Mesenchymal Stem Cell-derived Type II Alveolar Epithelial Progenitor Cells Attenuate LPS-induced Acute Lung Injury and Reduce P63 Expression

Aim: Acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) is a severe clinical respiratory-failure disease mainly characterized by acute damage to the alveolar epithelium and pulmonary vascular endothelial cells. Stem cell therapy has emerged as a potential regenerative strategy for ARDS/ALI, however, the outcome is limited, and the underlying mechanisms are unclear. Introduction: We established a differentiation system for bone marrow-derived mesenchymal stem cellderived (BM-MSC) type II alveolar epithelial progenitor cells (AECIIs) and assessed their regulatory effects on lipopolysaccharide (LPS)-induced ALI. Methods: We induced BM-MSC differentiation into AECIIs using a specific conditioned medium. After 26 days of differentiation, 3×10⁵ BM-MSC-AECIIs were used to treat mice with LPS-induced ALI through tracheal injection. Results: After tracheal injection, BM-MSC-AECIIs migrated to the perialveolar area and reduced LPSinduced lung inflammation and pathological injury. RNA-seq suggested that P63 protein was involved in the effects of BM-MSC-AECIIs on lung inflammation. Conclusion: Our results suggest that BM-MSC-AECIIs may reduce LPS-induced acute lung injury by decreasing P63 expression.