Promotion of angiogenesis by mesenchymal stem cell exosomes: a new frontier in cutaneous wound healing

INTRODUCTION: Angiogenesis plays a pivotal role in cutaneous wound healing by restoring vascular supply to regenerating tissues. Mesenchymal stem cell-derived exosomes (MSC-exosomes) are emerging as potent acellular mediators of angiogenesis, thanks to their cargo of bioactive molecules and immunomodulatory effects. SOURCES OF DATA: This review synthesizes recent findings from in vivo and in vitro studies, including preclinical models of diabetic wounds, ischemic injuries, and burn healing. It draws upon peer-reviewed articles published in biomedical journals, with a focus on the mechanisms and efficacy of MSC-exosomes. AREAS OF AGREEMENT: MSC-derived exosomes enhance endothelial cell proliferation, migration, and tube formation. Their ability to activate pro-angiogenic signaling pathways, such as Wnt/β-catenin, AKT/eNOS, and angiopoietin/TIE2, is widely accepted. Additionally, their low immunogenicity, enhanced stability, and potential for bioengineered delivery systems are recognized advantages over other angiogenic therapies. AREAS OF CONTROVERSY: Challenges persist regarding the standardization of exosome isolation, characterization, and large-scale production. Debate also exists about their long-term safety and therapeutic consistency across MSC sources. GROWING POINTS: Incorporation of MSC-exosomes into hydrogels and scaffolds offers promising controlled delivery systems that enhance angiogenic efficacy. Preconditioning MSCs (e.g. with hypoxia or pharmacological agents) further improves the pro-angiogenic potency of exosomes. AREAS TIMELY FOR DEVELOPING RESEARCH: Future efforts should prioritize clinical translation by developing GMP-compliant production protocols, optimizing delivery strategies, and conducting rigorous clinical trials to assess safety, dosing, and therapeutic efficacy across diverse wound types.