Conditional reprogramming of pediatric airway epithelial cells: A new human model to investigate early‐life respiratory disorders
One of the main limitations of studying the human infant airway epithelium is the lack of robust AEC culture systems. Prior studies have demonstrated that the use of human infant AEC cultures is a powerful strategy to investigate early‐life respiratory disorders7; however, airway sampling in this age group is a major challenge. Here we present a strategy to optimize nasal and bronchial infant AEC cultures using conditionally reprogrammed cells (CRC).11 The purpose of generating CRC is to enhance proliferative and survival capacity as primary AEC cannot survive multiple passages.11 The CRC method combines exposure to a Rho kinase (ROCK) inhibitor Y‐27632 and a fibroblast‐derived feeder layer or conditioned medium (medium from irradiated fibroblasts) to reprogram primary AEC into progenitor cells.11 The induction of CRC results from reprogramming of the entire cell population rather than the selection of a minor subpopulation11; thus, CRC are life‐extended preserving the AEC phenotype. Although CRC generation has been described in human adult bronchial and nasal epithelium,12 our study is the first to adapt CRC technology to develop a human‐based model of the newborn and infant airway epithelium. The impact of this work is that it presents a clinically and scientifically relevant human‐based approach to investigate the developmental immunobiology of the airway epithelium and the pathogenesis of respiratory disorders that begin in early life.