2D cell cultures 3D cell cultures Animals
Tissue Architecture Cells are unnaturally polarized and mainly exposed to culture medium and rigid substrates Cells interact with ECM and adjacent cells in 3D. They secrete and remodel ECM Integrated response from interactions among all tissues and organs
Gene expression pattern Physiological tumor properties are constricted in 2D and, thus, expression patterns Key expression pattern in tumor biology is recreated (apoptosis resistance, etc.) Human responses are not accurately captured (drug toxicity, metabolization, etc.)
Molecular gradients Cells are submitted to uniformly rich oxygenation and drug accessibility Oxygen and drug delivery is controlled by simple diffusion Vascularization regulates oxygen and drug delivery, together with drug clearance
Drug discovery applicability Inexpensive and simple to apply for high-throughput screening More realistic drug response than 2D. Easier to apply than animal models Expensive, time-consuming, poor cell-level imaging and ethically controversial
Table 1: Comparison of cell morphology and physiology in two-dimensional (2D) cultures, three-dimensional (3D) cultures and animals.
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