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Improving the Quality of iPSC-derived Cardiomyocytes by Providing Intercellular Cues during Scalable Manufacturing

Test-Bed Involved: iPSC-CM

 

Pure populations of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can be differentiated using small molecules to guide the cells through developmental transitions.  However, this efficient differentiation process lacks the cues provided by neighboring cardiac cells during heart development, resulting in iPSC-CMs that do not fully mature to adult-like states.  The fetal phenotypes of these cells make them ill-suited for cardiac regenerative therapies since they pose arrhythmogenic risks when implanted to the heart and cannot generate sufficient forces to improve cardiac function. In this project we will test the hypothesis that cues from co-cultured or co-differentiated cardiac stromal cells, endothelial cells, and macrophages will improve the safety and potency of iPSC-CMs, assessed by acquisition of maturation phenotypes.

 

Aim 1: Assess effects of iPSC-CM co-culture with iPSC-derived cardiac fibroblasts and endothelial cells on iPSC-CM structural, metabolic, and electromechanical maturity.

Aim 2: Develop scalable production of myocardial organoids in 3D suspension culture.