Abstract
Background: ABCA3 is expressed on the limiting membrane of lamellae bodies in alveolar epithelial type 2 cells (AT2). Deficient ABCA3 causes the dysfunction of surfactant transportation. Patients with ABCA3 mutations show severe RDS or interstitial lung diseases. However, the role of ABCA3 mutations in the disease development is not fully understood.
Resident stem/progenitor cells in the alveoli play an important role during alveolar injury and repair. We reported an alveolar epithelial progenitor cell population (AEPCs) in human lungs (Lab invest 2011; 91:363-378). AEPCs co-expressed proSP-C and CD90, and differentiated into AT2-like cells in vitro. Unlike AT2, AEPCs are easily cultured, and therefore useful to reveal the pathogenesis of lung diseases.
Aims and objectives: To analyze the functional differences in AEPCs isolated from a patient with ABCA3 mutation.
Methods: AEPCs were established from the lung of an 8-year-old boy, who underwent the lung transplantation for ILD with the compound heterozygous mutations in ABCA3 gene (Eur J Pediatr. 2013; 172:953–957). We compared the proliferation rate, the number of colonies, and the markers with AEPCs from normal lungs (normal-AEPCs).
Results: Colonies were expanded 13 to 14 days after seeding whereas 5 to 7 days from normal-AEPCs. The number of colonies was 3 to 5 per culture plate whereas 30 to 50 in normal-AEPCs. Expanded colonies co-expressed proSP-C and CD90, which is consistent with the definition of AEPCs. The expression of proSP-C in the expanded colonies, ABCA3-null AEPCs, was weaker than that in normal-AEPCs.
Conclusion: We established AEPCs from the ABCA3 mutant lung. ABCA3-null AEPCs showed different characteristics from normal-AEPCs.
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