Cardiomyocytes Derived from MHC-Homozygous Induced Pluripotent Stem Cells Exhibit Reduced Allogeneic Immunogenicity in MHC-Matched Non-human Primates

• Published in: Stem cell reports Vol. 6; no. 3; pp. 312 - 320
• Main Authors: Kawamura, Takuji, Miyagawa, Shigeru, Fukushima, Satsuki, Maeda, Akira, Kashiyama, Noriyuki, Kawamura, Ai, Miki, Kenji, Okita, Keisuke, Yoshida, Yoshinori, Shiina, Takashi, Ogasawara, Kazumasa, Miyagawa, Shuji, Toda, Koichi, Okuyama, Hiroomi, Sawa, Yoshiki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.03.2016; Elsevier
• Subjects: Animals; Cell Line; Haplotypes; Heterozygote; Histocompatibility Antigens Class I - immunology; Host vs Graft Reaction; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - immunology; Induced Pluripotent Stem Cells - transplantation; Macaca; Male; Myocytes, Cardiac - cytology; Myocytes, Cardiac - immunology; Myocytes, Cardiac - transplantation; Stem Cell Transplantation; Transplantation, Homologous
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2016.01.012

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. [Display omitted] •Cardiomyocytes from iPSCs can treat heart disease•iPSC-CMs were transplanted into MHC-matched or unmatched cynomolgus macacques•Matched iPSC-CM grafts had better survival and less host rejection immune response•Immunosuppression was still required for successful allogeneic iPSC-CM engraftment In this article, Sawa and colleagues examined whether transplantation of cardiomyocytes generated from induced pluripotent stem cells could alleviate immune-mediated rejection in major histocompatibility antigen-matched non-human primates. Transplantation of matched tissue prevented allogeneic immune rejection and enhanced engraftment with appropriate immunosuppressants. Thus, banked iPSCs with simple MHC profiles might be useful for regenerative therapy for a variety of pathologies.