Combination Treatment with Human Adipose Tissue Stem Cell-derived Exosomes and Fractional CO2 Laser for Acne Scars: A 12-week Prospective, Double-blind, Randomized, Split-face Study

Abstract

A variety of applications of human adipose tissue stem cell-derived exosomes have been suggested as novel cell-free therapeutic strategies in the regenerative and aesthetic medical fields. This study evaluated the clinical efficacy and safety of adipose tissue stem cell-derived exosomes as an adjuvant therapy after application of fractional CO2 laser for acne scars. A 12-week prospective, double-blind, randomized, split-face trial was performed. A total of 25 patients received 3 consecutive treatment sessions of fractional CO2 laser to the whole face, with a follow-up evaluation. Post-laser treatment regimens were applied; for each patient, one side of the face was treated with adipose tissue stem cell-derived exosomes gel and the other side was treated with control gel. Adipose tissue stem cell-derived exosomes-treated sides had achieved a significantly greater improvement than the control sides at the final follow-up visit (percentage reduction in échelle d'évaluation clinique des cicatrices d'acné scores: 32.5 vs 19.9%, p < 0.01). Treatment-related erythema was milder, and post-treatment downtime was shorter on the applications of human adipose tissue stem cell-derived exosomes-treated side. In conclusion, the combined use of this novel material with resurfacing devices would provide synergistic effects on both the efficacy and safety of atrophic acne scar treatments.

Keywords: acne scar; fractional laser; adipose tissue stem cell-derived exosomes.

Fig. 1

Characterization of adipose tissue stem cell-derived exosomes (ASCE). (A) Representative plot of particle concentration and size distribution of ASCE, as measured by nanoparticle tracking analysis (NTA). (B) Cryo-transmission electron microscopy image of ASCE. Scale bar: 200 nm. (C) Signal intensities of exosome surface markers. ASCE were analysed using flow cytometry after staining with anti-CD9, -CD63, and -CD81 antibodies. (D) Levels of exosome exclusionary markers, calnexin and cytochrome C, in ASCE compared with cell lysate. Data are presented as the mean ± standard deviation (SD) of 3 independent experiments.

Fig. 2

Evaluation of scar improvement based on échelle d’évaluation clinique des cicatrices d’acné (ECCA) scores. (A) Mean percentage changes in total ECCA scores and mean changes in ECCA scores for (B) V-shaped (icepick), (C) U-shaped (boxcar), and (D) M-shaped (rolling) atrophic scars on the adipose tissue stem cell-derived exosomes (ASCE) and control sides. *p < 0.05 compared with baseline; ^†p < 0.05 between the 2 sides. Error bars indicate standard errors. PT: post-treatment.

Fig. 3

Clinical photographs of the adipose tissue stem cell-derived exosomes (ASCE) and control sides at baseline and 6 weeks after 3 treatment sessions in a 30-year-old male.

Fig. 4

Three-dimensional image analyses for atrophic scar, enlarged skin pore, and skin surface roughness using Antera 3D^® CS. (A–D) Clinical photographs and analysed images of the adipose tissue stem cell-derived exosomes (ASCE) and control sides at baseline and at the final follow-up visit. (B) The depths of atrophic scars are shown as colours (white<yellow<green<blue<purple). (C) The depths of enlarged skin pores are shown as colours (white<yellow<orange<green<blue). (D) The vertical deviations of the skin surface are shown as colours: [downward] purple<blue<green<white <yellow<red [upward]. Mean percent changes in (E) atrophic scar volume, (F) mean pore volume, and (G) skin surface roughness on the ASCE and control sides. *p < 0.05 compared with baseline. Error bars indicate standard errors. PT: post-treatment.

Fig. 5

Evaluation of: (A) pain, (B) erythema, (C) oedema, and (D) dryness on both adipose tissue stem cell-derived exosomes (ASCE) and control sides for post-treatment 7 days.

Fig. 6

Clinical photographs of the adipose tissue stem cell-derived exosomes (ASCE) and control sides for post-treatment 4 days in a 31-year-old male.