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

Abstract

Adult lung resident stem/progenitor cells, including P63⁺ progenitor cells, have demonstrated the capacity for regeneration of lung epithelium in preclinical models. Here, we report a clinical trial of intrapulmonary P63⁺ progenitor cell transplantation in 28 participants with stage II to IV chronic obstructive pulmonary disease (COPD). Autologous P63⁺ progenitor cells were isolated from the airway basal layer of participants in the intervention group via bronchoscopic brushing, cultured for 3 to 5 weeks, and then transplanted back into the lungs via bronchoscopy at 0.7 × 10⁶ to 5.2 × 10⁶ cells per kilogram of body weight. Twenty patients were evaluable at the end of the study (intervention group, <i>n</i> = 17; control group, <i>n</i> = 3). No grade 3 to 5 adverse events (AEs) or serious AEs occurred. Although bronchoscopy-associated AEs were recorded in participants in the intervention group, other AEs were not substantial different between groups. Twenty-four weeks after transplantation, participants in the intervention group displayed improvement in gas transfer capacity [diffusing capacity of the lung for carbon monoxide (DLCO) change from baseline: +18.2%], whereas the control group experienced a decrease (DLCO change from baseline: -17.4%; <i>P</i> = 0.008). Furthermore, participants in the intervention group showed >30-meter increase in walking distance within 6 minutes. Transcriptomic analysis of progenitor cells isolated from responding and nonresponding individuals in the intervention group showed that higher expression of <i>P63</i> was associated with treatment efficacy. In conclusion, transplantation of cultured P63⁺ lung progenitor cells was safe and might represent a potential therapeutic strategy for COPD.