Stem Cell-Based Tissue-Engineered Laryngeal Replacement
Stem Cell-Based Tissue-Engineered Laryngeal Replacement
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DOI：
10.5966/sctm.2016-0130
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发表时间：
2017-02-01
影响因子：
6
通讯作者：
Birchall, Martin A.
中科院分区：
文献类型：
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作者：
Ansari, Tahera;Lange, Peggy;Birchall, Martin A.
喉部疾病患者可能有严重的吞咽、发声和呼吸功能相关的发病率，常规治疗效果欠佳。组织工程方法的目标是恢复声带和维持呼吸功能，同时限制再生组织中疤痕的程度。在药物非临床研究质量管理规范的条件下，我们在负压下使用去污剂和酶对猪喉进行脱细胞处理，以产生包含软骨、肌肉和粘膜的脱细胞支架。为了在临床试验前评估安全性和功能性，将接种有人骨髓源性间充质干细胞和组织工程化口腔粘膜片的脱细胞半喉原位植入六只猪中。将接种的移植物留在原位6个月，并使用计算机断层扫描成像、支气管镜检查和粘膜刷检进行评估，同时进行发音记录和组织学分析。移植物未引起不良呼吸功能，也未影响吞咽或发声。由连续上皮覆盖的退化声带很容易识别。总之，所提出的组织工程方法是喉缺损的一种可行的替代疗法。
Patients with laryngeal disorders may have severe morbidity relating to swallowing, vocalization, and respiratory function, for which conventional therapies are suboptimal. A tissue-engineered approach would aim to restore the vocal folds and maintain respiratory function while limiting the extent of scarring in the regenerated tissue. Under Good Laboratory Practice conditions, we decellularized porcine larynges, using detergents and enzymes under negative pressure to produce an acellular scaffold comprising cartilage, muscle, and mucosa. To assess safety and functionality before clinical trials, a decellularized hemilarynx seeded with human bone marrow-derived mesenchymal stem cells and a tissue-engineered oral mucosal sheet was implanted orthotopically into six pigs. The seeded grafts were left in situ for 6 months and assessed using computed tomography imaging, bronchoscopy, and mucosal brushings, together with vocal recording and histological analysis on explantation. The graft caused no adverse respiratory function, nor did it impact swallowing or vocalization. Rudimentary vocal folds covered by contiguous epithelium were easily identifiable. In conclusion, the proposed tissue-engineered approach represents a viable alternative treatment for laryngeal defects.