Autologous transplantation of P63+ lung progenitor cells for chronic obstructive pulmonary disease therapy

Background: Current COPD treatment is largely based on bronchodilator, which improves airflow limitation but has little effect on the pulmonary tissue regeneration. In recent decade, the adult lung resident stem/progenitor cells have been extensively studied and many identified progenitor populations, including the P63+ progenitor cells, are proven to have remarkable lung epithelium regeneration capability in animal models. Aim: This first-in-human clinical trial aim to investigate the safety and efficacy of autologous P63+ lung progenitor cell transplantation in COPD patients. Methods: 20 COPD patients (DLCO <80% pred) were recruited into control group (n=3) and cell treatment group(n=17). Patients were autologously transplanted with 0.7~5.3x106 cells/kg through bronchoscopy, followed by subsequent assessment for safety and efficacy within 24 weeks. Results: The cell treatment was well tolerated by all patients. After cell transplantation, the median DLCO% of treated patients increased from 30.00 (IQR 25.0, 41.65) at baseline to 39.70 (IQR 31.60, 48.30) at 12 weeks, and then increased to 40.30 (IQR 27.30, 48.89) at 24 weeks (24 weeks Cohen's d=0.593, 95% CI: -0.094, 1.280) (p value=0.001). Meanwhile, the average SGRQ score and the median 6MWD of patients of cell therapy group were decreased (from 51.3 at baseline to 44.2) and increased (from 410m to 447m) at 24 weeks, respectively. Two patients with mild emphysema showed resolution of the lesions at 24 weeks by CT imaging. Conclusion: Intra-pulmonary administration of P63+ lung progenitor cells in patients with COPD seems feasible and safe, and points to significant improvement in gas exchange capacity after cell therapy.