To evaluate the functionality of CFTR in patients with idiopathic pancreatitis (PI), rectal biopsies were performed from 11 patients on which the transport of bicarbonate and chlorine ions was measured. The ICM assay showed that patients with variants in the CFTR protein have a defect in bicarbonate secretion. Furthermore, two subjects with chlorine transport defect were more specifically diagnosed as CF.
Then, 25 3D organoids originated from PI patients were developed and the researchers report that CF derived organoids show a different morphological conformation compared to those originating from PI patients. The latter has similar characteristics to organoids derived from healthy subjects or CF carriers. To investigate the role of modulators on CFTR-mediated bicarbonate transport, researchers developed 2D organoids. These organoids showed to be an effective experimental model reproducing the behaviour of the CFTR protein (wild type and mutated) and a useful tool to evaluate the effect of CFTR correctors. Other assays developed in 2D organoids (real-time measurements such as confocal reflectometry of fluid height and pH-Stat) have not been shown to be sensitive and accurate enough.
During this project, the researchers set the necessary assays and experimental models and they will proceed with their study with the FFC project #5/2020, an extension of the one just completed.

Pubblication

• Caldrer S, Bergamini G, Sandri A et al. Cystic fibrosis transmembrane conductance regulator functional evaluations in a 542X+/IVS8Tn: T7/9 patient with acute recurrent pancreatitis, World Journal of Clinical Cases, 2019 Nov 26;7(22):3757-3764.