Patient-derived cell cultures are novel multicellular systems freshly isolated from primary organs by mechanical and enzymatic dissociation. In this system, cells grown on a proprietary matrix grow as 3D organoids which are composed of cell clusters maintaining the complex composition of the tissue of origin. This structures are able to self-organize, preserving the original tissue architecture and marker expression.
IN VITRO TOXICITY ASSAYS
Drug toxicity is the major reason for withdrawal of approved drugs from the market. While toxicity testing has been traditionally completed in the preclinical phase, it has become obvious that a failure at this stage results in significant setbacks and economic loss.
To address the challenge, cpo offers a panel of in vitro toxicology assays that are designed for the early stages of drug discovery utilizing cutting-edge technologies, such as semi-automated 3D cell culture screenings. By working with us, you have immediate access to these assays without major capital and time investment to establish these assays in-house. Designed with you project's needs in mind, our assays are valuable for evaluating compound liabilities early in the drug discovery process.
LARGE MOLECULE BIOLOGICALS
The types of therapeutics used to treat cancer are the most diverse among therapeutic areas. Of growing success and interest has been large molecule therapeutics for oncology, especially humanized monoclonal antibodies (mAbs). MAbs are generally targeted to cell surface receptors, or the ligands of these receptors, to block various oncogenic hallmarks (e.g., uncontrolled cell proliferation). PD3D™ services can help profile cell surface antigen expression for a mAb's target and identify drug responsiveness in the same assay.
Druggable epigenetic modulators undergo oncogenic mutation and are seen as attractive therapeutic targets. However, inhibition of some epigenetic targets results in a significantly delayed drug response that is not revealed by conventional, short term cell growth assays. To address this issue, we have established 2D and 3D assays with extended duration to yield robust response data. Of course any other slow-acting therapeutics are likely benefit from these extended protocols.
Cancer is a multi-dimensional disease driven by genetic instability and selective pressure to continue to persist. As such, an ever changing tumor presents a formidable challenge to effectively treat. Given this challenge, a strategy aiming to eliminate multiple traits and/or to prevent the tumor from developing resistance mechanism to circumventing treatment is essential. To support this, combinations of therapeutics (small-molecules or biologics) are tested on PD3D™ cell lines in a dose response matrix.
Simply put, cells in 3D environments are much more similar to cells in a living organism (in vivo) than flat, unnaturally thin, single layer cells grown on 2D plastic.
Shape: Typical cells in 3D are ellipsoids with dimensions of 10-30 μm. Cells in 2D are flat with typical thickness of 3 μm.
Environment: Typical cells in 3D have nearly 100% of their surface area exposed to other cells or matrix. Cells in 2D have approximately 50% of their surface area exposed to fluid, approximately 50% exposed to the flat culture surface or intermediate, and a very small percent exposed to other cells.
Behavior: Cells in 3D, as compared to 2D, show differences in: Differentiation, Drug Metabolism, Expression (Gene, Protein), General Cell Function, In Vivo Relevance, Morphology, Proliferation, Response to Stimuli, and Viability.
Unnaturally shaped cells in unnatural environments would be expected to function ... unnaturally. In the mid-late 20th century, the unnatural shape of cultured cells was actually a plus - when viewed through a common microscope it's quite convenient to view flat, thin shapes in single layers. Good, if you want to identify and study what mitochondria are. Not so good, if you want to predict the complex behavior of a biological system of many different interacting cell types functioning in three dimensional environments, for example the response of a human being to a potential drug.
Today, there is increasing awareness of the drawbacks of 2D cell culture and the related effect on the value of the research being performed. Not surprisingly, scientists are shifting their focus to cells cultured in 3D, as illustrated by the publications graph below. This website is dedicated to providing a single information source for cell culture researchers undertaking the challenge of implementing 3D techniques to create more relevant in vitro models of complex biological systems.
As assays become more sophisticated, it is often necessary to tailor parameters to the specific question that is being asked. Our experience working with a variety of different molecules, such as kinase inhibitors, epigenetic modulators and large molecule biologics, ensures that we can generate the best study design for your project.