TY - JOUR
T1 - MHC matching improves engraftment of iPSC-derived neurons in non-human primates
AU - Morizane, Asuka
AU - Kikuchi, Tetsuhiro
AU - Hayashi, Takuya
AU - Mizuma, Hiroshi
AU - Takara, Sayuki
AU - Doi, Hisashi
AU - Mawatari, Aya
AU - Glasser, Matthew F.
AU - Shiina, Takashi
AU - Ishigaki, Hirohito
AU - Itoh, Yasushi
AU - Okita, Keisuke
AU - Yamasaki, Emi
AU - Doi, Daisuke
AU - Onoe, Hirotaka
AU - Ogasawara, Kazumasa
AU - Yamanaka, Shinya
AU - Takahashi, Jun
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
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.
UR - https://www.scopus.com/pages/publications/85028565936
U2 - 10.1038/s41467-017-00926-5
DO - 10.1038/s41467-017-00926-5
M3 - Article
C2 - 28855509
AN - SCOPUS:85028565936
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 385
ER -