Table 3.

List of unresolved issues in EV studies and possible solutions

IssuePossible solution
Lack of selective targets in exosome secretion Differentiation by location. Unconventional exosome inhibitors such as proton pump inhibitors might work in the acidic BM109 
Chemotherapy triggering the release of chemoexosomes might upregulate potential targets 
Insufficient insight into the different secretion routes Cargo profiling on the different routes by KO studies 
Standardization of isolation techniques Large consortium studies to compare different techniques at different sites to determine if cargo results are valid 
Unsuitable isolation procedures for a clinical setting Research into more feasible strategies without compromising exosome purity 
Release of exosomes in the bloodstream, unassociated to MM, triggered by underlying pathologies such as chronic inflammation For flow cytometry: always add an MM marker (CD38/CD138)
For RNA analysis: an extra immunomagnetic isolation step, using an MM marker could be considered 
IssuePossible solution
Lack of selective targets in exosome secretion Differentiation by location. Unconventional exosome inhibitors such as proton pump inhibitors might work in the acidic BM109 
Chemotherapy triggering the release of chemoexosomes might upregulate potential targets 
Insufficient insight into the different secretion routes Cargo profiling on the different routes by KO studies 
Standardization of isolation techniques Large consortium studies to compare different techniques at different sites to determine if cargo results are valid 
Unsuitable isolation procedures for a clinical setting Research into more feasible strategies without compromising exosome purity 
Release of exosomes in the bloodstream, unassociated to MM, triggered by underlying pathologies such as chronic inflammation For flow cytometry: always add an MM marker (CD38/CD138)
For RNA analysis: an extra immunomagnetic isolation step, using an MM marker could be considered 
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