Skip to main content
Top
Published in:

Open Access 26-07-2023 | Original Paper

Phenotypic screening in Organ-on-a-Chip systems: a 1537 kinase inhibitor library screen on a 3D angiogenesis assay

Authors: Camilla Soragni, Karla Queiroz, Chee Ping Ng, Arthur Stok, Thomas Olivier, Dora Tzagkaraki, Jeroen Heijmans, Johnny Suijker, Sander P. M. de Ruiter, Aleksandra Olczyk, Marleen Bokkers, Frederik Schavemaker, Sebastian J. Trietsch, Henriëtte L. Lanz, Paul Vulto, Jos Joore

Published in: Angiogenesis | Issue 1/2024

Login to get access

Abstract

Modern drug development increasingly requires comprehensive models that can be utilized in the earliest stages of compound and target discovery. Here we report a phenotypic screening exercise in a high-throughput Organ-on-a-Chip setup. We assessed the inhibitory effect of 1537 protein kinase inhibitors in an angiogenesis assay. Over 4000 micro-vessels were grown under perfusion flow in microfluidic chips, exposed to a cocktail of pro-angiogenic factors and subsequently exposed to the respective kinase inhibitors. Efficacy of compounds was evaluated by reduced angiogenic sprouting, whereas reduced integrity of the main micro-vessel was taken as a measure for toxicity. The screen yielded 53 hits with high anti-angiogenicity and low toxicity, of which 44 were previously unassociated with angiogenic pathways. This study demonstrates that Organ-on-a-Chip models can be screened in high numbers to identify novel compounds and targets. This will ultimately reduce bias in early-stage drug development and increases probability to identify first in class compounds and targets for today’s intractable diseases.
Appendix
Available only for authorised users
Literature
1.
go back to reference DiMasi JA, Grabowski HG, Hansen RW (2016) Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ 47:20–33PubMedCrossRef DiMasi JA, Grabowski HG, Hansen RW (2016) Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ 47:20–33PubMedCrossRef
4.
go back to reference Booij TH, Price LS, Danen EHJ (2019) 3D cell-based assays for drug screens: challenges in imaging, image analysis, and high-content analysis. SLAS Discov 24:615–627PubMedPubMedCentralCrossRef Booij TH, Price LS, Danen EHJ (2019) 3D cell-based assays for drug screens: challenges in imaging, image analysis, and high-content analysis. SLAS Discov 24:615–627PubMedPubMedCentralCrossRef
5.
go back to reference Astashkina A, Mann B, Grainger DW (2012) A critical evaluation of in vitro cell culture models for high-throughput drug screening and toxicity. Pharmacol Ther 134:82–106PubMedCrossRef Astashkina A, Mann B, Grainger DW (2012) A critical evaluation of in vitro cell culture models for high-throughput drug screening and toxicity. Pharmacol Ther 134:82–106PubMedCrossRef
6.
go back to reference Senkowski W, Zhang X, Olofsson MH, Isacson R, Höglund U, Gustafsson M, Nygren P, Linder S, Larsson R, Fryknäs M (2015) Three-dimensional cell culture-based screening identifies the anthelmintic drug nitazoxanide as a candidate for treatment of colorectal cancer. Mol Cancer Ther 14:1504–1516PubMedCrossRef Senkowski W, Zhang X, Olofsson MH, Isacson R, Höglund U, Gustafsson M, Nygren P, Linder S, Larsson R, Fryknäs M (2015) Three-dimensional cell culture-based screening identifies the anthelmintic drug nitazoxanide as a candidate for treatment of colorectal cancer. Mol Cancer Ther 14:1504–1516PubMedCrossRef
