Table I.

Models for Study of Skin Repigmentation

Model specie		Model type	Findings	Ref.
Mouse
	SLFTg1-1 injected with anti-c-Kit monoclonal antibody ACK2	Repigmentation non-vitiligo humanized	This transgenic mouse expresses in the basal layer steel factor (SLF), forced using the Krt14 promoter. As a result, these mice presented hyperpigmented areas (gums, paws, etc.) that are unpigmented, or hypopigmented in the wild-type mice; treatment with the anti-c-KIT (ACK2) antibody eliminated c-Kit-dependent melanoblasts in the hair follicle and induced complete skin and hair depigmentation maintained for at least 1 week after birth; there was a population of residual melanocyte stem cells c-Kit((−))/Dct(+) maintained in the skin of the SLF transgenic mice; this population was able to migrate and cover most of the epidermis after several months	26
	K14-SLF/+; Dct-lacZ/+ double transgenic (Tg/+)	Repigmentation non-vitiligo humanized	The K14-SLF; Dct-LacZ/+ double transgenic (Tg/+) expresses SLF mutation and the lacZ reporter gene under the control of the Dct promoter; these mice were treated with ACK2 antibody at neonatal stage; melanocyte stem cells exited the bulge and migrated along the ORS to the inferfollicular epidermis in the presence of SLF expressed by epidermal keratinocytes; close to the epidermal surface some melanocytes became pigmented, indicative of active differentiation; the findings provided evidence that the bulge stem cells represent a reservoir for epidermal melanocytes	27
	F1 hairless HR-1 × HR/De	Repigmentation non-vitiligo	These mice are homozygous or heterozygous dominant for the main coat color genes; starting at 2 weeks of age, they lose their hair coat rapidly due to an abnormal second hair cycle, becoming completely hairless at week 3. At week 4 they are depigmented. They represent a unique model in which delayed pigmented spots are induced long after UV irradiation; the melanocyte precursors with migratory ability were observed to exit the hair follicle bulge and move along the infundibulum to the epidermis following UVB exposure; melanocyte stem cells proliferated in the bulge and differentiated into melanoblasts that migrated to the epidermis and became melanotic cells	48
	Dct-LacZ+	Repigmentation non-vitiligo	Following the exposure to UVB or upon induction of a wound on the back of the mouse, melanocyte stem cells were shown to exit the bulge and migrate along the ORS infundibulum without proliferation; they proliferated and differentiated in the epidermis	98
	Mc1re/e	Repigmentation non-vitiligo	The wounded Mc1re/e mice (expressing a non-functional Melanocortin 1 receptor - Mc1r) presented a lower number of melanocyte stem cells that directly migrated from bulge to the epidermis, as compared to its control littermate Mc1r+/+ mice, suggesting impaired migration in the mutant mice Mc1re/e; this finding suggested that the defective melanocyte migration of Mc1re/e mice is attributed to the lack of Mc1r function	98
	Tyr-CreERT2; β-cateninfl(ex3)/+	Pigmentation non-vitiligo	Wnt-stimulated melanocyte stem cell differentiation into pigment-producing melanocyte, and that the subsequent induction of aberrant β-catenin activation was followed by ectopic pigmentation in the bulge, a region devoid of pigment	118
Human
	Punch grafts	Repigmentation vitiligo	Punch grafts were done on depigmented vitiligo lesions, and then they were exposed to Khellin + UV light. Immunostaining experiments revealed the migratory capacity of melanocytes (horizontal migration to depigmented areas)	119
	Skin biopsies	Repigmentation vitiligo	Skin biopsies taken from vitiligo untreated patients and from patients treated with NBUVB for 3 and 6 months were triple immunostained using melanocyte antibodies (anti-DCT, anti-C-KIT, anti-TYR, or anti-PAX3), anti-KI-67 antibody (labels proliferative cells) and/or anti-MCAM antibody (MCAM being associated with motile phenotypes), and a keratinocyte antibody (anti-K14); NBUVB was associated with a significant increase in the number of melanocytes in the infundibulum and with restoration of the normal melanocyte population in the epidermis, which was lacking in the untreated vitiligo biopsies; several precursor populations (melanocyte stem cells, melanoblasts, and other immature phenotypes), and progressively differentiating melanocytes, some with putative migratory and/or proliferative abilities, were identified	4

DCT, dopachrome tautomerase; MC1R, melanocortin 1 receptor; NBUVB, narrow band ultraviolet B; ORS, outer root sheath; Tyr, tyrosinase; UV, ultraviolet.