- Zhao, Tongbiao;
- Zhang, Zhen-ning;
- Westenskow, Peter D;
- Todorova, Dilyana;
- Hu, Zheng;
- Lin, Tongxiang;
- Rong, Zhili;
- Kim, Jinchul;
- He, Jingjin;
- Wang, Meiyan;
- Clegg, Dennis O;
- Yang, Yong-guang;
- Zhang, Kun;
- Friedlander, Martin;
- Xu, Yang
The breakthrough of induced pluripotent stem cell (iPSC) technology has raised the possibility that patient-specific iPSCs may become a renewable source of autologous cells for cell therapy without the concern of immune rejection. However, the immunogenicity of autologous human iPSC (hiPSC)-derived cells is not well understood. Using a humanized mouse model (denoted Hu-mice) reconstituted with a functional human immune system, we demonstrate that most teratomas formed by autologous integration-free hiPSCs exhibit local infiltration of antigen-specific T cells and associated tissue necrosis, indicating immune rejection of certain hiPSC-derived cells. In this context, autologous hiPSC-derived smooth muscle cells (SMCs) appear to be highly immunogenic, while autologous hiPSC-derived retinal pigment epithelial (RPE) cells are immune tolerated even in non-ocular locations. This differential immunogenicity is due in part to abnormal expression of immunogenic antigens in hiPSC-derived SMCs, but not in hiPSC-derived RPEs. These findings support the feasibility of developing hiPSC-derived RPEs for treating macular degeneration.