7.
go back to reference Wenzel C, Riefke B, Gründemann S, Krebs A, Christian S, Prinz F, Osterland M, Golfier S, Räse S, Ansari N, Esner M, Bickle M, Pampaloni F, Mattheyer C, Stelzer EH, Parczyk K, Prechtl S, Steigemann P (2014) 3D high-content screening for the identification of compounds that target cells in dormant tumor spheroid regions. Exp Cell Res 323:131–143PubMedCrossRef Wenzel C, Riefke B, Gründemann S, Krebs A, Christian S, Prinz F, Osterland M, Golfier S, Räse S, Ansari N, Esner M, Bickle M, Pampaloni F, Mattheyer C, Stelzer EH, Parczyk K, Prechtl S, Steigemann P (2014) 3D high-content screening for the identification of compounds that target cells in dormant tumor spheroid regions. Exp Cell Res 323:131–143PubMedCrossRef
10.
go back to reference Herpers B, Eppink B, James MI, Cortina C, Cañellas-Socias A, Boj SF, Hernando-Momblona X, Glodzik D, Roovers RC, van de Wetering M, Bartelink-Clements C, Zondag-van der Zande V, Mateos JG, Yan K, Salinaro L, Basmeleh A, Fatrai S, Maussang D, Lammerts van Bueren JJ, Chicote I, Serna G, Cabellos L, Ramírez L, Nuciforo P, Salazar R, Santos C, Villanueva A, Stephan-Otto Attolini C, Sancho E, Palmer HG, Tabernero J, Stratton MR, de Kruif J, Logtenberg T, Clevers H, Price LS, Vries RGJ, Batlle E, Throsby M (2022) Functional patient-derived organoid screenings identify MCLA-158 as a therapeutic EGFR × LGR5 bispecific antibody with efficacy in epithelial tumors. Nat Cancer 3:418–436PubMedCrossRef Herpers B, Eppink B, James MI, Cortina C, Cañellas-Socias A, Boj SF, Hernando-Momblona X, Glodzik D, Roovers RC, van de Wetering M, Bartelink-Clements C, Zondag-van der Zande V, Mateos JG, Yan K, Salinaro L, Basmeleh A, Fatrai S, Maussang D, Lammerts van Bueren JJ, Chicote I, Serna G, Cabellos L, Ramírez L, Nuciforo P, Salazar R, Santos C, Villanueva A, Stephan-Otto Attolini C, Sancho E, Palmer HG, Tabernero J, Stratton MR, de Kruif J, Logtenberg T, Clevers H, Price LS, Vries RGJ, Batlle E, Throsby M (2022) Functional patient-derived organoid screenings identify MCLA-158 as a therapeutic EGFR × LGR5 bispecific antibody with efficacy in epithelial tumors. Nat Cancer 3:418–436PubMedCrossRef
11.
go back to reference Calandrini C, van Hooff SR, Paassen I, Ayyildiz D, Derakhshan S, Dolman MEM, Langenberg KPS, van de Ven M, de Heus C, Liv N, Kool M, de Krijger RR, Tytgat GAM, van den Heuvel-Eibrink MM, Molenaar JJ, Drost J (2021) Organoid-based drug screening reveals neddylation as therapeutic target for malignant rhabdoid tumors. Cell Rep 36:109568PubMedCrossRef Calandrini C, van Hooff SR, Paassen I, Ayyildiz D, Derakhshan S, Dolman MEM, Langenberg KPS, van de Ven M, de Heus C, Liv N, Kool M, de Krijger RR, Tytgat GAM, van den Heuvel-Eibrink MM, Molenaar JJ, Drost J (2021) Organoid-based drug screening reveals neddylation as therapeutic target for malignant rhabdoid tumors. Cell Rep 36:109568PubMedCrossRef
13.
