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Quantifying Metabolic Transfer Mediated by Extracellular Vesicles Using Exo-MFA: An Integrated Empirical and Computational Platform

Part of the Methods in Molecular Biology book series (MIMB,volume 2088)


Extracellular vesicles (EVs) are ubiquitous nanoscale particles released from many different types of cells. They have been shown to contain proteins, DNA, RNA, miRNA, and, most recently, metabolites. These particles can travel through the intercellular space and bloodstream to have regulatory effects on distant recipients. When an EV reaches a target cell, it is taken up and degraded to release its contents for utilization within the cell. In addition to regulatory effects, EVs have been shown to supplement the high metabolic demands of recipient cells in a nutrient-deprived tumor microenvironment. We developed an integrated empirical and computational platform to quantify metabolic contribution of source cell-derived EVs to recipient cells. The versatile Exo-MFA software tool utilizes 13C stable-isotope tracing data to quantify the metabolic contributions of EVs from a source cell type on a recipient cell type. This is accomplished by creating EV-depleted culture medium, producing isotope-labeled EVs from the source cells, isolating the labeled EVs from the culture supernatant, culturing the recipient cells in the presence of the labeled EVs, and measuring the resulting metabolite levels across several time points.

Key words

  • Extracellular vesicles
  • Exosomes
  • Exo-MFA
  • Stable-isotope tracing
  • 13-Carbon metabolic flux analysis
  • Multicellular metabolic flux analysis

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This work was supported by grants from the National Institute of Health (R01-CA222251, R01-CA204969, and R01-CA227622) awarded to D.N.

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Correspondence to Deepak Nagrath .

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Achreja, A., Meurs, N., Nagrath, D. (2020). Quantifying Metabolic Transfer Mediated by Extracellular Vesicles Using Exo-MFA: An Integrated Empirical and Computational Platform. In: Nagrath, D. (eds) Metabolic Flux Analysis in Eukaryotic Cells. Methods in Molecular Biology, vol 2088. Humana, New York, NY.

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0158-7

  • Online ISBN: 978-1-0716-0159-4

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