Successful Transplantation of Retinal Pigment Epithelial Cells from MHC Homozygote iPSCs in MHC-Matched Models

• Published in: Stem cell reports Vol. 7; no. 4; pp. 635 - 648
• Main Authors: Sugita, Sunao, Iwasaki, Yuko, Makabe, Kenichi, Kamao, Hiroyuki, Mandai, Michiko, Shiina, Takashi, Ogasawara, Kazumasa, Hirami, Yasuhiko, Kurimoto, Yasuo, Takahashi, Masayo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.10.2016; Elsevier
• Subjects: Animals; Biomarkers; Epithelial Cells - cytology; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelial Cells - transplantation; Heterozygote; Histocompatibility Testing; Homozygote; Immunohistochemistry; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Macaca fascicularis; Major Histocompatibility Complex - genetics; Major Histocompatibility Complex - immunology; Retinal Pigment Epithelium - cytology; Tissue Donors; Transplantation, Homologous
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2016.08.010

There is an ongoing controversy as to whether major histocompatibility complex (MHC) matching is a solution for allogeneic stem cell transplantation. In the present study, we established retinal pigment epithelial (RPE) cells from induced pluripotent stem cells (iPSCs) in MHC homozygote donors. We observed no rejection signs in iPSC-derived RPE allografts of MHC-matched animal models without immunosuppression, whereas there were immune attacks around the graft and retinal tissue damage in MHC-mismatched models. In an immunohistochemical examination of MHC-mismatched allografts, the transplanted RPE sheets/cells were located in the subretinal space, but the RPE exhibited inflammatory and hypertrophic changes, and many inflammatory cells, e.g., Iba1+ cells, MHC class II+ cells, and CD3+ T cells, invaded the graft area. Conversely, these inflammatory cells poorly infiltrated the area around the transplanted retina if MHC-matched allografts were used. Thus, cells derived from MHC homozygous donors could be used to treat retinal diseases in histocompatible recipients. [Display omitted] •We established RPE cells from iPSCs in MHC homozygote animals•MHC-mismatching transplantation caused immune attacks of iPS-RPE allografts•MHC-matching transplantation appeared to prevent the attacks of the allografts•T cells responded to allogeneic iPS-RPE, but failed to respond to MHC homozygote RPE In this article, Takahashi and colleagues show the allogeneic immune response, such as immune rejection, to iPSC-derived retinal pigment epithelial (RPE) cells by inflammatory cells in vivo. However, the immune reaction does not occur when iPS-RPE cells established from MHC homozygous donors were transplanted.