go back to reference Kühnl J, Tao TP, Brandmair K, Gerlach S, Rings T, Müller-Vieira U, Przibilla J, Genies C, Jaques-Jamin C, Schepky A, Marx U, Hewitt NJ, Maschmeyer I (2021) Characterization of application scenario-dependent pharmacokinetics and pharmacodynamic properties of permethrin and hyperforin in a dynamic skin and liver multi-organ-chip model. Toxicology. https://doi.org/10.1016/j.tox.2020.152637CrossRefPubMed Kühnl J, Tao TP, Brandmair K, Gerlach S, Rings T, Müller-Vieira U, Przibilla J, Genies C, Jaques-Jamin C, Schepky A, Marx U, Hewitt NJ, Maschmeyer I (2021) Characterization of application scenario-dependent pharmacokinetics and pharmacodynamic properties of permethrin and hyperforin in a dynamic skin and liver multi-organ-chip model. Toxicology. https://​doi.​org/​10.​1016/​j.​tox.​2020.​152637CrossRefPubMed
14.
go back to reference Oleaga C, Bernabini C, Smith AST, Srinivasan B, Jackson M, McLamb W, Platt V, Bridges R, Cai Y, Santhanam N, Berry B, Najjar S, Akanda N, Guo X, Martin C, Ekman G, Esch MB, Langer J, Ouedraogo G, Cotovio J, Breton L, Shuler ML, Hickman JJ (2016) Multi-organ toxicity demonstration in a functional human in vitro system composed of four organs. Sci Rep 6:1–17CrossRef Oleaga C, Bernabini C, Smith AST, Srinivasan B, Jackson M, McLamb W, Platt V, Bridges R, Cai Y, Santhanam N, Berry B, Najjar S, Akanda N, Guo X, Martin C, Ekman G, Esch MB, Langer J, Ouedraogo G, Cotovio J, Breton L, Shuler ML, Hickman JJ (2016) Multi-organ toxicity demonstration in a functional human in vitro system composed of four organs. Sci Rep 6:1–17CrossRef
15.
go back to reference Sung JH, Kam C, Shuler ML (2010) A microfluidic device for a pharmacokinetic-pharmacodynamic (PK-PD) model on a chip. Lab Chip 10:446–455PubMedCrossRef Sung JH, Kam C, Shuler ML (2010) A microfluidic device for a pharmacokinetic-pharmacodynamic (PK-PD) model on a chip. Lab Chip 10:446–455PubMedCrossRef
16.
go back to reference Vernetti L, Gough A, Baetz N, Blutt S, Broughman JR, Brown JA, Foulke-Abel J, Hasan N, In J, Kelly E, Kovbasnjuk O, Repper J, Senutovitch N, Stabb J, Yeung C, Zachos NC, Donowitz M, Estes M, Himmelfarb J, Truskey G, Wikswo JP, Taylor DL (2017) Functional coupling of human microphysiology systems: intestine, liver, kidney proximal tubule, blood–brain barrier and skeletal muscle. Sci Rep 7:1–15 Vernetti L, Gough A, Baetz N, Blutt S, Broughman JR, Brown JA, Foulke-Abel J, Hasan N, In J, Kelly E, Kovbasnjuk O, Repper J, Senutovitch N, Stabb J, Yeung C, Zachos NC, Donowitz M, Estes M, Himmelfarb J, Truskey G, Wikswo JP, Taylor DL (2017) Functional coupling of human microphysiology systems: intestine, liver, kidney proximal tubule, blood–brain barrier and skeletal muscle. Sci Rep 7:1–15
17.
go back to reference Rogers MT, Gard AL, Gaibler R, Mulhern TJ, Strelnikov R, Azizgolshani H, Cain BP, Isenberg BC, Haroutunian NJ, Raustad NE, Keegan PM, Lech MP, Tomlinson L, Borenstein JT, Charest JL, Williams C (2021) A high-throughput microfluidic bilayer co-culture platform to study endothelial-pericyte interactions. Sci Rep 11:1–14CrossRef Rogers MT, Gard AL, Gaibler R, Mulhern TJ, Strelnikov R, Azizgolshani H, Cain BP, Isenberg BC, Haroutunian NJ, Raustad NE, Keegan PM, Lech MP, Tomlinson L, Borenstein JT, Charest JL, Williams C (2021) A high-throughput microfluidic bilayer co-culture platform to study endothelial-pericyte interactions. Sci Rep 11:1–14CrossRef
