Aims: To study the effect of Adipose-derived stem cells (ADSCs) on fibrosis
of hypertrophic scar-derived fibroblasts (HSFs) and its concrete mechanism.
Background: ADSCs have been reported to reduce collagen production and fibroblast
proliferation in co-culture experiments. Conditioned medium from adipose-derived stem
cells (ADSCs-CM) has successfully inhibited fibrosis by decreasing the expression of
collagen type І (Col1) and α-smooth muscle actin (α-SMA) in rabbit ear scar models.
Hepatocyte growth factor (HGF), the primary growth factor in ADSCs-CM, has been
shown to reverse fibrosis in various fibrotic diseases.
Objective: To test the hypothesis that ADSCs inhibit fibrosis of HSFs through the
secretion of HGF.
Methods: HSFs were treated with DMEM containing 0%, 10%, 50% and 100%
concentration of ADSCs-CM. The effect of ADSCs-CM on the viability was determined
by cell viability assay, and the collagen production in HSFs was examined by Sirius red
staining. Expression and secretion of fibrosis and degradation proteins were detected
separately. After measuring the concentration of HGF in ADSCs-CM, the same number
of HSFs were treated with 50% ADSCs-CM or HGF. HGF activity in ADSCs-CM was
neutralized with a goat anti-human HGF antibody.
Results: The results demonstrated that ADSCs-CM dose-dependently decreased cell
viability, expression of fibrosis molecules, and tissue inhibitor of metalloproteinases-1
(TIMP-1), and significantly increased matrix metalloproteinase-1 (MMP-1) expression in
HSFs. Collagen production and the ratio of collagen type І and type III (Col1/Col3) were
also suppressed by ADSCs-CM in a dose-dependent manner. When HSFs were
cultured with either 50% ADSCs-CM or HGF (1 ng/ml), a similar trend was observed in
gene expression and protein secretion. Adding an HGF antibody to both groups returned
protein expression and secretion to basal levels but did not significantly affect the
fibrosis factors in the control group.
Conclusion: Our findings revealed that adipose-derived stem cell-secreted HGF
effectively inhibits fibrosis-related factors and regulates extracellular matrix (ECM)
remodeling in hypertrophic scar fibroblasts.