Mesenchymal Stem Cell and Islet Co-Transplantation Promotes Graft Revascularization and Function

Abstract

Our results demonstrate the improvement of islet graft morphology and function by co-transplantation with MSCs. This improvement is attributable, at least in part, to the promotion of graft revascularization mediated by MSCs.

Gene Therapy and Stem Cell Therapy to Improve the Outcome of Human Islet Transplantation

“…Compared with previous studies using immunodeficient animals [52,54], the duration of insulin independence in humanized mice was significantly reduced [79], suggesting the existence of immune rejection. However, the introduction of human immunity also led to GvHD, a fetal disease characterized by the attack to the recipient's major organs by the infused xenogeneic immunocytes.…”

“…Other studies suggested that BMSCs may also differentiate into endothelial cells and directly assist the neo-vessel formation [53]. Silva et al reported the transdifferentiation of BMSCs into an endothelial phenotype in a canine ischemia model, which is supported by the report from Ito et al that BMSCs directly differentiate into a van-willebrand-factor-positive vascular endothelial cell type to improve the islet graft morphology and function [54]. However, these results should be explained cautiously because the new-formed vessels may arise from native BMSCs instead of infused BMSCs.…”

“…There are two hypotheses: 1) through the secretion of immunosuppressive cytokines, such as IL-10 and TGFβ [130]; and 2) through cell surface molecules of BMSCs to inhibit T cell activity and proliferation [71]. Previous reports showed that the co-transplantation of islets with primary BMSCs prevented the allogeneic rejection and helped engraftment of islets, but one common feature in all these studies was that the BMSCs were incompetent to reverse the blood glucose levels of recipients in the acute stage (<3 weeks) after transplantation, suggesting the slow engraftment of transplanted islets [43,54,116]. To make the situation even worse, the hyperglycemia caused by slow engraftment in turn accelerated the apoptotic islet cell death [95].…”

“…However, it should be noted that BMSCs alone, through systemic administration or local transplantation, were less competent to prevent the islet loss immediately after transplantation, which accounts for more than 70% of islet loss in the first week after transplantation [95,96]. This phenomenon probably explains the inadequate control of the blood glucose level in the early stage (< 3 weeks) after transplantation in most islet/MSC co-transplantation studies [54,116]. Because traditional gene transfer into human islets is less efficient and time consuming and BMSC mediated cell therapy is less competent to prevent the acute graft loss, we planned to utilize BMSC mediated gene therapy in this study.…”

“…In vitro expanded BMSCs co-infused into liver. Reduce islet number needed for reversal of diabetes promote revascularization [54]. Rat.…”