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首页> 外文期刊>Biomaterials Science >Microenvironmental determinants of organized iPSC-cardiomyocyte tissues on synthetic fibrous matrices
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Microenvironmental determinants of organized iPSC-cardiomyocyte tissues on synthetic fibrous matrices

机译：合成纤维基质组织IPSC - 心肌细胞组织的微环境确定性

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Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) show great potential for engineering myocardium to study cardiac disease and create regenerative therapies. However, iPSC-CMs typically possess a late embryonic stage phenotype, with cells failing to exhibit markers of mature adult tissue. This is due in part to insufficient knowledge and control of microenvironmental cues required to facilitate the organization and maturation of iPSC-CMs. Here, we employed a cell-adhesive, mechanically tunable synthetic fibrous extracellular matrix (ECM) consisting of electrospun dextran vinyl sulfone (DVS) fibers and examined how biochemical, architectural, and mechanical properties of the ECM impact iPSC-CM tissue assembly and subsequent function. Exploring a multidimensional parameter space spanning cell-adhesive ligand, seeding density, fiber alignment, and stiffness, we found that fibronectin-functionalized DVS matrices composed of highly aligned fibers with low stiffness optimally promoted the organization of functional iPSC-CM tissues. Tissues generated on these matrices demonstrated improved calcium handling and increased end-to-end localization of N-cadherin as compared to micropatterned fibronectin lines or fibronectin-coated glass. Furthermore, DVS matrices supported long-term culture (45 days) of iPSC-CMs; N-cadherin end-to-end localization and connexin43 expression both increased as a function of time in culture. In sum, these findings demonstrate the importance of recapitulating the fibrous myocardial ECM in engineering structurally organized and functional iPSC-CM tissues.
机译：源自诱导多能干细胞（IPSC-CMS）的心肌细胞显示出工程心肌的巨大潜力，以研究心脏病并产生再生疗法。然而，IPSC-CM通常具有晚期胚胎阶段表型，细胞未能出现成熟成人组织的标记。这部分是由于知识和控制促进IPSC-CMS组织和成熟所需的微环境提示的知识和控制。在这里，我们使用由Electur纺Dextran乙烯基砜（DVS）纤维组成的细胞粘合剂，机械可调谐合成纤维细胞外基质（ECM），并检查了ECM冲击IPSC-CM组织组件和随后的功能的生物化学，建筑和力学性能。 。探索多维参数空间跨越细胞粘性配体，播种密度，纤维排列和刚度，我们发现由具有低刚度的高度对准纤维组成的纤维凝集素官能化DVS矩阵最佳地促进了功能性IPSC-CM组织的组织。与微明坦的纤维连接蛋白系或纤维连接蛋白涂覆的玻璃相比，在这些基质上产生的组织显示出改善的钙处理和N-Cadherin的端到端定位。此外，DVS矩阵支持的IPSC-CMS的长期培养（45天）; N-Cadherin端到端定位和Connexin43表达既增加培养时间的时间。总而言之，这些研究结果证明了在结构组织和功能性IPSC-CM组织中重新携带纤维心肌ECM的重要性。

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