biostudies-literatureLee SEuropean Research CouncilNHLBI NIH HHSNIGMS NIH HHS1279-1291https://www.ebi.ac.uk/biostudies/studies/S-EPMC12533503biostudies-literatureUnknown137(10)<h4>Background</h4>Induction of cardiomyocyte proliferation in situ represents a promising strategy for myocardial regeneration following injury. However, cardiomyocytes possess intrinsic inhibitory mechanisms that attenuate pro-proliferative signaling and constrain their expansion. We hypothesized that cell-cell contact is a key suppressor of cardiomyocyte proliferation. We aimed to delineate the underlying molecular pathways to enable sustained proliferation in 3-dimensional contexts.<h4>Methods</h4>Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were cultured at varying plating densities to examine the impact of cell-cell contact on cell cycle activity. Phosphoproteomic profiling was performed in sparse versus dense cultures to identify signaling alterations. CondCirculation researchIGFBP2 Mediates Human iPSC-Cardiomyocyte Proliferation in a Cellular Contact-Dependent Manner.PMC12533503RM1 GM131981R01 HL171574788381101141820F32 HL142205Yun JLee SHeinrich PRobinson HRKim BHudson JEWu SMWu JCMoretti AHumphrey SJGoodyer WRLee JMin SPaik DTKang YLee DBuikema JWCho SWBelbachir NGaldos FXfalseIGFBP2 Mediates Human iPSC-Cardiomyocyte Proliferation in a Cellular Contact-Dependent Manner.<h4>Background</h4>Induction of cardiomyocyte proliferation in situ represents a promising strategy for myocardial regeneration following injury. However, cardiomyocytes possess intrinsic inhibitory mechanisms that attenuate pro-proliferative signaling and constrain their expansion. We hypothesized that cell-cell contact is a key suppressor of cardiomyocyte proliferation. We aimed to delineate the underlying molecular pathways to enable sustained proliferation in 3-dimensional contexts.<h4>Methods</h4>Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were cultured at varying plating densities to examine the impact of cell-cell contact on cell cycle activity. Phosphoproteomic profiling was performed in sparse versus dense cultures to identify signaling alterations. Cond2025-01-01T00:00:00Z2025 Oct2026-06-10T05:17:17.96Z2026-06-10T03:07:17.375ZS-EPMC125335034103139610.1161/CIRCRESAHA.125.32652210.1161/circresaha.125.326522