Exosomes Produced from 3D Cultures of MSCs by Tangential Flow Filtration Show Higher Yield and Improved Activity
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Authors
Haraszti, Reka AMiller, Rachael
Stoppato, Matteo
Sere, Yves Y.
Coles, Andrew H.
Daou, Marie-Claire
Wollacott, Rachel
Sapp, Ellen
Dubuke, Michelle L.
Li, Xuni
Shaffer, Scott A.
DiFiglia, Marian
Wang, Yan
Aronin, Neil
Khvorova, Anastasia
UMass Chan Affiliations
Mass Spectrometry FacilityDepartment of Medicine
RNA Therapeutics Institute
MassBiologics
Document Type
Journal ArticlePublication Date
2018-12-05Keywords
exosomesmesenchymal stem cell
tangential flow filtration
Cell Biology
Cells
Molecular Biology
Nucleic Acids, Nucleotides, and Nucleosides
Therapeutics
Metadata
Show full item recordAbstract
Exosomes can deliver therapeutic RNAs to neurons. The composition and the safety profile of exosomes depend on the type of the exosome-producing cell. Mesenchymal stem cells are considered to be an attractive cell type for therapeutic exosome production. However, scalable methods to isolate and manufacture exosomes from mesenchymal stem cells are lacking, a limitation to the clinical translation of exosome technology. We evaluate mesenchymal stem cells from different sources and find that umbilical cord-derived mesenchymal stem cells produce the highest exosome yield. To optimize exosome production, we cultivate umbilical cord-derived mesenchymal stem cells in scalable microcarrier-based three-dimensional (3D) cultures. In combination with the conventional differential ultracentrifugation, 3D culture yields 20-fold more exosomes (3D-UC-exosomes) than two-dimensional cultures (2D-UC-exosomes). Tangential flow filtration (TFF) in combination with 3D mesenchymal stem cell cultures further improves the yield of exosomes (3D-TFF-exosomes) 7-fold over 3D-UC-exosomes. 3D-TFF-exosomes are seven times more potent in small interfering RNA (siRNA) transfer to neurons compared with 2D-UC-exosomes. Microcarrier-based 3D culture and TFF allow scalable production of biologically active exosomes from mesenchymal stem cells. These findings lift a major roadblock for the clinical utility of mesenchymal stem cell exosomes.Source
Mol Ther. 2018 Dec 5;26(12):2838-2847. doi: 10.1016/j.ymthe.2018.09.015. Epub 2018 Sep 22. Link to article on publisher's site
DOI
10.1016/j.ymthe.2018.09.015Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40884PubMed ID
30341012Related Resources
ae974a485f413a2113503eed53cd6c53
10.1016/j.ymthe.2018.09.015