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

Author

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  • Romina Aron Badin

    (CEA, DRF, Institute of Biology François Jacob, Molecular Imaging Research Center (MIRCen)
    CNRS, CEA, Paris-Sud Univ., Paris-Saclay Univ., Neurodegenerative Diseases Laboratory (UMR9199))

  • Aurore Bugi

    (CECS, I-STEM, AFM)

  • Susannah Williams

    (CEA, DRF, Institute of Biology François Jacob, Molecular Imaging Research Center (MIRCen)
    CNRS, CEA, Paris-Sud Univ., Paris-Saclay Univ., Neurodegenerative Diseases Laboratory (UMR9199))

  • Marta Vadori

    (CORIT, Ospedale Giustinianeo, Padova, ITALY)

  • Marie Michael

    (CECS, I-STEM, AFM)

  • Caroline Jan

    (CEA, DRF, Institute of Biology François Jacob, Molecular Imaging Research Center (MIRCen)
    CNRS, CEA, Paris-Sud Univ., Paris-Saclay Univ., Neurodegenerative Diseases Laboratory (UMR9199))

  • Alberto Nassi

    (Padua University Hospital)

  • Sophie Lecourtois

    (CEA, DRF, Institute of Biology François Jacob, Molecular Imaging Research Center (MIRCen)
    CNRS, CEA, Paris-Sud Univ., Paris-Saclay Univ., Neurodegenerative Diseases Laboratory (UMR9199))

  • Antoine Blancher

    (Université de Toulouse, CNRS, Inserm, Université Paul Sabatier (UPS))

  • Emanuele Cozzi

    (CORIT, Ospedale Giustinianeo, Padova, ITALY
    Padua University Hospital)

  • Philippe Hantraye

    (CEA, DRF, Institute of Biology François Jacob, Molecular Imaging Research Center (MIRCen)
    CNRS, CEA, Paris-Sud Univ., Paris-Saclay Univ., Neurodegenerative Diseases Laboratory (UMR9199))

  • Anselme L. Perrier

    (Inserm U861, I-STEM, AFM
    UEVE U861, I-STEM, AFM)

Abstract

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.

Suggested Citation

  • Romina Aron Badin & Aurore Bugi & Susannah Williams & Marta Vadori & Marie Michael & Caroline Jan & Alberto Nassi & Sophie Lecourtois & Antoine Blancher & Emanuele Cozzi & Philippe Hantraye & Anselme , 2019. "MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12324-0
    DOI: 10.1038/s41467-019-12324-0
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