title: Cardiomyocytes Derived from MHC-Homozygous Induced Pluripotent Stem Cells Exhibit Reduced Allogeneic Immunogenicity in MHC-Matched Non-human Primates.
abstract: Induced pluripotent stem cells (iPSCs) can serve as a source of cardiomyocytes (CMs) to treat end-stage heart failure; however, transplantation of genetically dissimilar iPSCs even within species (allogeneic) can induce immune rejection. We hypothesized that this might be limited by matching the major histocompatibility complex (MHC) antigens between the donor and the recipient. We therefore transplanted fluorescence-labeled (GFP) iPSC-CMs donated from a macaque with homozygous MHC haplotypes into the subcutaneous tissue and hearts of macaques having heterozygous MHC haplotypes (MHC-matched; group I) or without identical MHC alleles (group II) in conjunction with immune suppression. Group I displayed a higher GFP intensity and less immune-cell infiltration in the graft than group II. However, MHC-matched transplantation with single or no immune-suppressive drugs still induced a substantial host immune response to the graft. Thus, the immunogenicity of allogeneic iPSC-CMs was reduced by MHC-matched transplantation although a requirement for appropriate immune suppression was retained for successful engraftment.
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Kawamura
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyagawa
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Satsuki
authors.initials: S
authors.lastname: Fukushima
authors.affiliation: Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Maeda
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kashiyama
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Kawamura
authors.affiliation: Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Kyoto 606-8507, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Miki
authors.affiliation: Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Kyoto 606-8507, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Okita
authors.affiliation: Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Kyoto 606-8507, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiina
authors.affiliation: Department of Pathology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Ogasawara
authors.affiliation: Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Miyagawa
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Toda
authors.affiliation: Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Okuyama
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan. Electronic address: sawa-p@surg1.med.osaka-u.ac.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
mesh_terms: D000818:Animals; D002460:Cell Line; D006239:Haplotypes; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006789:Host vs Graft Reaction; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D008251:Macaca; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous
chemical_list: D015395:Histocompatibility Antigens Class I