Benefits of Adopting 3D Cell Culture

Utilising the benefits of 3D culture will improve the understanding of cancer biology, eliminate poor drug candidates, and reveal new physiologically relevant targets.

FREMONT, CA: Scientists have been developing 3D tissue culture models to bridge the gap between in vitro experiments used for discovery and screening and in vivo experiments used for efficacy and safety assessment before conducting clinical trials. It is reasoning to use 3D models with customised microenvironments to dissect cancer biology and develop therapeutic screens, and the evidence that they are better than 2D and early-stage animal testing is rapidly emerging.

Alters Proliferation and Cell Morphology

Growing cancer cells in a flat monolayer proliferate at a relatively uniform rate across the surface. However, growing the same cells in 3D induces zones of differential proliferation, with cell division occurring on the outside of the spheroid. This results in a mild reduction in the proliferation rate. Producing tumour cell lines in 3D ovarian epithelial cells with default apical-basal polarity induces histological morphology reminiscent of the tumour type from which they were derived. The variable responses to 3D culture in Matrigel showcase innate variations in malignancies from diverse organs and how the microenvironment influences cells to produce clinically-relevant observations. Therefore, 3D culture will help to study tumour morphology and understand differences between lines from tumours of similar and dissimilar organs and tissues.

Reveals a More Realistic Drug Response

Growing cells as 3D spheroids increase resistance to chemotherapy when compared to the same cells grown in monolayers. 

The most explicit explanation for enhanced resistance is that the cells on the side of the spheroid are protected from drug penetration by the cells on the outside of the spheroid. When leukemic cell lines are co-cultured with bone marrow mesenchymal stem cells in a 3D system, the 3D culture provides chemoprotection from doxorubicin.

In addition, pancreatic cancer cell lines and newly isolated pancreatic cells from a pancreatic cancer mouse model highlighted increased expression of various drug resistance genes and microRNAs causing increased drug resistance in 3D culture. These results demonstrate that 3D culture recapitulated several mechanisms of drug resistance found in tumours in vivo, providing the opportunity to dissect the mechanisms and test multidrug therapy regimens in vitro before proceeding to animal models and clinical trials.

3D models can be more realistic and controllable than human cancer animal xenografts, where tumour cells are transplanted to sites that do not reflect the microenvironment of the original tumour. Even when the transplantation area is orthotopic, species differences between rodents and human physiology fail to build the intricate tumour microenvironment. Despite these limitations, there are a few efficacies and toxicity aspects that will require evaluation in animal models before human clinical trials. However, preclinical studies utilising the 3D culture advantages early will greatly improve the understanding of cancer biology, reduce poor drug candidates, and reveal new physiologically relevant targets that will have been missed in 2D screens. Furthermore, establishing a 3D model system saves time and money by generating significantly realistic results earlier.