title: Evaluation of electroporation-induced adverse effects on adipose-derived stem cell exosomes.
abstract: In the recent years, the possibility of utilizing extracellular vesicles for drug delivery purposes has been investigated in various models, suggesting that these vesicles may have such potential. In addition to the choice of donor cell type for vesicle production, a major obstacle still exists with respect of loading the extracellular vesicles efficiently with the drug of choice. One of the proposed solutions to this problem has been drug loading by electroporation, where small pores are created in the membrane of the extracellular vesicles, hereby allowing for free diffusion of the drug compound into the interior of the vesicle. We investigated the utility of adipose-derived stem cells (ASCs) as an efficient exosome donor cell type with a particular focus on the treatment of glioblastoma multiforme (GBM). In addition, we evaluated electroporation-induced effects on the ASC exosomes with respect to their endogenous potential of stimulating GBM proliferation, and morphological changes to single and multiple ASC exosomes. We found that electroporation does not change the endogenous stimulatory capacity of ASC exosomes on GBM cell proliferation, but mediates adverse morphological changes including aggregation of the exosomes. In order to address this issue, we have successfully optimized the use of a trehalose-containing buffer system as a way of maintaining the structural integrity of the exosomes.
authors: Laboratory for Cancer Biology, Institute of Health Science and Technology, Aalborg University, Fredrik Bajers Vej 3B, 9220, Aalborg Ø, Denmark.|Laboratory for Neurobiology, Institute of Health Science and Technology, Aalborg University, Fredrik Bajers Vej 3B, 9220, Aalborg Ø, Denmark.
authors: Kasper Bendix
authors: KB
authors: Johnsen
authors: Laboratory for Cancer Biology, Institute of Health Science and Technology, Aalborg University, Fredrik Bajers Vej 3B, 9220, Aalborg Ø, Denmark.
authors: Johann Mar
authors: JM
authors: Gudbergsson
authors: Laboratory for Cancer Biology, Institute of Health Science and Technology, Aalborg University, Fredrik Bajers Vej 3B, 9220, Aalborg Ø, Denmark.
authors: Martin Najbjerg
authors: MN
authors: Skov
authors: Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, Aarhus C, 8000, Aarhus, Denmark.
authors: Gunna
authors: G
authors: Christiansen
authors: Institute of Physics and Nanotechnology, Aalborg University, Skjernvej 4, 9220, Aalborg Ø, Denmark.
authors: Leonid
authors: L
authors: Gurevich
authors: Laboratory for Neurobiology, Institute of Health Science and Technology, Aalborg University, Fredrik Bajers Vej 3B, 9220, Aalborg Ø, Denmark.
authors: Torben
authors: T
authors: Moos
authors: Laboratory for Cancer Biology, Institute of Health Science and Technology, Aalborg University, Fredrik Bajers Vej 3B, 9220, Aalborg Ø, Denmark. megd@hst.aau.dk.
authors: Meg
authors: M
authors: Duroux
keywords: Adipose-derived stem cells; Drug delivery; Electroporation; Exosomes; Extracellular vesicles; Glioblastoma multiforme; Trehalose