State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory, Guangzhou Institute of Respiratory Disease, Guangzhou, Guangdong, People's Republic of China.
Department of Pulmonary and Critical Care Medicine, Huizhou Municipal Central Hospital, Huizhou, Guangdong, People's Republic of China.
Stem Cells Transl Med. 2023 Dec 18;12(12):838-848. doi: 10.1093/stcltm/szad062.
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.
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.
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.
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.
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非常重要，并且在治疗气管狭窄方面具有很大的潜力。
在犬中进行了一项实验研究，以探讨自体基底细胞移植在恢复气道稳态方面的治疗效果。首先，通过单细胞 RNA 测序分析复发性气管狭窄患者的气道黏膜。然后，犬被随机分为气管狭窄、支架、支架+细胞和支架+细胞+生物凝胶组。支架+细胞和支架+细胞+生物凝胶组犬的气道自体基底细胞在建模后移植到狭窄气道上。在支架+细胞+生物凝胶组中，在基底细胞移植前在气道上涂覆生物凝胶。支气管镜治疗后，对犬进行 16 周的随访。
单细胞 RNA 测序显示，RBTS 患者气道中基底细胞拥挤，正常气道上皮细胞缺失。在犬模型中成功进行了自体气道基底细胞移植，同时进行了生物凝胶涂层。随访观察表明，支架+细胞+生物凝胶组的存活时间明显延长，存活率（100%）明显高于其他组。在病理和支气管镜检查结果方面，接受自体基底细胞移植的犬显示肉芽组织增生减少，并且气道重新上皮化，具有功能成熟的上皮细胞。
自体气道基底细胞移植可能成为气道再上皮化的一种新型再生治疗方法，并抑制良性气管狭窄的复发性肉芽组织增生。
