{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T16:11:38Z","timestamp":1783008698798,"version":"3.54.5"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Georgetown University Medical Center Student Research Grant Program"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>There are limited treatments for dyschromia in burn hypertrophic scars (HTSs). Initial work in Duroc pig models showed that 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 in an animal model and patient samples. In a Duroc pig model, melanocyte presence was confirmed using<jats:italic>en face<\/jats:italic>staining. Patients with dyschromic HTSs had demographic, injury details, and melanin indices collected. Punch biopsies were taken of regions of hyper-, hypo-, or normally pigmented scar and skin. Biopsies were processed to obtain epidermal sheets (ESs). A subset of ESs were<jats:italic>en face<\/jats:italic>stained with melanocyte marker, S100\u03b2. Melanocytes were isolated from a different subset. Melanocytes were treated with NDP \u03b1-MSH, a pigmentation stimulator. mRNA was isolated from cells, and was used to evaluate gene expression of melanin-synthetic genes. In patient and pig scars, regions of hyper-, hypo-, and normal pigmentation had significantly different melanin indices. S100\u03b2<jats:italic>en face<\/jats:italic>staining showed that regions of hyper- and hypo-pigmentation contained the same number of melanocytes, but these cells had different dendricity\/activity. Treatment of hypo-pigmented melanocytes with NDP \u03b1-MSH produced melanin by microscopy. Melanin-synthetic genes were upregulated in treated cells over controls. While traditionally it may be thought that hypopigmented regions of burn HTS display this phenotype because of the absence of pigment-producing cells, these data show that inactive melanocytes are present in these scar regions. By treating with a pigment stimulator, cells can be induced to re-pigment.<\/jats:p>","DOI":"10.1371\/journal.pone.0248985","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T20:33:03Z","timestamp":1616704383000},"page":"e0248985","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Hypopigmented burn hypertrophic scar contains melanocytes that can be signaled to re-pigment by synthetic alpha-melanocyte stimulating hormone in vitro"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2292-4960","authenticated-orcid":true,"given":"Bonnie C.","family":"Carney","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taryn E.","family":"Travis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren T.","family":"Moffatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6969-2648","authenticated-orcid":true,"given":"Laura S.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa M.","family":"McLawhorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia M.","family":"Simbulan-Rosenthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean S.","family":"Rosenthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey W.","family":"Shupp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"issue":"10","key":"pone.0248985.ref001","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1038\/jid.2015.197","article-title":"Race and Melanocortin 1 Receptor Polymorphism R163Q Are Associated with Post-Burn Hypertrophic Scarring: A Prospective Cohort Study","volume":"135","author":"RF Sood","year":"2015","journal-title":"The Journal of investigative dermatology"},{"issue":"4","key":"pone.0248985.ref002","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0305-4179(03)00067-6","article-title":"What is the prevalence of hypertrophic scarring following burns?","volume":"29","author":"KM Bombaro","year":"2003","journal-title":"Burns: journal of the International Society for Burn Injuries"},{"issue":"2","key":"pone.0248985.ref003","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1097\/BCR.0000000000000224","article-title":"A primer on pigmentation","volume":"36","author":"DG Greenhalgh","year":"2015","journal-title":"Journal of burn care & research: official publication of the American Burn Association"},{"key":"pone.0248985.ref004","article-title":"Pigmentation Diathesis of Hypertrophic Scar: An Examination of Known Signaling Pathways to Elucidate the Molecular Pathophysiology of Injury-Related Dyschromia","author":"BC Carney","year":"2018","journal-title":"J Burn Care Res"},{"issue":"E1","key":"pone.0248985.ref005","doi-asserted-by":"crossref","first-page":"E14","DOI":"10.1038\/skinbio.2011.6","article-title":"Molecular aspects of tanning","volume":"131","author":"BA Gilchrest","year":"2011","journal-title":"The Journal of investigative dermatology"},{"issue":"9","key":"pone.0248985.ref006","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1007\/s00018-009-8703-8","article-title":"Cellular mechanisms regulating human melanogenesis","volume":"66","author":"HY Park","year":"2009","journal-title":"Cell Mol Life Sci"},{"key":"pone.0248985.ref007","first-page":"19","article-title":"MC1R: Front and Center in the Bright Side of Dark Eumelanin and DNA Repair","author":"VB Swope","year":"2018","journal-title":"International journal of molecular sciences"},{"issue":"1","key":"pone.0248985.ref008","doi-asserted-by":"crossref","first-page":"30","DOI":"10.5114\/pdia.2013.33376","article-title":"Skin melanocytes: biology and development","volume":"30","author":"M Cichorek","year":"2013","journal-title":"Postepy Dermatol Alergol"},{"issue":"1","key":"pone.0248985.ref009","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1097\/BCR.0000000000000154","article-title":"A multimodal assessment of melanin and melanocyte activity in abnormally pigmented hypertrophic scar","volume":"36","author":"TE Travis","year":"2015","journal-title":"J Burn Care Res"},{"key":"pone.0248985.ref010","article-title":"Treatment Strategies for Hypopigmentation in the Context of Burn Hypertrophic Scars. 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