Journal of dermatological science · 2016
Bone marrow derived mesenchymal stem cells inhibit the proliferative and profibrotic phenotype of hypertrophic scar fibroblasts and keloid fibroblasts through paracrine signaling.
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Fang Fengjun, Huang Ru-Lin, Zheng Yongchao, Liu Ming, Huo Ran
Аннотация
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-β1, and transforming growth factor-β2, in HSFs and KFs at both transcriptional and translational levels. In contrast, the expression of antifibrotic genes, such as transforming growth factor-β3 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.
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-β1, and transforming growth factor-β2, in HSFs and KFs at both transcriptional and translational levels. In contrast, the expression of antifibrotic genes, such as transforming growth factor-β3 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.
Предметные рубрики MeSH
AdolescentAdultBone Marrow CellsCell ProliferationCells, CulturedCicatrix, HypertrophicCollagen Type IConnective Tissue Growth FactorCulture Media, ConditionedDecorinExtracellular MatrixFemaleFibroblastsFibronectinsHumansKeloidMaleMesenchymal Stem CellsMiddle AgedParacrine CommunicationPlasminogen Activator Inhibitor 1Real-Time Polymerase Chain ReactionSkinTransforming Growth Factor beta1Transforming Growth Factor beta2Transforming Growth Factor beta3Wound HealingYoung Adult