Hiwatashi Nao, Hirano Shigeru, Mizuta Masanobu, Kobayashi Toshiki, Kawai Yoshitaka, Kanemaru Shin-Ichi, Nakamura Tatsuo, Ito Juichi, Kawai Katsuya, Suzuki Shigehiko
Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan.
Department of Otolaryngology, Vanderbilt University, Nashville, TN, USA.
J Tissue Eng Regen Med. 2017 May;11(5):1598-1609. doi: 10.1002/term.2060. Epub 2015 Jun 29.
Vocal fold scar remains a therapeutic challenge. Basic fibroblast growth factor (bFGF) was reported to have regenerative effects for vocal fold scar, although it has the disadvantage of rapid absorption in vivo. A collagen-gelatin sponge (CGS) can compensate for the disadvantage by providing a sustained release system. The current study evaluated the efficacy of CGS combined with bFGF on vocal fold scar, using rat fibroblasts for an in vitro model and a canine in vivo model. We prepared fibroblasts from scarred vocal folds (sVFs) in rats and showed that bFGF accelerated cell proliferation and suppressed expression levels of cleaved caspase 3 and α-smooth muscle actin. Has 1, Has 3, Fgf2, Hgf and Vegfa mRNA levels were significantly upregulated, while Col1a1 and Col3a1 were dose-dependently downregulated, with a maximum effect at 100 ng/ml bFGF. In an in vivo assay, 6 weeks after lamina propria stripping, beagles were divided into three groups: CGS alone (CGS group); CGS with bFGF (7 µg/cm ; CGS + bFGF group); or a sham-treated group. Vibratory examination revealed that the glottal gap was significantly reduced in the bFGF group and the two implanted groups, whereas the CGS + bFGF group showed higher mucosal wave amplitude. Histological examination revealed significantly restored hyaluronic acid and elastin redistribution in the CGS + bFGF group and reductions in dense collagen deposition. These results provide evidence that CGS and bFGF combination therapy may have therapeutic potential and could be a promising tool for treating vocal fold scar. Copyright © 2015 John Wiley & Sons, Ltd.
声带瘢痕仍然是一个治疗难题。据报道，碱性成纤维细胞生长因子（bFGF）对声带瘢痕具有再生作用，尽管它在体内存在快速吸收的缺点。胶原 - 明胶海绵（CGS）可以通过提供缓释系统来弥补这一缺点。本研究使用大鼠成纤维细胞建立体外模型和犬体内模型，评估了CGS联合bFGF对声带瘢痕的疗效。我们从大鼠瘢痕化声带（sVFs）中制备了成纤维细胞，并表明bFGF可加速细胞增殖，抑制裂解的半胱天冬酶3和α - 平滑肌肌动蛋白的表达水平。Has 1、Has 3、Fgf2、Hgf和Vegfa的mRNA水平显著上调，而Col1a1和Col3a1呈剂量依赖性下调，在100 ng/ml bFGF时达到最大效应。在体内试验中，固有层剥离6周后，将比格犬分为三组：单独使用CGS（CGS组）；CGS联合bFGF（7 μg/cm；CGS + bFGF组）；或假手术治疗组。振动检查显示，bFGF组和两个植入组的声门间隙显著减小，而CGS + bFGF组的黏膜波幅更高。组织学检查显示，CGS + bFGF组的透明质酸和弹性蛋白重新分布明显恢复，致密胶原沉积减少。这些结果表明，CGS和bFGF联合治疗可能具有治疗潜力，可能是治疗声带瘢痕的一种有前景的工具。版权所有© 2015 John Wiley & Sons, Ltd.
