Cardiac inducing colonies secrete paracrine factors that significantly suppress TGFβ-induced cardiac fibroblast activation and induce migration and proliferation of cardiomyocytes in an in vitro model.
Paracrine factors from cardiac inducing colonies demonstrate anti-fibrotic and pro-reparative effects in vitro, suggesting a potential therapeutic approach for myocardial fibrosis.
p-value: p=<0.0001
Myocardial fibrosis (MF), a common event that develops after myocardial infarction, initially is a reparative process but eventually leads to heart failure and sudden cardiac arrest. In MF, the infarct area is replaced by a collagenous-based scar induced by "excessive" collagen deposition from activated cardiac fibroblasts. The scar prevents ventricular wall thinning; however, over time it expands to noninfarcted myocardium. Therapies to prevent fibrosis include reperfusion, anti-fibrotic agents, and ACE inhibitors. Paracrine factor (PF)/stem cell research has recently gained significance as a therapy. We consistently find that cardiac inducing colonies (CiCs) (derived from human germline pluripotent stem cells) secrete PFs at physiologically relevant concentrations that suppress cardiac fibroblast activation and excessive extracellular matrix protein secretion. These factors also affect human cardiomyocytes and endothelial cells by inducing migration/proliferation of both populations into a myocardial wound model. Finally, CiC factors modulate matrix turnover and proinflammation. Taking the results together, we show that CiCs could help tip the balance from fibrosis toward repair.
Mahapatra et al. (Wed,) conducted a other in Myocardial fibrosis. Cardiac inducing colonies conditioned media (CiC-CM) and recombinant paracrine factor (rPF) cocktail vs. TGFβ-activated human cardiac fibroblasts or untreated cells was evaluated on Fibrotic protein expression (ASMA, PER, COL I) (p=<0.0001). Cardiac inducing colonies secrete paracrine factors that significantly suppress TGFβ-induced cardiac fibroblast activation and induce migration and proliferation of cardiomyocytes in an in vitro model.