PMID- 28855509 OWN - NLM STAT- MEDLINE DCOM- 20171221 LR - 20200306 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 8 IP - 1 DP - 2017 Aug 30 TI - MHC matching improves engraftment of iPSC-derived neurons in non-human primates. PG - 385 LID - 10.1038/s41467-017-00926-5 [doi] LID - 385 AB - The banking of human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cells (iPSCs) is considered a future clinical strategy for HLA-matched cell transplantation to reduce immunological graft rejection. Here we show the efficacy of major histocompatibility complex (MHC)-matched allogeneic neural cell grafting in the brain, which is considered a less immune-responsive tissue, using iPSCs derived from an MHC homozygous cynomolgus macaque. Positron emission tomography imaging reveals neuroinflammation associated with an immune response against MHC-mismatched grafted cells. Immunohistological analyses reveal that MHC-matching reduces the immune response by suppressing the accumulation of microglia (Iba-1+) and lymphocytes (CD45+) into the grafts. Consequently, MHC-matching increases the survival of grafted dopamine neurons (tyrosine hydroxylase: TH+). The effect of an immunosuppressant, Tacrolimus, is also confirmed in the same experimental setting. Our results demonstrate the rationale for MHC-matching in neural cell grafting to the brain and its feasibility in a clinical setting.Major histocompatibility complex (MHC) matching improves graft survival rates after organ transplantation. Here the authors show that in macaques, MHC-matched iPSC-derived neurons provide better engraftment in the brain, with a lower immune response and higher survival of the transplanted neurons. FAU - Morizane, Asuka AU - Morizane A AD - Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, 606-8507, Japan. FAU - Kikuchi, Tetsuhiro AU - Kikuchi T AUID- ORCID: 0000-0003-2332-4967 AD - Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, 606-8507, Japan. FAU - Hayashi, Takuya AU - Hayashi T AD - RIKEN Center for Life Science Technologies (CLST), Hyogo, 650-0047, Japan. FAU - Mizuma, Hiroshi AU - Mizuma H AUID- ORCID: 0000-0001-8970-9486 AD - RIKEN Center for Life Science Technologies (CLST), Hyogo, 650-0047, Japan. FAU - Takara, Sayuki AU - Takara S AD - RIKEN Center for Life Science Technologies (CLST), Hyogo, 650-0047, Japan. FAU - Doi, Hisashi AU - Doi H AD - RIKEN Center for Life Science Technologies (CLST), Hyogo, 650-0047, Japan. FAU - Mawatari, Aya AU - Mawatari A AD - RIKEN Center for Life Science Technologies (CLST), Hyogo, 650-0047, Japan. FAU - Glasser, Matthew F AU - Glasser MF AD - Department of Neuroscience, Washington University School of Medicine, St. Louis, M0, 63110, USA. FAU - Shiina, Takashi AU - Shiina T AD - Department of Molecular Life Science, Tokai University, School of Medicine, Kanagawa, 259-1143, Japan. FAU - Ishigaki, Hirohito AU - Ishigaki H AD - Department of Pathology, Shiga University of Medical Science, Shiga, 520-2192, Japan. FAU - Itoh, Yasushi AU - Itoh Y AD - Department of Pathology, Shiga University of Medical Science, Shiga, 520-2192, Japan. FAU - Okita, Keisuke AU - Okita K AUID- ORCID: 0000-0001-5806-1090 AD - Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto, 606-8507, Japan. FAU - Yamasaki, Emi AU - Yamasaki E AD - Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, 606-8507, Japan. FAU - Doi, Daisuke AU - Doi D AD - Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, 606-8507, Japan. FAU - Onoe, Hirotaka AU - Onoe H AD - RIKEN Center for Life Science Technologies (CLST), Hyogo, 650-0047, Japan. AD - Department of Neuroscience, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan. FAU - Ogasawara, Kazumasa AU - Ogasawara K AD - Department of Pathology, Shiga University of Medical Science, Shiga, 520-2192, Japan. FAU - Yamanaka, Shinya AU - Yamanaka S AD - Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto, 606-8507, Japan. AD - Gladstone Institute of Cardiovascular Disease, San Francisco, CA, 94158, USA. FAU - Takahashi, Jun AU - Takahashi J AUID- ORCID: 0000-0003-3642-9186 AD - Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, 606-8507, Japan. jbtaka@cira.kyoto-u.ac.jp. AD - Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan. jbtaka@cira.kyoto-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170830 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (HLA Antigens) SB - IM MH - Animals MH - Dopaminergic Neurons/immunology/*transplantation MH - Female MH - Graft Rejection/*immunology MH - HLA Antigens/*genetics MH - Haplotypes MH - Immunohistochemistry MH - Induced Pluripotent Stem Cells/*transplantation MH - Lymphocytes/immunology MH - Macaca MH - Major Histocompatibility Complex/*immunology MH - Male MH - Microglia/immunology MH - Positron-Emission Tomography PMC - PMC5577234 COIS- S.Y. is a scientific advisor of iPS Academia Japan without salary. The remaining authors declare no competing financial interests. EDAT- 2017/09/01 06:00 MHDA- 2017/12/22 06:00 PMCR- 2017/08/30 CRDT- 2017/09/01 06:00 PHST- 2017/06/13 00:00 [received] PHST- 2017/08/07 00:00 [accepted] PHST- 2017/09/01 06:00 [entrez] PHST- 2017/09/01 06:00 [pubmed] PHST- 2017/12/22 06:00 [medline] PHST- 2017/08/30 00:00 [pmc-release] AID - 10.1038/s41467-017-00926-5 [pii] AID - 926 [pii] AID - 10.1038/s41467-017-00926-5 [doi] PST - epublish SO - Nat Commun. 2017 Aug 30;8(1):385. doi: 10.1038/s41467-017-00926-5.