18.
go back to reference Trietsch SJ, Israëls GD, Joore J, Hankemeier T, Vulto P (2013) Microfluidic titer plate for stratified 3D cell culture. Lab Chip 13:3548–3554PubMedCrossRef Trietsch SJ, Israëls GD, Joore J, Hankemeier T, Vulto P (2013) Microfluidic titer plate for stratified 3D cell culture. Lab Chip 13:3548–3554PubMedCrossRef
19.
go back to reference Trietsch SJ, Naumovska E, Kurek D, Setyawati MC, Vormann MK, Wilschut KJ, Lanz HL, Nicolas A, Ng CP, Joore J, Kustermann S, Roth A, Hankemeier T, Moisan A, Vulto P (2017) Membrane-free culture and real-time barrier integrity assessment of perfused intestinal epithelium tubes. Nat Commun 8:1–7CrossRef Trietsch SJ, Naumovska E, Kurek D, Setyawati MC, Vormann MK, Wilschut KJ, Lanz HL, Nicolas A, Ng CP, Joore J, Kustermann S, Roth A, Hankemeier T, Moisan A, Vulto P (2017) Membrane-free culture and real-time barrier integrity assessment of perfused intestinal epithelium tubes. Nat Commun 8:1–7CrossRef
20.
go back to reference Ragelle H, Dernick K, Khemais S, Keppler C, Cousin L, Farouz Y, Louche C, Fauser S, Kustermann S, Tibbitt MW, Westenskow PD (2020) Human retinal microvasculature-on-a-chip for drug discovery. Adv Healthc Mater 9:1–10CrossRef Ragelle H, Dernick K, Khemais S, Keppler C, Cousin L, Farouz Y, Louche C, Fauser S, Kustermann S, Tibbitt MW, Westenskow PD (2020) Human retinal microvasculature-on-a-chip for drug discovery. Adv Healthc Mater 9:1–10CrossRef
21.
go back to reference van Duinen V, Zhu D, Ramakers C, van Zonneveld AJ, Vulto P, Hankemeier T (2019) Perfused 3D angiogenic sprouting in a high-throughput in vitro platform. Angiogenesis 22:157–165PubMedCrossRef van Duinen V, Zhu D, Ramakers C, van Zonneveld AJ, Vulto P, Hankemeier T (2019) Perfused 3D angiogenic sprouting in a high-throughput in vitro platform. Angiogenesis 22:157–165PubMedCrossRef
22.
go back to reference Vulto P, Podszun S, Meyer P, Hermann C, Manz A, Urban GA (2011) Phaseguides: a paradigm shift in microfluidic priming and emptying. Lab Chip 11:1596–1602PubMedCrossRef Vulto P, Podszun S, Meyer P, Hermann C, Manz A, Urban GA (2011) Phaseguides: a paradigm shift in microfluidic priming and emptying. Lab Chip 11:1596–1602PubMedCrossRef
23.
go back to reference Iversen PW, Eastwood BJ, Sittampalam GS, Cox KL (2006) A comparison of assay performance measures in screening assays: signal window, Z′ factor, and assay variability ratio. J Biomol Screen 11:247–252PubMedCrossRef Iversen PW, Eastwood BJ, Sittampalam GS, Cox KL (2006) A comparison of assay performance measures in screening assays: signal window, Z′ factor, and assay variability ratio. J Biomol Screen 11:247–252PubMedCrossRef
24.
go back to reference Zhang JH, Chung TDY, Oldenburg KR (1999) A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J Biomol Screen 4:67–73PubMedCrossRef Zhang JH, Chung TDY, Oldenburg KR (1999) A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J Biomol Screen 4:67–73PubMedCrossRef
26.
