A step towards standardized manufacturing of mesenchymal stromal cell-derived extracellular vesicles

Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs), tiny packages released by MSCs, contain a payload of molecules that could hold the key to treating various diseases. But before we can fully harness their potential, we need to understand how to consistently manufacture them.

Scientists have been working to establish standardized methods for producing these EVs. They often rely on traditional, static 2D systems, which means cells grow on flat surfaces in a controlled environment. However, to optimize this process, researchers need to identify the critical factors that influence the production of these EVs.

A team of researchers at the University of Applied Sciences Mittelhessen explored this challenge by studying how different conditions affect MSCs and the EVs they produce. They looked at factors like the type of surface the cells were grown on, the composition of the culture media, and even the temperature at which the cells were cultivated.

Surprisingly, they found that the surfaces and media that promoted the most MSC growth didn’t always result in the highest-quality EVs. In fact, MSCs seeded at lower densities produced EVs with better functional properties compared to higher densities. It seems that having fewer MSCs allowed them to focus more on producing high-quality EVs rather than just multiplying rapidly.

Temperature also played a role. While a normal body temperature of 37°C might seem like the obvious choice for culturing cells, it wasn’t necessarily the best for EV production. Lower temperatures might have resulted in fewer EVs, but those that were produced were more effective at promoting cell migration—a key function of EVs in the body.

The researchers also noticed a link between cell proliferation and EV production. Cells that were actively dividing didn’t necessarily churn out the most EVs, but the ones they did produce were particularly potent. By monitoring glucose consumption, they could even estimate how many EVs would be produced—a valuable tool for optimizing manufacturing processes.

What does all of this mean for the future of EV production? It means that by carefully controlling these factors—like cell density, culture conditions, and temperature—we can boost the yield and quality of MSC-derived EVs. And the best part? These optimizations don’t require fancy equipment or complex procedures. By integrating these findings into standardized manufacturing processes, we can make EV production more efficient and reliable, paving the way for their use in early clinical trials.

In essence, this research brings us one step closer to unlocking the full potential of MSC-derived EVs—a promising avenue for future therapies. As we continue to refine our understanding of how to manufacture these tiny but mighty vesicles, we move ever closer to harnessing their power for the benefit of patients worldwide.

Barekzai J, Refflinghaus L, Okpara M, Tasto L, Tertel T, Giebel B, Czermak P, Salzig D. (2024) Process development for the production of mesenchymal stromal cell-derived extracellular vesicles in conventional 2D systems. Cytotherapy [Epub ahead of print]. [article]

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