Scaling Living Cells: How Bioreactor Technology Is Shaping the Future of Cell Therapy

For those whose biology knowledge might be a bit rusty: what exactly is cell therapy?

 “At its core, cell therapy is quite simple. It means using living cells as a treatment. Most current therapies rely on small molecules or antibodies, essentially chemical compounds. With cell therapy, you use a patient’s own cells or donor cells to treat disease.

This is not entirely new. Stem cell transplants for leukemia have been around for quite some time. What is new is the speed at which the field is developing, with promising applications in cancer treatment, tissue repair and the regeneration of lost bodily functions.”

Those cells need to be produced and cultivated. Your company has developed a bioreactor called the Osilaris. What does the bioreactor do exactly?

 “Cell therapy is complex because you are working with living systems. Cells continuously respond to their environment, so maintaining a stable and well-controlled environment is crucial.

Osilaris creates those ideal conditions: a constant temperature of 37 degrees Celsius, controlled pH, carefully regulated oxygen levels and a supply of nutrients. These conditions can be adjusted. For example, depending on the cell type, you can work with higher or lower oxygen concentrations.

One major advantage is scale. We can start of with small volumes and expand to large volumes in a single system. At maximum capacity a single cultivation bag can accommodate a surface area equivalent to roughly 200 traditional T175 culture flasks. That saves enormous amounts of plastic, time and manual labour. And because the environment is tightly controlled, the outcomes are far more consistent.”

Who is using these systems today? Are they already in clinical use, or mainly in research?

“The Osilaris system has been on the market for about two years. It is mainly used by academic hospitals, pharma, and centers that translate R&D into clinical applications and thus want to scale up cell production.

It is also important to note that bioreactors are not limited to cell therapy. They are used for drug screening, disease modelling and even applications such as cultivated meat. All of these rely on controlled cell production.”

There are several companies developing and selling bioreactors. What sets your platform apart?

“One of the most widely used systems in the field is the Prodigy. It is a simple, plug-and-play solution, but it is mainly designed for a single application: CAR-T therapy.

CAR-T is a rapidly growing field, but it is also moving towards in vivo CAR-T, where the therapy is generated inside the patient’s body and external cell expansion is no longer required.

Our system was designed as a flexible platform. We can work with suspension cell types such as CAR-T, but also with adherent human cell types. Moreover, the technology is scalable: you can start with very small volumes, for example from a patient biopsy, and gradually expand to clinically relevant cell numbers.

Other distinctive functions, such as a specialised gas exchange system, allows to culture without  a liquid interface. And while the tubing set may look complex, it enables a lot of flexibility: additional sensors, sampling, and integration with upstream and downstream processes. That level of versatility is hard to find elsewhere on the market.”

Your product has been on the market for two years now. What are the main challenges you see in the field?

 “Without question, the biggest challenge is cost. Many cell therapies currently reach the market with price tags of hundreds of thousands of euros per patient. That is simply not sustainable in the long run.”

Where do those costs mainly come from?

“It is a combination of factors. Pharmaceutical margins play a role, of course. At the same time, you see academic hospitals wanting to produce therapies in-house to reduce costs.

Operational costs are also very high. Many processes are still manual and labour-intensive, which is why the field is moving towards automation.

But automation is challenging. Cells from different donors behave slightly differently. Even if you run the same process a hundred times, you still need to fine-tune it each time. That requires extensive monitoring: knowing when to feed cells, when to scale up, and when cells are under stress. For that, you need large amounts of data.”

You are also involved in NXTGEN Hightech’s Biomedical Cell Production Technologies programme. What is its objective?

 “The goal is to develop the next generation of cell production technologies, with automation and consistent yields at the core.

We work along several pillars. One example is new sensor technology developed by partners from Eindhoven University of Technology, enabling continuous monitoring of the process. That allows us to detect cellular stress in real time and adjust conditions accordingly.

Another important focus is animal component-free culture media. This avoids ethical concerns and significantly reduces variability, since animal serum differs from batch to batch.

With a total of thirteen partners, we bring together technology developers and end users to advance the entire cell production chain.”

What progress has been made so far?

 “An important early step was bringing all partners together: both technology developers and end users. That ensures innovations are directly aligned with real-world needs.

On the technical side, we have already demonstrated continuous measurement of relevant stress markers, such as LDH. We have also developed new animal component-free media that is now moving towards market introduction.”

Finally, where do you see the biggest opportunities at the intersection of medtech and biomaterials?

“That overlap already exists. Within our consortium, for example, we work with partners developing microcarriers: biomaterials that cells can attach to. That is how we achieve such large surface areas in relatively small cultivation volumes.

For more complex applications, the real opportunity lies in combining biomaterials with cells. Biomaterials alone can already be therapeutic, but truly complex tissues require cells as well. Think of vascularisation, or neural and cardiac tissues. It is technically challenging, but the potential is enormous.”

Are there any cell types your platform cannot handle?

“So far, we have not found any.”