Cardiac Tissue Engineering Models of Inherited and Acquired Cardiomyopathies
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.
Key wordsTissue engineering Genetic cardiomyopathy Acquired cardiomyopathy Contractility Models of disease Stem cells
This work was supported by NIH/NHLBI K01HL133424 (ICT), NIH/NHLBI 1F30HL134283-01A1 (JM), American Heart Association 15POST25090116 (DKC), and NIH/NHLBI R01HL132226 (KDC).
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