Airway Epithelial Cultures of Children with Esophageal Atresia as a Model to Study Respiratory Tract Disorders

Esophageal atresia (EA) is a rare birth defect in which respiratory tract disorders are a major cause of morbidity. It remains unclear whether respiratory tract disorders are in part caused by alterations in airway epithelial cell functions such as the activity of motile cilia. This can be studied using airway epithelial cell culture models of patients with EA. Therefore, the aim of this study was to evaluate the feasibility to culture and functionally characterize motile cilia function in the differentiated air–liquid interface cultured airway epithelial cells and 3D organoids derived from nasal brushings and bronchoalveolar lavage (BAL) fluid from children with EA. We demonstrate the feasibility of culturing differentiated airway epithelia and organoids of nasal brushings and BAL fluid of children with EA, which display normal motile cilia function. EA patient-derived airway epithelial cultures can be further used to examine whether alterations in epithelial functions contribute to respiratory disorders in EA.

[1]  Han Liu,et al.  Multiomics Analysis of a DNAH5-Mutated PCD Organoid Model Revealed the Key Role of the TGF-β/BMP and Notch Pathways in Epithelial Differentiation and the Immune Response in DNAH5-Mutated Patients , 2022, Cells.

[2]  E. Bleecker,et al.  Low CC16 mRNA Expression Levels in Bronchial Epithelial Cells Are Associated with Asthma Severity. , 2022, American journal of respiratory and critical care medicine.

[3]  K. To,et al.  Human Nasal Organoids Model SARS-CoV-2 Upper Respiratory Infection and Recapitulate the Differential Infectivity of Emerging Variants , 2022, mBio.

[4]  L. Kapitein,et al.  Measuring cystic fibrosis drug responses in organoids derived from 2D differentiated nasal epithelia , 2022, Life Science Alliance.

[5]  F. Stossi,et al.  The Human Nose Organoid Respiratory Virus Model: an Ex Vivo Human Challenge Model To Study Respiratory Syncytial Virus (RSV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pathogenesis and Evaluate Therapeutics , 2022, mBio.

[6]  R. Lutter,et al.  Imprinting of bronchial epithelial cells upon in vivo rhinovirus infection in people with asthma , 2021, ERJ Open Research.

[7]  S. Wenzel,et al.  15LO1 dictates glutathione redox changes in asthmatic airway epithelium to worsen type 2 inflammation , 2021, The Journal of clinical investigation.

[8]  R. Nagatomi,et al.  Kakkonto Inhibits Cytokine Production Induced by Rhinovirus Infection in Primary Cultures of Human Nasal Epithelial Cells , 2021, Frontiers in Pharmacology.

[9]  W. Chung,et al.  Developmental basis of trachea-esophageal birth defects. , 2021, Developmental biology.

[10]  P. Beales,et al.  Higher throughput drug screening for rare respiratory diseases: readthrough therapy in primary ciliary dyskinesia , 2021, European Respiratory Journal.

[11]  Grace X. Y. Zheng,et al.  Progenitor identification and SARS-CoV-2 infection in human distal lung organoids , 2020, Nature.

[12]  P. Lackie,et al.  A Revised Protocol for Culture of Airway Epithelial Cells as a Diagnostic Tool for Primary Ciliary Dyskinesia , 2020, Journal of clinical medicine.

[13]  Kari C. Nadeau,et al.  Distribution of ACE2, CD147, CD26, and other SARS‐CoV‐2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID‐19 risk factors , 2020, Allergy.

[14]  J. C. Love,et al.  Rho/SMAD/mTOR triple inhibition enables long-term expansion of human neonatal tracheal aspirate-derived airway basal cell-like cells , 2020, Pediatric Research.

[15]  Matthew J. Vincent,et al.  Regenerative Metaplastic Clones in COPD Lung Drive Inflammation and Fibrosis , 2020, Cell.

[16]  Fabian J Theis,et al.  SARS-CoV-2 Receptor ACE2 is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Enriched in Specific Cell Subsets Across Tissues , 2020, SSRN Electronic Journal.

[17]  R. Hynds,et al.  Ciliated Epithelial Cell Differentiation at Air-Liquid Interface Using Commercially Available Culture Media. , 2019, Methods in molecular biology.

[18]  H. Hedenström,et al.  Pulmonary function in children and adolescents after esophageal atresia repair , 2019, Pediatric pulmonology.

[19]  A. Oudenaarden,et al.  Long‐term expanding human airway organoids for disease modeling , 2019, The EMBO journal.

[20]  Y. Miller,et al.  Exhaustion of Airway Basal Progenitor Cells in Early and Established Chronic Obstructive Pulmonary Disease , 2017, American journal of respiratory and critical care medicine.

[21]  Hongmei Mou,et al.  Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells. , 2016, Cell stem cell.

[22]  P. Thota,et al.  Long-term esophageal and respiratory outcomes in children with esophageal atresia and tracheoesophageal fistula , 2015, Gastroenterology report.

[23]  B. Weynand,et al.  Polymeric immunoglobulin receptor down-regulation in chronic obstructive pulmonary disease. Persistence in the cultured epithelium and role of transforming growth factor-β. , 2014, American journal of respiratory and critical care medicine.

[24]  W. Hop,et al.  Respiratory morbidity and growth after open thoracotomy or thoracoscopic repair of esophageal atresia. , 2012, Journal of pediatric surgery.

[25]  M. Pakarinen,et al.  Long-term results of esophageal atresia: Helsinki experience and review of literature , 2011, Pediatric Surgery International.

[26]  R. Hegele,et al.  Intrinsic phenotypic differences of asthmatic epithelium and its inflammatory responses to respiratory syncytial virus and air pollution. , 2011, American journal of respiratory cell and molecular biology.

[27]  T. Haahtela,et al.  Repaired oesophageal atresia: respiratory morbidity and pulmonary function in adults , 2010, European Respiratory Journal.

[28]  D. Fitzpatrick,et al.  Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome. , 2006, Human molecular genetics.

[29]  C. Beardsmore,et al.  Respiratory function in childhood following repair of oesophageal atresia and tracheoesophageal fistula , 1999, Archives of disease in childhood.

[30]  J. Warner,et al.  New associations of primary ciliary dyskinesia syndrome , 1993, Pediatric pulmonology.

[31]  P. Phelan,et al.  Respiratory morbidity after repair of oesophageal atresia and tracheo-oesophageal fistula. , 1993, Archives of disease in childhood.

[32]  M. Wailoo,et al.  The trachea in children with tracheo‐oesophageal fistula , 1979, Histopathology.

[33]  J. Emery,et al.  Squamous epithelium in the respiratory tract of children with tracheo-oesophageal fistula, and 'retention lung'. , 1971, Archives of disease in childhood.