Division of Neonatology and Newborn Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Department of Neonatology, Children's Medical Center, the Second Hospital of Shandong University, 250033, Jinan, Shangdong, China.
Pediatr Res. 2021 Feb;89(3):502-509. doi: 10.1038/s41390-020-0925-3. Epub 2020 May 4.
Bronchopulmonary dysplasia remains one of the most common complications 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 progenitor cell populations in culture.
We supplemented Rho/SMAD signaling inhibition with mTOR inhibition to generate epithelial basal cell-like cell lines from tracheal aspirates of neonates.
Single-cell RNA-sequencing confirmed the presence of epithelial cells in tracheal aspirates obtained from intubated neonates. Using Rho/SMAD/mTOR triple signaling inhibition, neonatal tracheal aspirate-derived (nTAD) basal cell-like cells can be expanded long term and retain the ability to differentiate into pseudostratified airway epithelium.
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.
Airway epithelial basal cell-like cell lines were derived from human neonatal tracheal aspirates. mTOR inhibition significantly extends in vitro proliferation of neonatal tracheal aspirate-derived basal cell-like cells (nTAD BCCs). nTAD BCCs can be differentiated into functional airway epithelium. nTAD BCCs provide a novel model to investigate perinatal lung development and diseases.
尽管围产期护理有了显著的改善，支气管肺发育不良仍然是早产儿最常见的并发症之一。人类肺部发育和疾病的功能建模，如 BPD，受到我们获取肺部和维持相关祖细胞群体在培养中的能力的限制。
我们用 mTOR 抑制来补充 Rho/SMAD 信号抑制，从新生儿的气管吸出物中生成上皮基底细胞样细胞系。
单细胞 RNA 测序证实了从插管新生儿的气管吸出物中存在上皮细胞。通过 Rho/SMAD/mTOR 三重信号抑制，可以长期扩增新生儿气管吸出物衍生的（nTAD）基底细胞样细胞，并保留分化为假复层气道上皮的能力。
我们的数据表明，新生儿气管吸出物来源的上皮细胞可以提供一种新的体外人类细胞模型，用于研究新生儿肺部发育和疾病。
气道上皮基底细胞样细胞系是从人新生儿的气管吸出物中分离出来的。mTOR 抑制显著延长了新生儿气管吸出物衍生的基底细胞样细胞（nTAD BCC）的体外增殖。nTAD BCC 可以分化为功能性气道上皮。nTAD BCC 为研究围产期肺部发育和疾病提供了一种新的模型。
