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3D Culture is a Better Predictor of in vivo Drug Response than 2D Culture: A Growth Factor Study Comparative Review

Priyadarshini N. Canning

Objective: To observe the effects of basic fibroblast growth factor and glial cell line-derived neurotrophic factor on 2D and 3D culture determining the cell survival rate, cell proliferation and insulin secretion function of pancreatic betacell (β-cell) spheroids following treatment with different doses of these growth factors in vitro.

Design: betaTC-6 cells cultured in monolayer and spheroid cultures were treated with three different doses of FGF-2 (10,100,1000ng/mL) and GDNF (100,200,400 ng/mL). A cell-based WST-8 assay was used to determine the proliferation and survival rate of the β-cell in both the culture models. Insulin ELISA was performed to determine the insulin secretion function in vitro.

Results: The results obtained on the 2D culture differ markedly from the results obtained on the 3D culture. Spheroids seeded at 500 and 1000 cells/spheroid showed improved cell proliferation when treated with 10 ng/mL FGF-2. However, this same dose of FGF-2 showed cytotoxic effects on 2D500 and 2D1000 culture. S500 spheroids treated with GDNF showed high cell proliferation at all doses of GDNF. 2D500 cultures showed slight improvement in cell proliferation at 100 and 400 ng/mL but did not show any such improvement at 200 ng/mL of GDNF.

Conclusion: Recently 3D culture models are gaining popularity in studies such as drug discovery and drug development for their ability to mimic the in vivo environment quite accurately. This study showed that 3D culture model is a better predictor of in vivo response to growth factors compared to the 2D culture model.