Cardiac Tissue Engineering Models of Inherited and Acquired Cardiomyopathies.

Cardiac Tissue Engineering Models of Inherited and Acquired Cardiomyopathies.
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遗传性和获得性心肌病的心脏组织工程模型。

DOI:
10.1007/978-1-4939-8597-5_11
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发表时间:
2018
期刊:
Methods in molecular biology (Clifton, N.J.)
影响因子:
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通讯作者:
Costa,KevinD
Costa,KevinD
中科院分区:
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文献类型:
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作者:
Turnbull,IreneC;Mayourian,Joshua;Murphy,JackF;Stillitano,Francesca;Ceholski,DelaineK;Costa,KevinD

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人类心脏的仿生体外模型的缺乏对心脏病建模领域的进展构成了关键障碍。人类工程心脏组织(hECTs)-自主跳动的结构,概括了天然心肌生理学的关键方面-提供了一个有吸引力的替代传统的体外模型。在这里,我们描述了使用hECTs来推进我们对心脏疾病的理解和建模,以测试治疗干预措施,重点是在遗传性和获得性心肌病的背景下的收缩功能障碍。本章主要讨论了四个主要步骤:(1)从人诱导多能干细胞来源的心肌细胞制备hECTs(2)在这两个平台上的hECT收缩功能的数据采集;(3)遗传性受磷蛋白-R14缺失-扩张型心肌病的hECT建模;(4)冷冻损伤和阿霉素诱导的获得性心肌病hECT模型。
The lack of biomimetic in vitro models of the human heart has posed a critical barrier to progress in the field of modeling cardiac disease. Human engineered cardiac tissues (hECTs)—autonomous, beating structures that recapitulate key aspects of native cardiac muscle physiology—offer an attractive alternative to traditional in vitro models. Here we describe the use of hECTs to advance our understanding and modeling of cardiac diseases in order to test therapeutic interventions, with a focus on contractile dysfunction in the setting of inherited and acquired forms of cardiomyopathies. Four major procedures are discussed in this chapter: (1) preparation of hECTs from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) on single-tissue and multitissue bioreactors; (2) data acquisition of hECT contractile function on both of these platforms; (3) hECT modeling of hereditary phospholamban-R14 deletion-dilated cardiomyopathy; and (4) cryo-injury and doxorubicin-induced hECT models of acquired cardiomyopathy.