Title : Extracellular vesicles derived from the medicated plasma of buyang huanwu decoction–preconditioned neural stem cells accelerate neurological impairment recovery following an ischemic stroke
Abstract:
The acquired neurological impairment of survivors following an ischemic stroke poses a serious risk to their quality of life and health. Due to the disadvantage of direct transplantation, the application of neural stem cell (NSC) transplantation is limited. These cells promote neurogenesis through secreted extracellular vesicles (NSC-EVs), which present an effective therapeutic option. However, the quantity of NSC-EVs in the adult brain is actually insufficient, which restrains their clinical application. Buyang Huanwu Decoction (BHD), a classic traditional Chinese decoction, is promising to alleviate neurological impairment following an ischemic stroke. It was speculated that BHD might promote the recovery of neurological function through the NSC-EVs. The medicated plasma of BHD (MP-BHD) was used to precondition NSCs and then the EVs (BHD-NSC-EVs) were isolated. Middle cerebral artery occlusion (MCAO) models were built and subsequently treated with phosphate-buffered saline (PBS)/BHD/NSC-EVs/BHD-NSC-EVs through intra-gastric administration or tail vein injection respectively. The effects were evaluated via animal ethology, imageology, and histology. The proliferation, differentiation, and migration of the NSCs were also determined in terms of different study groups. Next-generation sequencing (NGS) of micro ribonucleic acid (miRNA) profiles was performed to explore the mechanism behind the neurogenesis of NSCs induced by BHD-NSC-EVs. The BHD-NSC-EVs treatment accelerated the neurological recovery of the MCAO models and promoted NSC proliferation and differentiation, while more interestingly, the MP-BHD treatment promoted the large-scale generation of functional miRNA encapsulated in the BHD-NSC-EVs. The NGS revealed that miR-124-5p, miR-9a-5p, miR-137-5p, and miR-184 might play critical roles in the neurogenesis of NSCs induced by BHD-NSC-EVs. The effects of BHD-NSC-EVs were essentially more significant than those of BHD and NSC-EVs alone. In replacing BHD or NSCs, the preconditioned NSC-EVs present a more efficient strategy for ischemic stroke. The preconditioning of stem cells-derived EVs via the medicated plasma of Chinese herbs, based on the clinical efficacy of TCM, may present a newly promising therapeutic strategy for related diseases
