IGDR | SpOC
SpOC – Spheroid on a Chip
Where spheroids can change the drug development pipeline: 90% failure rate in clinical phase
Whereas 2D culture models are able to provide large amounts of relatively inexpensive data, this type of model weakly represent the complex pathophysiology in patients. In addition, they often require computational modeling and systems biology approaches to predict in vivo drug responses. Despite this, in the drug development pipeline, cells in a dish (2D culture) are widely used, which is probably one of the causes for the 90% failure rate of a drug candidate in the clinical phase. It highlights the poor predictability capacity of such 2D models.
There is an urgent need for more physiologically relevant models to better predict drug (adverse) effects in vitro during the drug development early phase. Spheroids are part of them.
3D cell culture
FIELD OF APPLICATIONS
SPHEROIDS: A NEW TOOL IN THE DRUG DEVELOPMENT PIPELINE
In an organ, a cell needs to be considered together with its whole environment. Each cell is surrounded by a myriad of other cells, either of the same types or not. This entire environment allows cells interactions and contacts in 3 dimensions and also creates physical constraints. The classical culture cell models are for now mainly in 2D, meaning that this environment is far from the 3D environment of a cell located in an organ (other cells, extracellular matrix, interstitium…). There is a need for a 3D model with the advantage of 2D cell lines cultures (easy to do, reproducible, cheap) and approaching the 3-dimensional organization of an organ. The solution is called SPHEROIDS.
Spheroids are 3D spherical organoids displaying an increase in cell density and biological functionality in comparison to classical monolayer cell culture. Spheroids are often considered as an intermediate to mimic the level of organization of a tissue/organ.
The SpOC (Spheroids On a Chip) project aims at cultivating kidney cancer cells spheroids for at least 5 days in a microfluidic device that ensures the micro-environment control of the culture. Cherry Biotech will design the microfluidic device, and in collaboration with IGDR, applied it to the drug development, particularly in the lead identification phase, where the having access to a relevant model is crucial.
SPHEROIDS IN A CHIP AND SCREENING CAPACITY
Thanks to the development of SpOC device, we are now able to cultivate spheroids up to 5 days and perform drug exposure test. Taking advantages of the picture taken with the SpOC device of spheroids expose to drugs, we are now developing a computational algorithm to early detect morphologic changes. These algorithms are based on adjacent pixels contrast and/or derivative measurement methods.
Using artificial (neuronal network technologies) allows us to train the system to the detection of small changes in the spheroids growth rate/behavior, that might be characteristic of a drug effect. Furthermore, the device allows the staining of a specific target (proteins, biochemical compounds,…) that might also be used by the artificial intelligence algorithm to better predict the drug effect on the spheroids.