Extracellular Vesicles and Their Mimetics: A Comparative Study of Their Pharmacological Activities and Immunogenicity Profiles

Extracellular vesicles (EVs), which are miniaturised carriers loaded with functional proteins, lipids, and nucleic acid material, are naturally secreted by cells and show intrinsic pharmacological effects in several conditions. As such, they have the potential to be used for the treatment of various human diseases. However, the low isolation yield and laborious purification process are obstacles to their translation for clinical use. To overcome this problem, our lab developed cell-derived nanovesicles (CDNs), which are EV mimetics produced by shearing cells through membrane-fitted spin cups. To evaluate the similarities between EVs and CDNs, we compare the physical properties and biochemical composition of monocytic U937 EVs and U937 CDNs. Besides having similar hydrodynamic diameters, the produced CDNs had proteomic, lipidomic, and miRNA profiles with key communalities compared to those of natural EVs. Further characterisation was conducted to examine if CDNs could exhibit similar pharmacological activities and immunogenicity when administered in vivo. Consistently, CDNs and EVs modulated inflammation and displayed antioxidant activities. EVs and CDNs both did not exert immunogenicity when administered in vivo. Overall, CDNs could serve as a scalable and efficient alternative to EVs for further translation into clinical use.

Automated summary

Extracellular vesicles (EVs) are miniaturised carriers that naturally secrete functional proteins, lipids, and nucleic acid material and have intrinsic pharmacological effects in human diseases. However, their low isolation yield and laborious purification process hinder their clinical translation. To overcome this, our lab developed cell-derived nanovesicles (CDNs), mimetics of EVs created by shearing cells through membrane-fitted spin cups. We compared the physical properties and biochemical composition of monocytic U937 EVs and U937 CDNs to evaluate their similarities. CDNs exhibited similar hydrodynamic diameters and shared proteomic, lipidomic, and miRNA profiles with natural EVs. Furthermore, CDNs exhibited similar pharmacological activities and immunogenicity to EVs when administered in vivo. CDNs could be a scalable and efficient alternative to EVs in clinical use.