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Successful Transplantation of Retinal Pigment Epithelial Cells from MHC Homozygote iPSCs in MHC-Matched Models.
Stem Cell Reports. 2016 10 11; 7(4):635-648.SC

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+Show Affiliations

Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.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.Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.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.Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Kanagawa 259-1193, Japan.Department of Pathology, Shiga University of Medical Science, Ohtsu 520-2192, Japan.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.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.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.

Pub Type(s)

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

Language

eng

PubMed ID

27641649

Citation

Sugita, Sunao, et al. "Successful Transplantation of Retinal Pigment Epithelial Cells From MHC Homozygote iPSCs in MHC-Matched Models." Stem Cell Reports, vol. 7, no. 4, 2016, pp. 635-648.
Sugita S, Iwasaki Y, Makabe K, et al. Successful Transplantation of Retinal Pigment Epithelial Cells from MHC Homozygote iPSCs in MHC-Matched Models. Stem Cell Reports. 2016;7(4):635-648.
Sugita, S., Iwasaki, Y., Makabe, K., Kamao, H., Mandai, M., Shiina, T., Ogasawara, K., Hirami, Y., Kurimoto, Y., & Takahashi, M. (2016). Successful Transplantation of Retinal Pigment Epithelial Cells from MHC Homozygote iPSCs in MHC-Matched Models. Stem Cell Reports, 7(4), 635-648. https://doi.org/10.1016/j.stemcr.2016.08.010
Sugita S, et al. Successful Transplantation of Retinal Pigment Epithelial Cells From MHC Homozygote iPSCs in MHC-Matched Models. Stem Cell Reports. 2016 10 11;7(4):635-648. PubMed PMID: 27641649.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Successful Transplantation of Retinal Pigment Epithelial Cells from MHC Homozygote iPSCs in MHC-Matched Models. AU - Sugita,Sunao, AU - Iwasaki,Yuko, AU - Makabe,Kenichi, AU - Kamao,Hiroyuki, AU - Mandai,Michiko, AU - Shiina,Takashi, AU - Ogasawara,Kazumasa, AU - Hirami,Yasuhiko, AU - Kurimoto,Yasuo, AU - Takahashi,Masayo, Y1 - 2016/09/15/ PY - 2016/04/27/received PY - 2016/08/14/revised PY - 2016/08/16/accepted PY - 2016/9/20/pubmed PY - 2017/11/29/medline PY - 2016/9/20/entrez SP - 635 EP - 648 JF - Stem cell reports JO - Stem Cell Reports VL - 7 IS - 4 N2 - 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. SN - 2213-6711 UR - https://www.unboundmedicine.com/medline/citation/27641649/Successful_Transplantation_of_Retinal_Pigment_Epithelial_Cells_from_MHC_Homozygote_iPSCs_in_MHC_Matched_Models_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-6711(16)30177-1 DB - PRIME DP - Unbound Medicine ER -