Airway disease decreases the therapeutic potential of epithelial stem cells

Respir Res. 2024 Jan 12;25(1):28. doi: 10.1186/s12931-024-02667-8.

Abstract

Backgorund: Tissue-engineered tracheal grafts (TETG) can be recellularized by the host or pre-seeded with host-derived cells. However, the impact of airway disease on the recellularization process is unknown.

Methods: In this study, we determined if airway disease alters the regenerative potential of the human tracheobronchial epithelium (hTBE) obtained by brushing the tracheal mucosa during clinically-indicated bronchoscopy from 48 pediatric and six adult patients.

Results: Our findings revealed that basal cell recovery and frequency did not vary by age or region. At passage 1, all samples produced enough cells to cellularize a 3.5 by 0.5 cm2 graft scaffold at low cell density (~ 7000 cells/cm2), and 43.75% could cellularize a scaffold at high cell density (~ 100,000 cells/cm2). At passage 2, all samples produced the number of cells required for both recellularization models. Further evaluation revealed that six pediatric samples (11%) and three (50%) adult samples contained basal cells with a squamous basal phenotype. These cells did not form a polarized epithelium or produce differentiated secretory or ciliated cells. In the pediatric population, the squamous basal cell phenotype was associated with degree of prematurity (< 28 weeks, 64% vs. 13%, p = 0.02), significant pulmonary history (83% vs. 34%, p = 0.02), specifically with bronchopulmonary dysplasia (67% vs. 19%, p = 0.01), and patients who underwent previous tracheostomy (67% vs. 23%, p = 0.03).

Conclusions: In summary, screening high-risk pediatric or adult population based on clinical risk factors and laboratory findings could define appropriate candidates for airway reconstruction with tracheal scaffolds.

Level of evidence: Level III Cohort study.

Keywords: Host epithelium; Squamous basal cell; Tracheal brushing.

MeSH terms

  • Adult
  • Carcinoma, Squamous Cell*
  • Child
  • Cohort Studies
  • Epithelial Cells / pathology
  • Epithelium
  • Humans
  • Infant, Newborn
  • Respiration Disorders*
  • Stem Cells
  • Trachea / pathology
  • Trachea / surgery