Efficacy of Human UC-MSC-derived Exosomes and BM-MSC-derived Exosomes in Atrophic Acne Scar Treated With Ablative Fractional CO2 Laser: a Split-face Randomized Controlled Prospective Study

Atrophic acne scars are a common sequela of acne vulgaris and are associated with significant psychosocial burden, including reduced self-esteem and impaired quality of life. Despite the availability of multiple treatment modalities, complete resolution remains challenging. Among current options, ablative fractional carbon dioxide (CO₂) laser is considered one of the most effective approaches due to its ability to induce dermal remodeling and stimulate collagen production. However, its clinical use is limited by downtime, risk of adverse effects such as post-inflammatory hyperpigmentation, and the need for multiple treatment sessions.

Exosomes derived from mesenchymal stem cells (MSCs) have recently emerged as a promising adjunctive therapy in dermatology. These nano-sized extracellular vesicles contain bioactive molecules, including growth factors, cytokines, and nucleic acids, which play a key role in intercellular communication and tissue regeneration. Preclinical studies have demonstrated that MSC-derived exosomes enhance fibroblast proliferation, promote collagen synthesis, and modulate inflammatory responses by shifting macrophage polarization toward an anti-inflammatory phenotype. These mechanisms suggest that exosomes may improve wound healing and optimize outcomes following laser-based treatments.

This study is a randomized, double-blind, split-face, controlled prospective clinical trial designed to evaluate the efficacy and safety of human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSC-exo) and bone marrow mesenchymal stem cell-derived exosomes (BM-MSC-exo) as an adjunct to ablative fractional CO₂ laser in the treatment of atrophic acne scars. The study was conducted at the Dermatology and Skin Aesthetics Department, University Medical Center, Ho Chi Minh City, Vietnam.

A total of 22 adult participants with bilateral atrophic acne scars were enrolled. All participants underwent two sessions of ablative fractional CO₂ laser treatment at 4-week intervals. Immediately after each laser session, one side of the face was treated with a topical exosome solution (containing hUC-MSC-exo and BM-MSC-exo), while the contralateral side received a hyaluronic acid-based control solution. Participants continued applying the assigned topical treatment twice daily for two additional days following each session. Allocation of treatment sides was randomized, and both participants and outcome assessors were blinded to group assignment.

Clinical assessments were performed at baseline (T0), 4 weeks after the first session (T1), and 4 weeks after the second session (T2). The primary outcome was the percentage improvement in the Echelle d'Évaluation Clinique des Cicatrices d'Acné (ECCA) score from baseline to T2. Secondary outcomes included changes in ECCA scores by scar subtype (ice-pick, boxcar, and rolling scars), skin texture improvement measured using the VISIA® imaging system, Investigator's Global Assessment (IGA), patient satisfaction, and healing-related parameters.

Safety evaluation included monitoring and recording all adverse events, such as erythema, edema, pain, crusting, post-inflammatory hyperpigmentation, acne flare, infection, and scarring. The severity and duration of these events were compared between exosomes and control sides.

This study aims to determine whether the addition of hUC-MSC-exo and BM-MSC-exo can enhance the clinical efficacy of fractional CO₂ laser in improving atrophic acne scars while maintaining a favorable safety profile. The findings may provide evidence for a novel adjunctive approach to optimize acne scar treatment outcomes.