Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
What are 2D cell cultures and in what way are they limited?
For over fifty years now, we have used 2D cell cultures to culture a variety of cells such as epithelial and blood cells and these are excellent for maintaining cells in their inherent state, under controlled, temperature and other conditions. However, they are limited in preserving the genotype and the phenotype of the original tissue these cells came from.
Why do 2D models not accurately reflect the in vivo cellular environment?
There are several factors but probably the biggest one is that they are inaccurate epigenetically and possibly genetically. We also know that there are a multitude of physiological signals that would usually occur in the tissue and we cannot be sure whether the right kind of extracellular matrices or other factors needed during the transitions are there long-term in 2D tissue culture.
How do 3D cell cultures differ from 2D cell cultures?
3D cell culture is really a way of giving what we do with tissue culture a more physical and relevant context.
The third dimension is a very important element to the organization of the cells and how they really are in the tissue. They may be clumped together, for example, and have complex 3 dimensional structures rather than being spread out flat on a plastic surface.
Also, we are trying to improve the culture conditions to introduce more and more signals, to really recreate the in vivo environment as much as we can in vitro.
What are the main benefits of 3D cell cultures?
There are probably two main benefits. For the basic biologist, it means they can really start looking at cells in a more natural, physiologically relevant environment instead of in a relatively artificial context.
For those trying to target the disease, they can really start to understand processes at the tissue level, not just the cellular level.
Although this is difficult to achieve, the benefits are considerable because what you discover using 3D culture is really much closer to what you would find in vivo, than you find with 2D culture.
Even the most obvious processes that spring to mind, such as cell division, are completely different in the 3D environment, because the constraints on the cells are completely different in 3D than they are in 2D.
When you unflatten cells, they can get as far away from each other as they like and organize themselves into any shape or form. In the 3D culture, for example, the division is much more compact because the neighbouring cells and matrix are accommodated for. Even things that we think wouldn’t be affected by 3D culture, could be affected.
How useful are 3D cell cultures in accelerating drug development?
This is something that we think about quite a lot. When we use 2D culture, what we’re really trying to do is to create an intermediate mode, where we can understand cell development processes before a drug is moved to the animal modelling stage, where it really is challenged by the complexity of 3D culture.
We would like to be able to see the same 3D complexity in vitro, in order for drugs to succeed in the long term.
At the moment, most of the drugs don’t fail in vitro, they fail in vivo… in animals, or, more worryingly, in humans. They often fail during clinical trials that have progressed to the third phase, which is incredibly expensive.
We strongly believe that if we can select the right drugs using 3D models, we can improve on what is currently a poor rate of drug development and also extremely costly.
Do you think 3D cell cultures will one day replace 2D cell cultures altogether, or will there still be a need for both?
One can hardly replace the ease of using 2D culture because you would need another way of passaging cells from one day to the other. We do have a new product called the product extractor which we may be able to use to culture cells in 3D.
3D culture is a fantastic opportunity to really challenge the way we do tissue culture altogether. For example, we can take a primary tissue, put it in strata, and see whether or not we can really passage it with minimal interference… passage, after passage, after passage.
Of course, tissue culture is not the same as the body, but I think the technology is getting more complex and can be used in combination with the work that we are already doing in 2D, rather than exclusively replacing it.
How do AMSBIO’s matrices for 3D cell culture differ from others on the market?
We already have a variety of 3D solutions. One is related to the strata and is basically porous polystyrene that enables cells to grow in three dimensions. It has been proven to support a multitude of cells, especially in the stem cell differentiation market. It is already used in oncology drug development and has enabled 3D cell growth without disturbing cell functionality.
There are now different versions of natural matrices called basement membrane extracts (BMEs) on the market. There is a matrix called BME1 that is 3D qualified and guarantees the support of normal cell differentiation inside the matrix; there is BME 2 which is specifically designed to support organoid growth and there is BME3, which supports xenograft development.
Overall, we are really starting to push the idea that there isn’t one 3D solution, but several. We have actually generated a handbook describing all our physiologically relevant cell culture solutions. I included quite a lot of different applications for people who want to use culture and cannot decide which application is best.
What are AMSBIO’s plans for the future?
Our plans are generally two-fold. One is to increase the number of solutions that we have and we are constantly speaking to customers and using their feedback to decide what we need to improve on.
We are looking for new matrices, other approaches and combinations of approaches. For example, we have a line of biometics that we are now pushing to combine with other 3D solutions to see if that could improve certain applications.
Also, this year, we are really going to push the development of cell-based assays to accommodate demands from the industry for 3D. This is what we are aiming to do in 2014.
Where can readers find more information?
They can download our Physiologically Relevant Culture Handbook here: http://www.news-medical.net/offers/AMSBIO-Physiologically-Relevant-Cell-Culture-Handbook.aspx
For further information:-
About Dr. Elad Katz
Elad Katz has trained originally as a chemist in Israel. In 2000 he completed a PhD in Immunology at the University of Glasgow. In a series of post-doctoral appointments, he developed unique three-dimensional models to study first the transforming abilities of oncogenic viruses and then the invasive behaviour of human breast cancers.
Dr. Katz is an established expert in understanding clinical needs and translating them into the cell biology sphere, especially in the context of drug discovery.
Elad Katz is now working as a Senior Scientist for AMS Biotechnology and runs its laboratory facility, located at BioCity Scotland. He regularly advises, collaborates and develops independently solutions for several diseases. This includes understanding the unique tissue microenvironment that is required to develop complex disease models, challenges involving current imaging and other techniques and finding the best solution based on either existing technologies or combinations of them.
Current projects utilise a variety of scaffolds (natural and synthetic), primary patient materials and micro-fluidics for drug discovery models with better predictive power.