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On-line Access: 2022-08-26

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Bio-Design and Manufacturing  2022 Vol.5 No.4 P.687-699

http://doi.org/10.1007/s42242-022-00204-4


Generation of ring-shaped human iPSC-derived functional heart microtissues in a Mbius strip configuration


Author(s):  Yan Xu, Jingqi Qi, Wenyan Zhou, Xing Liu, Longbo Zhang, Xudong Yao & Hongwei Wu

Affiliation(s):  Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; more

Corresponding email(s):   0617555@zju.edu.cn, wuhongwei@hnca.org.cn

Key Words:  Human iPSCs, Ring-shaped myocardial microtissue, Ring-shaped cardiac tissue, Myocardial tube


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Yan Xu, Jingqi Qi, Wenyan Zhou, Xing Liu, Longbo Zhang, Xudong Yao & Hongwei Wu. Generation of ring-shaped human iPSC-derived functional heart microtissues in a Mbius strip configuration[J]. Journal of Zhejiang University Science D, 2022, 5(4): 687-699.

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Abstract: 
Although human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been used for disease modeling and drug discovery, clinically relevant three-dimensional (3D) functional myocardial microtissues are lacking. Here, we developed a novel ring-shaped cardiac microtissue comprised of chamber-specific tissues to achieve a geometrically non-orientable ventricular myocardial band, similar to a Mbius loop. The ring-shaped cardiac tissue was constructed of hiPSC-CMs and human cardiac fibroblasts (hCFs) through a facile cellular self-assembly approach. It exhibited basic anatomical structure, positive cardiac troponin T (cTnT) immunostaining, regular calcium transients, and cardiac-like mechanical strength. The cardiac rings can be self-assembled and scaled up into various sizes with outstanding stability, suggesting their potential for precise therapy, pathophysiological investigation, and large-scale drug screening.

中南大学吴宏伟、浙大姚旭东等 | 模拟莫比乌斯环构建环状人类诱导多能干细胞衍生的功能性心脏微组织

本研究论文首次将莫比乌斯(Möbius)模拟心脏结构的概念引入心脏微组织的构建,获得具有成熟的细胞外基质和良好的力学性能的心脏微组织。目前,心脏微组织的构建很大程度上依赖于二维细胞培养和动物模型。二维细胞培养成本低且易于应用,但无法预测药物疗效和毒性检测。动物模型由于人和动物之间的生理差异,包括心跳速度、电生理学、肌丝组成、能量学和钙循环,可能无法检测药物的副作用或者模拟疾病的进展。此外,伦理和监管问题一直限制着动物实验。因此,迫切需要开发新的平台来了解心脏病的进展、疾病管理和药物筛选。在这里,我们开发了一种由腔特异性组织组成的新型环状心脏微组织,以模拟出几何上类似于Möbius环的心室心肌带。心脏环状组织由人类诱导多能干细胞来源的心肌细胞(hiPSC-CMs)和人心脏成纤维细胞组成,通过便捷高效的细胞自组装,表现出心脏的基本解剖结构,心肌肌钙蛋白T (cTnT)免疫染色阳性,钙瞬变规则,心脏样机械强度等特性。研究显示,心脏环可以自组装并被放大成各种尺寸,具有出色的稳定性,展现出其在精确治疗、病理生理学研究和大规模药物筛选方面的潜力。

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