声带损伤后固有层细胞外基质无序沉积、紊乱排列，由此导致不可逆的发音障碍是目前国内外治疗的难点。我们前期研究虽然发现脂肪间充质干细胞及其复合物对损伤声带修复再生有一定作用，但干细胞移植入损伤部位后存活率低，并未全部分化为相应的靶组织细胞，使其作用受到限制。本项目拟重点探讨脂肪间充质干细胞 "旁分泌"调控机制在促进损伤声带修复中的作用：利用Transwell共培养体系对脂肪间充质干细胞和正常、急慢性声带损伤成纤维细胞共培养，通过测定声带成纤维细胞及内源性干细胞增殖及迁移能力，检测细胞外基质分泌、合成变化以及细胞因子表达变化，探索脂肪间充质干细胞及相应靶细胞可能的调控机制；进一步通过中和抗体实验筛选旁分泌相关特异性细胞因子；最后将特异性细胞因子基因转染至脂肪间充质干细胞，植入损伤声带动物模型，增强脂肪间充质干细胞"旁分泌"作用，以最大程度的促进声带固有层的修复重建，为声带损伤的治疗提供依据。

Irreversible dysphonia caused by irregular deposition and organization of extracellular matrix in the lamina propria after vocal fold injuries is difficult to treat. In our previous studies, we found that adipose-derived mesenchymal stem cells-extracelluar matrix complex can promote the vocal fold regeneration, but we also found that the survival rate of the stem cells was very low and not all of them can differentiate to the target cells after implantation. So the ability of stem cells to promote tissue regeneration was limited. To explore the paracrine mechanism of adipose-derived mesenchymal stem cells and its role in the vocal fold regeneration, we plan to utilize the transwell system to coculture adipose-derived mesenchymal stem cell and fibroblasts (normal vocal fold, acute injuried vocal fold and chronic injuried vocal fold), then detect the proliferation and migration of vocal fold fibroblasts and endogenous stem cells, and measure the changes of cytokines and extracellular matrix. Then we apply the neutralization tests to screen the cytokines which play specific roles in the paracrine mechanism. At last, we transfect the genes of specific cytokines to adipose-derived mesenchymal stem cells, then transplant the transfected cells into the injuried vocal folds to achieve the restoration of structure in the lamina propria to the extreme.