Airway epithelial stem cell chimerism in cystic fibrosis lung transplant recipients
| Autor: | Scott W. Lallier, Susan D. Reynolds, Guy Brock, Estelle Cormet-Boyaka, Cynthia L Hill, Mahelet Tadesse, Rachael E. Rayner, Hemant K. Parekh, Alfahdah Alsudayri, Don Hayes |
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| Rok vydání: | 2020 |
| Předmět: |
Pulmonary and Respiratory Medicine
congenital hereditary and neonatal diseases and abnormalities Pathology medicine.medical_specialty Cystic Fibrosis medicine.medical_treatment Bronchi Respiratory Mucosa Cystic fibrosis Bronchial brushing Chimerism medicine Lung transplantation Humans neoplasms Lung business.industry Stem Cells Epithelial Cells respiratory system medicine.disease Epithelium nervous system diseases medicine.anatomical_structure Ion homeostasis Pediatrics Perinatology and Child Health Respiratory epithelium Stem cell business Lung Transplantation |
| Zdroj: | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 20(1) |
| ISSN: | 1873-5010 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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