Mesenchymal stromal cell injection promotes vocal fold scar repair without long-term engraftment.
Mesenchymal stromal cell injection promotes vocal fold scar repair without long-term engraftment.
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DOI：
10.1016/j.jcyt.2016.07.005
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发表时间：
2016-10
期刊：
影响因子：
4.5
通讯作者：
Thibeault SL
中科院分区：
文献类型：
--
作者：
Bartlett RS;Guille JT;Chen X;Christensen MB;Wang SF;Thibeault SL
再生医学有望恢复声带瘢痕患者的声音。随着实验性治疗接近临床转化，仍存在一些考虑因素。我们的目的是使用临床上可接受的材料、临床前样本量和剂量比较，评估四种骨髓间充质干细胞（BM-MSC）和可调透明质酸水凝胶（HyStem-VF）治疗声带瘢痕的疗效和生物相容性。损伤84只家兔的声带，并在6周后注射四种治疗变化（BM-MSC、HyStem-VF和两种浓度的HyStem-VF中的BM-MSC）。在治疗后2、4和10周，采用流变学、实时聚合酶链反应（PCR）和组织学评估疗效。由病理学家筛选肺、肝、肾、脾和声带的生物相容性。在所有水凝胶注射组中均发现持续性炎症。BM-MSC单独治疗似乎是最有效和安全的，提供了粘弹性的早期解决，与期望的细胞外基质重塑一致的基因表达（与损伤对照相比，更少的纤连蛋白、胶原1α2、胶原3、前胶原、转化生长因子[TGF]β1、α平滑肌肌动蛋白、白细胞介素-1 β、白细胞介素-17 β和肿瘤坏死因子[TNF]）和最小的炎症。在BM-MSC处理的声带中的人β肌动蛋白表达在2周后是最小的，这表明来自BM-MSC的旁分泌信号传导可能促进了组织修复。
Regenerative medicine holds promise for restoring voice in patients with vocal fold scarring. As experimental treatments approach clinical translation, several considerations remain. Our objective was to evaluate efficacy and biocompatibility of four bone marrow mesenchymal stromal cell (BM-MSC) and tunable hyaluronic acid based hydrogel (HyStem-VF) treatments for vocal fold scar using clinically acceptable materials, a preclinical sample size and a dosing comparison. Vocal folds of 84 rabbits were injured and injected with four treatment variations (BM-MSC, HyStem-VF, and BM-MSC in HyStem-VF at two concentrations) 6 weeks later. Efficacy was assessed with rheometry, real-time polymerase chain reaction (PCR) and histology at 2, 4 and 10 weeks following treatment. Lung, liver, kidney, spleen and vocal folds were screened for biocompatibility by a pathologist. Persistent inflammation was identified in all hydrogel-injected groups. The BM-MSC alone treatment appeared to be the most efficacious and safe, providing an early resolution of viscoelasticity, gene expression consistent with desirable extracellular matrix remodeling (less fibronectin, collagen 1α2, collagen 3, procollagen, transforming growth factor [TGF]β1, alpha smooth muscle actin, interleukin-1β, interleukin-17β and tumor necrosis factor [TNF] than injured controls) and minimal inflammation. Human beta actin expression in BM-MSC–treated vocal folds was minimal after 2 weeks, suggesting that paracrine signaling from the BM-MSCs may have facilitated tissue repair.