Modulated Gene Expression in 3D Cell Culture:
Implications for Drug Discovery
In vitro cell models are essential for validating the efficacy of drug candidates. However, large numbers of compounds are discontinued in subsequent phases of clinical studies. The reason for these failures is poor predictability of 2D cell cultures1, which could not mimic physiological conditions. Thus, it is important that the cell model used in testing drug candidates is physiologically relevant and closely mimics in vivo conditions by expressing appropriate receptors, drug transporters and essential proteins for cell growth and survival.
Cells grown in 3D environment (3D scaffolds, 3D hydrogels, 3D multiwell plates and 3D bioreactors) influences the spatial organization of receptors and interactions with neighboring cells, thereby influencing the gene expression and cellular behavior2. A number of studies demonstrated that behaviors of cells in 3D cultures are similar to the in vivo conditions; some of the genes and proteins which are modulated in 3D cultures in comparison with 2D cultures across various cell lines are listed below.
| Gene/Protein Name | Primary cells/Cell Line | Modulation in 3D culture | References |
|---|---|---|---|
| Cell adhesion proteins | C2C12, Skeletal myoblasts, Huh7, MCF-7 | Increase | 208367633 192159494 196043765 145329956 |
| Metabolic & Cytoskeletal proteins | HepG2, 3T3-L1 | Increase | 209250557, 158694248, 194027869 |
| Antioxidant proteins | MDCK | Increase | 2071800810 |
| Cytoskeletal proteins | Fibroblasts | Increase | 2080894011 |
| Mesenchymal genes and Pro-metastatic genes | 293T | Increase | 2061523812 |
| Immune response and Apoptosis genes | L1236 | Increase | 1791797213 |
| Kinases | MC3T3-E1 | Increase | 1797308314 |
| Extracellular matrix and cell adhesion proteins | Primary smooth muscle cells, Microvascular endothelial cells, Primary-Bronchi smooth muscle cells | Increase | 1885412215 168885916 1934643117 |
| Osteogenesis proteins | H1 (Human embryonic stem cells) | Increase | 1822455718 |
| Iron Metabolism proteins, Mitochondrial proteins | HepG2 | Decrease | 209250557 |
| Kinases | HT1080, MC3T3-E1 | Decrease | 1670757214 2050728419 |
| Cytoskeletal proteins | Smooth muscle cells and Fibroblasts, Primary human ovarian fibroblasts, Primary-Smooth muscle cell (arota) | Decrease | 2080894011 1844815620 1834236621 |
| Cell division genes | L1236 | Decrease | 1791797213 |
| Extracellular matrix proteins | Chondrocytes | Decrease | 2147950122 |
Materials
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References
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