Differential fates of biomolecules delivered to target cells via extracellular vesicles Masamitsu Kanadaa, Michael H. Bachmanna, Jonathan W. Hardya, Daniel Omar Frimannson, Laura Bronsarta, Andrew Wanga, Matthew D. Sylvester, Tobi L. Schmidt, Roger L. Kasparc, Manish J. Buttea, A. C. Matin, and Christopher H. Contag THE JOURNAL OF Proceedings of the National Academy of Sciences February 23, 2015, 報告學生: 洪世哲 指導老師:張新侯 評講學生: 林祐延 學長 陳菟汶 學姐演講日期:2015/04/14 Abstract: Extracellular vesicles (EVs) are naturally secreted by most cells into the extracellular environment, and although their designations remain controversial. EVs can classify exosomes and microvesicles (MVs), based on their size, composition, and biogenesis. They are assumed to play a roles in cell–cell communication via transfer of biomolecules between cells. The authors think 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, the authors 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 can transfer the reporter function to recipient cells. And in de novo experiment also can confirm. They use reporter protein expression in recipient cells resulted only from plasmid DNA (pDNA) after delivery via MVs. In addition to, they also want to confirm if EVs also can deliver mRNA to cell. The authors found reporter mRNA was delivered to recipient cells by both EV types, but was rapidly degraded without being translated. Finally,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. 1. Extracellular vesicles: Exosomes, microvesicles, and friend Raposo G, Stoorvogel W (2013) s. J Cell Biol 200(4):373–383. 2. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Valadi H, et al. (2007) Nat Cell Biol 9(6):654–659