MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates

Nat Commun. 2019 Sep 25;10(1):4357. doi: 10.1038/s41467-019-12324-0.


Cell therapy products (CTP) derived from pluripotent stem cells (iPSCs) may constitute a renewable, specifically differentiated source of cells to potentially cure patients with neurodegenerative disorders. However, the immunogenicity of CTP remains a major issue for therapeutic approaches based on transplantation of non-autologous stem cell-derived neural grafts. Despite its considerable side-effects, long-term immunosuppression, appears indispensable to mitigate neuro-inflammation and prevent rejection of allogeneic CTP. Matching iPSC donors' and patients' HLA haplotypes has been proposed as a way to access CTP with enhanced immunological compatibility, ultimately reducing the need for immunosuppression. In the present work, we challenge this paradigm by grafting autologous, MHC-matched and mis-matched neuronal grafts in a primate model of Huntington's disease. Unlike previous reports in unlesioned hosts, we show that in the absence of immunosuppression MHC matching alone is insufficient to grant long-term survival of neuronal grafts in the lesioned brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Cytotoxicity, Immunologic / immunology
  • Disease Models, Animal
  • Graft Rejection / immunology*
  • Histocompatibility Testing
  • Humans
  • Huntington Disease / immunology
  • Huntington Disease / therapy*
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / immunology
  • Induced Pluripotent Stem Cells / transplantation*
  • Major Histocompatibility Complex / immunology*
  • Neurons / cytology
  • Neurons / immunology
  • Neurons / transplantation*
  • Primates
  • Rats, Nude
  • Transplantation, Autologous