Developmental cues from epicardial cells simultaneously promote cardiomyocyte proliferation and electrochemical maturation.

ABSTRACT: Accumulating evidence indicates that maturation limits cardiomyocyte proliferation. We expand on that theory by co-culturing human induced pluripotent stem cell (hiPSC)-cardiomyocytes (CM) with epicardial cells (EPCs) and epicardial-derived cells in both 2D co-cultures and 3D engineered heart tissues (EHTs). In 2D co-cultures, the percentage of proliferating CM increased in parallel with stark electrophysiologic improvements. Single-cell transcriptomics revealed a significant shift in the bulk CM population of the epicardial-CM co-cultures as characterized by more fetal-like myofilament isoforms but with enhanced pathways associated with electrochemical maturation. The 3D-EHTs containing EPCs showed more limited proliferation but a similar improvement in CM electrophysiologic function. Nex

SUBMITTER: Givens SE 

PROVIDER: S-EPMC12365841 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature