Abstract
ObjectivesVocal fold (VF) scarring remains a therapeutic challenge. Granulocyte-macrophage colony-stimulating factor (GM-CSF) facilitates epithelial wound healing, and recently, growth factor therapy has been applied to promote tissue repair. This study was undertaken to investigate the effect of GM-CSF on VF wound healing in vivo and in vitro.MethodsVF scarring was induced in New Zealand white rabbits by direct injury. Immediately thereafter, either GM-CSF or PBS was injected into the VFs of rabbits. Endoscopic, histopathological, immunohistochemical, and biomechanical evaluations of VFs were performed at 3 months post-injury. Human vocal fold fibroblasts (hVFFs) were cultured with GM-CSF. Production of type I and III collagen was examined immunocytochemically, and the synthesis of elastin and hyaluronic acids was evaluated by ELISA. The mRNA levels of genes related to ECM components and ECM production-related growth factors, such as HGF and TGF-ß1, were examined by real time RT-PCR.ResultsThe GM-CSF-treated VFs showed reduced collagen deposition in comparison to the PBS-injected controls (P<0.05). Immunohistochemical staining revealed lower amounts of type I collagen and fibronectin in the GM-CSF-treated VFs (P<0.05 and P<0.01, respectively). Viscous and elastic shear moduli of VF samples were significantly lower in the GM-CSF group than in the PBS-injected group (P<0.001 and P<0.01, respectively). Mucosal waves in the GM-CSF group showed significant improvement when compared to the PBS group (P = 0.0446). GM-CSF inhibited TGF-β1-induced collagen synthesis by hVFFs (P<0.05) and the production of hyaluronic acids increased at 72 hours post-treatment (P<0.05). The expressions of HAS-2, tropoelastin, MMP-1, HGF, and c-Met mRNA were significantly increased by GM-CSF, although at different time points (P<0.05).ConclusionThe present study shows that GM-CSF offers therapeutic potential for the remodeling of VF wounds and the promotion of VF regeneration.
Highlights
Vocal folds (VFs) are vital for voice production via aerodynamically driven oscillation of pliable, layered VF mucosa
The remodeling of extracellular matrix (ECM) composition and organization by encouraging VF fibroblasts to synthesize favorable ECM components during the wound healing phase has been the focus of a number of studies undertaken to prevent or mitigate scarring
We hypothesized that Granulocyte-macrophage colony-stimulating factor (GM-CSF) would promote wound remodeling following VF injury, and that the local administration of GM-CSF would improve VF regeneration. To prove this hypothesis and to assess the potential of GM-CSF as a novel therapeutic candidate for VF wound healing, we investigated the effects of injection of GM-CSF on VF wound healing in a rabbit model and investigated the mechanisms involved using in vitro cultured human VF fibroblasts
Summary
Vocal folds (VFs) are vital for voice production via aerodynamically driven oscillation of pliable, layered VF mucosa. Harmonious oscillation of VF mucosa, which is important for the maintenance of voice quality, is mainly attributed to the biomechanics of the layered structure of VFs. The biomechanical properties of VF layers are primarily characterized by their extracellular matrix (ECM) composition and organization [1]. VF injury caused by vocal abuse, surgery, or inflammation commonly results in VF scarring, which disrupts the layered structure of VFs, alters the biomechanical properties of layered VFs, and possibly leads to intractable dysphonia [2]. The remodeling of ECM composition and organization by encouraging VF fibroblasts to synthesize favorable ECM components during the wound healing phase has been the focus of a number of studies undertaken to prevent or mitigate scarring
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
