Research progress on the effects of M1/M2 macrophages on the differentiation and maturation of stem cell-derived cardiomyocytes: a review

• M1 macrophages inhibit cardiac differentiation and maturation of SC-CMs via pro-inflammatory cytokines (TNF-α, IL-1β) that suppress Wnt/β-catenin signaling and disrupt sarcomeric organization and calcium handling. • M2 macrophages promote SC-CM maturation through trophic factors (IGF-1, HGF) that enhance electrophysiological properties, metabolic reprogramming to oxidative phosphorylation, and angiogenesis via VEGF. • The cardiac immune microenvironment, particularly macrophage polarization, plays a dual regulatory role in SC-CM fate, offering a novel axis for improving cardiac regeneration therapies. • Emerging strategies such as optimized transplantation timing, co-transplantation with immunomodulatory cells, engineered exosomes, and smart biomaterials aim to harness macrophage polarization to create a favorable niche for SC-CM survival and integration.