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Improving bioreactors used in stem cell therapies

Biomedical Engineering

Oxford chemical and biomedical engineer and Director of the Oxford Centre for Tissue Engineering and Bioprocessing Professor Cathy (Hua) Ye has spent years developing technology to support stem cell development. Here she shares more about her latest work to improve the production process.

What is the aim of your research?

A bioreactor – a vessel that aids a biological reaction (such as) cell proliferation, is a crucial component in developing stem cell therapies. In stem cell therapies and regenerative medicines, different types of cells are used for developing different therapies. The design of these vessels needs to change to create the most suitable environments for each cell type. We set out to see how we could improve the design and environment within a bioreactor to optimise results.

Please tell us about the research process.

Most of the cells in our body need a surface to attach to in order to grow, so if you want to grow lots of them for clinical treatment, you need to provide a very large surface area.

Design-wise, we added tiny particles into the vessel for cells to attach to, and set out to create a more efficient process by providing a much larger surface area for the cells to attach to in a fixed volume – using less space to deliver large-scale culture of stem cells. We used 3D printing and computational fluid dynamics to optimise the design.

"It is a long process which requires commitment and dedication and good communication and collaboration between different teams."

This cell culture process involved steps such as stirring the particles so nutrients were distributed evenly to all cells in the bioreactor, monitoring cell growth, and removing cell metabolic waste products. We also developed a prototype bioreactor based on the new design to be assessed, which proved we had found a way for the culture of cells to be optimised.

Why are the findings important?

Regenerative medicine and stem cell therapy are major areas of exploration targeting incurable diseases, from neurodegenerative conditions to kidney failure. Typically, you take a tiny number of cells, for example stem cells, from patients. But to use these for therapeutic purposes, you need a huge number of them. By optimising the environment for cell growth and using automation, the process becomes much more efficient and robust.

"The improved approach... can play a role in medical research and clinical trials to help find cures for diseases."

This is why our research into bioreactor design is so important. The improved approach enables large-scale cell growth to provide the best quality cells more efficiently and cost-effectively. This means it can play a role in medical research and clinical trials to help find cures for diseases.

There are also wider benefits. At the moment, cell therapy treatments are expensive, but by making the process more efficient, we will reduce costs so more patients around the world can access this treatment. One day we would be able to make spare organs, which could have transformative effects for patients.

What has been the advantage of having your research published?

Having our findings published makes sure they reach a wider audience. Scientists around the world read each other’s publications to track the research progress in relevant fields, which helps them to identify unresolved problems but also fosters collaboration between different research groups. It is incredibly rewarding when clinicians get in touch to say the technology could be used to solve their problems.

"It is incredibly rewarding when clinicians get in touch to say the technology could be used to solve their problems."

It is also crucial for new opportunities and applications. You also never know where your research can lead you. Following this research, I was approached by a former PhD student of the department and have teamed up with him to explore how the new process could work with animal cell culture to make sustainable lab-grown meat. Our company is IVY Farm Technologies, and we’re hoping to be able to offer products to consumers by 2023.

I’m keen to raise awareness among the public of the potential benefits stem cells offer, alongside the opportunities new technology provides.

What challenges did you face?

We faced several challenges during the research process. Cell therapy and tissue engineering is incredibly interdisciplinary, I’m not a cell biologist or clinician, so I needed to understand more beyond my own discipline, as did my team.

"Clinicians set the initial problem... we then think about a way to provide and maintain the environment for cells."

There are also broader challenges to consider when creating tissues to replace diseased ones, also known as regenerative medicine. Clinicians set the initial problem; cell biologists then tell us which cells to use and their preferred growth environment, and we then think about a way to provide and maintain the environment for cells. Some of these can be ways to maintain nutrient supply to tissues grown outside human body without blood capillary network, and also deciding which cells to use, whether a patient’s own cells or donated cells, which both have pros and cons.

It is a long process which requires commitment and dedication and good communication and collaboration between different teams.

This interview was part of Elsevier’s celebration of the work of Oxford-based researchers across a range of disciplines to tie in with the IF Oxford Science and Ideas Festival.

Main image: Professor Ye (2nd from R) in her lab.

Cathy Ye

Professor Cathy Ye (pictured) was one of five researchers Elsevier interviewed before the 2021 Oxford Science and Ideas Festival. Here, they talk about their unusual research.

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