Neural stem cell-derived exosomes-loaded adhesive hydrogel controlled-release promotes cerebral angiogenesis and neurological function in ischemic stroke

• Published in: Experimental neurology 2023-12, Vol.370, p.114547-114547, Article 114547
• Main Authors: Gu, Chenyang, Li, Yajing, Liu, Jiale, Liu, Sitian, Long, Jun, Zhang, Qiankun, Duan, Wenjie, Feng, Tingle, Huang, Jiajun, Qiu, Yunhui, Ahmed, Waqas, Cai, Hengsen, Hu, Yong, Wu, Yaobin, Chen, Lukui
• Format: Article
• Language: English
• Subjects: Adhesive hydrogel; Angiogenesis; Controlled-release; Exosome; Ischemic stroke; Neural stem cell
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2023.114547

Ischemic stroke has become one of the leading diseases for international death, which brings burden to the economy and society. Exosomes (Exos) derived following neural stem cells (NSCs) stimulation promote neurogenesis and migration of NSCs. However, Exos themselves are easily to be removed in vivo. Our study is to investigate whether adhesive hyaluronic acid (HAD) hydrogel loading NSCs-derived-Exo (HAD-Exo) would promote the recovery of ischemic stroke. A mouse model of middle cerebral artery occlusion (MCAO) was established. PBS, Exo, HAD, and HAD-Exo groups were independently stereotactically injected in mice, respectively. The modified neurological severity score scale and behaviour tests were used to evaluate neurological improvement. Neuroimagings were used to observe the improvement of cerebral infarct volume and vessels. Immunofluorescence staining was used to verify the expression of vascular and cell proliferation-related proteins. The structural and mechanical property of HAD and HAD-Exo were detected. Behavioral results showed that HAD-Exo significantly improved neurological functions, especially motor function. Neuroimagings showed that HAD-Exo significantly promoted infarct volume and angiogenesis. Immunofluorescence staining showed that HAD-Exo significantly promoted the cerebral angiogenesis and anti-inflammation. NSCs derived exosomes-loaded adhesive HAD hydrogel controlled-release could promote cerebral angiogenesis and neurological function for ischemic stroke. •Catechol-grafted hyaluronic acid (HAD), as a delivery scaffold is suitable for releasing exosomes continuously at the ischemic area of ischemic stroke.•The HAD-Exo complex maintained the biological activity of exosomes, enhanced angiogenesis, and improved neurological function.•The topically injected HAD-Exo complex provided a promising strategy for clinical translation of ischemic stroke.