Use of a hollow fiber bioreactor to collect extracellular vesicles from cells in culture

Current approaches for collection of extracellular vesicles (EV) are based on classical cell culture media production. This involves collection from cells grown in flasks, and can require multiple rounds of centrifugation or filtration, followed by ultracentrifugation or density gradient centrifugation. There are several limitations of these approaches, for example, they require a large input volume, the yield and concentration is low, and the process is time consuming. Most cell cultures require the use of fetal bovine serum which contains a large amount of endogenous EV that can contaminate isolations of cell-derived EVs. Researchers at the Mayo Clinic describe how the use of cell cultures within a hollow fiber bioreactor could address many of these limitations and produce a continuous source of highly concentrated EVs without contamination from serum EVs, and that are suitable for downstream applications.

Schematic diagram of hollow fiber bioreactor


The reservoir bottle contains medium. A perfusion pump circulates medium through the closed circuit. Fresh medium perfuses through the hollow fibers to nurture the cells growing within the cartridges. Cell growth can be monitored by metabolic products such as glucose and lactate that permeate into the circulating medium by gradient diffusion

Yan IK, Shukla N, Borrelli DA, Patel T. (2018) Use of a Hollow Fiber Bioreactor to Collect Extracellular Vesicles from Cells in Culture. Methods Mol Biol 1740:35-41. [abstract]

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