Development of a three-dimensional pre-vascularized scaffold-free contractile cardiac patch for treating heart disease
Development of a three-dimensional pre-vascularized scaffold-free contractile cardiac patch for treating heart disease
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DOI：
10.1016/j.healun.2015.06.001
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发表时间：
2016-01-01
影响因子：
8.9
通讯作者：
Morita, Shigeki
中科院分区：
文献类型：
--
作者：
Noguchi, Ryo;Nakayama, Koichi;Morita, Shigeki
背景：我们研究的目的是开发一种完全无支架的、有活力的、可收缩的心脏组织，能够移植到受损的原生心脏中。方法：我们的技术是基于细胞自组装性质的基本特征。我们将大鼠新生心室心肌细胞、人真皮成纤维细胞和人冠状动脉微动脉内皮细胞的混合物镀在超低附着板上，形成可收缩的心脏球体。首先，确定了3种细胞源的最佳细胞比例。接下来，将大约1 x 10(4)个最优球体融合成贴片状结构，并评估这些贴片的形态特征和机械功能。最后将心脏补片移植至F344裸鼠心脏，移植后进行组织学研究。结果：电生理和机械上证实了心脏贴片的同步跳动。移植后5天进行的组织学研究显示移植物是可存活的，移植物组织内具有功能良好的微血管结构。结论：我们认为将无支架三维组织工程技术应用于心脏再生治疗是可行的，并期望该技术将成为治疗终末期心力衰竭的一种有前景的工具。(C) 2016年国际心肺移植学会。版权所有。
BACKGROUND: The aim of our study was to develop a completely scaffold-free, viable, contractile cardiac tissue capable of being grafted into the damaged native heart.METHODS: Our technology is based on the fundamental characteristics of the self-assembling nature of cells. We created contractile cardiac spheroids by plating a mixture of rat neonatal ventricular cardiomyocytes, human dermal fibroblasts, and human coronary microartery endothelial cells in ultralow attachment plates. First, the optimal cell ratios for the 3 cell sources were determined. Next, approximately 1 x 10(4) optimal spheroids were fused into a patch-like construct, and the morphologic characteristics and mechanical functions of these patches were evaluated. Finally, the cardiac patches were grafted into the hearts of F344 nude rats, and histologic studies were performed after transplantation.RESULTS: Synchronous beating of the cardiac patch was confirmed electrophysiologically and mechanically. A micronetwork of endothelial cells was also demonstrated in the construct, and the histologic study performed 5 days after transplantation showed the grafts to be viable, with functioning microvascular structures inside the graft tissue.CONCLUSIONS: We consider the application of our scaffold-free 3-dimensional tissue engineering technology to cardiac regeneration therapy is feasible and expect that this technology will become a promising tool for the treatment of end-stage heart failure. (C) 2016 International Society for Heart and Lung Transplantation. All rights reserved.