Adipose-Derived Stem Cells Inhibit Epidermal Melanocytes through an Interleukin-6–Mediated Mechanism

Background: Several investigators have postulated that human adipose-derived stem cells can be used for skin rejuvenation, but there have been few reports about their direct effects on human epidermal melanocytes. The authors studied the effects on melanocytes, and the causative agent of those effects was further investigated in this study. Methods: Human epidermal melanocytes were divided into three groups and cultured in adipose-derived stem cell–conditioned medium, human dermal fibroblast–conditioned medium, or control medium. Concentrations of melanogenic cytokines in these media were measured using enzyme-linked immunosorbent assay kits. After 3 and 7 days of incubation, cell proliferation, melanin content, tyrosinase activity, and melanogenic gene expression were measured. Interleukin-6–neutralizing antibodies were mixed with adipose-derived stem cell–conditioned medium in which human epidermal melanocytes were cultured, and melanocyte growth and melanogenesis were measured again. Results: Interleukin-6 concentrations in adipose-derived stem cell– and human epidermal melanocyte–conditioned media were 1373 and 495 pg/ml, respectively. Both types of medium suppressed melanocyte proliferation and melanin synthesis (p < 0.05), but adipose-derived stem cell–conditioned medium was more effective than human dermal fibroblast–conditioned medium in inhibition of human epidermal melanocyte proliferation, melanin synthesis, and tyrosinase activity (p < 0.05). Interleukin-6–neutralizing antibody sufficiently reversed the antimelanogenic effects of adipose-derived stem cell–conditioned medium such that human epidermal melanocyte proliferation, melanin content, tyrosinase activity, and tyrosinase mRNA levels were restored (p < 0.05). Conclusions: Adipose-derived stem cell–conditioned medium inhibited melanocyte proliferation and melanin synthesis by down-regulating melanogenic enzymes. Interleukin-6 plays a pivotal role in inhibition of melanocytes.