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

Nat Commun. 2017 Aug 30;8(1):385. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopaminergic Neurons / immunology
  • Dopaminergic Neurons / transplantation*
  • Female
  • Graft Rejection / immunology*
  • HLA Antigens / genetics*
  • Haplotypes
  • Immunohistochemistry
  • Induced Pluripotent Stem Cells / transplantation*
  • Lymphocytes / immunology
  • Macaca
  • Major Histocompatibility Complex / immunology*
  • Male
  • Microglia / immunology
  • Positron-Emission Tomography


  • HLA Antigens