Better gene therapy through automated cell particle production

Interview with Lena Felser, Research Associate Bio-Adaptive Production, Fraunhofer Institute for Production Technology IPT

The automated production of therapeutically applicable extracellular vesicles (EVs) could change the future of cell and gene therapy. In the "RauPE" research project, experts from the Fraunhofer IPT, the start-up BioThrust and Essen University Hospital are working on developing innovative technologies for the cost-effective and scalable production of these promising biological products.

Lena Felser explains the challenges and goals of this project in an interview with MEDICA-tradefair.com.

Ms. Felser, how did the idea for the RauPE project come about?

Lena Felser: We have already worked on other projects in the field of laboratory automation for cell and gene therapy, such as the AutoCRAT project. We discovered that mesenchymal stem cells have great potential, particularly in the treatment of degenerative diseases such as osteoarthritis. It was later discovered that the extracellular vesicles (EV) released by these cells are also therapeutically beneficial. This was one of the key motivations for starting this project. At the same time, we faced challenges such as high production costs and the difficulty of obtaining sufficient EVs of consistent quality.

What are the biggest technical hurdles in the production of EVs?

Lena Felser: One major problem is the cultivation method. Mesenchymal stem cells normally grow adherently, i.e. they adhere to a surface, which makes scaling difficult. To solve this problem, the cells are cultivated on so-called microcarriers, small plastic beads in bioreactors. However, conventional bioreactors generate air bubbles and shear forces due to their agitation and oxygen supply, which can damage the sensitive cells. Added to this is the natural heterogeneity of the cells, which makes it difficult to ensure consistent product quality.

How does the project address these challenges?

Lena Felser: We rely on the membrane stirrer bioreactor from our partner BioThrust. This enables a bubble-free oxygen supply and avoids shear forces. This makes cultivation gentler and enables larger volumes. We are also working with Essen University Hospital, which has developed a clonal, immortalized cell line. This cell line eliminates natural heterogeneity and ensures consistent results. We would like to combine these solutions with our expertise in laboratory automation at the Fraunhofer IPT.

What are the specific aims of the project?

Lena Felser: The name RauPE stands for "Robust, automated production of therapeutically applicable extracellular vesicles". We want to make production scalable and robust so that a consistently high product quality is always guaranteed in the end. To this end, we are working on a fully automated platform, AUTOSTEM. By automating the processes, not only can throughput be increased, but production costs can also be reduced and, above all, process reproducibility and thus product quality can be increased. With our approach, we hope to make EVs usable for a broad therapeutic spectrum.

How do you test the new technologies?

Lena Felser: We are currently testing our processes with water, which are known as abiotic experiments. We simulate the actual steps that are later carried out with cells and culture medium. In this way, we ensure that the automation works flawlessly before we use valuable materials. The mesenchymal stem cells are then cultivated and the success of the process is checked by means of quality controls.

What potential applications do you see for extracellular vesicles?

Lena Felser: The vesicles have an incredibly broad therapeutic potential, for example in the treatment of degenerative, inflammatory diseases or against cancer. In the project, we are initially concentrating on mesenchymal stem cells as a starting point, due to their immunoregulatory effect. In the long term, however, EVs secreted by other cell types could be used to develop specific therapies.

What is the project schedule?

Lena Felser: The project will run for three years and started in July 2024. Next year, we want to start cultivating the cells and deliver the first EVs to Essen University Hospital for analysis. Methods for characterizing the EVs will then be developed there. We are optimistic that we will be able to make significant progress in robust, automated EV production by the end of the project.