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Cardiomyocytes Derived from MHC-Homozygous Induced Pluripotent Stem Cells Exhibit Reduced Allogeneic Immunogenicity in MHC-Matched Non-human Primates.
Stem Cell Reports. 2016 Mar 08; 6(3):312-20.SC

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+Show Affiliations

Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Kyoto 606-8507, Japan.Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Kyoto 606-8507, Japan.Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Kyoto 606-8507, Japan.Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan.Department of Pathology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.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.

Pub Type(s)

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

Language

eng

PubMed ID

26905198

Citation

Kawamura, Takuji, et al. "Cardiomyocytes Derived From MHC-Homozygous Induced Pluripotent Stem Cells Exhibit Reduced Allogeneic Immunogenicity in MHC-Matched Non-human Primates." Stem Cell Reports, vol. 6, no. 3, 2016, pp. 312-20.
Kawamura T, Miyagawa S, Fukushima S, et al. Cardiomyocytes Derived from MHC-Homozygous Induced Pluripotent Stem Cells Exhibit Reduced Allogeneic Immunogenicity in MHC-Matched Non-human Primates. Stem Cell Reports. 2016;6(3):312-20.
Kawamura, T., Miyagawa, S., Fukushima, S., Maeda, A., Kashiyama, N., Kawamura, A., Miki, K., Okita, K., Yoshida, Y., Shiina, T., Ogasawara, K., Miyagawa, S., Toda, K., Okuyama, H., & Sawa, Y. (2016). Cardiomyocytes Derived from MHC-Homozygous Induced Pluripotent Stem Cells Exhibit Reduced Allogeneic Immunogenicity in MHC-Matched Non-human Primates. Stem Cell Reports, 6(3), 312-20. https://doi.org/10.1016/j.stemcr.2016.01.012
Kawamura T, et al. Cardiomyocytes Derived From MHC-Homozygous Induced Pluripotent Stem Cells Exhibit Reduced Allogeneic Immunogenicity in MHC-Matched Non-human Primates. Stem Cell Reports. 2016 Mar 8;6(3):312-20. PubMed PMID: 26905198.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiomyocytes Derived from MHC-Homozygous Induced Pluripotent Stem Cells Exhibit Reduced Allogeneic Immunogenicity in MHC-Matched Non-human Primates. AU - Kawamura,Takuji, AU - Miyagawa,Shigeru, AU - Fukushima,Satsuki, AU - Maeda,Akira, AU - Kashiyama,Noriyuki, AU - Kawamura,Ai, AU - Miki,Kenji, AU - Okita,Keisuke, AU - Yoshida,Yoshinori, AU - Shiina,Takashi, AU - Ogasawara,Kazumasa, AU - Miyagawa,Shuji, AU - Toda,Koichi, AU - Okuyama,Hiroomi, AU - Sawa,Yoshiki, Y1 - 2016/02/18/ PY - 2015/06/26/received PY - 2016/01/14/revised PY - 2016/01/15/accepted PY - 2016/2/25/entrez PY - 2016/2/26/pubmed PY - 2016/12/15/medline SP - 312 EP - 20 JF - Stem cell reports JO - Stem Cell Reports VL - 6 IS - 3 N2 - 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. SN - 2213-6711 UR - https://www.unboundmedicine.com/medline/citation/26905198/Cardiomyocytes_Derived_from_MHC_Homozygous_Induced_Pluripotent_Stem_Cells_Exhibit_Reduced_Allogeneic_Immunogenicity_in_MHC_Matched_Non_human_Primates_ DB - PRIME DP - Unbound Medicine ER -