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

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.

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.

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.

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.

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.

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.