Bone marrow derived mesenchymal stem cells inhibit the proliferative and profibrotic phenotype of hypertrophic scar fibroblasts and keloid fibroblasts through paracrine signaling

Autor: Ming Liu, Fengjun Fang, Ran Huo, Yongchao Zheng, Ru-Lin Huang
Rok vydání: 2015
Předmět:
0301 basic medicine
Male
Pathology
Decorin
medicine.medical_treatment
Biochemistry
Extracellular matrix
Keloid
Cells
Cultured
Skin
biology
Chemistry
Middle Aged
Cell biology
Extracellular Matrix
Female
Adult
medicine.medical_specialty
Adolescent
Cicatrix
Hypertrophic
Bone Marrow Cells
Dermatology
Real-Time Polymerase Chain Reaction
Collagen Type I
Transforming Growth Factor beta1
03 medical and health sciences
Hypertrophic scar
Paracrine signalling
Transforming Growth Factor beta2
Young Adult
Transforming Growth Factor beta3
Paracrine Communication
Plasminogen Activator Inhibitor 1
medicine
Humans
Molecular Biology
Cell Proliferation
Wound Healing
Growth factor
Connective Tissue Growth Factor
Mesenchymal Stem Cells
Fibroblasts
medicine.disease
Fibronectins
Fibronectin
030104 developmental biology
Culture Media
Conditioned
biology.protein
Wound healing
Zdroj: Journal of dermatological science. 83(2)
ISSN: 1873-569X
Popis: 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-β 1 , and transforming growth factor-β 2 , in HSFs and KFs at both transcriptional and translational levels. In contrast, the expression of antifibrotic genes, such as transforming growth factor-β 3 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.
Databáze: OpenAIRE
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