Project R-12170

Innovative technology platform for continuous production and isolation of extracellular vesicles from stem cells (Research)

Stroke is one of leading causes of death worldwide for which novel therapeutic strategies are highly needed. Therapy based on bone marrow-derived mesenchymal stromal cells (BM-MSCs) is promising as it directly promotes regeneration of the injury area. The therapeutic potential of BM-MSCs is mediated by secretome-derived paracrine factors, with extracellular vesicles (EVs) increasingly understood to play a main role. However, translation of EV-based therapy into the clinic is hampered by scarce scalability of current technologies for EV production and isolation, which deliver insufficient batches and low yields. This project aims to develop a novel technology for continuous production of BM-MSC-EVs, using a hollow-fiber bioreactor for high-density 3D cell culture, coupled in-line with tangential-flow filtration for the purification of EVs. The interactions of EVs with filter membranes will be analyzed to define the most suitable materials. 3D bioreactor cell cultures shall be developed and coupled with filtration to purify EVs, initially in a batch model and then integrated into an in-line continuous process. Each step of the optimization of the system is based on an evaluation of the functional properties of the produced EVs. This project will significantly boost the translation of BM-MSC-EVs into the clinics, allowing for the first time simultaneous EV production and isolation in a continuous flow.

01 November 2021 - 31 October 2025