<br>富含纤维蛋白的心脏细胞外基质水凝胶促进体外血管生成,ACS Biomaterials Science & Engineering

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富含纤维蛋白的心脏细胞外基质水凝胶促进体外血管生成
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2023-01-11 , DOI: 10.1021/acsbiomaterials.2c01148
Rubia Shaik ₁ , Jiazhu Xu ₂ , Yong Wang ₃ , Yi Hong ₂ , Ge Zhang ₁

Affiliation

血管生成对于心肌梗死后的心脏修复至关重要。促进血管生成已被证明是治疗心肌梗死的有效方法。已经探索了诱导心肌血管生成的几种不同策略，包括血管生成基因、蛋白质、microRNA、细胞和细胞外囊泡的外源递送。已经研究了各种类型的可注射水凝胶用于心脏组织修复。心脏再生中最有前途的可注射水凝胶之一是源自脱细胞猪心肌的心脏细胞外基质水凝胶。它可以通过经心内膜分娩进行微创输送。心脏细胞外基质水凝胶的安全性和有效性已在小型和大型动物心肌梗死模型以及临床试验中得到证明。心脏细胞外基质水凝胶治疗益处的主要机制已被阐明，并参与免疫反应的调节、与心力衰竭进展和纤维化相关的通路的下调、心肌收缩重要基因的上调以及增强心肌细胞与干细胞的分化和成熟。然而，尚无报道由心脏细胞外基质水凝胶诱导的有效毛细血管网络形成。在这项研究中，我们测试了将纤维蛋白基质掺入心脏细胞外基质水凝胶中以改善水凝胶血管生成特性的可行性。我们的体外结果表明，富含纤维蛋白的心脏细胞外基质水凝胶可以诱导人脐静脉内皮细胞形成稳健的内皮细胞管，并促进人间充质干细胞球体的发芽。从这项研究中获得的信息对于未来富含纤维蛋白的心脏细胞外基质水凝胶促进心肌血管生成的体内评估非常关键。

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Fibrin-Enriched Cardiac Extracellular Matrix Hydrogel Promotes In Vitro Angiogenesis

Angiogenesis is essential for cardiac repair after myocardial infarction. Promoting angiogenesis has been demonstrated as an effective approach for myocardial infarction treatment. Several different strategies for inducing myocardial angiogenesis have been explored, including exogenous delivery of angiogenic genes, proteins, microRNAs, cells, and extracellular vesicles. Various types of injectable hydrogels have been investigated for cardiac tissue repair. One of the most promising injectable hydrogels in cardiac regeneration is a cardiac extracellular matrix hydrogel that is derived from decellularized porcine myocardium. It can be delivered minimally invasively via transendocardial delivery. The safety and efficacy of cardiac extracellular matrix hydrogels have been shown in small and large animal myocardial infarction models as well as clinical trials. The main mechanisms underlying the therapeutic benefits of cardiac extracellular matrix hydrogels have been elucidated and involved in the modulation of the immune response, downregulation of pathways related to heart failure progression and fibrosis, upregulation of genes important for cardiac muscle contraction, and enhancing cardiomyocyte differentiation and maturation from stem cells. However, no potent capillary network formation induced by cardiac extracellular matrix hydrogels has been reported. In this study, we tested the feasibility of incorporating a fibrin matrix into cardiac extracellular matrix hydrogels to improve the angiogenic properties of the hydrogel. Our in vitro results demonstrate that fibrin-enriched cardiac extracellular matrix hydrogels can induce robust endothelial cell tube formation from human umbilical vein endothelial cells and promote the sprouting of human mesenchymal stem cell spheroids. The obtained information from this study is very critical toward the future in vivo evaluation of fibrin-enriched cardiac extracellular matrix hydrogels in promoting myocardial angiogenesis.

更新日期：2023-01-11

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