Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
Laryngoscope. 2024 Oct;134(10):4239-4245. doi: 10.1002/lary.31499. Epub 2024 May 13.
Animal models for laryngotracheal stenosis (LTS) are critical to understand underlying mechanisms and study new therapies. Current animal models for LTS are limited by small airway sizes compared to human. The objective of this study was to develop and validate a novel, large animal ovine model for LTS.
Sheep underwent either bleomycin-coated polypropylene brush injury to the subglottis (n = 6) or airway stent placement (n = 2) via suspension microlaryngoscopy. Laryngotracheal complexes were harvested 4 weeks following injury or stent placement. For the airway injury group, biopsies (n = 3 at each site) were collected of tracheal scar and distal normal regions, and analyzed for fibrotic gene expression. Lamina propria (LP) thickness was compared between injured and normal areas of trachea.
No mortality occurred in sheep undergoing airway injury or stent placement. There was no migration of tracheal stents. After protocol optimization, LP thickness was significantly increased in injured trachea (Sheep #3: 529.0 vs. 850.8 um; Sheep #4: 933.0 vs. 1693.2 um; Sheep #5: 743.7 vs. 1378.4 um; Sheep #6: 305.7 vs. 2257.6 um). A significant 62-fold, 20-fold, 16-fold, 16-fold, and 9-fold change of COL1, COL3, COL5, FN1, and TGFB1 was observed in injured scar specimen relative to unaffected airway, respectively.
An ovine LTS model produces histologic and transcriptional changes consistent with fibrosis seen in human LTS. Airway stent placement in this model is safe and feasible. This large airway model is a reliable and reproducible method to assess the efficacy of novel LTS therapies prior to clinical translation.
N/A Laryngoscope, 134:4239-4245, 2024.
喉气管狭窄（LTS）的动物模型对于理解潜在机制和研究新疗法至关重要。与人类相比，目前 LTS 的动物模型气道较小。本研究的目的是开发和验证一种新的、大型动物绵羊 LTS 模型。
绵羊通过悬雍垂显微镜喉镜接受博来霉素涂层聚丙烯刷损伤（n=6）或气道支架放置（n=2）。损伤或支架放置后 4 周收获喉气管复合体。对于气道损伤组，收集气管瘢痕和远端正常区域的活检（每个部位 3 个样本），并分析纤维化基因表达。比较损伤和正常气管的固有层（LP）厚度。
接受气道损伤或支架放置的绵羊均未发生死亡。气管支架无迁移。在方案优化后，损伤的气管 LP 厚度显著增加（绵羊 #3：529.0 对 850.8 μm；绵羊 #4：933.0 对 1693.2 μm；绵羊 #5：743.7 对 1378.4 μm；绵羊 #6：305.7 对 2257.6 μm）。与未受影响的气道相比，COL1、COL3、COL5、FN1 和 TGFB1 在损伤的瘢痕标本中分别观察到 62 倍、20 倍、16 倍、16 倍和 9 倍的变化。
绵羊 LTS 模型产生的组织学和转录变化与人类 LTS 中的纤维化一致。在该模型中，气道支架放置是安全且可行的。这种大气道模型是在临床转化前评估新型 LTS 治疗方法疗效的可靠且可重复的方法。
无。喉镜，134：4239-4245，2024。
