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Updated: Nov 30, 2025
Generation of Airway Epithelial Cell Air-Liquid Interface Cultures from Human Pluripotent Stem Cells
Published on: June 14, 2022
Airway epithelial stem cell chimerism in cystic fibrosis lung transplant recipients
Don Hayes1, Rachael E Rayner2, Cynthia L Hill3
1Section of Pulmonary Medicine, Nationwide Children's Hospital, Columbus, OH, USA; Departments of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA; Internal Medicine, The Ohio State University College of Medicine, Columbus, OH, USA; Surgery, The Ohio State University College of Medicine, Columbus, OH, USA; Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
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.
