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Cell Rep. 2019 Feb 12;26(7):1701-1708.e3. doi: 10.1016/j.celrep.2019.01.068.

Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis.

Author information

1
Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, 3584 EA Utrecht, the Netherlands.
2
Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, 3584 EA Utrecht, the Netherlands; Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht University, 3584 CT Utrecht, the Netherlands.
3
Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands.
4
Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, 3584 EA Utrecht, the Netherlands.
5
Department of Pulmonology, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
6
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands.
7
Department of Respiratory Medicine, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
8
University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Department of Pediatric Pulmonology and Pediatric Allergology and GRIAC Research Institute, 9713 GZ Groningen, the Netherlands.
9
Department of Pediatric Pulmonology, Radboud University Medical Center, Amalia Children's Hospital, 6525 GA Nijmegen, the Netherlands.
10
Department of Pulmonology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, the Netherlands.
11
Department of Pediatrics, Division of Respiratory Medicine and Allergology, Erasmus MC-Sophia Children's Hospital, University Medical Center, 3015 GD Rotterdam, the Netherlands.
12
Department of Pulmonology, Haga Teaching Hospital, 2545 AA The Hague, the Netherlands.
13
Hubrecht Organoid Technology (HUB), 3584 CM Utrecht, the Netherlands.
14
Department of Gastroenterology and Hepatology, Erasmus University Medical Center, 3015 GD Rotterdam, the Netherlands.
15
Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, 3584 EA Utrecht, the Netherlands; Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht University, 3584 CT Utrecht, the Netherlands. Electronic address: j.beekman@umcutrecht.nl.
16
Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, 3584 EA Utrecht, the Netherlands. Electronic address: k.vanderent@umcutrecht.nl.

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.

KEYWORDS:

CFTR; cystic fibrosis; drug response; organoids; personalized treatment; predicting; stem cell cultures

PMID:
30759382
DOI:
10.1016/j.celrep.2019.01.068
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