HIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction

Aims: 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. Methods and...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Qingjie Wang, Le Zhang, Zhiqin Sun, Boyu Chi, Ailin Zou, Lipeng Mao, Xu Xiong, JianGuang Jiang, Ling Sun, Wenwu Zhu, Yuan Ji
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Hypoxia inducible factor-1α Extracellular Vesicles Mesenchymal stem cells myocardial infarction Medicine (General) R5-920 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5bea22ab8ba9433c8cb453b9ae8fad67
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5bea22ab8ba9433c8cb453b9ae8fad67
record_format	dspace
spelling	oai:doaj.org-article:5bea22ab8ba9433c8cb453b9ae8fad672021-12-02T05:03:33ZHIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction2590-006410.1016/j.mtbio.2021.100171https://doaj.org/article/5bea22ab8ba9433c8cb453b9ae8fad672021-09-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S259000642100079Xhttps://doaj.org/toc/2590-0064Aims: 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. Methods and results: 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. Conclusion: 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.Qingjie WangLe ZhangZhiqin SunBoyu ChiAilin ZouLipeng MaoXu XiongJianGuang JiangLing SunWenwu ZhuYuan JiElsevierarticleHypoxia inducible factor-1αExtracellular VesiclesMesenchymal stem cellsmyocardial infarctionMedicine (General)R5-920Biology (General)QH301-705.5ENMaterials Today Bio, Vol 12, Iss , Pp 100171- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hypoxia inducible factor-1α Extracellular Vesicles Mesenchymal stem cells myocardial infarction Medicine (General) R5-920 Biology (General) QH301-705.5
spellingShingle	Hypoxia inducible factor-1α Extracellular Vesicles Mesenchymal stem cells myocardial infarction Medicine (General) R5-920 Biology (General) QH301-705.5 Qingjie Wang Le Zhang Zhiqin Sun Boyu Chi Ailin Zou Lipeng Mao Xu Xiong JianGuang Jiang Ling Sun Wenwu Zhu Yuan Ji HIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction
description	Aims: 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. Methods and results: 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. Conclusion: 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.
format	article
author	Qingjie Wang Le Zhang Zhiqin Sun Boyu Chi Ailin Zou Lipeng Mao Xu Xiong JianGuang Jiang Ling Sun Wenwu Zhu Yuan Ji
author_facet	Qingjie Wang Le Zhang Zhiqin Sun Boyu Chi Ailin Zou Lipeng Mao Xu Xiong JianGuang Jiang Ling Sun Wenwu Zhu Yuan Ji
author_sort	Qingjie Wang
title	HIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction
title_short	HIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction
title_full	HIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction
title_fullStr	HIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction
title_full_unstemmed	HIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction
title_sort	hif-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (rgd) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/5bea22ab8ba9433c8cb453b9ae8fad67
work_keys_str_mv	AT qingjiewang hif1aoverexpressioninmesenchymalstemcellderivedexosomeencapsulatedarginineglycineaspartatergdhydrogelsboosttherapeuticefficacyofcardiacrepairaftermyocardialinfarction AT lezhang hif1aoverexpressioninmesenchymalstemcellderivedexosomeencapsulatedarginineglycineaspartatergdhydrogelsboosttherapeuticefficacyofcardiacrepairaftermyocardialinfarction AT zhiqinsun hif1aoverexpressioninmesenchymalstemcellderivedexosomeencapsulatedarginineglycineaspartatergdhydrogelsboosttherapeuticefficacyofcardiacrepairaftermyocardialinfarction AT boyuchi hif1aoverexpressioninmesenchymalstemcellderivedexosomeencapsulatedarginineglycineaspartatergdhydrogelsboosttherapeuticefficacyofcardiacrepairaftermyocardialinfarction AT ailinzou hif1aoverexpressioninmesenchymalstemcellderivedexosomeencapsulatedarginineglycineaspartatergdhydrogelsboosttherapeuticefficacyofcardiacrepairaftermyocardialinfarction AT lipengmao hif1aoverexpressioninmesenchymalstemcellderivedexosomeencapsulatedarginineglycineaspartatergdhydrogelsboosttherapeuticefficacyofcardiacrepairaftermyocardialinfarction AT xuxiong hif1aoverexpressioninmesenchymalstemcellderivedexosomeencapsulatedarginineglycineaspartatergdhydrogelsboosttherapeuticefficacyofcardiacrepairaftermyocardialinfarction AT jianguangjiang hif1aoverexpressioninmesenchymalstemcellderivedexosomeencapsulatedarginineglycineaspartatergdhydrogelsboosttherapeuticefficacyofcardiacrepairaftermyocardialinfarction AT lingsun hif1aoverexpressioninmesenchymalstemcellderivedexosomeencapsulatedarginineglycineaspartatergdhydrogelsboosttherapeuticefficacyofcardiacrepairaftermyocardialinfarction AT wenwuzhu hif1aoverexpressioninmesenchymalstemcellderivedexosomeencapsulatedarginineglycineaspartatergdhydrogelsboosttherapeuticefficacyofcardiacrepairaftermyocardialinfarction AT yuanji hif1aoverexpressioninmesenchymalstemcellderivedexosomeencapsulatedarginineglycineaspartatergdhydrogelsboosttherapeuticefficacyofcardiacrepairaftermyocardialinfarction
_version_	1718400652011372544

HIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction

Ejemplares similares