| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2077311 | Cell Stem Cell | 2015 | 7 Pages |
•Hu-mice offer a model to study immune responses to autologous hiPSC derivatives•Hu-mice reveal differential immune responses to hiPSC-derived SMCs and RPEs•Misexpression of immunogenic antigens in hiPSC-derived SMCs leads to T cell response•hiPSC-RPEs are tolerated even in non-ocular sites, supporting their clinical use
SummaryThe 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.
Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (198 K)Download as PowerPoint slide
