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dc.contributor.authorHaraszti, Reka A
dc.contributor.authorMiller, Rachael
dc.contributor.authorStoppato, Matteo
dc.contributor.authorSere, Yves Y.
dc.contributor.authorColes, Andrew H.
dc.contributor.authorDaou, Marie-Claire
dc.contributor.authorWollacott, Rachel
dc.contributor.authorSapp, Ellen
dc.contributor.authorDubuke, Michelle L.
dc.contributor.authorLi, Xuni
dc.contributor.authorShaffer, Scott A.
dc.contributor.authorDiFiglia, Marian
dc.contributor.authorWang, Yan
dc.contributor.authorAronin, Neil
dc.contributor.authorKhvorova, Anastasia
dc.date2022-08-11T08:09:52.000
dc.date.accessioned2022-08-23T16:46:27Z
dc.date.available2022-08-23T16:46:27Z
dc.date.issued2018-12-05
dc.date.submitted2019-01-07
dc.identifier.citation<p>Mol Ther. 2018 Dec 5;26(12):2838-2847. doi: 10.1016/j.ymthe.2018.09.015. Epub 2018 Sep 22. <a href="https://doi.org/10.1016/j.ymthe.2018.09.015">Link to article on publisher's site</a></p>
dc.identifier.issn1525-0016 (Linking)
dc.identifier.doi10.1016/j.ymthe.2018.09.015
dc.identifier.pmid30341012
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40884
dc.description.abstractExosomes 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=30341012&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277553/
dc.subjectexosomes
dc.subjectmesenchymal stem cell
dc.subjecttangential flow filtration
dc.subjectCell Biology
dc.subjectCells
dc.subjectMolecular Biology
dc.subjectNucleic Acids, Nucleotides, and Nucleosides
dc.subjectTherapeutics
dc.titleExosomes Produced from 3D Cultures of MSCs by Tangential Flow Filtration Show Higher Yield and Improved Activity
dc.typeJournal Article
dc.source.journaltitleMolecular therapy : the journal of the American Society of Gene Therapy
dc.source.volume26
dc.source.issue12
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3687
dc.identifier.contextkey13578944
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/3687
dc.contributor.departmentMass Spectrometry Facility
dc.contributor.departmentDepartment of Medicine
dc.contributor.departmentRNA Therapeutics Institute
dc.contributor.departmentMassBiologics
dc.source.pages2838-2847


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