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Stereotactically intracerebral transplantation of neural stem cells for ischemic stroke attenuated inflammatory responses and promoted neurogenesis: an experimental study with monkeys

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机构： [1]Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. [2]Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. [3]Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. [4]Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. [5]Department of Orthopaedics, Peking University First Hospital, Beijing 100034, China. [6]School of Medicine, Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen 518172, Guangdong, China. [7]State Key Laboratory of Common Mechanism Research for Major Diseases, Beijing 100005, China.

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Ischemic stroke is a common neurovascular disorder with high morbidity and mortality. However, the underlying mechanism of stereotactically intracerebral transplantation of human neural stem cell (hNSC) is not well elucidated.Four days after ischemic stroke induced by Rose Bengal photo-thrombosis, 7 cynomolgus monkeys were transplanted with hNSCs or vehicles stereotactically and followed up for 84 days. Behavioral assessments, magnetic resonance imaging, blood tests, and pathological analysis were performed before and after treatment. The proteome profiles of the left and right precentral gyrus and hippocampus were evaluated. Extracellular vesicle micro-RNA (miRNA) from the peripheral blood was extracted and analyzed.hNSC transplantation reduced the remaining infarcted lesion volume of cynomolgus monkeys with ischemic stroke without remarkable side effects. Proteomic analyses indicated that hNSC transplantation promoted GABAergic and glutamatergic neurogenesis, and restored the mitochondrial electron transport chain function in the ischemic infarcted left precentral gyrus or hippocampus. Immunohistochemical staining and qRT-PCT confirmed the promoting effects on neurogenesis and revealed that hNSCs attenuated post-infarct inflammatory responses by suppressing resident glia activation and mediating peripheral immune cell infiltration. Consistently, miRNA-sequencing revealed the miRNAs which were related to these pathways were down-regulated after hNSC transplantation.This study indicates that hNSCs can be effectively and safely used to treat ischemic stroke by promoting neurogenesis, regulating post-infarct inflammatory responses, and restoring mitochondrial function in both the infarct region and hippocampus.Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

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出版当年[2023]版：

大类 | 2 区医学

小类 | 2 区外科

最新[2023]版：

大类 | 2 区医学

小类 | 2 区外科

第一作者：

第一作者机构： [1]Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. [2]Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.

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通讯机构： [1]Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. [7]State Key Laboratory of Common Mechanism Research for Major Diseases, Beijing 100005, China.

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