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

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.

SUBMITTER: Carney BC

PROVIDER: S-EPMC7993611 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: As a fibrotic disease with a high incidence, the pathogenesis of hypertrophic scarring is still not fully understood, and the treatment of this disease is also challenging. In recent years, human adipose-derived mesenchymal stem cells (AD-MSCs) have been considered an effective treatment for hypertrophic scars. This study mainly explored whether the therapeutic effect of AD-MSCs on hypertrophic scars is associated with oxidative-stress-related proteins. Methods: AD-MSCs were isolated from adipose tissues and characterized through flow cytometry and a differentiation test. Afterwards, coculture, cell proliferation, apoptosis, and migration were detected. Western blotting and a quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect oxidative stress-related genes and protein expression in hypertrophic scar fibroblasts (HSFs). Flow cytometry was used to detect reactive oxygen species (ROS). A nude mouse animal model was established; the effect of AD-MSCs on hypertrophic scars was observed; and hematoxylin and eosin staining, Masson's staining, and immunofluorescence staining were performed. Furthermore, the content of oxidative-stress-related proteins, including nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), B-cell lymphoma 2(Bcl2), Bcl2-associated X(BAX) and caspase 3, was detected. Results: Our results showed that AD-MSCs inhibited HSFs' proliferation and migration and promoted apoptosis. Moreover, after coculture, the expression of antioxidant enzymes, including HO-1, in HSFs decreased; the content of reactive oxygen species increased; and the expression of Nrf2 decreased significantly. In animal experiments, we found that, at 14 days after injection of AD-MSCs into human hypertrophic scar tissue blocks that were transplanted onto the dorsum of nude mice, the weight of the tissue blocks decreased significantly. Hematoxylin and eosin staining and Masson's staining demonstrated a rearrangement of collagen fibers. We also found that Nrf2 and antioxidant enzymes decreased significantly, while apoptotic cells increased after AD-MSC treatment. Conclusions: Our results demonstrated that AD-MSCs efficiently cured hypertrophic scars by promoting the apoptosis of HSFs and by inhibiting their proliferation and migration, which may be related to the inhibition of Nrf2 expression in HSFs, suggesting that AD-MSCs may provide an alternative therapeutic approach for the treatment of hypertrophic scars.

Project description:ObjectiveThe aim of the study was to determine the longitudinal validity, reproducibility, responsiveness and interpretability of the adult version of the Brisbane Burn Scar Impact Profile, a patient-report measure of health-related quality of life.MethodsA prospective longitudinal cohort study of patients with or at risk of burn scarring was conducted at three assessment points (at baseline around the time of wound healing, one to two weeks post-baseline and 1-month post-baseline). Participants attending a major metropolitan adult burn centre at baseline were recruited. Participants completed the Brisbane Burn Scar Impact Profile and the 36-item Short Form Health Survey and Patient Observer Scar Assessment Scale. Intraclass Correlation Coefficients (ICCs), smallest detectable change, percentage of those who improved, stayed the same or worsened and Area under the Receiver Operating Characteristic Curve (AUC) were used to test the aim.ResultsData were included for 118 participants at baseline, 68 participants at one to two weeks and 57 participants at 1-month post-baseline. All groups of items had acceptable reproducibility, except for the overall impact of burn scars (ICC = 0.69), the impact of sensations which was not expected to be stable (ICC = 0.63), mobility and daily activities (ICC = 0.63, 0.67 respectively). The responsiveness of six out of seven groups of items able to be tested against external criterion was supported (AUC = 0.72-0.75). Hypothesised correlations of changes in the Brisbane Burn Scar Impact Profile items with changes in criterion measures generally supported longitudinal validity (e.g., nine out of thirteen hypotheses using the SF-36 as an external criterion were supported). Internal consistency estimates, item-total and inter-item correlations indicated there was likely redundancy of some groups of items, particularly in the relationships and social interaction, appearance and emotional reactions items (Chronbach's alpha range = 0.94-0.95).ConclusionSupport was found for the reproducibility, longitudinal validity, responsiveness and interpretability of most groups of Brisbane Burn Scar Impact Profile items and some individual items in the test population. Potential redundancy of items should be investigated further.

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

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