Serum Deprivation of Mesenchymal Stem Cells Improves Exosome Activity and Alters Lipid and Protein Composition
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AuthorsHaraszti, Reka A.
Dubuke, Michelle L.
Coles, Andrew H.
Didiot, Marie C.
Sere, Yves Y.
Leszyk, John D.
Alterman, Julia F.
Godinho, Bruno M. D. C.
Hassler, Matthew R.
Shaffer, Scott A.
UMass Chan AffiliationsGraduate School of Biomedical Sciences, Interdisciplinary Graduate Program
Program in Molecular Medicine
Department of Biochemistry and Molecular Pharmacology
Mass Spectrometry Facility
Department of Medicine
RNA Therapeutics Institute
Document TypeJournal Article
Amino Acids, Peptides, and Proteins
Enzymes and Coenzymes
Nucleic Acids, Nucleotides, and Nucleosides
MetadataShow full item record
AbstractExosomes can serve as delivery vehicles for advanced therapeutics. The components necessary and sufficient to support exosomal delivery have not been established. Here we connect biochemical composition and activity of exosomes to optimize exosome-mediated delivery of small interfering RNAs (siRNAs). This information is used to create effective artificial exosomes. We show that serum-deprived mesenchymal stem cells produce exosomes up to 22-fold more effective at delivering siRNAs to neurons than exosomes derived from control cells. Proteinase treatment of exosomes stops siRNA transfer, indicating that surface proteins on exosomes are involved in trafficking. Proteomic and lipidomic analyses show that exosomes derived in serum-deprived conditions are enriched in six protein pathways and one lipid class, dilysocardiolipin. Inspired by these findings, we engineer an "artificial exosome," in which the incorporation of one lipid (dilysocardiolipin) and three proteins (Rab7, Desmoplakin, and AHSG) into conventional neutral liposomes produces vesicles that mimic cargo delivering activity of natural exosomes.
iScience. 2019 May 27;16:230-241. doi: 10.1016/j.isci.2019.05.029. [Epub ahead of print] Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/41056
Full author list omitted for brevity. For the full list of authors, see article.
RightsCopyright 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as Copyright 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).