MhAtriCell

An added dimension in cell culture models

Most tissues in a disease environment exist in a 3-dimensional structure, yet conventional cell culture methods do not always reflect this. By developing a 3-dimensional microenvironment, researchers in the MHAtriCell project aim to provide a more realistic representation of what cells will experience in vivo, as Dr Helena Azevedo explains

The conventional approach to

studying the progress of a disease is to culture cells on a 2-dimensional plastic surface, yet there are some limitations to this approach, particularly with respect to a tumour environment. Most tumours exist in a 3-dimensional environment, so current methods are not representative of the conditions that cells experience in vivo, which is an important aspect in terms of testing drugs. “Sometimes drugs shown to be active in a 2-dimensional environment then fail in vivo. This is believed to be because the way they are being tested is not really realistic,” explains Dr Helena Azevedo. Based at Queen Mary University of London, Dr Azevedo is the Principal Investigator of the MHAtriCell project, which aims to create more realistic cell culture models. “We propose creating a hydrogel, a polymer matrix that contains a lot of water. Typically, these types of environments are very good for culturing cells, because most of our tissues also contain a high volume of water,” she continues. “We want to recreate, in this 3-D environment, what cells would experience in vivo.” because certain cancer cells over-express this polymer,” explains Dr Azevedo. Another important element in these matrices are peptides, which cross-link the hyaluronic acid to form a hydrogel. “We have the ability to synthesise peptides, which are like short versions of proteins. So they contain amino-acids, like proteins, but they are short versions,” continues Dr Azevedo. “We are creating what we call collagen-like peptides, with the aim of mimicking the structure of proteins. There are several proteins in the tumour environment – one of the most abundant proteins is collagen, which is a very important structural protein.”

The actual matrix is formed by selfassembly, after hyaluronic acid and peptides have been mixed together in a relatively simple process. Researchers can include different types of functionality on the peptides, such as sequences that can be recognised by cells or enzymes, which means that the matrix is dynamic in nature rather than static. “It allows interaction with cells and can be degraded by cells, as cells express different enzymes. This is important because it offers an opportunity

to study the migration of cells for example,” explains Dr Azevedo. This could also allow researchers to study how a tumour progresses and develops. “We can look at metastasis and how cells respond to different stimuli, or to different drugs. So we think this is a more realistic platform to both study disease progression and test drugs,” says Dr Azevedo. “Ultimately, we want this matrix to be available to cancer researchers. We want this to be a platform on which they can perform their studies.”

We propose creating a hydrogel, a polymer matrix that contains a lot of water. Typically, these types of environments are very good for culturing cells, because most of our tissues also contain a high volume of water

Tumour environments

There are many variables to consider in this research, as tumour environments are typically highly complex, and cancer cells can adapt their morphology in line with wider changes. Researchers are creating novel matrices to recreate this type of tumour environment; one important component is hyaluronic acid, which is found in human tissues. “Hyaluronic acid has been used as a diagnostic marker of different cancers,

The prime consideration in this regard is creating a realistic model, but practicality is also an important issue, so that researchers can use it easily. The matrix itself is relatively easy to make, while Dr Azevedo says it can also be customised to different types of cancer. “For example, we can include different sequences that are recognized by matrix metalloproteinases, enzymes which are over-expressed in cancer cells that are responsible for degrading the matrix,” she outlines. The hydrogel could provide an effective platform to investigate the effect of different matrix metalloproteinases, understand their role in cancer, and eventually develop targeted therapies. “If we find that these enzymes are really implicated in cell migration, then one potential therapy would be to inhibit these enzymes, to block the migration of cells,” says Dr Azevedo. “If we block their migration then it could be easier to treat the tumour, because then cells would be localised.”

Hyaluronan-rich matrices crosslinked with collagen-like peptides for the 3D culture of ovarian cancer cells (MHAtriCell)

School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS T: +44 (0) 207 882 5502 E: h.azevedo@qmul.ac.uk W: https://www.sems.qmul.ac.uk /research/projects/?rid=1223 Dr Helena Azevedo is a Senior Lecturer in Biomedical Engineering & Biomaterials at the School of Engineering and Materials Science, Queen Mary, University of London (QMUL) in the UK. Her research work focuses on the molecular design of self-assembling biomaterials for applications in cell culture, drug delivery and tissue regeneration.

MHAtriCell team

Dr Jayati Banerjee is a Marie Curie postdoctoral fellow at QMUL. Her research centres on developing higher order self-supporting supramolecular hydrogels through self-assembly of simple building blocks, such as polysaccharides and peptides, for applications in tissue engineering and regenerative medicine.