Hiwatashi Nao, Bing Renjie, Kraja Iv, Branski Ryan C
NYU Voice Center, Department of Otolaryngology-Head and Neck Surgery, New York University School of Medicine, New York, New York, U.S.A.
Laryngoscope. 2017 Jan;127(1):E35-E41. doi: 10.1002/lary.26121. Epub 2016 Jun 27.
OBJECTIVES/HYPOTHESIS: Mesenchymal stem cells (MSCs) hold therapeutic promise for vocal fold scar, yet the precise mechanism(s) underlying tissue level changes remain unclear. We hypothesize that MSCs interact with native fibroblasts to favorably affect healing. Furthermore, we hypothesize that these interactions vary based on MSC source.
Vocal fold fibroblasts (VFFs), adipose-derived stem cells, and bone marrow-derived stem cells (BMSCs) were extracted from Sprague-Dawley rats; and a coculture model was employed culturing VFFs ± transforming growth factor (TGF-β1) (10 ng/mL) ± MSCs. Monoculture MSCs were also prepared as a control. Both extracellular matrix (ECM) and components of the TGF-β signaling pathway were analyzed via polymerase chain reaction and western blotting.
Significantly decreased TGF-β1 mRNA and α-smooth muscle actin protein was observed in VFFs in response to TGF-β1 in the coculture with both MSCs (P < 0.05, P < 0.01). BMSCs significantly downregulated collagen I (P < 0.05), collagen III (P < 0.05), Smad3 (P < 0.01), and TGF-β1 receptor I (P < 0.01) mRNA in VFFs. Hyaluronic synthase-1 and 2 increased in cocultured BMSCs when compared with monocultured BMSCs at baseline and in response to TGF-β1 (P < 0.01).
MSCs had a favorable effect on ECM regulation as well as suppression of TGF-β1 signaling in VFF. Bidirectional paracrine signaling was also observed as VFFs altered ECM regulation in MSCs. These data provide insight into the regenerative effects of MSCs and provide a foundation for clinical application.
NA Laryngoscope, 127:E35-E41, 2017.
目的/假设：间充质干细胞（MSCs）对声带瘢痕具有治疗潜力，但组织水平变化的具体机制仍不清楚。我们假设MSCs与天然成纤维细胞相互作用，对愈合产生有利影响。此外，我们假设这些相互作用因MSC来源而异。
从Sprague-Dawley大鼠中提取声带成纤维细胞（VFFs）、脂肪来源干细胞和骨髓来源干细胞（BMSCs）；采用共培养模型，培养VFFs±转化生长因子（TGF-β1）（10 ng/mL）±MSCs。也制备了单培养的MSCs作为对照。通过聚合酶链反应和蛋白质印迹法分析细胞外基质（ECM）和TGF-β信号通路的成分。
在与两种MSCs共培养时，VFFs中TGF-β1 mRNA和α-平滑肌肌动蛋白显著减少（P < 0.05，P < 0.01）。BMSCs显著下调VFFs中I型胶原（P < 0.05）、III型胶原（P < 0.05）、Smad3（P < 0.01）和TGF-β1受体I（P < 0.01）mRNA。与基线时和对TGF-β1反应时的单培养BMSCs相比，共培养的BMSCs中透明质酸合酶-1和2增加（P < 0.01）。
MSCs对VFF中的ECM调节以及TGF-β1信号的抑制具有有利作用。还观察到双向旁分泌信号，因为VFFs改变了MSCs中的ECM调节。这些数据为MSCs的再生作用提供了见解，并为临床应用奠定了基础。
NA《喉镜》，127：E35-E41，2017年。
