Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning
By Sigrid A. Langhans. Frontiers in Pharmacology, 2018
1,281 citations recorded by the source corpus.
Drug development is a lengthy and costly process that proceeds through several stages from target identification to lead discovery and optimization, preclinical validation and clinical trials culminating in approval for clinical use. An important step in this process is high-throughput screening (HTS) of small compound libraries for lead identification. Currently, the majority of cell-based HTS is being carried out on cultured cells propagated in two-dimensions (2D) on plastic surfaces optimized for tissue culture. At the same time, compelling evidence suggests that cells cultured in these non-physiological conditions are not representative of cells residing in the complex microenvironment of a tissue. This discrepancy is thought to be a significant contributor to the high failure rate in drug discovery, where only a low percentage of drugs investigated ever make it through the gamut of testing and approval to the market. Thus, three-dimensional (3D) cell culture technologies that more closely resemble in vivo cell environments are now being pursued with intensity as they are expected to accommodate better precision in drug discovery. Here we will review common approaches to 3D culture, discuss the significance of 3D cultures in drug resistance and drug repositioning and address some of the challenges of applying 3D cell cultures to high-throughput drug discovery.
Subfields: Biomedical Engineering, Cell Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/ced0c498329b3a184624ecaf1228293b44882775
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Citations in the corpus
- Is It Time to Start Transitioning From 2D to 3D Cell Culture? (2020, background): “The results showed a cell culture model in which toxic effects in human heart tissue could be studied due to how closely the cardiac spheroids resembled in vivo features of the human heart (Langhans, 2018).”
- 3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs (2018, background): “However, synthetic materials may lack in sites for cellular adhesion and require the addition of ECM proteins, growth factors, hormones, or other biologically active molecules to mimic the niche in which the cells naturally reside (Knight & Przyborski, 2015; Langhans, 2018).”