Intestinal organoids as model for cystic fibrosis

Abstract

Recent advances in adult stem cell culture technology have enabled long-term in vitro expansion of intestinal organoids or ‘mini-guts’. In this thesis, we used the organoid model to develop a novel assay to measure function of CFTR, the protein mutated in subjects with cystic fibrosis (CF). This methodology enables accurate quantitation of the individual's residual CFTR function and response to CFTR-restoring drugs. It was used to (i) establish relations between the CFTR genotype, residual CFTR function, and response to therapy, (ii) discover novel approaches for optimal repair of mutant CFTR and (iii) guide the development of personalized/precision medicine for CF patients. The potential of the model has been provided, validation of its predictive capacity is next. This assay will play an important role in the development of future therapeutic options that aim to bring curative treatments to all CF subjects.