TY - JOUR
T1 - Interfering with endolysosomal trafficking enhances release of bioactive exosomes
AU - Ortega, Francisco G.
AU - Roefs, Marieke T.
AU - de Miguel Perez, Diego
AU - Kooijmans, Sander A.
AU - de Jong, Olivier G.
AU - Sluijter, Joost P.
AU - Schiffelers, Raymond M.
AU - Vader, Pieter
N1 - Funding Information:
FO thanks Fundación Ramón Areces for supporting him through a study abroad postdoctoral program. JS, MR, and PV are supported by H2020 ERC-2016-COG EVICARE (725229). PV is supported by a VENI Fellowship from the Netherlands Organization for Scientific Research (NWO). George Posthuma is gratefully acknowledged for technical assistance in electron microscopy experiments. FO thanks Fundación Ramón Areces for supporting him through a study abroad postdoctoral program. JS, MR, and PV are supported by H2020 ERC-2016-COG EVICARE ( 725229). PV is supported by a VENI Fellowship from the Netherlands Organization for Scientific Research (NWO). George Posthuma is gratefully acknowledged for technical assistance in electron microscopy experiments.
Publisher Copyright:
© 2019 The Authors
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Exosomes are cell-derived extracellular vesicles of 30-150 nm in size and are involved in intercellular communication. Because of their bioactive cargo, consisting of proteins, RNA and lipids, and their natural ability to deliver these biomolecules to recipient cells, exosomes are increasingly being studied as novel drug delivery vehicles or as cell-free approaches to regenerative medicine. However, one of the major hurdles for clinical translation of therapeutic strategies based on exosomes is their low yield when produced under standard culture conditions. Exosomes are vesicles of endocytic origin and are released when multivesicular endosomes fuse with the plasma membrane. Here, we demonstrate that interfering with endolysosomal trafficking significantly increases exosome release. Furthermore, these exosomes retain their regenerative bioactivity as demonstrated by pro-survival and angiogenesis assays using both cardiomyocytes and endothelial cells. These results may be employed to increase exosome production for studying biological functions or to improve clinical translation of exosome-based therapeutics.
AB - Exosomes are cell-derived extracellular vesicles of 30-150 nm in size and are involved in intercellular communication. Because of their bioactive cargo, consisting of proteins, RNA and lipids, and their natural ability to deliver these biomolecules to recipient cells, exosomes are increasingly being studied as novel drug delivery vehicles or as cell-free approaches to regenerative medicine. However, one of the major hurdles for clinical translation of therapeutic strategies based on exosomes is their low yield when produced under standard culture conditions. Exosomes are vesicles of endocytic origin and are released when multivesicular endosomes fuse with the plasma membrane. Here, we demonstrate that interfering with endolysosomal trafficking significantly increases exosome release. Furthermore, these exosomes retain their regenerative bioactivity as demonstrated by pro-survival and angiogenesis assays using both cardiomyocytes and endothelial cells. These results may be employed to increase exosome production for studying biological functions or to improve clinical translation of exosome-based therapeutics.
KW - Exosomes
KW - Vesicle biogenesis
KW - Extracellular vesicles
KW - Endolysosomal trafficking
KW - Exosome functionality
KW - Regenerative medicine
UR - https://www.scopus.com/pages/publications/85067616972
U2 - 10.1016/j.nano.2019.102014
DO - 10.1016/j.nano.2019.102014
M3 - Article
C2 - 31152797
SN - 1549-9634
VL - 20
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
M1 - 102014
ER -