Extracellular vesicles from medicated plasma of Buyang Huanwu decoction-preconditioned neural stem cells accelerate neurological recovery following ischemic stroke

Jun Long; Chenyang Gu; Qiankun Zhang; Jiale Liu; Jiajun Huang; Yajing Li; Yifan Zhang; Rong Li; Waqas Ahmed; Jianfeng Zhang; Ahsan Ali Khan; Hengsen Cai; Yong Hu; Lukui Chen

doi:10.3389/fcell.2023.1096329

Extracellular vesicles from medicated plasma of Buyang Huanwu decoction-preconditioned neural stem cells accelerate neurological recovery following ischemic stroke

Front Cell Dev Biol. 2023 Mar 1:11:1096329. doi: 10.3389/fcell.2023.1096329. eCollection 2023.

Authors

Jun Long¹, Chenyang Gu¹, Qiankun Zhang¹, Jiale Liu¹, Jiajun Huang¹, Yajing Li², Yifan Zhang¹, Rong Li¹, Waqas Ahmed³, Jianfeng Zhang¹, Ahsan Ali Khan⁴, Hengsen Cai⁵, Yong Hu⁶, Lukui Chen¹

Affiliations

¹ Department of Neurosurgery, Neuroscience Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
² Affiliated Dongguan Hospital, Southern Medical University (Dongguan People's Hospital), Guangzhou, China.
³ Department of Neurology, Affiliated Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
⁴ Section of Neurosurgery, The Aga Khan University, Karachi, Pakistan.
⁵ Department of Neurosurgery, The Second People's Hospital of Pingnan, Pingnan, China.
⁶ Department of Orthopedics and Traumatology, The University of Hong Kong, Hongkong SAR, China.

Abstract

Introduction: The neurological impairment of survivors after ischemic stroke poses a serious risk to their quality of life and health. Effective therapeutic options are still lacking. Neural stem cells (NSCs) promote neurogenesis via secreted extracellular vesicles (NSC-EVs), which would be a potential therapeutic option, but the insufficient quantity of NSC-EVs in vivo restrains clinical application. Buyang Huanwu Decoction (BHD), a classic traditional Chinese medicine (TCM) decoction, is promising to alleviate neurological impairment after ischemic stroke. It was speculated that BHD might promote neurological recovery through the NSC-EVs. Methods: The medicated plasma of BHD (MP-BHD) was prepared to precondition NSCs and isolate EVs (BHD-NSC-EVs). Middle cerebral artery occlusion (MCAO) models and primary NSCs were administered to evaluate the therapeutic effect. Next-generation sequencing was performed to explore the mechanism. Results: The BHD-NSC-EVs more significantly accelerated neurological recovery after MCAO and promoted NSCs proliferation and differentiation than BHD and NSC-EVs alone. MP-BHD enhanced the largescale generation of BHD-NSC-EVs, which encapsulated functional miRNA and may play critical roles in neurogenesis. Discussion: In replacing BHD or NSCs, the preconditioned NSC-EVs present a more efficient therapeutic strategy for ischemic stroke. Based on the clinical efficacy of TCM, the preconditioning of NSC-derived EVs via the MP of TCM herbs would presents a newly promising therapeutic strategy for neurological diseases.

Keywords: Buyang Huanwu decoction; extracellular vesicles; ischemic stroke; medicated plasma; miRNAs profiles; neural stem cells; neurogenesis.

Grants and funding

This work was sponsored by National Key R&D Program of China (2022YFA1104900 and 2022YFA1104904), Natural Science Foundation of Guangdong Province (2021A1515010013), Department of Education of Guangdong Province (2021ZDZX2011), Traditional Chinese Medicine Bureau of Guangdong Province (20221275), Guangzhou Municipal Science and Technology Project (202201011760) and President Foundation of Integrated Hospital of Traditional Chinese Medicine of Southern Medical University (1202101003 and 1202103007).