Background: Recent advancements in regenerative medicine have introduced mesenchymal stem cell–derived exosomes (MSC-Exos) as a novel therapeutic approach. Exosomes are extracellular vesicles containing proteins, lipids, and RNAs capable of modulating cellular behavior and promoting tissue regeneration. A systematic review of human studies is warranted to summarize outcomes, assess therapeutic value, and guide clinical applications.
Objectives: This systematic review synthesizes current evidence on mesenchymal stem cell–derived exosomes for cutaneous scars, aging, and hyperpigmentation, with a focus on functional and aesthetic outcomes.
Method: A comprehensive search of PubMed, Scopus, Embase, Web of Science, and Google Scholar (January 2010–July 2025) was performed following 2020 PRISMA guidelines. Eligible studies included studies that were randomized controlled trials, pilot studies, case series, and case reports involving human participants treated with MSC-Exos. Outcomes assessed were scar remodeling, pigmentation, skin regeneration, recurrence, and adverse events. Data extraction and bias assessment were conducted independently.
Result: Six studies (
n = 99; age 19–72 years) from diverse regions, including the United States, the Republic of Korea, and México, were included. MSC-Exos therapy showed promising improvements in reducing scar thickness (32.5% vs. 19.9%,
p < 0.01), wrinkle parameters were reduced by 1 (2.4–14.4% vs. 6.6–7.1%,
p < 0.05), and elasticity was enhanced (+11.3% vs. −3.3%,
p = 0.002) Additional benefits included hydration (+6.5% vs. +4.5%,
p = 0.37) and reduced melanin index (−9.9% vs. −1%,
p = 0.44). The Global Aesthetic Improvement Scale score showed significant improvement (
p = 0.005). Using the Investigator Global Assessment, 16 out of 25 areas treated with exosomes showed significant improvement (grade ≥ 2), compared to 12 out of 25 areas in the control group (
p = 0.02), indicating that exosome treatment led to more visible improvement. Complete resolution of icepick scars, partial improvement of boxcar/rolling scars, and no recurrence of keloids (18/21) were reported. Adverse events were mild and transient.
Conclusions: Early human evidence suggests that MSC-Exos may offer potential therapeutic benefits for scars, hyperpigmentation, and skin aging, with favorable short-term safety profiles. However, the current evidence remains preliminary due to small sample sizes, heterogeneous study designs, and limited follow-up durations. Larger, well-designed randomized trials are needed to confirm long-term efficacy and safety.
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