title: Successful Transplantation of Retinal Pigment Epithelial Cells from MHC Homozygote iPSCs in MHC-Matched Models.
abstract: 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.
authors.affiliation: Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Sunao
authors.initials: S
authors.lastname: Sugita
authors.affiliation: Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine and Dental Sciences, Tokyo 113-8519, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Makabe
authors.affiliation: Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Ophthalmology, Kawasaki Medical School, Okayama 701-0192, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamao
authors.affiliation: Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Mandai
authors.affiliation: Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Kanagawa 259-1193, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiina
authors.affiliation: Department of Pathology, Shiga University of Medical Science, Ohtsu 520-2192, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Ogasawara
authors.affiliation: Department of Ophthalmology, Institute of Biomedical Research and Innovation Hospital, Kobe 650-0047, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe 650-0047, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Hirami
authors.affiliation: Department of Ophthalmology, Institute of Biomedical Research and Innovation Hospital, Kobe 650-0047, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe 650-0047, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kurimoto
authors.affiliation: Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: mretina@cdb.riken.jp.
authors.forename: Masayo
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D015415:Biomarkers; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation*; D006579:Heterozygote; D006650:Histocompatibility Testing; D006720:Homozygote; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008252:Macaca fascicularis; D008285:Major Histocompatibility Complex / Q000235:genetics* / Q000276:immunology; D055213:Retinal Pigment Epithelium / Q000166:cytology*; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers