Table 1.

Characteristics of 2D versus 3D cell culture models.

Characteristic	2D	3D	Refs.
In vivo-like	Poor resemblance of the 3D architecture of tumor tissue	Mimic the 3D structure of in vivo tumor tissues	[21]
Proliferation	Cells grown in monolayers proliferate faster than in 3D tumor models	A relatively slow proliferation rate is similar to that of human tumor cells	[22]
Polarity	Partial polarization	A precise portrayal of cell polarization	[23]
Morphology	Flat and sheet-like cells with a stretched appearance	Form aggregated cells.	[24]
Rigidity	Strong rigid (about 3 × 109 Pascals)	Less rigid (>4000 Pascals)	[25]
Cellular interactions	Limited cellular interactions and cellular extracellular matrix	Exhibit cellular interactions and cell-extracellular matrix-like solid tumors	[16]
Gene/protein expression	Alterations in gene expression, mRNA splicing, topology, and biochemistry of cells, often show discrepancies in gene/protein levels when compared to in vivo models	Genes and protein expressions in solid tumors pertinently resemble 3D tumor models	[26,27]
Response to therapeutics	Monolayer cell cultures are more susceptible to drugs than human tumors	Tumor cells in 3D cultures exhibit drug resistance characteristics similar to those observed in vivo human tumors	[16,26]
Culture formation	Takes minutes–hours	Take hours–days	[28]
Culture quality	Good performance, reproducible, long-term culture, ease of interpretation, and culture simplicity	Poor performance and reproducibility, difficult interpretation, and cultures
Access to growth factors	Constant exposure of cells to oxygen, nutrients, metabolites, and signaling molecules (as opposed to in vivo)	Limited distribution of oxygen, nutrients, metabolites, and signaling molecules (similar to in vivo)	[16,29]
Cost of maintenance	Cost-effective, abundant commercially available tests and media	Costly, laborious, and lack of commercially available tests	[30]