Regenerative efficacy of fibroblast growth factor for the treatment of aged vocal fold: From animal model to clinical application

• Published in: Clinical otolaryngology Vol. 46; no. 1; pp. 131 - 137
• Main Authors: Ban, Myung Jin, Lee, Seung Chul, Park, Jae Hong, Park, Ki Nam, Kim, Hee Kyung, Lee, Seung Won
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.01.2021
• Subjects: Aged; Aging - pathology; animal experimentation; Animal models; Animals; Atrophy; Clinical trials; Collagen (type I); Complications; Disease Models, Animal; dysphonia; Dysphonia - etiology; Dysphonia - pathology; Dysphonia - prevention & control; Female; Fibroblast growth factors; Fibroblast Growth Factors - therapeutic use; Fibroblasts; Gene expression; Growth factors; Humans; Hyaluronic acid; Injection; Lamina propria; Larynx; Male; Matrix metalloproteinase; Matrix metalloproteinases; Metalloproteinase; Middle Aged; Patients; Procollagen; Prospective Studies; Rats; Rats, Sprague-Dawley; Rodents; Side effects; vocal cord; Vocal Cords - drug effects; Vocal Cords - pathology; Vocal organs; Voice; voice quality; fibroblast growth factors; voice quality; prospective studies; aged; animal experimentation; vocal cord; dysphonia
• ISSN: 1749-4478; 1749-4486
• DOI: 10.1111/coa.13597

Objectives We assessed fibroblast growth factor (FGF) regenerative efficacy in an aged vocal fold rat model and confirmed it in a prospective clinical trial. Design, setting, and participants For animal experiments, 48 Sprague‐Dawley rats were divided into two groups: 24 six‐month‐olds (young group) and 24 twenty‐four‐month‐olds (old group). FGF was injected once a week thrice into the left vocal fold of the old group, dividing them into two sub‐groups (injected [left] and uninjected [right]). Additionally, we conducted a prospective clinical trial for 38 patients with aged atrophic vocal fold. Main outcome measures A month post‐injection, excised larynx from the three groups was subjected to comparative histopathological (ratio of relative lamina propria to total vocal fold) and mRNA expression analysis (of procollagen I, hyaluronic acid synthase (HAS)‐2 and matrix metalloproteinase (MMP)‐2) by real‐time PCR. We performed perceptual, stroboscopic, acoustic aerodynamic test and Voice Handicap Index survey prior to and 1, 6 and 12 months after FGF injection. Results In rats, the relative lamina propria ratio increased after FGF injection. Procollagen I mRNA level decreased, whereas that of HAS‐2 and MMP‐2 increased significantly in the injected compared to the uninjected old group. Enrolled patients showed improved subjective and objective voice parameters after FGF injection, and these were maintained for a year. Potential side effects were not observed. Conclusions Animal experiments and prospective clinical trial suggest that FGF injection to vocal fold can significantly improve voice quality until one year, without complications, and is effective for aged atrophic vocal fold treatment.