The long-term survival and functional maturation of human iNPC-derived neurons in the basal forebrain of cynomolgus monkeys

Abstract

Human induced neural stem/progenitor cells (iNPCs) are a promising source of cells for stem cell-based therapy. The therapeutic potential of human iNPCs has been extensively tested in animal models, including both mouse and monkey models. However, the comprehensive characterization of grafted iNPCs in the brain of non-human primates has been lagged behind. In this study, we transplanted human iNPCs into the basal forebrain of adult cynomolgus monkeys. We found that grafted iNPCs predominantly differentiated into neurons that displayed long-term survival up to 12 months. Additionally, iNPC-derived human neurons gradually matured in term of morphology and subtype differentiation. More excitingly, we observed that human neurons displayed electrophysiological activities resembling those of mature neurons, indicating the acquisition of functional membrane properties. Collectively, this study systematically characterized human iNPCs in the brain of non-human primates, and will provide invaluable clues for developing safe and effective stem cell-based therapies for different brain disorders.

Keywords

non-human primatess / cerebral cell transplantation / human induced neural stem/progenitor cells / neuronal differentiation / functional maturation

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2022 The Author(s) 2022. Published by Oxford University Press on behalf of Higher Education Press.