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Serum Deprivation of Mesenchymal Stem Cells Improves Exosome Activity and Alters Lipid and Protein Composition.
Haraszti, Reka Agnes; Miller, Rachael; Dubuke, Michelle L; Rockwell, Hannah E; Coles, Andrew H; Sapp, Ellen; Didiot, Marie-Cecile; Echeverria, Dimas; Stoppato, Matteo; Sere, Yves Y; Leszyk, John; Alterman, Julia F; Godinho, Bruno M D C; Hassler, Matthew R; McDaniel, Justice; Narain, Niven R; Wollacott, Rachel; Wang, Yang; Shaffer, Scott A; Kiebish, Michael A; DiFiglia, Marian; Aronin, Neil; Khvorova, Anastasia.
Afiliação
  • Haraszti RA; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA. Electronic address: rharaszti@gmail.com.
  • Miller R; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA; Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
  • Dubuke ML; Mass Spectrometry Facility, Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Shrewsbury, MA, USA.
  • Rockwell HE; BERG LLC, Framingham, MA, USA.
  • Coles AH; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
  • Sapp E; Mass General Institute for Neurodegenerative Disease, Boston, MA, USA.
  • Didiot MC; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
  • Echeverria D; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
  • Stoppato M; MassBiologics, Boston, MA, USA.
  • Sere YY; MassBiologics, Boston, MA, USA.
  • Leszyk J; Mass Spectrometry Facility, Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Shrewsbury, MA, USA.
  • Alterman JF; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
  • Godinho BMDC; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
  • Hassler MR; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
  • McDaniel J; BERG LLC, Framingham, MA, USA.
  • Narain NR; BERG LLC, Framingham, MA, USA.
  • Wollacott R; MassBiologics, Boston, MA, USA.
  • Wang Y; MassBiologics, Boston, MA, USA.
  • Shaffer SA; Mass Spectrometry Facility, Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Shrewsbury, MA, USA.
  • Kiebish MA; BERG LLC, Framingham, MA, USA.
  • DiFiglia M; Mass General Institute for Neurodegenerative Disease, Boston, MA, USA.
  • Aronin N; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA; Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA. Electronic address: neil.aronin@umassmed.edu.
  • Khvorova A; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA. Electronic address: anastasia.khvorova@umassmed.edu.
iScience ; 16: 230-241, 2019 Jun 28.
Article em En | MEDLINE | ID: mdl-31195240
Exosomes 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: IScience Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: IScience Ano de publicação: 2019 Tipo de documento: Article