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

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 ?1) after double-stranded (ds) RNA exposure. RESULTS:CRC derived from primary AEC of neonates/infants and young children exhibited: (i) augmented proliferative capacity and life extension, (ii) preserved airway epithelial phenotype after multiple passages, (iii) robust immune responses characterized by the expression of innate antiviral genes and parallel nasal/bronchial production of IFN ?1 after exposure to dsRNA, and (iv) induction of airway epithelial inflammatory and remodeling responses to dsRNA (eg, 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.

SUBMITTER: Wolf S

PROVIDER: S-EPMC5868353 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Wolf S S Perez G F GF Mukharesh L L Isaza N N Preciado D D Freishtat R J RJ Pillai D D Rose M C MC Nino G G

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 20171122 8

<h4>Background</h4>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.<h4>Methods</h4>We collected nasal and/or bronchial AEC from a total of 23 subje ...[more]

PMID: 28981980

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Project description:BackgroundAlthough pesticide use is widespread, the possible effect of early-life exposure to organophosphate (OP) on pediatric respiratory health is not well described.ObjectivesWe investigated the relationship between early-life exposure to OPs and respiratory outcomes.MethodsParticipants included 359 mothers and children from the CHAMACOS birth cohort. Dialkyl phosphate (DAP) metabolites of OP pesticides, specifically diethyl (DE) and dimethyl (DM) phosphate metabolites, were measured in urine from mothers twice during pregnancy (mean = 13 and 26 weeks gestation) and from children five times during childhood (0.5-5 years). Childhood DAP concentrations were estimated by the area under curve (AUC). Mothers reported their child's respiratory symptoms at 5 and 7 years of age. We used generalized estimating equations (GEE) to examine associations of prenatal and childhood DAP concentrations with repeated measures of respiratory symptoms and exercise-induced coughing at 5 and 7 years of age, adjusting for child's sex and age, maternal smoking during pregnancy, secondhand tobacco smoke, season of birth, PM2.5, breastfeeding, mold and cockroaches in home, and distance from highway.ResultsHigher prenatal DAP concentrations, particularly DE, were nonsignificantly associated with respiratory symptoms in the previous 12 months at 5 or 7 years of age [adjusted odds ratio (aOR) per 10-fold increase = 1.44; 95% CI: 0.98, 2.12]. This association was strongest with total DAP and DE from the second half of pregnancy (aOR per 10-fold increase = 1.77; 95% CI: 1.06, 2.95; and 1.61; 95% CI: 1.08, 2.39, respectively). Childhood DAP, DE, and DM concentrations were associated with respiratory symptoms and exercise-induced coughing in the previous 12 months at 5 or 7 years of age (total DAPs: aOR per 10-fold increase = 2.53; 95% CI: 1.32, 4.86; and aOR = 5.40; 95% CI: 2.10, 13.91, respectively).ConclusionsEarly-life exposure to OP pesticides was associated with respiratory symptoms consistent with possible asthma in childhood.

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

Publications

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

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