Cardiovascular research has considerably benefited from in vitro models of cardiac tissue. Two important elements of these constructs, cardiac cells and the extracellular matrix (ECM), play essential roles that mimic the structural and functional aspects of myocardium. Here, we compared decellularized ECM from cardiac muscle (D‐CM), skeletal muscle (D‐SM), aorta (D‐Ao), liver (D‐Liv), small intestine submucosa (D‐SIS), and human umbilical cord (D‐hUC) in terms of their biocompatibility and potential for differentiation of human embryonic stem cell‐derived cardiac progenitor cells (hESC‐derived CPCs) to cardiovascular lineage cells. The decellularization procedure successfully removed resident cells of the tissues but preserved ECM components such as laminin and fibronectin, which was identified by histological studies of decellularized tissue (D‐tissues) and immunostaining. Encapsulation of hESC‐derived CPCs and human umbilical vein endothelial cells within hydrogels that were obtained from all decellularized tissues did not induce cytotoxicity after 10 days of culture. Upregulation of cardiac specific genes, cTNT and αMHC, as well as the presence of cTNT⁺ cardiomyocytes were also observed in CPCs cultured on D‐CM, D‐SM, D‐Liv, and D‐SIS, which showed their support for cardiogenic differentiation. However, D‐CM provided substantially higher expression of cardiac markers compared to the other D‐tissues. The endothelial and smooth muscle specific genes, CD31 and PDGFRα, were upregulated in cells cultured on D‐Ao and D‐hUC, which reflected their support for vascular lineage cell differentiation. In conclusion, it might be imperative to use decellularized tissue of muscle origins in combination with naturally derived vascular tissues to generate in vitro vascularized human cardiac microtissues.

中文翻译：

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脱细胞肌肉衍生的水凝胶支持体外心脏微组织制造。

心血管研究从心脏组织的体外模型中获益匪浅。这些构建体的两个重要元素，心肌细胞和细胞外基质 (ECM)，在模拟心肌的结构和功能方面发挥着重要作用。在这里，我们比较了来自心肌 (D-CM)、骨骼肌 (D-SM)、主动脉 (D-Ao)、肝脏 (D-Liv)、小肠粘膜下层 (D-SIS) 和人脐带的脱细胞 ECM (D-hUC) 的生物相容性和将人胚胎干细胞衍生的心脏祖细胞（hESC 衍生的 CPC）分化为心血管谱系细胞的潜力。去细胞程序成功地去除了组织的常驻细胞，但保留了 ECM 成分，如层粘连蛋白和纤连蛋白，这是通过脱细胞组织（D-组织）和免疫染色的组织学研究确定的。将 hESC 衍生的 CPC 和人脐静脉内皮细胞封装在从所有脱细胞组织中获得的水凝胶中，在培养 10 天后不会引起细胞毒性。心脏特定基因的上调，在 D-CM、D-SM、D-Liv 和 D-SIS 上培养的 CPC 中也观察到cTNT和αMHC以及 cTNT ⁺心肌细胞的存在，这表明它们支持心源性分化。然而，与其他 D-组织相比，D-CM 提供了显着更高的心脏标志物表达。的内皮细胞和平滑肌特异基因，CD31和PDGFRα，在d-鳌和d-HUC培养的细胞，这反映了他们的血管谱系细胞分化的支持被上调。总之，将肌肉来源的脱细胞组织与天然来源的血管组织结合使用以产生体外血管化的人心脏微组织可能是必要的。