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
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.