55 Melanocytes in Hypopigmented Burn Scar Can Be Stimulated to Produce Melanin

Abstract

Abstract Introduction Currently, there are limited clinical treatments for dyschromia in burn hypertrophic scars (HTSs). Initial pilot work in a Duroc pig model showed that melanocyte quantity does not influence pigmentation. Regions of scar that are light or dark have equal numbers of melanocytes. This study aims to confirm melanocyte presence in regions of hypo- and hyper-pigmentation. If melanocytes are present, pigmentation stimulators may be a useful therapy. Methods Following IRB approval, patients with dyschromic HTSs were enrolled and demographic, injury and treatment details, and melanin indices by Skin Color Catch probes (SCC) were collected. Punch biopsies were taken of distinct regions of hyper-, hypo-, or normally pigmented scar and skin. Biopsies were processed to obtain epidermal sheets (ESs). A subset of ESs were stained using en face staining with melanocyte marker, S100b. Melanocytes were isolated from a different subset. Melanocytes were treated with NDP a-MSH, a pigmentation stimulator. mRNA was isolated from cells, and qRT-PCR was used to evaluate gene expression of melanin-synthetic genes, tyrosinase (TYR), tyrosinase-related protein-1 (TYRP1) and dopachrome tautomerase (DCT). Results 8 patients were enrolled and the cohort included patients with Fitzpatrick skin types 5 (n=6) and 3 (n=2). HTSs ranged from 4 to 395 months old and dyschromia developed mainly due to healing by re-epithelialization and was refractory to prior scar treatments. By SCC, regions of hyper-, hypo-, and normal pigmentation had significantly different melanin indices (864.9 ± 19.8 vs. 627.1 ± 30.3 vs. 786.5 ± 21.4, p< 0.01). S100b en face staining showed that regions of hyper- and hypo-pigmentation contained the same number of melanocytes (14.6 ± 3.1 vs. 14.5 ± 3.2 melanocytes/HPF (n=5, p=0.99), but these cells had different dendricity, or activity (3.9 ± 0.5 vs. 0.4 ± 0.2 dendrites/cell (n=5, p< 0.0001). When hypo-pigmented melanocytes were treated with NDP a-MSH, cells produced melanin visible by bright-field microscopy (n=3). TYR, TYRP1, and DCT gene expression were upregulated in treated cells compared to controls. Conclusions While traditionally, it may be thought that hypo-pigmented regions of burn HTS display this phenotype because of the absence of pigment-producing cells, these data show that melanocytes are present in these scar regions. The cells are present, but they are inactive in pigment production. By treating the cells with a pigment stimulator, cells can be induced to re-pigment. Applicability of Research to Practice Patients were asked, on a scale of 1–10 with 1 being “no, not at all”, and 10 being “yes, very much”, “Is the scar color different from the color of your normal skin at present?” All patients rated this question as 10/10, indicating that scar dyschromia is a pervasive problem. Patients’ quality of life may be improved with the development of treatments for hypopigmentation.