Leiden University Scholarly Publications

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Booij, T.H. (2017)

Phenotypic screening with 3D cell-based assays

Doctoral Thesis
Traditional drug discovery approaches have been hampered by (in vitro) cell-culture models that poorly represent the situation in the human body. Principally, cells grow in the body in a three-dimensional (3D) environment that cannot generally be captured using cell culture methods. For this reason, cell-culture models have been developed where cells grow in a 3D-environment, which allows them to form structures that are more comparable to tissue in the body. However, the full complexity of these advanced cell-culture models can only be fully used for routine drug testing if the cell culture model can be used on a large scale (also termed high-throughput screening or HTS), and if the readout can capture all of the biological complexity reflected by the 3D-cultured cells (high-content screening or HCS). Due to these technological limitations, 3D cellular models are not yet routinely applied in drug and drug-target discovery. This thesis describes the development of fully-scalable...Show moreTraditional drug discovery approaches have been hampered by (in vitro) cell-culture models that poorly represent the situation in the human body. Principally, cells grow in the body in a three-dimensional (3D) environment that cannot generally be captured using cell culture methods. For this reason, cell-culture models have been developed where cells grow in a 3D-environment, which allows them to form structures that are more comparable to tissue in the body. However, the full complexity of these advanced cell-culture models can only be fully used for routine drug testing if the cell culture model can be used on a large scale (also termed high-throughput screening or HTS), and if the readout can capture all of the biological complexity reflected by the 3D-cultured cells (high-content screening or HCS). Due to these technological limitations, 3D cellular models are not yet routinely applied in drug and drug-target discovery. This thesis describes the development of fully-scalable 3D cell-culture screening platforms in the context of cancer and polycystic kidney disease.Show less
3D cell culture
HTS
HCS
Phenotypic profiling
PKD
Cancer
Screening
All authors
Booij, T.H.
Supervisor
Water, B. van de; Peters, D.J.M.
Co-supervisor
Price, L.S.
Committee
Irth, H.; Bouwstra, J.A.; IJzerman, A.P.; Ovaa, H.; Masereeuw, R.; Jennings, P.
Qualification
Doctor (dr.)
Awarding Institution
LACDR, Science, Leiden University
Date
2017-12-20
ISBN (print)
9789402808711