| Literature DB >> 30759382 |
Gitte Berkers1, Peter van Mourik1, Annelotte M Vonk2, Evelien Kruisselbrink2, Johanna F Dekkers3, Karin M de Winter-de Groot1, Hubertus G M Arets1, Rozemarijn E P Marck-van der Wilt1, Jasper S Dijkema1, Maaike M Vanderschuren1, Roderick H J Houwen4, Harry G M Heijerman5, Eduard A van de Graaf5, Sjoerd G Elias6, Christof J Majoor7, Gerard H Koppelman8, Jolt Roukema9, Marleen Bakker10, Hettie M Janssens11, Renske van der Meer12, Robert G J Vries13, Hans C Clevers3, Hugo R de Jonge14, Jeffrey M Beekman15, Cornelis K van der Ent16.
Abstract
In vitro drug tests using patient-derived stem cell cultures offer opportunities to individually select efficacious treatments. Here, we provide a study that demonstrates that in vitro drug responses in rectal organoids from individual patients with cystic fibrosis (CF) correlate with changes in two in vivo therapeutic endpoints. We measured individual in vitro efficaciousness using a functional assay in rectum-derived organoids based on forskolin-induced swelling and studied the correlation with in vivo effects. The in vitro organoid responses correlated with both change in pulmonary response and change in sweat chloride concentration. Receiver operating characteristic curves indicated good-to-excellent accuracy of the organoid-based test for defining clinical responses. This study indicates that an in vitro assay using stem cell cultures can prospectively select efficacious treatments for patients and suggests that biobanked stem cell resources can be used to tailor individual treatments in a cost-effective and patient-friendly manner.Entities:
Keywords: CFTR; cystic fibrosis; drug response; organoids; personalized treatment; predicting; stem cell cultures
Mesh：
Year: 2019 PMID： 30759382 DOI： 10.1016/j.celrep.2019.01.068
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423