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Advanced Drug Delivery Reviews
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Advanced Drug Delivery Reviews
Article . 2021 . Peer-reviewed
http://dx.doi.org/10.1016/j.ad...
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Scaled preparation of extracellular vesicles from conditioned media

Authors: Staubach, Simon; Bauer, Fabiola Nardi; Tertel, Tobias; Börger, Verena; Stambouli, Oumaima; Salzig, Denise; Giebel, Bernd;

Scaled preparation of extracellular vesicles from conditioned media

Abstract

Extracellular vesicles (EVs) especially of mesenchymal stem/stomal cells (MSCs) are increasingly considered as biotherapeutic agents for a variety of different diseases. For translating them effectively into the clinics, scalable production processes fulfilling good manufacturing practice (GMP) are needed. Like for other biotherapeutic agents, the manufacturing of EV products can be subdivided in the upstream and downstream processing and the subsequent quality control, each of them containing several unit operations. During upstream processing (USP), cells are isolated, stored (cell banking) and expanded; furthermore, EV-containing conditioned media are produced. During downstream processing (DSP), conditioned media (CM) are processed to obtain concentrated and purified EV products. CM are either stored until DSP or are directly processed. As first unit operation in DSP, clarification removes remaining cells, debris and other larger impurities. The key operations of each EV DSP is volume-reduction combined with purification of the concentrated EVs. Most of the EV preparation methods used in conventional research labs including differential centrifugation procedures are limited in their scalability. Consequently, it is a major challenge in the therapeutic EV field to identify appropriate EV concentration and purification methods allowing scale up. As EVs share several features with enveloped viruses, that are used for more than two decades in the clinics now, several principles can be adopted to EV manufacturing. Here, we introduce and discuss volume reducing and purification methods frequently used for viruses and analyze their value for the manufacturing of EV-based therapeutics.

Keywords

Chromatography, Polymers, Extracellular vesicles, Exosomes, Medium supplements, scaled EV production, Downstream processing, EV purification, EV concentration, Filtration, Centrifugation, Chromatography, Extracellular Vesicles, Culture Media, Conditioned, Viruses, Animals, Chemical Precipitation, Humans, Ultracentrifugation, Filtration

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
OpenAIRE UsageCountsViews provided by UsageCounts
downloads
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103
Top 1%
Top 10%
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42
90