title: Humanized Mice Reveal Differential Immunogenicity of Cells Derived from Autologous Induced Pluripotent Stem Cells.
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.
authors: 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.
authors: Tongbiao
authors: T
authors: Zhao
authors: Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 920932, USA.
authors: Zhen-ning
authors: ZN
authors: Zhang
authors: Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors: Peter D
authors: PD
authors: Westenskow
authors: Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 920932, USA.
authors: Dilyana
authors: D
authors: Todorova
authors: First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors: Zheng
authors: Z
authors: Hu
authors: The Second Clinical Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong 510006, China.
authors: Tongxiang
authors: T
authors: Lin
authors: Cancer Research Institute, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors: Zhili
authors: Z
authors: Rong
authors: Cancer Research Institute, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors: Jinchul
authors: J
authors: Kim
authors: 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.
authors: Jingjin
authors: J
authors: He
authors: Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 920932, USA.
authors: Meiyan
authors: M
authors: Wang
authors: Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
authors: Dennis O
authors: DO
authors: Clegg
authors: First Hospital of Jilin University, Changchun, Jilin 130021, China; Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.
authors: Yong-guang
authors: YG
authors: Yang
authors: Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors: Kun
authors: K
authors: Zhang
authors: Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors: Martin
authors: M
authors: Friedlander
authors: 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.
authors: Yang
authors: Y
authors: Xu
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D002454:Cell Differentiation; D006801:Humans; D007109:Immunity; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000276:immunology; D055213:Retinal Pigment Epithelium / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013724:Teratoma / Q000473:pathology; D014182:Transplantation, Autologous
chemical_list: D000941:Antigens