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

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. Sentence Summary (250-300ch 2sentence one background one results) Matching iPSC donors' and patients' HLA haplotypes has been proposed as a way to generate cell therapy products with enhanced immunological compatibility. Here we show that MHC matching alone is insufficient to grant long-term survival of neuronal grafts in the lesioned brain of non-human primates.
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Submitted on : Tuesday, November 10, 2020 - 10:24:16 AM
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Romina Aron Badin, Aurore Bugi, Susannah Williams, Marta Vadori, Marie Michael, et al.. MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates. Nature Communications, Nature Publishing Group, 2019, 10, pp.4357. ⟨10.1038/s41467-019-12324-0⟩. ⟨cea-02997553⟩

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