Low Immunogenicity and Immunosuppressive Properties of Human ESC- and iPSC-Derived Retinas

Summary ESC- and iPSC-derived retinal transplantation is a promising therapeutic approach for disease with end-stage retinal degeneration, such as retinitis pigmentosa and age-related macular degeneration. We previously showed medium- to long-term survival, maturation, and light response of transplanted human ESC- and iPSC-retina in mouse, rat, and monkey models of end-stage retinal degeneration. Because the use of patient hiPSC-derived retina with a disease-causing gene mutation is not appropriate for therapeutic use, allogeneic transplantation using retinal tissue/cells differentiated from a stocked hESC and iPSC line would be most practical. Here, we characterize the immunological properties of hESC- and iPSC-retina and present their three major advantages: (1) hESC- and iPSC-retina expressed low levels of human leukocyte antigen (HLA) class I and little HLA class II in vitro, (2) hESC- and iPSC-retina greatly suppressed immune activation of lymphocytes in co-culture, and (3) hESC- and iPSC-retina suppressed activated immune cells partially via transforming growth factor β signaling. These results support the use of allogeneic hESC- and iPSC-retina in future clinical application.
Graphical abstract
Highlights • hESC- and iPSC-retinas poorly express HLA molecules • hESC- and iPSC-retinas have immunosuppressive properties • hESC- and iPSC-retinas can suppress allogeneic lymphocytes • hESC- and iPSC-retinas suppress immune cells via TGF-β signaling
In this article, Yamasaki, Sugita, and colleagues show that the immunogenicity and immunosuppressive properties of hESC- and iPSC-retinas was differentiated in vitro outside the immune-privileged site. TGF-β secreted by these retinas played a critical role of immunosuppressive properties against activated lymphocytes. These features suggested a low risk of immune rejection after transplantation of stem cell-retina in clinical applications.