Resveratrol promotes the survival and neuronal differentiation of hypoxia-conditioned neuronal progenitor cells in rats
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RESEARCH ARTICLE
Resveratrol promotes the survival and neuronal differentiation of hypoxia-conditioned neuronal progenitor cells in rats with cerebral ischemia Yao Yao1, Rui Zhou1, Rui Bai2, Jing Wang1, Mengjiao Tu1, Jingjing Shi1, Xiao He1, Jinyun Zhou1, Liu Feng1, Yuanxue Gao1, Fahuan Song1, Feng Lan2, Xingguo Liu4, Mei Tian (
✉)1, Hong Zhang (✉)1,3,5,6
1 Department of Nuclear Medicine and PET-CT Center, The Second Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; 2Beijing Laboratory for Cardiovascular Precision Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; 3Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou 310027, China; 4Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; 5Shanxi Medical University, Taiyuan 030001, China; 6The College of Biomedical Engineering and Instrument Science of Zhejiang University, Hangzhou 310027, China
© Higher Education Press 2020
Abstract Hypoxia conditioning could increase the survival of transplanted neuronal progenitor cells (NPCs) in rats with cerebral ischemia but could also hinder neuronal differentiation partly by suppressing mitochondrial metabolism. In this work, the mitochondrial metabolism of hypoxia-conditioned NPCs (hcNPCs) was upregulated via the additional administration of resveratrol, an herbal compound, to resolve the limitation of hypoxia conditioning on neuronal differentiation. Resveratrol was first applied during the in vitro neuronal differentiation of hcNPCs and concurrently promoted the differentiation, synaptogenesis, and functional development of neurons derived from hcNPCs and restored the mitochondrial metabolism. Furthermore, this herbal compound was used as an adjuvant during hcNPC transplantation in a photothrombotic stroke rat model. Resveratrol promoted neuronal differentiation and increased the long-term survival of transplanted hcNPCs. 18-fluorine fluorodeoxyglucose positron emission tomography and rotarod test showed that resveratrol and hcNPC transplantation synergistically improved the neurological and metabolic recovery of stroke rats. In conclusion, resveratrol promoted the neuronal differentiation and therapeutic efficiency of hcNPCs in stroke rats via restoring mitochondrial metabolism. This work suggested a novel approach to promote the clinical translation of NPC transplantation therapy. Keywords neuronal progenitor cells; resveratrol; cerebral ischemia; neuronal differentiation; mitochondrial metabolism; positron emission tomography
Introduction Cerebral ischemia (i.e., stroke) is one of the leading causes of disability worldwide [1] and is characterized as neuronal cell loss and neuronal tissue damage due to the lack of blood flow [2]. Owing to the poor regenerative ability of the adult brain, stroke induced neuronal cell or tissue loss is permanent and results in long-term neurological dysfunction [3]. Therefo
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