Differential fates of biomolecules delivered to target cells via extracellular vesicles

Abstract

Extracellular vesicles (EVs), specifically exosomes and microvesicles (MVs), are presumed to play key roles in cell-cell communication via transfer of biomolecules between cells. The biogenesis of these two types of EVs differs as they originate from either the endosomal (exosomes) or plasma (MVs) membranes. To elucidate the primary means through which EVs mediate intercellular communication, we characterized their ability to encapsulate and deliver different types of macromolecules from transiently transfected cells. Both EV types encapsulated reporter proteins and mRNA but only MVs transferred the reporter function to recipient cells. De novo reporter protein expression in recipient cells resulted only from plasmid DNA (pDNA) after delivery via MVs. Reporter mRNA was delivered to recipient cells by both EV types, but was rapidly degraded without being translated. MVs also mediated delivery of functional pDNA encoding Cre recombinase in vivo to tissues in transgenic Crelox reporter mice. Within the parameters of this study, MVs delivered functional pDNA, but not RNA, whereas exosomes from the same source did not deliver functional nucleic acids. These results have significant implications for understanding the role of EVs in cellular communication and for development of EVs as delivery tools. Moreover, studies using EVs from transiently transfected cells may be confounded by a predominance of pDNA transfer.

Engineered exosome-mediated delivery of functionally active miR-26a and its enhanced suppression effect in HepG2 cells

“…In addition, consistent with previous reports, GAPDH was also detected in exosomes ( Figure 2F). 39 These results suggest that the isolated sample is exactly the exosome.…”

Advances of the interleukin-21 signaling pathway in immunity and angiogenesis

“…Knockout IL-21R resulted in less perfusion recovery following HLI in vivo. In particular, the activated STAT3 pathway and increase in the BCL-2/BCL-2-associated X protein ratio were involved in the in vitro and in vivo experiments (9). These results suggest that the elevated IL-21R levels in EC in ischemia muscle are adaptive.…”

“…Increasing evidence shows that IL-21 potently regulates innate and adaptive immune response (6)(7)(8). Furthermore, the role of IL-21 in angiogenesis has also been studied (9,10). In the present review, the recent advances regarding the role of IL-21 in immune cells and angiogenesis are discussed.…”

Cell‐to‐cell communication: microRNAs as hormones

“…Exosomes are the best characterized class of EVs; they are secreted by almost all cell types, are 40 to 100 nm in diameter, and are enriched in a 1.13–1.19 g·mL −1 fraction in a sucrose density gradient (Kanada et al ., 2015; Turturici et al ., 2014). The protein and lipid composition of exosomes reflects their cellular sources (Staubach et al ., 2009; Yim et al ., 2016).…”