Melanocyte stem cells as potential therapeutics in skin disorders

Abstract

Introduction: Melanocytes produce pigment granules that color both skin and hair. In the hair follicles melanocytes are derived from stem cells (MelSCs) that are present in hair bulges or sub-bulge regions and function as melanocyte reservoirs. Quiescence, maintenance, activation and proliferation of MelSCs are controlled by specific activities in the microenvironment that can influence the differentiation and regeneration of melanocytes. Therefore, understanding MelSCs and their niche may lead to use of MelSCs in new treatments for various pigmentation disorders.

Areas covered: We describe here pathophysiological mechanisms by which melanocyte defects lead to skin pigmentation disorders such as vitiligo and hair graying. The development, migration and proliferation of melanocytes and factors involved in the survival, maintenance and regeneration of MelSCs are reviewed with regard to the biological roles and potential therapeutic applications in skin pigmentation diseases.

Expert opinion: MelSC biology and niche factors have been studied mainly in murine experimental models. Human MelSC markers or methods to isolate them are much less well understood. Identification, isolation and culturing of human MelSCs would represent a major step toward new biological therapeutic options for patients with recalcitrant pigmentary disorders or hair graying. By modulating the niche factors for MelSCs, it may one day be possible to control skin pigmentary disorders and prevent or reverse hair graying.

Keywords: graying hair; melanocyte; melanocyte stem cell; pigmentation; vitiligo.

Figure 1

Possible related pathways in MelSC survival, maintenance, and differentiation. MITF, Bcl-2, B-Raf, C-Raf, TGF-b, Notch pathways are involved in MelSC survival and maintenance. PAX-3 and Wnt pathways are related to MelSC differentiation.

Figure 2

MelSC in vitiligo. In the vitiligious lesion, the number of functional melanocytes and MelSC is decreased compared with the adjacent non-vitiligious lesion. MelSC or melanocyte precursor cells can remain in the hair bulge and provide the chance of repigmentation. During the process of repigmentation after the treatment of vitiligo, repigmentation frequently starts in the perifollicular area from the hair bulge MelSC. Sox10, Kit, MC1R, and wnt7a are related to MelSC activation, migration, and differentiation.

Figure 3

MelSC in graying hair. Factors such as aging and genotoxic stress can induce hair graying through MelSC loss or MelSC differentiation into melanocytes. Repeated MelSC loss induces MelSC depletion and leads to hair graying. For hair pigmentation, not only MelSC maintenance but also melanogenesis of hair matrix melanocytes and melanin transfer to the hair shaft should occur. MelSC maintenance and activation are regulated by niche factors including Bcl-2, MITF, B-raf, C-raf, TGF-β, PAX3, Wnt, and Notch.

Figure 4

MelSC in wound healing. Wounded skin lacks melanocytes on the basal layer of the epidermis. As wound healing progresses, activated MelSC migrate to the epidermis from the hair bulge area rather than proliferating. The MelSC then proliferate into melanocytes to be the source of epidermal melanocytes and maintain the cutaneous epithelium biology. This migration and proliferation of MelSC after skin wounding is dependent on the MC1R–ACTH-α-MSH signaling pathway.