Resveratrol promotes the survival and neuronal differentiation of hypoxia-conditioned neuronal progenitor cells in rats with cerebral ischemia

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

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Acknowledgements

We thank Wei Yin from the Core Facilities, Zhejiang University School of Medicine for the technological support of fluorescence imaging. This study was sponsored by the National Key Research and Development Program of China (No. 2016YFA0100900), National Natural Science Foundation of China (NSFC) (Nos. 81761148029, 81725009, 81900255, and 82030049), the Fund for Shanxi “1331 Project” Key Innovative Research Team.

Compliance with ethics guidelines

Yao Yao, Rui Zhou, Rui Bai, Jing Wang, Mengjiao Tu, Jingjing Shi, Xiao He, Jinyun Zhou, Liu Feng, Yuanxue Gao, Fahuan Song, Feng Lan, Xingguo Liu, Mei Tian, and Hong Zhang declare that they have no conflicts of interests associated with this study. All animal protocols were approved by the Institutional Animal Care and Use Committee at Zhejiang University School of Medicine.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-021-0832-y and is accessible for authorized users.

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