High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array

By Y. Tung, A. Hsiao, S. Allen, Y. Torisawa, M. Ho, Shuichi Takayama. In Analysis, 2010

878 citations recorded by the source corpus.

Culture of cells as three-dimensional (3D) aggregates can enhance in vitro tests for basic biological research as well as for therapeutics development. Such 3D culture models, however, are often more complicated, cumbersome, and expensive than two-dimensional (2D) cultures. This paper describes a 384-well format hanging drop culture plate that makes spheroid formation, culture, and subsequent drug testing on the obtained 3D cellular constructs as straightforward to perform and adapt to existing high-throughput screening (HTS) instruments as conventional 2D cultures. Using this platform, we show that drugs with different modes of action produce distinct responses in the physiological 3D cell spheroids compared to conventional 2D cell monolayers. Specifically, the anticancer drug 5-fluorouracil (5-FU) has higher anti-proliferative effects on 2D cultures whereas the hypoxia activated drug commonly referred to as tirapazamine (TPZ) are more effective against 3D cultures. The multiplexed 3D hanging drop culture and testing plate provides an efficient way to obtain biological insights that are often lost in 2D platforms.

Subfields: Biomedical Engineering, Oncology

View Paper: https://www.semanticscholar.org/paper/d615ed9de6bda4b7c5a4691d4b30d9bbab0ee5b4

Citations in the corpus

• Opportunities and Challenges for use of Tumor Spheroids as Models to Test Drug Delivery and Efficacy (2012, neutral): “When treated with these drugs together, there was an additive effect on the cell death in 3D spheroids, since 5-FU targets proliferating cells in the peripheral layers of spheroids and TPZ kills cells in the hypoxic core of spheroids [59].”