Transforming Growth Factor Beta-1 (TGF-β1) Regulates Assembly of Cardiac Spheroids

Cells of all tissues in human body interact with their neighboring cells and components of the extracellular matrix thereby creating a unique 3D microenvironment. These interactions are realized through a complex network of biochemical and mechanical signals that are important in maintaining normal cellular homeostasis. Numerous attempts have been undertaken during the last two decades to develop 3D models for studying their properties and understanding the mechanisms of regulation of cell microenvironment in vivo. Cardiac spheroids (cardiospheres) are one these models of cardiac microenvironment. In this study we demonstrate that unique microenvironment formed in cardiospheres consists of stem/progenitor and mesenchymal cells surrounded by extracellular matrix proteins synthesized by these cells. TGF-β1 participates in the regulation of contraction of cells forming cardiospheres, promotes activation of the epithelial-mesenchymal transition and self-organization of cells, which leads to the formation of larger spheroids. Thereby, the effect of TGF-β1 on the cells of cardiospheres can serve as a model for studying the mechanisms of regulation of cardiac microenvironment.