mTOR Inhibition Enables Long-Term Expansion of Human Neonatal Tracheal Aspirate-Derived Airway Basal Stem Cells

Bronchopulmonary dysplasia remains one of the most common complication of prematurity, despite significant improvements in perinatal care. Functional modeling of human lung development and disease, like BPD, is limited by our ability to access the lung and to maintain relevant stem cell populations in culture. Single cell RNA-sequencing confirmed the presence of epithelial cells in tracheal aspirates obtained from intubated neonates. Using combined SMAD signaling inhibition and mTOR inhibition neonatal tracheal-aspirate derived (nTAD) basal stem cells can be expanded long-term and retain the ability to differentiate into pseudo-stratified airway epithelium. Conclusions: Our data demonstrate that neonatal tracheal aspirate-derived epithelial cells can provide a novel ex vivo human cellular model to study neonatal lung development and disease.

尽管围产期护理已取得显著进展，支气管肺发育不良（Bronchopulmonary dysplasia, BPD）仍是早产最常见的并发症之一。用于模拟人类肺发育与疾病（如BPD）的功能建模，受限于我们获取肺部样本以及在体外培养维持相关干细胞群的能力。单细胞RNA测序（single cell RNA-sequencing）已证实，插管新生儿的气管抽吸物中存在上皮细胞。通过联合应用SMAD信号通路抑制与mTOR信号通路抑制，可对新生儿气管抽吸物来源的基底干细胞（nTAD）进行长期扩增，且这些细胞仍保留分化为假复层气道上皮的能力。结论：本研究数据表明，新生儿气管抽吸物来源的上皮细胞可作为一种新型离体人类细胞模型，用于新生儿肺发育及肺部疾病的研究。