• M1 macrophages inhibit SC-CM differentiation and maturation via pro-inflammatory cytokines (TNF-α, IL-1β) that suppress Wnt/β-catenin signaling and maintain glycolytic metabolism.
• 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 immune microenvironment, particularly macrophage polarization, is a critical determinant of SC-CM transplantation success, influencing survival, integration, and functional recovery.
• Emerging therapeutic strategies, including optimized transplantation timing, co-transplantation with immunomodulatory cells, engineered exosomes, and smart biomaterials, aim to harness macrophage polarization to improve cardiac regeneration outcomes.
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