BACKGROUND The conducting airway epithelium is repaired by tissue specific stem cells (TSC). In response to mild/moderate injury, each TSC repairs a discrete area of the epithelium. In contrast, severe epithelial injury stimulates TSC migration and expands the stem cell's reparative domain. Lung transplantation (LTx) can cause a moderate/severe airway injury and the remodeled airway contains a chimeric mixture of donor and recipient cells. These studies supported the hypothesis, LTx stimulates TSC migration resulting in epithelial chimerism. We tested this hypothesis in cystic fibrosis (CF) LTx patients. METHODS Airway mucosal injury was quantified using bronchoscopic imaging and a novel grading system. Bronchial brushing was used to recover TSC from 10 sites in the recipient and allograft airways. TSC chimerism was quantified by short tandem repeat analysis. TSC self-renewal and differentiation potential were assayed using the clone forming cell frequency and air-liquid-interface methods. Electrophysiology was used to determine if TSC chimerism altered epithelial ion channel activity. RESULTS LTx caused a mild to moderate airway mucosal injury. Donor and recipient TSC were identified in 91% of anastomotic sites and 93% of bronchial airways. TSC chimerism did not alter stem cell self-renewal or differentiation potential. The frequency of recipient TSC was proportional to CF Transmembrane Conductance Regulator (CFTR)-dependent ion channel activity and 33% of allograft regions were at risk for abnormal CFTR activity. CONCLUSIONS LTx in CF patients stimulates bidirectional TSC migration across the anastomoses. TSC chimerism may alter ion homeostasis and compromise the host defense capability of the allograft airway epithelium.

中文翻译：

---

囊性纤维化肺移植受者气道上皮干细胞嵌合

背景传导气道上皮由组织特异性干细胞(TSC)修复。为了应对轻度/中度损伤，每个 TSC 修复上皮的离散区域。相反，严重的上皮损伤会刺激 TSC 迁移并扩大干细胞的修复域。肺移植 (LTx) 可导致中度/重度气道损伤，并且重塑的气道包含供体和受体细胞的嵌合混合物。这些研究支持假设，LTx 刺激 TSC 迁移导致上皮嵌合。我们在囊性纤维化 (CF) LTx 患者中检验了这一假设。方法 使用支气管镜成像和新的分级系统对气道黏膜损伤进行量化。支气管刷洗用于从受体和同种异体移植气道的 10 个部位恢复 TSC。TSC嵌合体通过短串联重复分析进行量化。使用克隆形成细胞频率和气液界面方法测定 TSC 自我更新和分化潜能。电生理学用于确定 TSC 嵌合是否改变上皮离子通道活性。结果 LTx 引起轻度至中度气道黏膜损伤。在 91% 的吻合部位和 93% 的支气管气道中发现了供体和受体 TSC。TSC 嵌合体不改变干细胞自我更新或分化潜能。受体 TSC 的频率与 CF 跨膜电导调节剂 (CFTR) 依赖的离子通道活性成正比，33% 的同种异体移植区域存在 CFTR 活性异常的风险。结论 CF 患者中的 LTx 刺激跨吻合口的 TSC 双向迁移。