Category: Assay Development and Screening
Because of improved in vivo relevancy compared to 2D monolayer cell culture models, 3D cell culture models (spheroids, organoids, microtissues, etc.) are being rapidly adopted for use academic research, the study of disease, and as a tool for drug discovery. In drug discovery screening, it is common to assess the effect of small molecules and antibodies on cell proliferation (via Ki67 immunolabeling). However, one of the challenges with 3D cell culture is imaging, since 3D cell models are thick, often 200-500 microns, causing extensive light scattering, rendering these models opaque. Because of this, wide-field and confocal microscopy can characterize only the outermost layers of cells. This induces an inherent bias into results obtained from microscopic imaging of 3D cell models, since the outermost cells are most exposed to drug, nutrients, oxygen, etc. and thus may behave differently than cells in the interior. It was shown that by combining a rapid, in-plate, tissue clearing technique with high content laser confocal microscopy, the entire cell population contained in 3D cell culture models could be imaged and assessed for proliferation. Using this technique, the differential effect of antiproliferative drugs between the outer and inner cell populations in HepG2 spheroids was examined. This technique is useful to exploring the kinetics and penetration of compounds and antibodies in cancer drug screening.
Thomas Villani– CSO and Co-Founder, Visikol Inc, North Brunswick, NJ
CSO and Co-Founder
North Brunswick, NJ
Dr. Villani completed a PhD in Medicinal Chemistry at Rutgers University. After inventing Visikol at Rutgers University, Dr. Villani went on to co-found Visikol Inc. and is currently the CSO of Visikol Inc. At Visikol, Dr. Villani focuses on the development of novel assays and applications of tissue clearing in drug discovery and histological imaging.