The lack of an effective method of inducing immune tolerance is a major roadblock for human ESC-based therapies. ESCs were once considered immune-privileged due to the low expression of major histocompatibility complex (MHC) class I, MHC II, and costimulatory molecules161. Although undifferentiated ESCs might be immune-privileged, their differentiated derivatives can trigger cellular and humoral immune responses162. By contrast, autologous iPSCs may avoid the high cost and serious side effects associated with lifelong immunosuppression required for allogeneic cell transplantation163. Despite some controversy over the immunogenicity of undifferentiated iPSCs164, recent studies demonstrate that differentiation of iPSCs could result in loss of immunogenicity165–167.
