Humanized Mice Reveal Differential Immunogenicity of Cells Derived from Autologous Induced Pluripotent Stem Cells

TitleHumanized Mice Reveal Differential Immunogenicity of Cells Derived from Autologous Induced Pluripotent Stem Cells
Publication TypeJournal Article
Year of Publication2015
AuthorsZhao T, Zhang Z-ning, Westenskow PD, Todorova D, Hu Z, Lin T, Rong Z, Kim J, He J, Wang M, Clegg DO, Yang Y-guang, Zhang K, Friedlander M, Xu Y
JournalCell Stem Cell
Volume17
Issue3
Pagination353-9
Date Published2015 Sep 3
ISSN1875-9777
Abstract

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.

DOI10.1016/j.stem.2015.07.021
Alternate JournalCell Stem Cell
PubMed ID26299572
Grant ListEY021416 / EY / NEI NIH HHS / United States
EY11254 / EY / NEI NIH HHS / United States