go back to reference Song M, Finley SD (2018) Mechanistic insight into activation of MAPK signaling by pro-angiogenic factors. BMC Syst Biol 12:1–17CrossRef Song M, Finley SD (2018) Mechanistic insight into activation of MAPK signaling by pro-angiogenic factors. BMC Syst Biol 12:1–17CrossRef
27.
go back to reference Allen E, Walters IB, Hanahan D (2011) Brivanib, a dual FGF/VEGF inhibitor, is active both first and second line against mouse pancreatic neuroendocrine tumors developing adaptive/evasive resistance to VEGF inhibition. Clin Cancer Res 17:5299–5310PubMedPubMedCentralCrossRef Allen E, Walters IB, Hanahan D (2011) Brivanib, a dual FGF/VEGF inhibitor, is active both first and second line against mouse pancreatic neuroendocrine tumors developing adaptive/evasive resistance to VEGF inhibition. Clin Cancer Res 17:5299–5310PubMedPubMedCentralCrossRef
28.
go back to reference Ciuffreda L, Del Bufalo D, Desideri M, Di Sanza C, Stoppacciaro A, Ricciardi MR, Chiaretti S, Tavolaro S, Benassi B, Bellacosa A, Foá R, Tafuri A, Cognetti F, Anichini A, Zupi G, Milella M (2009) Growth-inhibitory and antiangiogenic activity of the MEK inhibitor PD0325901 in malignant melanoma with or without BRAF mutations. Neoplasia 11:720–731PubMedPubMedCentralCrossRef Ciuffreda L, Del Bufalo D, Desideri M, Di Sanza C, Stoppacciaro A, Ricciardi MR, Chiaretti S, Tavolaro S, Benassi B, Bellacosa A, Foá R, Tafuri A, Cognetti F, Anichini A, Zupi G, Milella M (2009) Growth-inhibitory and antiangiogenic activity of the MEK inhibitor PD0325901 in malignant melanoma with or without BRAF mutations. Neoplasia 11:720–731PubMedPubMedCentralCrossRef
29.
go back to reference Chung CH, Chang CH, Chen SS, Wang HH, Yen JY, Hsiao CJ, Wu NL, Chen YL, Huang TF, Wang PC, Yeh HI, Wang SW (2013) Butein inhibits angiogenesis of human endothelial progenitor cells via the translation dependent signaling pathway. Evid Based Complement Altern Med. https://doi.org/10.1155/2013/943187CrossRef Chung CH, Chang CH, Chen SS, Wang HH, Yen JY, Hsiao CJ, Wu NL, Chen YL, Huang TF, Wang PC, Yeh HI, Wang SW (2013) Butein inhibits angiogenesis of human endothelial progenitor cells via the translation dependent signaling pathway. Evid Based Complement Altern Med. https://​doi.​org/​10.​1155/​2013/​943187CrossRef
30.
go back to reference Gao Y, Rankin GO, Tu Y, Chen YC (2016) Theaflavin-3,3′-digallate decreases human ovarian carcinoma OVCAR-3 cell-induced angiogenesis via Akt and notch-1 pathways, not via MAPK pathways. Int J Oncol 48:281–292PubMedCrossRef Gao Y, Rankin GO, Tu Y, Chen YC (2016) Theaflavin-3,3′-digallate decreases human ovarian carcinoma OVCAR-3 cell-induced angiogenesis via Akt and notch-1 pathways, not via MAPK pathways. Int J Oncol 48:281–292PubMedCrossRef
32.
33.
go back to reference Zhao H, Liu L, Ma Y, Fang J, Fang W, Ma H, Zhang Y, Feng G, Hong S, Zeng S, Xie B, Ren J, Lin X, Zhang Y, Xi N, Jiang Y, Wu Y, Kang N, Li S, Zhang L (2020) A phase Ib study of a novel c-MET, AXL and VEGFR-2 inhibitor ningetinib and gefitinib combination therapy in Chinese EGFR-TKI resistant NSCLC with T790M negative. J Clin Oncol 38:9583CrossRef Zhao H, Liu L, Ma Y, Fang J, Fang W, Ma H, Zhang Y, Feng G, Hong S, Zeng S, Xie B, Ren J, Lin X, Zhang Y, Xi N, Jiang Y, Wu Y, Kang N, Li S, Zhang L (2020) A phase Ib study of a novel c-MET, AXL and VEGFR-2 inhibitor ningetinib and gefitinib combination therapy in Chinese EGFR-TKI resistant NSCLC with T790M negative. J Clin Oncol 38:9583CrossRef
