脂肪细胞疗法在人声带褶皱瘢痕体外纤维生成模型中的旁分泌效应

IF 2.5 4区 医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY
Mélanie Velier , Alexia Mattei , Stéphanie Simoncini , Jérémy Magalon , Laurent Giraudo , Laurent Arnaud , Antoine Giovanni , Francoise Dignat-George , Florence Sabatier , Markus Gugatschka , Tanja Grossmann
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引用次数: 0

摘要

目标/假设:声带褶皱(VF)瘢痕会导致严重的发音障碍,对患者的日常生活造成负面影响。由于声带褶皱的微观结构非常复杂,目前的治疗方案非常有限。来自脂肪组织的创新疗法,如基质血管成分(SVF)或脂肪衍生基质/干细胞(ASC),目前正在对这一适应症进行评估,旁分泌抗纤维化作用被认为是主要机制:方法:在一个创新的体外纤维生成模型中,利用人体VF纤维母细胞(hVFF)和大分子拥挤(MMC)原理,测试了来自健康供体的SVF和ASC的旁分泌抗纤维化作用。在与 ASC 或 SVF 间接共培养五天后,使用银染色、Western 印迹和 RT-qPCR 分析对 hVFF 中胶原的生物合成和α-平滑肌肌动蛋白(αSMA)的表达进行量化:结果:加入转化生长因子β1(TGFβ1)和 MMC 可促进纤维生成,其特点是纤维胶原沉积增强,并获得肌成纤维细胞表型(αSMA 过度表达)。脂肪衍生疗法导致αSMA表达减少,与SVF共同培养的hVFF中胶原蛋白含量降低:ASC和SVF通过旁分泌机制在体外纤维化模型中显著预防了纤维化,支持了脂肪源性细胞疗法在VF瘢痕中的进一步发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Paracrine Effects of Adipose-Derived Cellular Therapies in an in Vitro Fibrogenesis Model of Human Vocal Fold Scarring

Objectives/Hypothesis

Vocal folds (VF) scarring leads to severe dysphonia which negatively impacts daily life of patients. Current therapeutic options are limited due in large part to the high complexity of the micro-structure of the VF. Innovative therapies derived from adipose tissue such as stromal vascular fraction (SVF) or adipose derived stromal/ stem cells (ASC) are currently being evaluated in this indication and paracrine anti-fibrotic effects are considered as predominant mechanisms.

Methods

The paracrine anti-fibrotic effects of SVF and ASC from healthy donors were tested in an innovative in vitro fibrogenesis model employing human VF fiboblasts (hVFF) and the principles of macromolecular crowding (MMC). Biosynthesis of collogen and alpha-smooth-muscle actin (αSMA) expression in hVFF were quantified after five days of indirect coculture with ASC or SVF using silver stain, western blot and RT-qPCR analysis.

Results

Fibrogenesis was promoted by addition of transforming growth factor beta 1 (TGFβ1) combined with MMC characterized by an enhanced deposition of fibrillar collagens and the acquisition of a myofibroblast phenotype (overexpression of αSMA). Adipose-derived therapies led to a reduction in the αSMA expression and the collagen content was lower in hVFF co-cultivated with SVF.

Conclusions

ASC and SVF promoted significant prevention of fibrosis in an in vitro fibrogenesis model through paracrine mechanisms, supporting further development of adipose-derived cellular therapies in VF scarring.
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来源期刊
Journal of Voice
Journal of Voice 医学-耳鼻喉科学
CiteScore
4.00
自引率
13.60%
发文量
395
审稿时长
59 days
期刊介绍: The Journal of Voice is widely regarded as the world''s premiere journal for voice medicine and research. This peer-reviewed publication is listed in Index Medicus and is indexed by the Institute for Scientific Information. The journal contains articles written by experts throughout the world on all topics in voice sciences, voice medicine and surgery, and speech-language pathologists'' management of voice-related problems. The journal includes clinical articles, clinical research, and laboratory research. Members of the Foundation receive the journal as a benefit of membership.
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