再生(生物学)
纳米纤维
间充质干细胞
血管生成
体内
化学
MMP2型
组织工程
炎症
细胞生物学
细胞外基质
细胞
基质金属蛋白酶
癌症研究
免疫学
生物医学工程
材料科学
医学
纳米技术
下调和上调
生物化学
生物
生物技术
基因
作者
Yijie Zhou,Shuyun Liu,Meng Zhao,Chengshi Wang,Ling Li,Yujia Yuan,Lan Li,Guangneng Liao,William Bresette,Jie Zhang,Younan Chen,Jingqiu Cheng,Yanrong Lu,Jingping Liu
标识
DOI:10.1016/j.jconrel.2019.11.003
摘要
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown great potential for tissue repair, but their therapeutic capacity is limited by rapid clearance and short half-life. Herein, we purposed a hydrogel-based slow release strategy to enhance the therapeutic potency of EVs. A matrix metalloproteinase-2 (MMP2) sensitive self-assembling peptide (KMP2) hydrogel was used for the local delivery of MSC-EVs. The structure and controlled release properties of the KMP2 hydrogel were analyzed. The effects of the EV-loaded KMP2 hydrogel (KMP2-EVs) on cell apoptosis, inflammation and angiogenesis were evaluated in mice with renal ischemia-reperfusion (I/R) injury. In vitro, KMP2 formed a cross-linked nanofiber hydrogel to encapsulate MSC-EVs. KMP2 showed greater degradation and EV release in response to MMP2. The released EVs had similar structures and bioactivities as fresh, isolated EVs. In vivo, I/R mice treated with KMP2-EVs showed improved renal function by reducing tubular cell apoptosis, pro-inflammatory cytokine expression, and macrophage infiltration than mice receiving either EVs or KMP2. Moreover, KMP2-EVs showed better efficacy on promoting endothelial cell proliferation and angiogenesis than KMP2 or EVs alone, which subsequently decreased chronic renal fibrosis in I/R mice. This study highlighted that the EV-released KMP2 hydrogel is a promising cell-free therapy for tissue repair.
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