Conditional reprogramming of pediatric airway epithelial cells: a new human model to investigate early life respiratory disorders.

Conditional reprogramming of pediatric airway epithelial cells: a new human model to investigate early life respiratory disorders.

Pediatr Allergy Immunol. 2017 Oct 05;:

Authors: Wolf S, Perez GF, Mukharesh L, Isaza N, Preciado D, Freishtat RJ, Pillai D, Rose MC, Nino G

Abstract
BACKGROUND: Airway epithelial cells (AEC) are quite difficult to access in newborns and infants. It is critically important to develop robust life-extended models to conduct translational studies in this age group. We propose the use of a recently described cell-culture technology (conditionally reprogrammed cells - CRC) to generate continuous primary cell cultures from nasal and bronchial AEC of young children.
METHODS: We collected nasal and/or bronchial AEC from a total of 23 subjects of different ages including newborns/infants/toddlers (0-2 years; N=9), school age children (4-11 years; N=6), and a group of adolescent/adult donors (N=8). For CRC generation, we used conditioned medium from mitotically inactivated 3T3 fibroblasts and Rho-associated kinase (ROCK) inhibitor (Y-27632). Antiviral immune responses were studied using 25 key antiviral genes and protein production of type III epithelial interferon (IFN λ1) after double stranded (ds) RNA exposure.
RESULTS: CRC derived from primary AEC of neonates/infants and young children exhibited: 1) augmented proliferative capacity and life-extension, 2) preserved airway epithelial phenotype after multiple passages, 3) robust immune responses characterized by expression of innate antiviral genes and parallel nasal/bronchial production of IFN λ1 after exposure to dsRNA, and 4) induction of airway epithelial inflammatory and remodeling responses to dsRNA (e.g. CXCL8 and MMP9).
CONCLUSION: Conditional reprogramming of AEC from young children is a feasible and powerful translational approach to investigate early-life airway epithelial immune responses in humans. This article is protected by copyright. All rights reserved.

PMID: 28981980 [PubMed - as supplied by publisher]

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