iPSC modification strategies to induce immune tolerance

Human pluripotent stem cells (hPSCs) hold great promise in regenerative medicine. However, immune rejections remain one of the major obstacles to stem cell therapy. Though conventional immunosuppressants are available in clinics, the side effects prevent the wide application of hPSCs derivatives, compromising both survival rate and quality of life. In recent years, a myriad of strategies aimed at inducing immune tolerance specifically by engineering stem cells has been introduced to society. One strategy involves human leukocyte antigen (HLA) deletion through gene editing, affording allografts the capability to evade the host immune system. Another strategy involves immune cloak, which is the focus of this review, with emphasis on the overexpression of immune checkpoints and the blocking of immune cytotoxic pathways. Nevertheless, co-transplantation with mesenchymal stem cells (MSCs) and enhanced MSCs confers immune privilege to engraftments. This review summarizes recent studies on the intricacies of immune tolerance induction by engineering stem cells. In addition, we endeavor to deliberate upon the safety and limitations associated with this promising and potential therapeutic modality.