HGF and bFGF Secreted by Adipose-Derived Mesenchymal Stem Cells Revert the Fibroblast Phenotype Caused by Vocal Fold Injury in a Rat Model.

Summary Objective To investigate how adipose-derived mesenchymal stem cells (ADSCs), secreted hepatocyte growth factor (HGF), and basic fibroblast growth factor (bFGF) affect the fibroblast phenotype after vocal fold injury. Methods We cultured primary normal (uninjured) and injured vocal fold fibroblasts (VFFs). A transwell co-culture system of ADSCs and injured VFFs was constructed in vitro, then the effects of HGF or bFGF were inhibited. The proliferation, extracellular matrix (ECM) secretion and transformation of VFFs were observed. Results Compared with uninjured VFFs, the secretion of collagen by injured VFFs increased significantly, hyaluronan synthase 1 (HAS1) secretion decreased, and VFF transformation increased significantly. After co-culture with ADSCs, the proliferation of VFFs was accelerated and the transformation was inhibited. Co-culture inhibited the expression of type I and III collagen and promoted the expression of HAS1. When HGF or bFGF secretion was inhibited, the proliferation of injured VFFs was inhibited. The inhibitory effect on collagen was reduced by both groups, but this was more obvious with the anti-HGF group. The anti-bFGF group had a more prominent effect on HAS1 secretion after injury than the anti-HGF group but the difference was not statistically significant. The inhibition of the transformation of injured VFFs was reduced while α-smooth muscle actin was upregulated, which was more obvious with the anti-HGF group. Conclusions ADSCs and secreted HGF and bFGF can revert the fibroblast phenotype caused by vocal fold injury. The effects of HGF are more significant than bFGF on collagen secretion and the transformation of VFFs into myofibroblasts. However, bFGF is more effective than HGF in upregulating HAS1.