progress in this emerging extracellular vesicle biology help us to understand the
complexity of intercellular communication networks, following issues are remaining to be solved in more detail.
First of all, to facilitate the basic EV research and biomedical application of EVs,
it is critical that EVs should be specifically isolated from cellular debris and other
interfering components. The need for standard procedure to purify EVs is widely
recognized, however, ultracentrifugation-based techniques are still employed at
most, although other alternative procedures such as gel filtration, polymer-based
precipitation, and immunoaffinity-based chromatography techniques are currently
developed. Second, to overcome the major drawbacks for clinical use of EVs such
as low production yield and potential toxicity of naturally secreted vesicles,
EV-mimetic nanovesicle technologies should be further developed as novel alternatives to extracellular vesicle-based therapeutics, theranostics, drug delivery, and
vaccines [8, 68–76]. Lastly, EVs are too complex themselves in terms of their
structures, components, and biological functions. Furthermore, single cells produce
several different subtypes of EVs, suggesting that our body and environments are
full of a heterogeneous colloidal solution of complex diverse subtypes of EVs [1].
Thus, a holistic systems biology approach based on the concept of emergent
properties of EVs (Fig. 6.5) is critical to elucidate the complex pathological
functions of EVs, to decode the secrets of life as well as to develop novel EV-based
diagnostics and therapeutics against hard-to-cure diseases [1].
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