Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis

Gitte Berkers; Peter van Mourik; Annelotte M Vonk; Evelien Kruisselbrink; Johanna F Dekkers; Karin M de Winter-de Groot; Hubertus G M Arets; Rozemarijn E P Marck-van der Wilt; Jasper S Dijkema; Maaike M Vanderschuren; Roderick H J Houwen; Harry G M Heijerman; Eduard A van de Graaf; Sjoerd G Elias; Christof J Majoor; Gerard H Koppelman; Jolt Roukema; Marleen Bakker; Hettie M Janssens; Renske van der Meer; Robert G J Vries; Hans C Clevers; Hugo R de Jonge; Jeffrey M Beekman; Cornelis K van der Ent

doi:10.1016/j.celrep.2019.01.068

Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis

Gitte Berkers, Peter van Mourik, Annelotte M Vonk, Evelien Kruisselbrink, Johanna F Dekkers, Karin M de Winter-de Groot, Hubertus G M Arets, Rozemarijn E P Marck-van der Wilt, Jasper S Dijkema, Maaike M Vanderschuren, Roderick H J Houwen, Harry G M Heijerman, Eduard A van de Graaf, Sjoerd G Elias, Christof J Majoor, Gerard H Koppelman, Jolt Roukema, Marleen Bakker, Hettie M Janssens, Renske van der MeerRobert G J Vries, Hans C Clevers, Hugo R de Jonge, Jeffrey M Beekman, Cornelis K van der Ent

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

209 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1701-1708.e3
Journal	Cell Reports
Volume	26
Issue number	7
DOIs	https://doi.org/10.1016/j.celrep.2019.01.068
Publication status	Published - 12 Feb 2019

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Berkers, G., van Mourik, P., Vonk, A. M., Kruisselbrink, E., Dekkers, J. F., de Winter-de Groot, K. M., Arets, H. G. M., Marck-van der Wilt, R. E. P., Dijkema, J. S., Vanderschuren, M. M., Houwen, R. H. J., Heijerman, H. G. M., van de Graaf, E. A., Elias, S. G., Majoor, C. J., Koppelman, G. H., Roukema, J., Bakker, M., Janssens, H. M., ... van der Ent, C. K. (2019). Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis. Cell Reports, 26(7), 1701-1708.e3. https://doi.org/10.1016/j.celrep.2019.01.068

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title = "Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis",

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.",

author = "Gitte Berkers and {van Mourik}, Peter and Vonk, {Annelotte M} and Evelien Kruisselbrink and Dekkers, {Johanna F} and {de Winter-de Groot}, {Karin M} and Arets, {Hubertus G M} and {Marck-van der Wilt}, {Rozemarijn E P} and Dijkema, {Jasper S} and Vanderschuren, {Maaike M} and Houwen, {Roderick H J} and Heijerman, {Harry G M} and {van de Graaf}, {Eduard A} and Elias, {Sjoerd G} and Majoor, {Christof J} and Koppelman, {Gerard H} and Jolt Roukema and Marleen Bakker and Janssens, {Hettie M} and {van der Meer}, Renske and Vries, {Robert G J} and Clevers, {Hans C} and {de Jonge}, {Hugo R} and Beekman, {Jeffrey M} and {van der Ent}, {Cornelis K}",

year = "2019",

month = feb,

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doi = "10.1016/j.celrep.2019.01.068",

language = "English",

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Berkers, G, van Mourik, P, Vonk, AM, Kruisselbrink, E, Dekkers, JF, de Winter-de Groot, KM, Arets, HGM, Marck-van der Wilt, REP, Dijkema, JS, Vanderschuren, MM, Houwen, RHJ, Heijerman, HGM, van de Graaf, EA, Elias, SG, Majoor, CJ, Koppelman, GH, Roukema, J, Bakker, M, Janssens, HM, van der Meer, R, Vries, RGJ, Clevers, HC, de Jonge, HR, Beekman, JM & van der Ent, CK 2019, 'Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis', Cell Reports, vol. 26, no. 7, pp. 1701-1708.e3. https://doi.org/10.1016/j.celrep.2019.01.068

TY - JOUR

T1 - Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis

AU - Berkers, Gitte

AU - van Mourik, Peter

AU - Vonk, Annelotte M

AU - Kruisselbrink, Evelien

AU - Dekkers, Johanna F

AU - de Winter-de Groot, Karin M

AU - Arets, Hubertus G M

AU - Marck-van der Wilt, Rozemarijn E P

AU - Dijkema, Jasper S

AU - Vanderschuren, Maaike M

AU - Houwen, Roderick H J

AU - Heijerman, Harry G M

AU - van de Graaf, Eduard A

AU - Elias, Sjoerd G

AU - Majoor, Christof J

AU - Koppelman, Gerard H

AU - Roukema, Jolt

AU - Bakker, Marleen

AU - Janssens, Hettie M

AU - van der Meer, Renske

AU - Vries, Robert G J

AU - Clevers, Hans C

AU - de Jonge, Hugo R

AU - Beekman, Jeffrey M

AU - van der Ent, Cornelis K

PY - 2019/2/12

Y1 - 2019/2/12

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2019.01.068

DO - 10.1016/j.celrep.2019.01.068

M3 - Article

C2 - 30759382

SN - 2211-1247

VL - 26

SP - 1701-1708.e3

JO - Cell Reports

JF - Cell Reports

IS - 7

ER -

Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis

Abstract

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