The Fibroblast Microenvironment on the Differentiation and Maturation of Stem Cell–Derived Cardiomyocytes

Cardiac fibroblasts (CFs) are a critical component of the myocardial microenvironment and play essential roles in the differentiation and maturation of stem cell–derived cardiomyocytes (CMs). Accumulating evidence indicates that CFs shape a permissive microenvironment for CM lineage commitment, early expansion, and subsequent structural and functional maturation through the secretion of soluble factors, extracellular matrix remodeling, and contact-mediated interactions such as gap junctions. The CF microenvironment exerts stage-specific effects on differentiation efficiency, structural organization, electrophysiological properties, and metabolic maturation of CMs. This review summarizes the recent advances in understanding how the CF microenvironment regulates the differentiation and maturation of stem cell–derived CMs from a continuous developmental perspective and discusses current limitations and future directions in this field. Impact Statement The core innovation of this review lies in its unique perspective on the influence of fibroblast microenvironment on the differentiation and maturation of stem cell–derived cardiomyocytes. This review has certain academic value.