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Med Res Rev. 2017 Jul;37(4):907-935. doi: 10.1002/med.21426. Epub 2016 Dec 28.

Trends in Regenerative Medicine: Repigmentation in Vitiligo Through Melanocyte Stem Cell Mobilization.

Author information

1
Department of Dermatology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
2
Institute for In Vitro Sciences, Inc. (IIVS), Gaithersburg, MD.
3
Gates Center for Regenerative Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
4
Denver Department of Veterans Affairs Medical Center, Denver, CO.

Abstract

Vitiligo is the most frequent human pigmentary disorder, characterized by progressive autoimmune destruction of mature epidermal melanocytes. Of the current treatments offering partial and temporary relief, ultraviolet (UV) light is the most effective, coordinating an intricate network of keratinocyte and melanocyte factors that control numerous cellular and molecular signaling pathways. This UV-activated process is a classic example of regenerative medicine, inducing functional melanocyte stem cell populations in the hair follicle to divide, migrate, and differentiate into mature melanocytes that regenerate the epidermis through a complex process involving melanocytes and other cell lineages in the skin. Using an in-depth correlative analysis of multiple experimental and clinical data sets, we generated a modern molecular research platform that can be used as a working model for further research of vitiligo repigmentation. Our analysis emphasizes the active participation of defined molecular pathways that regulate the balance between stemness and differentiation states of melanocytes and keratinocytes: p53 and its downstream effectors controlling melanogenesis; Wnt/β-catenin with proliferative, migratory, and differentiation roles in different pigmentation systems; integrins, cadherins, tetraspanins, and metalloproteinases, with promigratory effects on melanocytes; TGF-β and its effector PAX3, which control differentiation. Our long-term goal is to design pharmacological compounds that can specifically activate melanocyte precursors in the hair follicle in order to obtain faster, better, and durable repigmentation.

KEYWORDS:

melanoblast; melanocyte stem cell; regeneration; repigmentation; vitiligo

PMID:
28029168
PMCID:
PMC5466503
[Available on 2017-07-01]
DOI:
10.1002/med.21426
[Indexed for MEDLINE]
Free PMC Article

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