Kc Pawan, Shah Mickey, Shaik Rubia, Hong Yi, Zhang Ge
Department of Biomedical Engineering, The University of Akron, Akron, Ohio 44325, United States.
Department of Integrated Bioscience, The University of Akron, Akron, Ohio 44325, United States.
ACS Biomater Sci Eng. 2020 Dec 14;6(12):6808-6818. doi: 10.1021/acsbiomaterials.0c00788. Epub 2020 Nov 4.
Cell sheet technology has demonstrated great promise in delivering a large amount of therapeutic cells for tissue repair, including in the myocardium. However, the lack of host integration remains one of the key challenges in using cell sheets for cardiac repair. Paracrine factors secreted by mesenchymal stem cells (MSCs) have been reported to facilitate tissue repair and regeneration in a variety of ways. It has been demonstrated that paracrine factors from MSCs could enhance scaffold recellularization and vascularization. In this study, we used an in vitro cardiac matrix mimic platform to examine the effects of hMSCs preseeding on the interactions between cell sheets and cardiac matrix. The fabricated human induced pluripotent stem cells-derived cardiomyocyte sheets were attached to a decellularized porcine myocardium slice with or without preseeding of hMSCs. The hMSCs preseeding significantly enhanced the interactions between cardiomyocyte sheets and cardiac matrix in terms of cell migration distance, cell distribution, and mature vascular and cardiomyocyte marker expressions in the matrix. Growth factor and matrix metalloproteinases array analysis suggested that hMSCs- induced vascularization and MMPs regulation are the two possible mechanisms that lead to the improved CMs and cardiac matrix interactions. Further examination of these two mechanisms will enable the development of new approaches to facilitate transplanted cells for tissue repair.
细胞片技术在为组织修复提供大量治疗性细胞方面已展现出巨大潜力，包括在心肌修复中。然而，缺乏与宿主的整合仍然是使用细胞片进行心脏修复的关键挑战之一。据报道，间充质干细胞（MSCs）分泌的旁分泌因子能够以多种方式促进组织修复和再生。已证实，MSCs的旁分泌因子可增强支架的再细胞化和血管化。在本研究中，我们使用体外心脏基质模拟平台来研究人骨髓间充质干细胞（hMSCs）预接种对细胞片与心脏基质之间相互作用的影响。将制备的人诱导多能干细胞来源的心肌细胞片附着于脱细胞猪心肌切片上，hMSCs进行或不进行预接种。在细胞迁移距离、细胞分布以及基质中成熟血管和心肌细胞标志物表达方面，hMSCs预接种显著增强了心肌细胞片与心脏基质之间的相互作用。生长因子和基质金属蛋白酶阵列分析表明，hMSCs诱导的血管化和MMPs调节是导致心肌细胞（CMs）与心脏基质相互作用改善的两种可能机制。对这两种机制的进一步研究将有助于开发新方法，以促进移植细胞用于组织修复。
