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

Romina Aron Badin (1, 2) , Aurore Bugi (3) , Susannah Williams (1, 2) , Marta Vadori (4) , Marie Michael (3) , Caroline Jan (1, 2) , Alberto Nassi (5) , Sophie Lecourtois (1, 2) , Antoine Blancher (6) , Emanuele Cozzi (5, 4) , Philippe Hantraye (1, 2) , Anselme Perrier (3)

1 MIRCEN - Molecular Imaging Research Center [Fontenay-aux-Roses]
2 LMN - Laboratoire des Maladies Neurodégénératives - UMR 9199
3 I-STEM - Institut des cellules souches pour le traitement et l'étude des maladies monogéniques
4 CORIT - Consorzio per la Ricerca sul Trapianto d'Organ = Consortium for Research in Organ Transplantation
5 AOUP - Azienda Ospedale Università di Padova = Hospital-University of Padua
6 CPTP - Centre de Physiopathologie Toulouse Purpan

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.

Mots clés: Huntington's disease; Immune evasion; Induced pluripotent stem cells

Domaines: Sciences du Vivant [q-bio]; Immunologie

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, In press, 10, pp.4357. ⟨10.1038/s41467-019-12324-0⟩. ⟨cea-02997553⟩