BACKGROUND Airway epithelium defects are a hallmark of recurrent benign tracheal stenosis (RBTS). Reconstructing an intact airway epithelium is of great importance in airway homeostasis and epithelial wound healing and has great potential for treating tracheal stenosis. METHODS An experimental study was conducted in canines to explore the therapeutic effect of autologous basal cell transplantation in restoring airway homeostasis. First, airway mucosae from human patients with recurrent tracheal stenosis were analyzed by single-cell RNA sequencing. Canines were then randomly divided into tracheal stenosis, Stent, Stent + Cells, and Stent + Cells + Biogel groups. Autologous airway basal cells of canines in the Stent + Cells and Stent + Cells + Biogel groups were transplanted onto the stenotic airway after modeling. A biogel was coated on the airway prior to basal cell transplantation in the Stent + Cells + Biogel group. After bronchoscopic treatments, canines were followed up for 16 weeks. RESULTS Single-cell RNA sequencing demonstrated packed airway basal cells and an absence of normal airway epithelial cells in patients with RBTS. Autologous airway basal cell transplantation, together with biogel coating, was successfully performed in the canine model. Follow-up observation indicated that survival time in the Stent + Cells + Biogel group was significantly prolonged, with a higher (100%) survival rate compared with the other groups. In terms of pathological and bronchoscopic findings, canines that received autologous basal cell transplantation showed a reduction in granulation hyperplasia as well as airway re-epithelialization with functionally mature epithelial cells. CONCLUSIONS Autologous airway basal cell transplantation might serve as a novel regenerative therapy for airway re-epithelialization and inhibit recurrent granulation hyperplasia in benign tracheal stenosis.

中文翻译：

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自体气道基底细胞移植可减轻复发性良性气管狭窄中的气道上皮缺陷。

背景技术气道上皮缺陷是复发性良性气管狭窄（RBTS）的标志。重建完整的气道上皮对于气道稳态和上皮伤口愈合具有重要意义，并且在治疗气管狭窄方面具有巨大潜力。方法在犬类中进行实验研究，探讨自体基底细胞移植恢复气道稳态的治疗效果。首先，通过单细胞 RNA 测序分析了患有复发性气管狭窄的人类患者的气道粘膜。然后将犬随机分为气管狭窄组、支架组、支架+细胞组和支架+细胞+生物凝胶组。支架+细胞组和支架+细胞+Biogel组的犬自体气道基底细胞在造模后移植到狭窄气道上。在支架+细胞+生物凝胶组中，在基础细胞移植之前将生物凝胶涂覆在气道上。支气管镜治疗后，对犬进行为期 16 周的随访。结果 单细胞 RNA 测序显示 RBTS 患者存在气道基底细胞堆积，且缺乏正常气道上皮细胞。自体气道基底细胞移植与生物凝胶涂层一起在犬模型中成功进行。随访观察表明，支架+细胞+生物凝胶组的存活时间显着延长，与其他组相比存活率更高（100%）。就病理和支气管镜检查结果而言，接受自体基底细胞移植的犬显示出肉芽增生减少以及功能成熟的上皮细胞气道上皮化的减少。结论 自体气道基底细胞移植可能作为气道上皮再生的一种新型再生疗法，并抑制良性气管狭窄的复发性肉芽增生。