Incorporation of small extracellular vesicles in sodium alginate hydrogel as a novel therapeutic strategy for myocardial infarction
Incorporation of small extracellular vesicles in sodium alginate hydrogel as a novel therapeutic strategy for myocardial infarction
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DOI：
10.7150/thno.32637
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发表时间：
2019-01-01
期刊：
影响因子：
12.4
通讯作者：
Hu, Xinyang
中科院分区：
文献类型：
--
作者：
Lv, Kaiqi;Li, Qingju;Hu, Xinyang
骨髓间充质干细胞（MSC）衍生的细胞外小泡（sEVs）已被广泛用于治疗心肌梗死（MI）。然而，低保留和短暂的治疗效果仍然是重大挑战。本研究旨在确定是否MSC衍生的sEVs在海藻酸钠水凝胶中的掺入增加了它们在心脏中的保留，从而提高治疗效果。方法：最佳的海藻酸钠水凝胶掺入sEVs系统，通过其sEVs的释放能力和水凝胶的流变性来确定。利用离体荧光成像来评估sEV在心脏中的保留。通过免疫荧光染色分析免疫调节和sEV对血管生成的影响。超声心动图和Masson三色染色用于估计心脏功能和梗死size.Results：交付的sEVs纳入藻酸盐水凝胶（sEVs-Gel）增强其在心脏中的保留。与sEVs单独治疗（sEVs）相比，sEVs-Gel治疗显著减少心肌细胞凋亡，并促进MI后第3天巨噬细胞的极化。sEVs-Gel治疗还增加了梗塞后四周的瘢痕厚度和血管生成。心脏功能和梗死面积的测量显着更好的sEVs-Gel组比sEVsONLY.CONCLUSION：交付的sEVs纳入藻酸盐水凝胶提供了一种新的方法，无细胞治疗和优化的sEVs心肌梗死的治疗效果。
Bone marrow mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) have been widely used for treating myocardial infarction (MI). However, low retention and short-lived therapeutic effects are still significant challenges. This study aimed to determine whether incorporation of MSC-derived sEVs in alginate hydrogel increases their retention in the heart thereby improving therapeutic effects.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.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.