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MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates
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MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates
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MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates
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Journal Article
MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates
2019
Overview
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.
Matching iPSC donors’ and patients’ HLA haplotypes has been proposed as a way to generate cell therapy products with enhanced immunological compatibility. Here the authors show that MHC matching alone is insufficient to grant long-term survival of neuronal grafts in the lesioned brain of non-human primates.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/1
/ 14/63
/ 45/77
/ 59/57
/ 64/86
/ Animals
/ Antigens
/ Cell Differentiation - immunology
/ Cytotoxicity, Immunologic - immunology
/ Graft Rejection - immunology
/ Grafting
/ Grafts
/ Histocompatibility antigen HLA
/ Humanities and Social Sciences
/ Humans
/ Huntington Disease - immunology
/ Huntington Disease - therapy
/ Induced Pluripotent Stem Cells - cytology
/ Induced Pluripotent Stem Cells - immunology
/ Induced Pluripotent Stem Cells - transplantation
/ Inhibitory postsynaptic potentials
/ Major histocompatibility complex
/ Major Histocompatibility Complex - immunology
/ Matching
/ Neurons
/ Primates
/ Science
/ Survival
