Exosomes, microvesicles, retrovirus-like particles and apoptotic bodies are extracellular vesicles that all cells secrete into extracellular space. Exosomes are particularly interesting to study in relation to diseases such as cancer and neurodegenerative, cardiovascular, metabolic and other complex diseases because they contribute to long-range intercellular communication and hold biomarker potential. Mora et al. (2015)1 propose that exosomes could be a valuable fraction to biobank.
One of the challenges in biobanking exosomes is the inconsistent nomenclature that currently exists around them in the literature. For example, the International Society of Extracellular Vesicles promotes referring to exosomes as extracellular vesicles rather than the specific subgroup, exosomes. They are supported in their nomenclature by the International Society of Thrombosis and Hemostasis. They base this on three recent findings: extracellular vesicles indistinguishable from exosomes were released directly from the plasma membrane of cells, diameters of exosomes were reported up to 250 nm, and proteins such as tetraspanins were shown not to be unique for exosomes. However, exosomes are most commonly classified in the literature by size restrictions of 30–100 nm, the authors note, despite the fact that they are considered to be outside of this range.
Mora et al. propose that exosome membrane composition could be profiled using mass spectrometry for use in functional biomarker discovery. At the same time, they note that there may be limitations imposed by freeze-thaw cycles on surface markers and therefore recommend that fresh fractions may be more reliable. Exosomes make for good biomarker candidates as signaling molecules, as previous studies have shown that exosomes transport oncogenes and onco-miRNAs to other cells.
Furthermore, the authors note potential uses for biobanked exosomes as therapeutic vehicles, for their ability to cross the blood-brain barrier and selectively reach target organs and cells. The main advantage of pursuing exosomes over other drug delivery methods is that exosomes are immunologically inert. The authors note, with concern, the fact that exosomes are being used in clinical trials prior to achieving a consensus definition.
Before biobanking exosomes, Mora et al. acknowledge the need for further studies comparing yields, purity and integrity according to the isolation procedure, because downstream analysis of exosome cargo can be impacted by isolation. Similarly, there is no specific information regarding the effect of anticoagulants in exosome collection and storage, nor have researchers evaluated optimal time, temperature, storage period, freezing-thaw cycles, thawing conditions or other storage variables for exosomes. Nonetheless, they infer that biobanks should assume an active role in establishing exosome biobanking because of their potential clinical applications.
1. Mora E.M., Álvarez-Cubela, S., and Oltra, E. (2015) “Biobanking of exosomes in the era of precision medicine: Are we there yet?” International Journal of Molecular Sciences, 17(1), doi: 10.3390/ijms17010013.