Negligible immunogenicity of induced pluripotent stem cells derived from human skin fibroblasts

Qiao Lu; Meixing Yu; Chongyang Shen; Xiaoping Chen; Ting Feng; Yongchao Yao; Jinrong Li; Hong Li; Wenwei Tu

doi:10.1371/journal.pone.0114949

Negligible immunogenicity of induced pluripotent stem cells derived from human skin fibroblasts

PLoS One. 2014 Dec 11;9(12):e114949. doi: 10.1371/journal.pone.0114949. eCollection 2014.

Authors

Qiao Lu¹, Meixing Yu², Chongyang Shen², Xiaoping Chen³, Ting Feng², Yongchao Yao³, Jinrong Li², Hong Li⁴, Wenwei Tu⁵

Affiliations

¹ The Joint Research Center of West China Second University Hospital of Sichuan University and Faculty of Medicine of the University of Hong Kong, Sichuan University, Chengdu, Sichuan, 610041, China; Department of Pediatrics, University Hospital of Hubei University for Nationalities, Enshi, Hubei, 445000, China.
² The Joint Research Center of West China Second University Hospital of Sichuan University and Faculty of Medicine of the University of Hong Kong, Sichuan University, Chengdu, Sichuan, 610041, China.
³ Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
⁴ The Joint Research Center of West China Second University Hospital of Sichuan University and Faculty of Medicine of the University of Hong Kong, Sichuan University, Chengdu, Sichuan, 610041, China; Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
⁵ The Joint Research Center of West China Second University Hospital of Sichuan University and Faculty of Medicine of the University of Hong Kong, Sichuan University, Chengdu, Sichuan, 610041, China; Department of Pediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

Abstract

Human induced pluripotent stem cells (hiPSCs) have potential applications in cell replacement therapy and regenerative medicine. However, limited information is available regarding the immunologic features of iPSCs. In this study, expression of MHC and T cell co-stimulatory molecules in hiPSCs, and the effects on activation, proliferation and cytokine production in allogeneic human peripheral blood mononuclear cells were examined. We found that no-integrate hiPSCs had no MHC-II and T cell co-stimulatory molecules expressions but had moderate level of MHC-I and HLA-G expressions. In contrast to human skin fibroblasts (HSFs) which significantly induced allogeneic T cell activation and proliferation, hiPSCs failed to induce allogeneic CD45+ lymphocyte and CD8+ T cell activation and proliferation but could induce a low level of allogeneic CD4+ T cell proliferation. Unlike HSFs which induced allogeneic lymphocytes to produce high levels of IFN-γ, TNF-α and IL-17, hiPSCs only induced allogeneic lymphocytes to produce IL-2 and IL-10, and promote IL-10-secreting regulatory T cell (Treg) generation. Our study suggests that the integration-free hiPSCs had low or negligible immunogenicity, which may result from their induction of IL-10-secreting Treg.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD4-Positive T-Lymphocytes / immunology*
Cell Proliferation / genetics
Fibroblasts / immunology*
Fibroblasts / metabolism
Humans
Induced Pluripotent Stem Cells / immunology*
Induced Pluripotent Stem Cells / metabolism
Interferon-gamma / biosynthesis
Interferon-gamma / immunology
Interleukin-10 / biosynthesis
Interleukin-10 / immunology
Interleukin-17 / biosynthesis
Interleukin-17 / immunology
Interleukin-2 / biosynthesis
Interleukin-2 / immunology
Skin / immunology*
Skin / metabolism
T-Lymphocytes, Regulatory / immunology
Tumor Necrosis Factor-alpha / biosynthesis
Tumor Necrosis Factor-alpha / immunology

Substances

IL10 protein, human
IL17A protein, human
Interleukin-17
Interleukin-2
TNF protein, human
Tumor Necrosis Factor-alpha
Interleukin-10
Interferon-gamma

Grants and funding

This work was supported in part by the grants from National Natural Science Foundation of China (NSFC) and the Research Grants Council (RGC) of Hong Kong Joint Research Scheme (N_HKU 747/11), National Natural Science Foundation of China (No. 81170606), and Doctoral Fund of Ministry of Education of China (No. 20120181110087). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.