Considerations when combining 3D cell culture with high throughput screening
Accurately predicting in vivo drug toxicity and efficacy is of paramount importance during pre-clinical testing phases – if a candidate drug fails during human trials, it represents a substantial waste of both time and money. Enhanced preclinical screening of candidate molecules using cell culture models that accurately represent in vivo effects under in vitro conditions can help to avoid this. In this blog, we explore some examples of how novel 3D approaches are improving drug discovery in cancer research. This blog is part of a three part series exploring this important topic (you can read part 1 and part 2 here).
The whole topic of phenotypic screening of 3D cell cultures is also explored in its entirety in our new 28 page e-book, which includes interviews with a wide range of industry-leading researchers and full details of some of the case studies described below – download it now.
Same cells, different response
While 3D cell culture is becoming better optimised for high throughput screening (HTS) programmes, it is often routinely used for smaller-scale validation experiments. Dr Olivier Pardo of Imperial College, London, highlighted the benefits of this approach at a recent
SMi Cell Culture conference. His data illustrate how tumour cells grown under 2D conditions respond differently to the same concentration of an anti-tumour drug when compared to 3D cell cultures, as cells in the 3D environment are more resistant to the compound. Dr Pardo’s studies also suggest that the different levels of oxygen availability in 2D vs 3D, as well as the extent of cell-cell contact, can influence therapeutic response to a drug compound.
3D cell culture systems can be used to generate data that is more biologically relevant. However, combining this approach with HTS workflows can still be challenging. Fortunately, innovative companies are meeting this challenge head-on, seeing it as an opportunity to capture market share by developing novel techniques that facilitate HTS assays using 3D cell culture on an industrial scale.
For example, InSphero, a company specialising in 3D culture, has developed scaffold-free 3D multicellular spheroids in a 96-well format. The company’s GravityPLUSTM system enables researchers to automate the classic hanging drop methodology, producing uniform spheroids and micro-tissues for compound testing.
In recent years a number of automation-friendly plate and assay formats have become commercially available to culture large numbers of cells in 3D, such as ultra low attachment and hanging drop plates for tumour spheroids and soft agar systems for cell colonies.
TTP Labtech’s acumen® Cellista is ideally suited for the rapid (5 minutes/plate) high throughput analysis of tumour spheroids and colonies, without the need to acquire a Z-stack of images.
Novel ways to render 3D culture amenable to HTS
A range of new technological advancements is allowing researchers to take advantage of the benefits offered by 3D cell culture, without compromising on throughput speed. From automated imagers capable of effectively capturing the detail offered by 3D cultures, to the development of fully synthetic, self-assembling nanofibres that support cells growing in high throughput microplates, this exciting field continues to redefine how compounds are screened and tested prior to clinical trials. To find out more, contact our specialist team to discuss your needs or arrange a demo of acumen Cellista.
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With over 28 pages, we couldn’t pack all the useful facts, case studies and insights found in our new e-book into a single blog! To read more about how 3D culture is revolutionising drug screening and hear directly from the researchers involved, download our new e-book from our website!