MiR146a-loaded engineered exosomes released from silk fibroin patch promote diabetic wound healing by targeting IRAK1.
MiR146a-loaded engineered exosomes released from silk fibroin patch promote diabetic wound healing by targeting IRAK1.
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从丝素蛋白贴片释放的装载 MiR146a 的工程外泌体通过靶向 IRAK1 促进糖尿病伤口愈合
DOI：
10.1038/s41392-022-01263-w
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发表时间：
2023-02-13
影响因子：
39.3
通讯作者：
Zhang, Cuiping
中科院分区：
文献类型：
--
作者：
Li, Qiankun;Hu, Wenzhi;Huang, Qilin;Yang, Jie;Li, Bingmin;Ma, Kui;Wei, Qian;Wang, Yaxi;Su, Jianlong;Sun, Mengli;Cui, Shengnan;Yang, Rungong;Li, Haihong;Fu, Xiaobing;Zhang, Cuiping
无法治愈的糖尿病伤口需要借助更新、更有效的策略来解决。外泌体联合生物材料持续递送治疗剂有望为慢性伤口治疗带来新的希望。在这里，经过修饰的工程外泌体有效地装载miR146a并附着在丝素蛋白贴片（SFP）上，被证明可以促进糖尿病伤口愈合。通过噬菌体展示筛选丝素结合肽（SFBP），构建SFBP- glucu - ms2 （SGM）和pac-miR146a-pac融合蛋白。设计的外泌体（SGM- exos、miR146a-Exos和SGM-miR146a-Exos）是从经SGM或/和pac-miR146a-pac蛋白转导的工程胎盘间充质干细胞（PMSCs）中分离出来的。Gluc信号表明SGM-Exo@SFP显著提高了SGM-Exo的结合率和稳定性。此外，在SGM-miR146a-Exos中，miR146a的加载效率比在miR146a- exos中高出10倍。与未治疗组、仅sgm - mir146a - exo治疗组和仅sfp治疗组相比，SGM-miR146a-Exo@SFP驱动伤口愈合，炎症、胶原沉积和新生血管减少。转录组学分析表明SGM-miR146a-Exo@SFP治疗具有抗炎和再生作用。在这里，我们展示了用于再生医学和组织工程的高效exosome@biomaterial-based miRNA递送系统。
Unhealable diabetic wounds need to be addressed with the help of newer, more efficacious strategies. Exosomes combined with biomaterials for sustained delivery of therapeutic agents are expected to bring new hope for chronic wound treatment. Here, the engineered exosomes modified for efficiently loading miR146a and attaching to silk fibroin patch (SFP) were demonstrated to promote diabetic wound healing. Silk fibroin binding peptide (SFBP) was screened through phage display, and SFBP-Gluc-MS2 (SGM) and pac-miR146a-pac fusion protein were constructed. The designed exosomes (SGM-Exos, miR146a-Exos, and SGM-miR146a-Exos) were isolated from the engineered placental mesenchymal stem cells (PMSCs) transduced with SGM or/and pac-miR146a-pac protein. Gluc signals indicated SGM-Exo@SFP markedly increased the binding rate and the stability of SGM-Exo. Moreover, the loading efficiency of miR146a in SGM-miR146a-Exos was ten-fold higher than that in miR146a-Exos. Superior to untreated, SGM-miR146a-Exo-only treated, and SFP-only treated groups, SGM-miR146a-Exo@SFP drived wound healing associated with less inflammation, collagen deposition, and neovascularization. The transcriptomics analysis suggested anti-inflammatory and regenerative effects with SGM-miR146a-Exo@SFP treatment. Here, we show efficient exosome@biomaterial-based miRNA delivery systems for regenerative medicine and tissue engineering.
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影响因子：
16
作者：
Lötvall J;Hill AF;Hochberg F;Buzás EI;Di Vizio D;Gardiner C;Gho YS;Kurochkin IV;Mathivanan S;Quesenberry P;Sahoo S;Tahara H;Wauben MH;Witwer KW;Théry C
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通讯作者：
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影响因子：
16
作者：
Hu, Hongxing;Dong, Lanlan;Liu, Zhongtang
通讯作者：
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