For induction therapy, although no clinical trials related to liver transplantation have been reported, two clinical trials on kidney transplantation confirmed the safety of MSCs as induction therapy for organ transplantation119,120

For induction therapy, although no clinical trials related to liver transplantation have been reported, two clinical trials on kidney transplantation confirmed the safety of MSCs as induction therapy for organ transplantation119,120. The obstacles to the clinical application of MSCs are decreasing, but large sample clinical trials involving MSCs are still needed to further study their clinical effects. Keywords: mesenchymal stromal cells, liver transplantation, immunosuppression, tolerance, clinical trial Introduction Liver transplantation has been deemed the best therapy for end-stage liver diseases, but recipients usually have to live with life-long immunosuppression1 (Figure 1). Although the standard pharmacological immunosuppressive treatment commonly Cangrelor Tetrasodium used in clinical practice can achieve the favorable results of long grafts and patients survival rates, the side effects (Figure 1) caused by the treatment are significant2. In addition to the drug toxicities, the risks of malignancies and opportunistic infections have been reported to be increasing significantly3. Immunomodulatory cell therapy, as a complementary plan to standard pharmacological immunosuppression, appears to be a solution to this problem. In transplantation cases, the ultimate goal of immunomodulatory cell therapy is to prolong solid-organ allograft survival with reduced, or even no, usage of systemic pharmacological immunosuppression4. Open in a separate window Figure 1. Common classes of immunosuppressive drugs in liver transplantation and the main side effects of immunosuppressive drugs. Mesenchymal stem cells (MSCs), a subpopulation of multipotent and non-hematopoietic cells initially isolated from bone marrow and reported Cangrelor Tetrasodium by Friedenstein et al. in 19705,6, are also called mesenchymal stromal cells and have been the focus of transplant scientists due to their great potential capacities for tissue repair and immunomodulation. Although no reports of large-scale clinical practices involving MSCs for liver transplantation have been found, and MSCs investigations remain mostly at the preclinical stage, the powerful immunomodulatory properties shown in recent reports make MSCs a promising Bmpr2 candidate therapy in clinical liver transplantation. In addition, the effects of MSCs can be improved Cangrelor Tetrasodium through gene modification and pretreatment, and the potential properties of MSCs show great promise in liver transplantation. Research Status of MSCs Cell therapy for immune rejection after organ transplantation is characterized mainly by its powerful immunomodulatory function. Although the immunomodulatory property seems to be a shared feature of all stromal cells including MSCs Cangrelor Tetrasodium and fibroblasts, the characteristics of MSCs (such as easy cultivation, expansion, and storage in vitro) make them more appropriate for organ transplantation7C9. Based on these characteristics, MSCs have been studied for immunosuppression after transplantation of various organs, including the liver, kidney, skin, etc. MSCs can be isolated from diverse sources, such as umbilical cord blood, peripheral blood, and adipose tissue, and all MSCs share many characteristics, including Cangrelor Tetrasodium cell phenotype and immunomodulatory properties10C15. MSCs can also be isolated from some other species such as mice, rats, and rabbits, and great differences exist among them in many aspects, such as the mechanisms of their immunomodulatory properties16. Moreover, MSCs isolated from different human tissues do not have the identical properties. For example, all MSCs secrete different cytokines, which may affect their immunosuppressive effects17. A unique and definitive marker has not yet been found for MSCs isolated from various sources; however, it is known that they lack the expression of major histocompatibility complex class II and costimulatory substances (including Compact disc80, Compact disc86, and Compact disc40), which characteristic seems to explain the reduced immunogenicity of MSCs18. Because of this low immunogenicity, in in vitro combined lymphocyte response (MLR) experiments, actually MSCs from third-party resources triggered a lymphocyte response19 hardly,20. Therefore, some authors think that MSCs through the recipient, donor, and third-party resources could possibly be feasible in organ transplantation actually, although this isn’t yet broadly accepted because of the lack of study evidence in the body and the consequences not being completely satisfactory21. Generally, as the 1st tissue that MSCs had been isolated, bone tissue marrow (BM) happens to be the main way to obtain MSCs for analysis. In medical research of organ transplantation, probably the most widely accepted practice would be to choose isolated through the BM from the donor or the recipient MSCs; however, analysts are thinking about seeking alternative resources of MSCs such as for example urine, placenta, and adipose cells, because of the small difficulty and amounts in isolating BM-MSCs. MSCs from other resources possess their very own immunoregulatory features also..