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 × 10 6 to 5.2 × 10 6 cells per kilogram of body weight. Twenty patients were evaluable at the end of the study (intervention group, n = 17; control group, n = 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%; P = 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 P63 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.

中文翻译：

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自体移植P63+肺祖细胞治疗慢性阻塞性肺疾病

成人肺常驻干细胞/祖细胞，包括 P63+祖细胞已在临床前模型中证明了肺上皮的再生能力。在这里，我们报告肺内 P63 的临床试验+对 28 名患有 II 期至 IV 期慢性阻塞性肺病 (COPD) 的参与者进行祖细胞移植。自体P63+通过支气管镜刷检从干预组参与者的气道基底层分离祖细胞，培养3至5周，然后通过支气管镜以0.7 × 10 移植回肺部6至 5.2 × 106每公斤体重的细胞数。研究结束时有 20 名患者可进行评估（干预组，n= 17；控制组，n= 3）。未发生 3 至 5 级不良事件 (AE) 或严重 AE。尽管干预组的参与者记录了与支气管镜检查相关的 AE，但其他 AE 在各组之间没有显着差异。移植后 24 周，干预组的参与者表现出气体传输能力的改善[肺一氧化碳 (DLCO) 扩散能力相对于基线的变化：+18.2%]，而对照组则出现下降（DLCO 相对于基线的变化）基线：-17.4%；磷= 0.008）。此外，干预组的参与者在 6 分钟内步行距离增加了 30 米以上。对干预组有反应和无反应个体分离的祖细胞进行转录组分析表明，P63与治疗效果相关。总之，培养的P63的移植+肺祖细胞是安全的，可能代表慢性阻塞性肺病的潜在治疗策略。