Intramyocardial Transplantation of Human iPS Cell-Derived Cardiac Spheroids Improves Cardiac Function in Heart Failure Animals.

Intramyocardial Transplantation of Human iPS Cell-Derived Cardiac Spheroids Improves Cardiac Function in Heart Failure Animals.
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DOI:
10.1016/j.jacbts.2020.11.017
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发表时间:
2021-03
期刊:
JACC. Basic to translational science
影响因子:
--
通讯作者:
Fujita J
Fujita J
中科院分区:
其他
文献类型:
--
作者:
Kawaguchi S;Soma Y;Nakajima K;Kanazawa H;Tohyama S;Tabei R;Hirano A;Handa N;Yamada Y;Okuda S;Hishikawa S;Teratani T;Kunita S;Kishino Y;Okada M;Tanosaki S;Someya S;Morita Y;Tani H;Kawai Y;Yamazaki M;Ito A;Shibata R;Murohara T;Tabata Y;Kobayashi E;Shimizu H;Fukuda K;Fujita J

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利用大规模二维培养系统将hiPSC分化为CM,并通过代谢纯化进行精制。hiPSC衍生的CM在特殊微孔板中发育成CS。CS和GH心肌内移植改善小型和大型动物模型的心功能。CM的植入和血管生成是改善心功能的机制。使用移植物注射装置进行CS心肌内移植是治疗HF的安全、有效和可行的策略。严重缺乏供体心脏阻碍了晚期心力衰竭患者的心脏移植。因此,心脏再生疗法作为一种替代疗法而备受期待。人诱导多能干细胞(hiPSC)是再生心肌细胞的现实细胞来源。hiPSC衍生的心肌细胞被高度期望帮助心脏的恢复。避免畸胎瘤的形成和心肌细胞的大规模培养对于临床环境是绝对必要的。纯心脏球体和明胶水凝胶的组合成功地恢复了降低的射血分数。本研究建立了可行的再生心肌细胞移植策略,包括再生心肌细胞移植装置。
hiPSCs are differentiated into CMs with large-scale 2-dimensional culture system, and refined by metabolic purification. hiPSC-derived CMs are developed into CSs in special microwell plates. Intramyocardial transplantation of CSs and GH improves cardiac function in small and large animal models. Engraftment of CMs and angiogenesis are mechanisms for improvement of cardiac function. Intramyocardial transplantation of CSs with a transplant injection device is a safe, effective, and feasible strategy for the treatment of HF. The severe shortage of donor hearts hampered the cardiac transplantation to patients with advanced heart failure. Therefore, cardiac regenerative therapies are eagerly awaited as a substitution. Human induced pluripotent stem cells (hiPSCs) are realistic cell source for regenerative cardiomyocytes. The hiPSC-derived cardiomyocytes are highly expected to help the recovery of heart. Avoidance of teratoma formation and large-scale culture of cardiomyocytes are definitely necessary for clinical setting. The combination of pure cardiac spheroids and gelatin hydrogel succeeded to recover reduced ejection fraction. The feasible transplantation strategy including transplantation device for regenerative cardiomyocytes are established in this study.
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