In vitro toxicology studies of extracellular vesicles

Sayantan Maji, Irene K. Yan, Mansi Parasramka, Swathi Mohankumar, Akiko Matsuda, Tushar C Patel

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Extracellular vesicles (EVs) are membrane-bound vesicles released from cells into the extracellular environment. There is emerging interest in the use of EVs as potential therapeutic interventions. We sought to evaluate the safety of EVs that may be therapeutically used by performing in vitro toxicological assessments. EVs were obtained from mesenchymal stem cells (MSC-EV) or from bovine milk (BM-EV) by differential ultracentrifugation, and quantitated using nanoparticle tracking analysis. Genotoxic effects, hematological effects, immunological effects and endotoxin production were evaluated at two dose levels. Neither MSC-EVs nor BM-EVs elicited detectable genotoxic effects using either the alkaline comet assay or micronucleus assay. Hemolysis was observed with BM-EVs but not with MSC-EVs. MSC-EVs did not have any significant effect on either spontaneous or collagen-induced platelet aggregation. In contrast, BM-EVs were noted to increase collagen-induced platelet aggregation, even though no spontaneous increase in platelet aggregation was noted. Both types of EVs induced leukocyte proliferation, which was greater with BM-EV. Neither MSC-EVs nor BM-EVs induced HL-60 phagocytosis, although BM-EVs decreased zymosan-induced phagocytosis. Furthermore, neither MSC-EVs nor BM-EVs induced nitric oxide production. Unlike MSC-EVs, BM-EVs tested positive for endotoxin and induced complement activation. There are significant differences in toxicological profiles between MSC-EVs and BM-EVs that may reflect variations in techniques for EV isolation, EV content or cross-species differences. The safety of MSC-EV supports their use for disease therapeutics, whereas detailed safety and toxicological assessment will be necessary before the use of BM-EVs.

Original languageEnglish (US)
Pages (from-to)310-318
Number of pages9
JournalJournal of Applied Toxicology
Volume37
Issue number3
DOIs
StatePublished - Mar 1 2017

Fingerprint

Platelets
Toxicology
Agglomeration
Endotoxins
Assays
Collagen
Zymosan
Stem cells
Nitric Oxide
Chemical activation
Nanoparticles
Membranes
Extracellular Vesicles
In Vitro Techniques
Platelet Aggregation
Safety
Phagocytosis

Keywords

  • bovine milk-extracellular vesicles
  • extracellular vesicles
  • mesenchymal stem cell-extracellular vesicles
  • toxicity

ASJC Scopus subject areas

  • Toxicology

Cite this

Maji, S., Yan, I. K., Parasramka, M., Mohankumar, S., Matsuda, A., & Patel, T. C. (2017). In vitro toxicology studies of extracellular vesicles. Journal of Applied Toxicology, 37(3), 310-318. https://doi.org/10.1002/jat.3362

In vitro toxicology studies of extracellular vesicles. / Maji, Sayantan; Yan, Irene K.; Parasramka, Mansi; Mohankumar, Swathi; Matsuda, Akiko; Patel, Tushar C.

In: Journal of Applied Toxicology, Vol. 37, No. 3, 01.03.2017, p. 310-318.

Research output: Contribution to journalArticle

Maji, S, Yan, IK, Parasramka, M, Mohankumar, S, Matsuda, A & Patel, TC 2017, 'In vitro toxicology studies of extracellular vesicles', Journal of Applied Toxicology, vol. 37, no. 3, pp. 310-318. https://doi.org/10.1002/jat.3362
Maji S, Yan IK, Parasramka M, Mohankumar S, Matsuda A, Patel TC. In vitro toxicology studies of extracellular vesicles. Journal of Applied Toxicology. 2017 Mar 1;37(3):310-318. https://doi.org/10.1002/jat.3362
Maji, Sayantan ; Yan, Irene K. ; Parasramka, Mansi ; Mohankumar, Swathi ; Matsuda, Akiko ; Patel, Tushar C. / In vitro toxicology studies of extracellular vesicles. In: Journal of Applied Toxicology. 2017 ; Vol. 37, No. 3. pp. 310-318.
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