34.
go back to reference Krishnamoorthy SK, Relias V, Sebastian S, Jayaraman V, Saif MW (2015) Management of regorafenib-related toxicities: a review. Ther Adv Gastroenterol 8:285–297CrossRef Krishnamoorthy SK, Relias V, Sebastian S, Jayaraman V, Saif MW (2015) Management of regorafenib-related toxicities: a review. Ther Adv Gastroenterol 8:285–297CrossRef
35.
go back to reference Wang Z, Xu J, Nie W, Huang G, Tang J, Guan X (2014) Risk of hypertension with regorafenib in cancer patients: a systematic review and meta-analysis. Eur J Clin Pharmacol 70:225–231PubMedCrossRef Wang Z, Xu J, Nie W, Huang G, Tang J, Guan X (2014) Risk of hypertension with regorafenib in cancer patients: a systematic review and meta-analysis. Eur J Clin Pharmacol 70:225–231PubMedCrossRef
36.
go back to reference Ivanyi P, Eggers H, Hornig M, Kasper B, Heissner K, Kopp HG, Kirstein M, Ganser A, Grünwald V (2020) Hepatic toxicity during regorafenib treatment in patients with metastatic gastrointestinal stromal tumors. Mol Clin Oncol 13:1–5CrossRef Ivanyi P, Eggers H, Hornig M, Kasper B, Heissner K, Kopp HG, Kirstein M, Ganser A, Grünwald V (2020) Hepatic toxicity during regorafenib treatment in patients with metastatic gastrointestinal stromal tumors. Mol Clin Oncol 13:1–5CrossRef
37.
go back to reference Van Duinen V, Van Den Heuvel A, Trietsch SJ, Lanz HL, Van Gils JM, Van Zonneveld AJ, Vulto P, Hankemeier T (2017) 96 perfusable blood vessels to study vascular permeability in vitro. Sci Rep 7:1–11 Van Duinen V, Van Den Heuvel A, Trietsch SJ, Lanz HL, Van Gils JM, Van Zonneveld AJ, Vulto P, Hankemeier T (2017) 96 perfusable blood vessels to study vascular permeability in vitro. Sci Rep 7:1–11
39.
40.
go back to reference Bamborough P, Drewry D, Harper G, Smith GK, Schneider K (2008) Assessment of chemical coverage of kinome space and its implications for kinase drug discovery. J Med Chem 51:7898–7914PubMedCrossRef Bamborough P, Drewry D, Harper G, Smith GK, Schneider K (2008) Assessment of chemical coverage of kinome space and its implications for kinase drug discovery. J Med Chem 51:7898–7914PubMedCrossRef
41.
go back to reference Perrin D, Frémaux C, Scheer A (2006) Assay development and screening of a serine/threonine kinase in an on-chip mode using caliper nanofluidics technology. J Biomol Screen 11:359–368PubMedCrossRef Perrin D, Frémaux C, Scheer A (2006) Assay development and screening of a serine/threonine kinase in an on-chip mode using caliper nanofluidics technology. J Biomol Screen 11:359–368PubMedCrossRef
42.
go back to reference Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J 451:313–328PubMedCrossRef Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J 451:313–328PubMedCrossRef
43.
go back to reference Zanella F, Rosado A, Blanco F, Henderson BR, Carnero A, Link W (2007) An HTS approach to screen for antagonists of the nuclear export machinery using high content cell-based assays. Assay Drug Dev Technol 5:333–341PubMedCrossRef Zanella F, Rosado A, Blanco F, Henderson BR, Carnero A, Link W (2007) An HTS approach to screen for antagonists of the nuclear export machinery using high content cell-based assays. Assay Drug Dev Technol 5:333–341PubMedCrossRef
