MHC matching improves engraftment of iPSC-derived neurons in non-human primates

• Published in: Nature communications Vol. 8; no. 1; pp. 385 - 12
• Main Authors: Morizane, Asuka, Kikuchi, Tetsuhiro, Hayashi, Takuya, Mizuma, Hiroshi, Takara, Sayuki, Doi, Hisashi, Mawatari, Aya, Glasser, Matthew F., Shiina, Takashi, Ishigaki, Hirohito, Itoh, Yasushi, Okita, Keisuke, Yamasaki, Emi, Doi, Daisuke, Onoe, Hirotaka, Ogasawara, Kazumasa, Yamanaka, Shinya, Takahashi, Jun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.08.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/1854/2812; 631/378/1687; 631/532/2064/2158; 692/308/2171; Animals; Antigens; Biomarkers; Brain; Dopamine; Dopaminergic Neurons - immunology; Dopaminergic Neurons - transplantation; Female; Graft Rejection - immunology; Haplotypes; HLA Antigens - genetics; Humanities and Social Sciences; Immune response; Immune system; Immunohistochemistry; Immunology; Induced Pluripotent Stem Cells - transplantation; Life sciences; Lymphocytes; Lymphocytes - immunology; Macaca; Major histocompatibility complex; Major Histocompatibility Complex - immunology; Male; Matching; Medicine; Microglia - immunology; multidisciplinary; Neurons; Neurosciences; Parkinson's disease; Pluripotency; Positron-Emission Tomography; Primates; Science; Science (multidisciplinary); Stem cells; Survival; Transplantation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-00926-5

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.