Journal
CELL STEM CELL
Volume 17, Issue 3, Pages 353-359Publisher
CELL PRESS
DOI: 10.1016/j.stem.2015.07.021
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Funding
- National Natural Science Foundation of China [81430032]
- Chinese Ministry of Science and Technology [2013CB966900, 2013ZX10002008-002]
- Strategic Priority Research Program of Chinese Academy of Sciences [XDA01040108]
- NIH Ruth L. Kirschstein National Research Service Award [EY021416]
- California Institute of Regenerative Medicine [TR1-01219]
- National Eye Institute of National Institutes of Health [EY11254]
- Early Translational Award from California Institute for Regenerative Medicine [TR1-01277]
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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 humaniPSC(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.
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