44.
go back to reference Hallyburton I, Grimaldi R, Woodland A, Baragaña B, Luksch T, Spinks D, James D, Leroy D, Waterson D, Fairlamb AH, Wyatt PG, Gilbert IH, Frearson JA (2017) Screening a protein kinase inhibitor library against Plasmodium falciparum. Malar J 16:1–11CrossRef Hallyburton I, Grimaldi R, Woodland A, Baragaña B, Luksch T, Spinks D, James D, Leroy D, Waterson D, Fairlamb AH, Wyatt PG, Gilbert IH, Frearson JA (2017) Screening a protein kinase inhibitor library against Plasmodium falciparum. Malar J 16:1–11CrossRef
45.
go back to reference Roskoski R (2007) Sunitinib: a VEGF and PDGF receptor protein kinase and angiogenesis inhibitor. Biochem Biophys Res Commun 356:323–328PubMedCrossRef Roskoski R (2007) Sunitinib: a VEGF and PDGF receptor protein kinase and angiogenesis inhibitor. Biochem Biophys Res Commun 356:323–328PubMedCrossRef
46.
go back to reference Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez JY, White DJ, Hartenstein V, Eliceiri K, Tomancak P, Cardona A (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9:676–682PubMedCrossRef Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez JY, White DJ, Hartenstein V, Eliceiri K, Tomancak P, Cardona A (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9:676–682PubMedCrossRef
47.
go back to reference Marr D, Hildreth E (1980) Theory of edge detection. Proc R Soc Lond Biol Sci 207:187–217CrossRefADS Marr D, Hildreth E (1980) Theory of edge detection. Proc R Soc Lond Biol Sci 207:187–217CrossRefADS
48.
go back to reference Ridler TW, Calvard S (1978) Picture thresholding using an interactive selection method. IEEE Trans Syst Man Cybern smc-8:630–632 Ridler TW, Calvard S (1978) Picture thresholding using an interactive selection method. IEEE Trans Syst Man Cybern smc-8:630–632
49.
go back to reference Soille P, Vincent LM (1990) Determining watersheds in digital pictures via flooding simulations. Visual communications and image processing'90: Fifth in a Series SPIE, pp 240–250 Soille P, Vincent LM (1990) Determining watersheds in digital pictures via flooding simulations. Visual communications and image processing'90: Fifth in a Series SPIE, pp 240–250
51.
go back to reference Zhang XD (2011) Illustration of SSMD, z score, SSMD*, z* score, and t statistic for hit selection in RNAi high-throughput screens. J Biomol Screen 16:775–785PubMedCrossRef Zhang XD (2011) Illustration of SSMD, z score, SSMD*, z* score, and t statistic for hit selection in RNAi high-throughput screens. J Biomol Screen 16:775–785PubMedCrossRef
52.
go back to reference Birmingham A, Selfors LM, Forster T, Wrobel D, Kennedy CJ, Shanks E, Santoyo-Lopez J, Dunican DJ, Long A, Kelleher D, Smith Q, Beijersbergen RL, Ghazal P, Shamu CE (2009) Statistical methods for analysis of high-throughput RNA interference screens. Nat Methods 6:569–575PubMedPubMedCentralCrossRef Birmingham A, Selfors LM, Forster T, Wrobel D, Kennedy CJ, Shanks E, Santoyo-Lopez J, Dunican DJ, Long A, Kelleher D, Smith Q, Beijersbergen RL, Ghazal P, Shamu CE (2009) Statistical methods for analysis of high-throughput RNA interference screens. Nat Methods 6:569–575PubMedPubMedCentralCrossRef
