Bone marrow derived mesenchymal stem cells inhibit the proliferative and profibrotic phenotype of hypertrophic scar fibroblasts and keloid fibroblasts through paracrine signaling.
J Dermatol Sci
; 83(2): 95-105, 2016 Aug.
Article
em En
| MEDLINE
| ID: mdl-27211019
ABSTRACT
BACKGROUND:
Hypertrophic scars and keloids, characterized by over-proliferation of fibroblasts and aberrant formation of the extracellular matrix (ECM), are considered fibrotic diseases. Accumulating evidence indicates that mesenchymal stem cells (MSCs) promote scar-free wound healing and inhibit fibrotic tissue formation, making them a potentially effective therapeutic treatment for hypertrophic scars and keloids.OBJECTIVE:
To investigate the paracrine effects of bone marrow derived MSCs (BMSCs) on the biological behavior of hypertrophic scar fibroblasts (HSFs) and keloid fibroblasts (KFs).METHODS:
Proliferative and profibrotic phenotype changes of the fibroblasts were analyzed by immunofluorescence staining, in-cell western blot, and real-time PCR.RESULTS:
BMSC-conditioned medium inhibited HSF and KF proliferation and migration, but did not induce apoptosis. Interestingly, normal skin fibroblast-conditioned medium exhibited no inhibitory effects on HSF or KF proliferation and migration. Furthermore, BMSC-conditioned medium significantly decreased expression of profibrotic genes, including connective tissue growth factor, plasminogen activator inhibitor-1, transforming growth factor-ß1, and transforming growth factor-ß2, in HSFs and KFs at both transcriptional and translational levels. In contrast, the expression of antifibrotic genes, such as transforming growth factor-ß3 and decorin, was substantially enhanced under the same culture conditions. Finally, we observed that BMSC-conditioned medium suppressed the ECM synthesis in HSFs and KFs, as indicated by decreased expression of collagen I and fibronectin and low levels of hydroxyproline in cell culture supernatant.CONCLUSION:
These findings suggest that BMSCs attenuate the proliferative and profibrotic phenotype associated with HSFs and KFs and inhibit ECM synthesis through a paracrine signaling mechanism.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cicatrização
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Cicatriz Hipertrófica
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Comunicação Parácrina
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Matriz Extracelular
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Células-Tronco Mesenquimais
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Fibroblastos
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Queloide
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article