HIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction.
HIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction.
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HIF-1α 在间充质干细胞衍生的外泌体封装的精氨酸-甘氨酸-天冬氨酸 (RGD) 水凝胶中过度表达可提高心肌梗死后心脏修复的治疗效果
DOI：
10.1016/j.mtbio.2021.100171
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Ji Y
中科院分区：
文献类型：
--
作者：
Wang Q;Zhang L;Sun Z;Chi B;Zou A;Mao L;Xiong X;Jiang J;Sun L;Zhu W;Ji Y
天然分泌的细胞外囊泡（EV）在干细胞介导的心脏保护中发挥重要作用。本研究旨在探讨低氧诱导因子-1 α（HIF-1α）工程化间充质干细胞（MSCs）诱导的血管内皮细胞（EVs）对大鼠急性心肌梗死（AMI）的保护作用及其机制。制备从HIF-1α工程化的MSC（HIF-1α-EVs）和对照MSC（NC-EVs）分离的EVs。在体外实验中，将EV与暴露于缺氧和血清剥夺（H/SD）的心肌细胞和内皮细胞一起孵育;在体内实验中，将EV注射到Sprague-Dawley大鼠的急性梗死心脏中。与NC-EVs相比，HIF-1α-EVs能显著抑制心肌细胞凋亡，促进内皮细胞血管生成，同时能显著缩小梗死大鼠的纤维化面积，增强心功能。经EVs/RGD-生物素水凝胶处理后，我们观察到HIF-1α-EVs在大鼠中的保留时间更长，稳定性更高，心脏功能更强。实时荧光定量PCR（qRT-PCR）结果显示，miRNA-221- 3 p在HIF-1α-EVs中高表达。在HIF-1α-EVs中抑制miR-221- 3 p后，HIF-1α EVs对凋亡和血管生成的生物学效应减弱。HIF-1α过表达的MSCs释放的EVs可通过上调miR-221- 3 p的表达促进内皮细胞血管生成和心肌细胞凋亡。RGD水凝胶可增强HIF-1α工程化MSC衍生EV的治疗功效。
Naturally secreted extracellular vesicles (EVs) play important roles in stem-mediated cardioprotection. This study aimed to investigate the cardioprotective function and underlying mechanisms of EVs derived from HIF-1α engineered mesenchymal stem cells (MSCs) in a rat model of AMI. EVs isolated from HIF-1α engineered MSCs (HIF-1α-EVs) and control MSCs (NC-EVs) were prepared. In in vitro experiments, the EVs were incubated with cardiomyocytes and endothelial cells exposed to hypoxia and serum deprivation (H/SD); in in vivo experiments, the EVs were injected in the acutely infarcted hearts of Sprague-Dawley rats. Compared with NC-EVs, HIF-1α-EVs significantly inhibited the apoptosis of cardiomyocytes and enhanced angiogenesis of endothelial cells; meanwhile, HIF-1α-EVs also significantly shrunk fibrotic area and strengthened cardiac function in infarcted rats. After treatment with EVs/RGD-biotin hydrogels, we observed longer retention, higher stability in HIF-1α-EVs, and stronger cardiac function in the rats. Quantitative real-time PCR (qRT-PCR) displayed that miRNA-221–3p was highly expressed in HIF-1α-EVs. After miR-221–3p was inhibited in HIF-1α-EVs, the biological effects of HIF-1α EVs on apoptosis and angiogenesis were attenuated. EVs released by MSCs with HIF-1α overexpression can promote the angiogenesis of endothelial cells and the apoptosis of cardiomyocytes via upregulating the expression of miR-221–3p. RGD hydrogels can enhance the therapeutic efficacy of HIF-1α engineered MSCs-derived EVs.
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影响因子：
20.1
作者：
Campostrini G;Windt LM;van Meer BJ;Bellin M;Mummery CL
通讯作者：
Mummery CL
影响因子：
6.1
作者：
Dokhanchi，Maryam;Pakravan，Katayoon;Babashah，Sadegh
通讯作者：
Babashah，Sadegh
影响因子：
5.2
作者：
Bhuniya, S;Park, SM;Kim, BH
通讯作者：
Kim, BH
影响因子：
6
作者：
Kang T;Jones TM;Naddell C;Bacanamwo M;Calvert JW;Thompson WE;Bond VC;Chen YE;Liu D
通讯作者：
Liu D
影响因子：
37.8
作者：
Liu, Yiwei;Luo, Qipeng;Zhang, Hao
通讯作者：
Zhang, Hao