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391 J. Cosmet. Sci., 73, 391–403 (November/December 2022) Address all correspondence to Tomohisa Hirobe, tmhirobe@ae.auone-net.jp Mesenchymal Stem Cell-Derived Factors Stimulate the Differentiation of Melanocytes in the Vitiliginous Skin in Combination With Phototherapy TOMOHISA HIROBE AND HISAO ENAMI Shinjuku Skin Clinic, Shinjuku, Tokyo, Japan (T.H., H.E.) Accepted for publication February 1, 2023. Synopsis Although vitiligo treatment is important for cosmetics, full recovery is still difficult. To better improve the efficacy of vitiligo treatment, we selected combined treatment with phototherapy and reconstitution therapy using elastin peptides and umbilical-cord-blood–derived mesenchymal stem cell culture supernatants (UCB- MSCCS). We surveyed whether this treatment can induce repigmentation and/or melanocyte proliferation and differentiation in vitiliginous skin. Punch biopsies of nonlesional, lesional, and treated skin from 51 patients were collected. Three different treatments were (1) monochromatic excimer light (MEL)/narrow-band ultraviolet light B (NB-UVB) (2) MEL/NB-UVB +multilayered treatment (MT) using Dermapen-treated regenerating skin supplemented with elastin peptides and (3) MEL/NB-UVB +multilayered treatment supplemented with key factors derived from stem cell cultures (MTK) consisting of MT and UCB-MSCCS. Although distinct repigmentation failed to be found, melanocyte differentiation and complete restoration of elastin fibers were frequently observed only in the skin treated with MEL/NB-UVB +MTK. Our methods are expected to be useful for developing cosmetics for vitiligo patients. INTRODUCTION Melanocytes differentiate from melanoblasts and produce melanin-laden melanosomes. Melanocytes transport melanosomes to keratinocytes and contribute to the expression of skin color through epidermal melanin pigmentation (1). Vitiligo is prevalent all over the world and its incidence is 0.1–2% of humans. Vitiligo is characterized by white patches caused by deficiency or dysfunction of epidermal melanocytes (2). Vitiliginous skin is serious cosmetically and socially, because white patches are present within visible skin areas such as the face, neck, and hands. Moreover, treatment outcomes are still cosmetically unsatisfactory. Monochromatic excimer light (MEL, 308 nm) and narrow-band ultraviolet light B (NB-UVB, 311 nm) have been used for one of the effective treatment modalities that can induce repigmentation (3,4). However, the treatment requires a long time and its efficacy is unsatisfactory. Skin wounding is also effective for inducing repigmentation (1). Numerous growth factors and cytokines are released from keratinocytes and fibroblasts during wound