Development of a programmable automated cell culture system to study the lung pathophysiology of Cystic Fibrosis-related diabetes
Analia J. Vazquez Cegla,
Cameron Hedden,
Barry R. Imhoff,
Guiying Cui,
Nael A. McCarty
Affiliations
Analia J. Vazquez Cegla
Division of Pulmonology, Asthma, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory + Children's Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA; Corresponding author. PACS Division, Dept. of Pediatrics, Emory University School of Medicine, Emory+Children's Cystic Fibrosis Center of Excellence (www.cfatl.org), 2015 Uppergate Drive, Atlanta, GA, 30322, USA.
Cameron Hedden
Neuroscience and Behavioral Biology Program, Emory College of Arts and Sciences, Emory University, Atlanta, GA, USA
Barry R. Imhoff
Division of Pulmonology, Asthma, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory + Children's Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA
Guiying Cui
Division of Pulmonology, Asthma, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory + Children's Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA
Nael A. McCarty
Division of Pulmonology, Asthma, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory + Children's Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA
The study of many diseases is limited by the in vitro systems available. Cystic Fibrosis-Related Diabetes (CFRD), the main co-morbidity of Cystic Fibrosis (CF), is a perfect example. Cells in vivo experience glucose fluctuations after meals. In contrast, cells cultured in vitro are initially exposed to high glucose media. Glucose gets progressively depleted until the next media change days later, which is not physiologically relevant and could negatively impact the results of research studies. To better study the mechanisms driving CFRD pathophysiology, we developed a programmable and automated cell culture system (PACCS) capable of mimicking acute hyperglycemic episodes experienced by CFRD patients after meals. We adapted a commercially available perfusion system and performed 3D modeling to develop this system. Results show that PACCS can be successfully used to culture airway epithelial cells, both immortalized and primary cells. Further, CF cells responded differently to meal-like conditioning when compared to controls, suggesting impaired adaptative responses in CF cells. Overall, PACCS will allow us to better study CFRD pathophysiology, and it could be used for a wide range of other applications.
