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

神经干细胞衍生的外泌体负载粘性水凝胶控释促进缺血性中风的脑血管生成和神经功能

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作者:Chenyang Gu, Yajing Li, Jiale Liu, Sitian Liu, Jun Long, Qiankun Zhang, Wenjie Duan, Tingle Feng, Jiajun Huang, Yunhui Qiu, Waqas Ahmed, Hengsen Cai, Yong Hu, Yaobin Wu, Lukui Chen

Conclusion

NSCs derived exosomes-loaded adhesive HAD hydrogel controlled-release could promote cerebral angiogenesis and neurological function for ischemic stroke.

Methods

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.

Objective

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.

Results

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.

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