Engineered Human Heart Slice for Testing Drug-Induced Arrhythmia

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The parent grant “Engineered Human Heart Slice for Testing Drug-Induced Arrhythmia” aims to develop an engineered hear slice (EHS) model that will have the ability to test for drug-induced, cardiac tachyarrhythmias. The cardiomyocytes in the EHS model are obtained from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). While hiPSC-CMs are a promising cell source for cardiomyocytes, these cells are limited in their maturation state. hiPSC- CMs are currently fetal-like in their development, and require stimulants to achieve an adult-like phenotype. The parent grant focuses on the use of electromechanical, biological, and maturation medias to attain such a phenotype in hiPSC-CMs. This leads to the goal of this supplemental research, which is to apply an alternate stimulant to aid in the maturation of hiPSC-CMs. This stimulant is the secretome from adipocytes (fat generating cells). The adipocytes will serve as a source of fatty acids, which have proven to be influential in the metabolic maturation of cardiomyocytes. The specific aim of this supplemental work is to investigate the beneficial (or pathological) role of the secretome from adipocytes derived from human Adipose-Derived Stem Cells (hASCs) as a maturation stimulant for hiPSC-CMs that are either untreated, sorted for CD36+ (a metabolic maturation marker), or derived from patients diagnosed with arrhythmogenic right ventricular cardiomyopathy. The supplemental research will also examine whether the responses of the hiPSC-CMs are enhanced in a more 3D environment consisting of decellularized cardiac tissue.