Incorporation of small extracellular vesicles in sodium alginate hydrogel as a novel therapeutic strategy for myocardial infarction

海藻酸钠水凝胶中加入小细胞外囊泡作为心肌梗死的新治疗策略

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作者:Kaiqi Lv, Qingju Li, Ling Zhang, Yingchao Wang, Zhiwei Zhong, Jing Zhao, Xiaoxiao Lin, Jingyi Wang, Keyang Zhu, Changchen Xiao, Changle Ke, Shuhan Zhong, Xianpeng Wu, Jinghai Chen, Hong Yu, Wei Zhu, Xiang Li, Ben Wang, Ruikang Tang, Jian'an Wang, Jinyu Huang, Xinyang Hu

Conclusion

Delivery of sEVs incorporated in alginate hydrogel provides a novel approach of cell-free therapy and optimizes the therapeutic effect of sEVs for MI.

Methods

The optimal sodium alginate hydrogel incorporating sEVs system was determined by its release ability of sEVs and rheology of hydrogel. Ex vivo fluorescence imaging was utilized to evaluate the retention of sEVs in the heart. Immunoregulation and effects of sEVs on angiogenesis were analyzed by immunofluorescence staining. Echocardiography and Masson's trichrome staining were used to estimate cardiac function and infarct size.

Results

The delivery of sEVs incorporated in alginate hydrogel (sEVs-Gel) enhanced their retention in the heart. Compared with sEVs only treatment (sEVs), sEVs-Gel treatment significantly decreased cardiac cell apoptosis and promoted the polarization of macrophages at day 3 after MI. sEVs-Gel treatment also increased scar thickness and angiogenesis at four weeks post-infarction. Measurement of cardiac function and infarct size were significantly better in the sEVs-Gel group than in the group treated with sEVs only.

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