Can a factor released by fat-derived stem cells curb fibrosis in scar cells?

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Researchers investigated how adipose-derived stem cells (ADSCs) affect fibrosis in hypertrophic scar-derived fibroblasts (HSFs), and the mechanism involved. Previous co-culture experiments had reported that ADSCs reduce collagen production and fibroblast proliferation. In rabbit ear scar models, ADSC-conditioned medium (ADSCs-CM) had inhibited fibrosis by decreasing expression of collagen type I (Col1) and α-smooth muscle actin (α-SMA). Hepatocyte growth factor (HGF), the primary growth factor in ADSCs-CM, had been shown to reverse fibrosis in various fibrotic diseases. The researchers tested the hypothesis that ADSCs inhibit HSF fibrosis by secreting HGF.

In a cell-culture experiment, HSFs were treated with DMEM containing 0%, 10%, 50% or 100% ADSCs-CM. Cell viability was assessed with a cell viability assay, and collagen production was examined using Sirius red staining. Expression and secretion of fibrosis and degradation proteins were measured separately. After measuring HGF concentration in ADSCs-CM, researchers treated equal numbers of HSFs with either 50% ADSCs-CM or HGF. They neutralized HGF activity in ADSCs-CM with a goat anti-human HGF antibody.

ADSCs-CM decreased cell viability, expression of fibrosis molecules and tissue inhibitor of metalloproteinases-1 (TIMP-1) in a dose-dependent manner, while significantly increasing matrix metalloproteinase-1 (MMP-1) expression in HSFs. Collagen production and the ratio of collagen type I to type III (Col1/Col3) also decreased with increasing ADSCs-CM concentration. HSFs cultured with either 50% ADSCs-CM or HGF at 1 ng/ml showed similar trends 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 fibrosis factors in the control group. The researchers concluded that HGF secreted by ADSCs inhibits fibrosis-related factors and regulates extracellular matrix (ECM) remodeling in hypertrophic scar fibroblasts.