Hypopigmented Hypertrophic Scar Can Be Treated With Synthetic Alpha Melanocyte Stimulating Hormone
Bonnie C. Carney1, Lauren T. Moffatt2, Cynthia M. Simbulan-Rosenthal1, Dean S. Rosenthal1, Jeffrey W. Shupp2.
1Department of Biochemistry, Georgetown University School of Medicine, Washington, DC, USA, 2Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC, USA.
BACKGROUND: Burn injuries often heal through abnormal wound healing mechanisms and result in hypertrophic scar (HTS) with dyschromia. The mechanism behind HTS dyschromia has not been studied and treatments are lacking. In previous work, we showed that regions of hypo-pigmented scar contain inactive melanocytes. Normal skin cells make melanin through keratinocyte secretion and binding of alpha-melanocyte stimulating hormone (α-MSH) to melanocyte melanocortin receptors to initiate melanogenesis by tyrosinase (TYR), tyrosinase-related protein-1 (TYRP1), and dopachrome tautomerase (DCT). In previous work, we showed that α-MSH expression is absent in hypo-pigmented scar. A nude mouse model of xenografted porcine dyschromic HTS was developed to test if supplying hypo-pigmented cells with α-MSH can re-pigment the scar.
METHODS: Dyschromic HTSs were created in Duroc pigs. Epidermal cells were derived from regions of hyper-, hypo-, or normally pigmented scar or skin. Dermal fibroblasts (DFs) were isolated separately. Wounds were created on nude mice and a grafting dome was placed. DFs were seeded on day 0. Epidermal cells were seeded on day 3. The dome was removed on day 7 and hypo-pigmented xenografts were treated with synthetic α-MSH delivered with microneedling. On day 10, the xenografts were excised. Sections were stained using H&E. RNA was isolated and qRT-PCR was performed for TYR, TYRP1, and DCT.
RESULTS: HTSDFs formed a dermis similar in structure and cellularity to HTS dermis from porcine HTS. When hyper-, hypo-, and normally-pigmented epidermal cells were seeded, a fully stratified epithelium was formed. In the xenograft, epidermal thickness by H&E staining was 0.11 vs. 0.06 μm in normal pig skin. Treated hypo-pigmented xenografts showed increased pigmentation and had increased transcription of TYR, TYRP1, and DCT compared to controls (TYR: 2.7 vs 0.3; TYRP1: 2.6 vs 0.3; DCT: 0.7 vs 0.3 fold change from control; n=3).
CONCLUSIONS: The developed nude mouse scar xenograft model can be used to study treatments for dyschromia. Hypo-pigmented regions of burn scar can be stimulated to make melanin by synthetic α-MSH.
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