PD3D™ - PATIENT DERIVED 3D CELL CULTURES

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.

PD3D™ services provide multi-parametric drug response data across a panel of over 200 genomically diverse patient-derived cancer cell strains that span 12 different cancer tissues. Therapeutics may be tested in the entire panel or a subset that contains any combination of the 200 available PD3D™ cell lines. Using high content imaging, simultaneous detection of anti-cancer activity and detection of pharmacodynamic biomarkers in a single, multiplexed assay may be provided.

PD3D™ services allow a detailed understanding of drug response that cannot be achieved by single endpoint assay profiling. Assay endpoints can be customized to measure up to four biological pathways or processes at once (cell viability, apoptosis, mitotic block and custom markers).

Genomic analysis of PD3D™ data enables the discovery of predictive biomarkers to help determine which genomic features may predispose patients to therapeutic response. Cell surface expression of your target antigen can be measured in live cells to correlate antigen expression with therapeutic response in the same assay.

PD3D™ can also provide quantitative binding analysis of therapeutic antibodies within the same multiplexed assay.

WHY CULTURE CELLS IN THREE DIMENSIONS?

INTUITIVELY ONE CAN APPRECIATE THAT WITH CELLS, FORM AFFECTS FUNCTION

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.

DESIGNING THE STUDIES TO MATCH YOUR PROJECT GOALS

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.    

LIVING CELL BANK

When a cell line is to be used over many screening cycles, a two-tiered cell banking system consisting of a master cell bank (MCB) and a working cell bank (WCB) is recommended. We at cpo follow this recommendation and ensure that cells of the MCB are characterized and extensively tested for contaminants such as bacteria, fungi, and mycoplasmas. Most cell strains also undergo PCR testing for viruses. 

Cells from the MCB are expanded to form the WCB, which is characterized for cell viability prior to use in the screening process. Our production cell bank is stored in two widely separated areas within the campus as well as at a distant site in order to avoid loss of the cell line. Dual-site storage of all cells is accomplished with on-site storage and off-site storage. In case you opt for an exclusive use of a cell culture, once your project is completed, any unused cells can either be returned to you or destroyed at your option. 

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