Dynamic cultivation of hMSCs for the production of extracellular vesicles in a 3D bioreactor system

Mesenchymal stem/stromal cells (MSCs) have garnered attention for their potential therapeutic applications, but harnessing their full power requires understanding and optimizing their extracellular vesicles (EVs). A recent study delves into the realm of 3D cell culture and hypoxic conditions to amplify the therapeutic effects of MSC-derived EVs.

Using a cutting-edge 3D bioreactor system, a team led by researchers at the University of Natural Resources and Life Sciences, Vienna and Leibniz University Hannover established a novel process for producing MSC-EVs under both normoxic and hypoxic conditions. Human adipose-derived MSCs were cultured on a 3D membrane for 7 days, followed by isolation and characterization of the resulting EVs.

Scheme of the 3D cell culture setting in vitro

Fig. 1

a The 3D bioreactor system VITVO® was connected to a perfusion pump in order to generate dynamic conditions during mesenchymal stem/stromal cell (MSC) cultivation. Flow rate was set to 1 mL/min in order to provide cells with an exchange of fresh nutrients from the cell culture medium as well as constant waste removal. b Workflow of cell culture regime performed for the cell culture and production as well as the harvest of MSC-derived extracellular vesicles

The findings were striking. Cultivating MSCs in the 3D bioreactor system led to a significant increase in MSC-EV concentration compared to traditional 2D culture methods. Moreover, the purity of the EVs, measured by the particle-to-protein ratio, was substantially higher in the 3D system.

Interestingly, while the concentration and size of EVs remained consistent between normoxic and hypoxic conditions, the total number of MSC-EVs, as well as the population of MSC-EVs expressing CD73 and CD90 surface markers, were elevated under normoxic conditions.

These results shed light on the potential of 3D bioreactor systems to enhance the production and purity of MSC-EVs, particularly under hypoxic conditions. The findings suggest that this approach could be valuable for screening optimal culture conditions to maximize the therapeutic potential of 3D-derived MSC-EVs.

In the realm of regenerative medicine, where MSC therapy holds promise for treating various diseases and injuries, optimizing the production of MSC-EVs is paramount. By harnessing the power of 3D bioreactor systems, researchers take a significant step forward in unlocking the full therapeutic potential of MSC-derived EVs, paving the way for more effective treatments and improved patient outcomes.

Almeria C, Weiss R, Keck M, Weber V, Kasper C, Egger D. (2024) Dynamic cultivation of human mesenchymal stem/stromal cells for the production of extracellular vesicles in a 3D bioreactor system. Biotechnol Lett [Epub ahead of print]. [article]

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