53.
go back to reference Mendez D, Gaulton A, Bento AP, Chambers J, De Veij M, Félix E, Magariños MP, Mosquera JF, Mutowo P, Nowotka M, Gordillo-Marañón M, Hunter F, Junco L, Mugumbate G, Rodriguez-Lopez M, Atkinson F, Bosc N, Radoux CJ, Segura-Cabrera A, Hersey A, Leach AR (2019) ChEMBL: towards direct deposition of bioassay data. Nucleic Acids Res 47:D930–D940PubMedCrossRef Mendez D, Gaulton A, Bento AP, Chambers J, De Veij M, Félix E, Magariños MP, Mosquera JF, Mutowo P, Nowotka M, Gordillo-Marañón M, Hunter F, Junco L, Mugumbate G, Rodriguez-Lopez M, Atkinson F, Bosc N, Radoux CJ, Segura-Cabrera A, Hersey A, Leach AR (2019) ChEMBL: towards direct deposition of bioassay data. Nucleic Acids Res 47:D930–D940PubMedCrossRef
54.
go back to reference Davies M, Nowotka M, Papadatos G, Dedman N, Gaulton A, Atkinson F, Bellis L, Overington JP (2015) ChEMBL web services: streamlining access to drug discovery data and utilities. Nucleic Acids Res 43:W612–W620PubMedPubMedCentralCrossRef Davies M, Nowotka M, Papadatos G, Dedman N, Gaulton A, Atkinson F, Bellis L, Overington JP (2015) ChEMBL web services: streamlining access to drug discovery data and utilities. Nucleic Acids Res 43:W612–W620PubMedPubMedCentralCrossRef
Metadata
Title
Phenotypic screening in Organ-on-a-Chip systems: a 1537 kinase inhibitor library screen on a 3D angiogenesis assay
Authors
Camilla Soragni
Karla Queiroz
Chee Ping Ng
Arthur Stok
Thomas Olivier
Dora Tzagkaraki
Jeroen Heijmans
Johnny Suijker
Sander P. M. de Ruiter
Aleksandra Olczyk
Marleen Bokkers
Frederik Schavemaker
Sebastian J. Trietsch
Henriëtte L. Lanz
Paul Vulto
Jos Joore
Publication date
26-07-2023
Publisher
Springer Netherlands
Published in
Angiogenesis / Issue 1/2024
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-023-09888-3

Other articles of this Issue 1/2024

Angiogenesis 1/2024 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Webinar | 06-02-2024 | 20:00 (CET)

Mastering chronic pancreatitis pain: A multidisciplinary approach and practical solutions

Severe pain is the most common symptom of chronic pancreatitis. In this webinar, experts share the latest insights in pain management for chronic pancreatitis patients. Experts from a range of disciplines discuss pertinent cases and provide practical suggestions for use within clinical practice.

Sponsored by: Viatris

Developed by: Springer Healthcare
Live Webinar | 01-10-2024 | 12:30 (CEST)

Recent advances in the use of CAR T-cell therapies in relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma

Live: Tuesday 1st October 2024, 12:30-14:00 (CEST)

In this live webinar, Professor Martin Dreyling and an esteemed, international panel of CAR-T experts will discuss the very latest data on the safety, efficacy and clinical impact of CAR T-cell therapies in the treatment of r/r DLBCL and r/r FL, as presented at ASH 2023, EU CAR-T 2024, and EHA 2024. 

Please note, this webinar is not intended for healthcare professionals based in the US and UK.

Sponsored by: Novartis Pharma AG

Chaired by: Prof. Martin Dreyling
Developed by: Springer Healthcare