The Efficacy of MSC-Derived Exosome-Based Therapies in Treating Scars, Aging and Hyperpigmentation: A Systematic Review of Human Clinical Outcomes

<b>Background:</b> 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. <b>Objectives:</b> 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. <b>Method:</b> 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. <b>Result:</b> Six studies (<i>n</i> = 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%, <i>p</i> < 0.01), wrinkle parameters were reduced by 1 (2.4-14.4% vs. 6.6-7.1%, <i>p</i> < 0.05), and elasticity was enhanced (+11.3% vs. -3.3%, <i>p</i> = 0.002) Additional benefits included hydration (+6.5% vs. +4.5%, <i>p</i> = 0.37) and reduced melanin index (-9.9% vs. -1%, <i>p</i> = 0.44). The Global Aesthetic Improvement Scale score showed significant improvement (<i>p</i> = 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 (<i>p</i> = 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. <b>Conclusions:</b> 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.