Self-Assembled Heterotypic Cardiac Spheroids from Human Pluripotent Stem Cells

Engineered cardiac tissue models aim to recapitulate the multicellular composition of the native myocardium by incorporating multiple tissue-relevant cell populations. Here, we describe the process of generating self-assembled cardiac microtissue spheroids comprised of heterotypic cardiac cell types. The absence of exogenous extracellular matrix (ECM) or scaffolding makes microtissue assembly dependent upon intercellular adhesion interactions over cell-ECM interactions, analogous to early development. Therefore, this approach creates a 3D platform to study how multicellular heterotypic interactions impact tissue structure, function, and phenotype.