Molecular and cellular pediatrics

Pluripotent stem cells for disease modeling and drug screening: new perspectives for treatment of cystic fibrosis?

PMID 26666881


Despite continuous improvements in treating clinical symptoms and the identification of single compounds that effectively rescue some rare mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), associated lung and liver pathologies remain largely untreatable and no real breakthrough is visible for the majority of patients suffering from cystic fibrosis (CF).Novel compounds have to be identified and tailored in combination to specific CFTR mutations, to different tissues, or even to the individual patient. Immortalized cell lines overexpressing mutant CFTR are typically used to screen candidate molecules but have proven to be poor predictors of clinical efficacy. The complexity of CFTR maturation and turnover requires the use of cellular models that closely recapitulate the specific properties of the clinically most affected organs. Importantly, current screening efforts based on primary airway cells or intestinal organoids cannot specifically target single rare CFTR mutations or mimic multiple cell types.In the near future, genetically engineered induced pluripotent stem cells will provide an excellent basis for personalized organotypic models of CF disease and biological screens for identification of CFTR potentiators and correctors.