians, as there are around 25–30% patients having no other alternative choices but accepting surgery . The past two decades have seen an explosion of scientific and clinical interest in stem cell transplantation for a variety of diseases including CD. There are several kinds of candidate stem cells with potential application for CD, such as hematopoietic stem cells (HSCs), amniotic fluid stem cells (AFSCs), induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) . Among them, HSCs and MSCs have been evaluated in clinical trials . Thus, the present review will focus on published clinical trials using HSCs and MSCs.