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Research Article

Biological nano agent produced by hypoxic preconditioning stem cell for stroke treatment

Xin-Chi Jiang1,2,§, Hong-Hui Wu1,§, Tianyuan Zhang1,2,§, Yun-Fei Dong1, Yao-Sheng Li1, Ting Huang1, An-Hao Tian3, Peng-Xiang Chen3, Xian-Ming Lin4, Ying-Zhi Huang5, Chong Liu3, Xiang-Nan Zhang6, Zhong Chen6, Yasuhiko Tabata7, Jian-Qing Gao1,2( )
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, China
Department of Pathology and Pathophysiology and Department of Neurosurgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310058, China
SinoCell Biotechnology Ltd., Ningbo 315000, China
Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Laboratory of Biomaterials, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8501, Japan

§ Xin-Chi Jiang, Hong-Hui Wu, and Tianyuan Zhang contributed equally to this work.

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Graphical Abstract

Hypoxic preconditioning neural stem cell can produce effective biological nano-agent, which significantly changed the therapeutic miRNA encapsulated in exosomes and achieved high therapeutic efficiency on middle cerebral artery occlusion mice.

Abstract

Exosomes make a significant contribution during stem cell-based therapy due to the abundant contents. Accumulating evidence implies exosomes can act as potential biological nano agents. We herein propose hypoxic preconditioning for neural stem cells (NSCs) that could produce hypoxic exosomes for efficient treatment of ischemic stroke. Hypoxic preconditioning on NSCs significantly altered the miRNAs encapsulated in exosomes. Notably, hypoxic exosomes could target the injured brain to regulate the microenvironment to inhibit neuroinflammation and promote blood–brain barrier permeability recovery. Additionally, the autologous NSCs in Nestin-CreER mice could be activated by hypoxic exosomes to facilitate nerve regeneration. After hypoxic preconditioning, exosomes further exerted therapeutic effects on both survival (25%) and behavioral outcomes in ischemic stroke mice. Overall, hypoxic preconditioning NSCs can produce effective nano agent and may represent a promising strategy for clinical neurorestorative therapy.

Keywords

exosomeshypoxia-preconditioningstem cellsischemic strokemicroenvironment

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Nano Research
Volume 16 Issue 5,
May 2023
Pages 7413-7421
DOI: 10.1007/s12274-023-5470-z
Cite this article:
Jiang X-C, Wu H-H, Zhang T, et al. Biological nano agent produced by hypoxic preconditioning stem cell for stroke treatment. Nano Research, 2023, 16(5): 7413-7421. https://doi.org/10.1007/s12274-023-5470-z
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Received: 04 November 2022
Revised: 25 December 2022
Accepted: 01 January 2023
Published: 27 February 2023
© Tsinghua University Press 2023
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