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Cell Stem Cell. 2015 Sep 3;17(3):353-9. doi: 10.1016/j.stem.2015.07.021. Epub 2015 Aug 20.

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

Author information

1
Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 920932, USA; State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
2
Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 920932, USA.
3
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
4
First Hospital of Jilin University, Changchun, Jilin 130021, China.
5
The Second Clinical Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong 510006, China.
6
Cancer Research Institute, Southern Medical University, Guangzhou, Guangdong 510515, China.
7
Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 920932, USA; Cancer Research Institute, Southern Medical University, Guangzhou, Guangdong 510515, China.
8
Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
9
First Hospital of Jilin University, Changchun, Jilin 130021, China; Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.
10
Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
11
Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 920932, USA; Cancer Research Institute, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address: yangxu@ucsd.edu.

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.

PMID:
26299572
DOI:
10.1016/j.stem.2015.07.021
[Indexed for MEDLINE]
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