Hypopigmented burn hypertrophic scar contains melanocytes that can be signaled to re-pigment by synthetic alpha-melanocyte stimulating hormone in vitro

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...

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Published in:PloS one Vol. 16; no. 3; p. e0248985
Main Authors: Carney, Bonnie C, Travis, Taryn E, Moffatt, Lauren T, Johnson, Laura S, McLawhorn, Melissa M, Simbulan-Rosenthal, Cynthia M, Rosenthal, Dean S, Shupp, Jeffrey W
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Published: United States Public Library of Science 25-03-2021
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Abstract 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 en face 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 en face stained with melanocyte marker, S100β. Melanocytes were isolated from a different subset. Melanocytes were treated with NDP α-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. S100β en face 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 α-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.
AbstractList 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 en face 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 en face stained with melanocyte marker, S100β. Melanocytes were isolated from a different subset. Melanocytes were treated with NDP α-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. S100β en face 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 α-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.
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 en face 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 en face stained with melanocyte marker, S100β. Melanocytes were isolated from a different subset. Melanocytes were treated with NDP α-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. S100β en face 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 α-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.
Author Travis, Taryn E
Johnson, Laura S
Rosenthal, Dean S
Moffatt, Lauren T
Simbulan-Rosenthal, Cynthia M
Carney, Bonnie C
Shupp, Jeffrey W
McLawhorn, Melissa M
AuthorAffiliation 1 Department of Biochemistry and Molecular and Cellular Biology, Georgetown University School of Medicine, Washington, DC, United States of America
2 Firefighters’ Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC, United States of America
Boston University School of Medicine, UNITED STATES
4 Department of Surgery, The Burn Center, MedStar Washington Hospital Center, Washington, DC, United States of America
3 Department of Surgery, Georgetown University School of Medicine, Washington, DC, United States of America
AuthorAffiliation_xml – name: Boston University School of Medicine, UNITED STATES
– name: 3 Department of Surgery, Georgetown University School of Medicine, Washington, DC, United States of America
– name: 1 Department of Biochemistry and Molecular and Cellular Biology, Georgetown University School of Medicine, Washington, DC, United States of America
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/33765043$$D View this record in MEDLINE/PubMed
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CitedBy_id crossref_primary_10_1007_s00266_023_03828_8
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2021 Carney et al 2021 Carney et al
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Snippet 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...
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SubjectTerms Animal models
Biochemistry
Biology
Biology and Life Sciences
Biopsy
c-Kit protein
Cellular biology
Colony-stimulating factor
Data analysis
Deoxyribonucleic acid
DNA
DNA damage
Editing
Endothelin ETB receptors
Eutrophication
Fibroblast growth factor 1
Fibroblast growth factor receptor 1
Firefighters
Funding
Gene expression
Genes
Granulocyte-macrophage colony stimulating factor
Growth factors
Health care facilities
Hospitals
Keratinocytes
Kinases
Laboratories
Leukocytes (granulocytic)
Macrophages
Medical research
Medicine
Medicine and Health Sciences
Melanin
Melanocytes
Methodology
Nerve growth factor receptors
p53 Protein
Patients
Phenotypes
Physical Sciences
Pigmentation
Pigments
Proopiomelanocortin
Prostaglandin E2
Proteins
Receptors
Research and analysis methods
Reviews
Scars
Signal transduction
Skin
Staining
Stem cell factor
Stem cells
Stimulators
Surgery
Swine
Transcription factors
Ultraviolet radiation
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Title Hypopigmented burn hypertrophic scar contains melanocytes that can be signaled to re-pigment by synthetic alpha-melanocyte stimulating hormone in vitro
URI https://www.ncbi.nlm.nih.gov/pubmed/33765043
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http://dx.doi.org/10.1371/journal.pone.0248985
Volume 16
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