The technology created by CelVivo enables generation of uniform, reproducible and functional spheroids and organoids. These 3D constructs mimic the function, structure and architecture of in vivo tissues.
Cancer is a disease characterised by uncontrolled growth of abnormal cells. As its progression relies on growth and replication, it can spread to multiple organs. One defining feature of cancer is the creation of abnormal cells that grow beyond their usual boundaries, and which can then invade adjoining parts of the body and metastasise to other organs.
The transformation of normal cells into malignant tumours is a multistep process, during which genetic mutations accumulate. Hanahan and Weinberg have described ten key changes that can occur during the transformation of a normal cell to a tumour cell; these features are considered hallmarks of cancer.
Most of the key techniques for cell culture were established during the 1950’s. The focus at that time was to make the cells proliferate as quickly as possible. This was done by allowing the cells to grow as monolayer cultures on essentially flat glass or plastic surfaces (i.e. in ‘2D’).
For a model to be relevant it must successfully replicate certain in vivo conditions.
Cells in 2D cultures usually can double their numbers within a few days. Cells in normal tissues, cancers and in 3D cultures usually double their numbers in months.
Cells grown in 2D show no tissue architecture whereas the same cells grown in 3D can spontaneously form structures which resemble their parental tissue. Key to this is that spheroids develop oxygen, nutrient and waste product gradients similar to those seen in tumours.
For a 3D cancer model to be relevant, it must successfully replicate the functionality demonstrated by the active tumour.
Reproducibility is inversely proportional to heterogeneity. Patients are heterogeneous. Their tumours are heterogeneous. The cells within a tumour are heterogeneous. It therefore makes no sense to increase this heterogeneity even further by growing the cells in conditions which force them to adapt.
Once cells have repaired the damage to their ECM (from 2D passaging), they enter a ‘dynamic equilibrium’ state: a state that resembles a functioning organ. Unperturbed, the cells execute their functions at a steady rate. Treated with a drug (or other biologically active molecules) they respond and when the drug is metabolised (or removed) the cell clusters return to their original dynamic equilibrium. In the ClinoReactors, cell clusters can remain in this dynamic equilibrium for weeks or months and this is an ideal starting point for experimentation.
Efficient and timely identification of malignant tumours forms the basis of cancer treatment. Recently, accurately detecting cancer-specific biomarkers have become the pathologist’s chosen tool to study biopsies. To build this toolkit with biomarkers specific to the myriad of cancer types, it is necessary to conduct gene expression profiling of the appropriate tissue. One way to do this is to employ 3D culture to study tumour extracts and cancer cell lines.
Example 3D cancer models developed using the ClinoStar:
Determining toxicity is a major need and it is challenging. Are you working with liver models for drug toxicity? Try this technology and book your ClinoStar demo by filling in the Demo Request form.
Why use 3D models for liver toxicity studies?
Previously, Fey & Wrzesinski conducted a toxicological analysis of six common drugs (acetaminophen, amiodarone, diclofenac, metformin, phenformin, and valproic acid). Results generated from this study demonstrated that primary hepatocyte and 3D spheroid data resulted in a much higher degree of correlation with in vivo lethal blood plasma levels. These results corroborate that 3D hepatocyte cultures are significantly different from 2D cultures and are more representative of the liver in vivo.
To better understand mechanisms of drugs toxicity using hepatocytes-based spheroids, watch the webinar delivered by Prof. Adelina Rogowska-Wrzesinska from the University of Southern Denmark. She explains how she investigates the mechanism of drug toxicity using 3D liver models.
A summary of this study can be found here.
If you would like to use the CelVivo
ClinoStar 3D cell culture system,
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