BackgroundFighting skin aging signs is one of the major challenges of the 21st century, recently, mesenchymal stem cells (MSCs) and microneedling (MN) have been applied for anti-aging. This study aims to evaluate the efficacy of the combination of MN and human umbilical cord-derived mesenchymal stem cells conditioned media (hUC-MSCs-CM) in skin brightness and rejuvenation. MethodsThirty volunteers with facial skin aging were recruited for the randomized, controlled split-face study. The left and right sides of the face were randomly applied with saline via MN or hUC-MSCs-CM via MN. Five sessions were performed for each volunteer at 2-week intervals. Two dermatologists evaluated the clinical improvement, in terms of skin brightness and texture. A satisfaction score based on a self-evaluation questionnaire was recorded at 2 weeks after the last treatment. The objective evaluation was recorded before the first treatment, and at 2 weeks after the last treatment. ResultsTwenty-eight volunteers with a mean (SD) age of 41 (6.54) years old completed the trial. The investigator's assessment for skin brightness and texture, and the self-satisfaction score revealed statistically better effects in hUC-MSCs-CM -plus-MN group than in MN alone (MN saline) group. No severe side effects were reported during the whole study period. Compared to MN alone group, the objective assessment revealed significant improvements in skin brightness (reduced melanin index, ultraviolet spots, and brown spots) and skin texture (reduced wrinkles and pores, and increased skin elasticity) in hUC-MSCs-CM-plus-MN group, while there were no obvious differences in skin hydration, trans-epidermal water loss, and the erythema index. ConclusionThe combination of hUC-MSCs-CM and MN exhibite anti-aging efficacy, and this could be used for facial rejuvenation in the future.