{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:55:38Z","timestamp":1791248138257,"version":"4.1.0"},"reference-count":185,"publisher":"Radiation Research Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2024,7,10]]},"abstract":"<jats:p>This historical review of extracellular vesicles in the setting of exposure to ionizing radiation (IR) traces our understanding of how vesicles were initially examined and reported in the literature in the late 1970s (for secreted exosomes) and early 1980s (for plasma membrane-derived, exfoliated vesicles) to where we are now and where we may be headed in the next decade. An emphasis is placed on biophysical properties of extracellular vesicles, energy consumption and the role of vesiculation as an essential component of membrane turnover. The impact of intercellular signal trafficking by vesicle surface and intra-vesicular lipids, proteins, nucleic acids and metabolites is reviewed in the context of biomarkers for estimating individual radiation dose after exposure to radiation, pathogenesis of disease and development of cell-free therapeutics. Since vesicles express both growth stimulatory and inhibitory molecules, a hypothesis is proposed to consider superposition in a shared space and entanglement of molecules by energy sources that are external to human cells. Implications of this approach for travel in deep space are briefly discussed in the context of clinical disorders that have been observed after space travel.<\/jats:p>","DOI":"10.1667\/rade-24-00078.1","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T20:01:40Z","timestamp":1720555300000},"page":"328-354","source":"Crossref","is-referenced-by-count":0,"title":["Biology of Exfoliation of Plasma Membrane-Derived Vesicles and the Radiation Response: Historical Background, Applications in Biodosimetry and Cell-Free Therapeutics, and Quantal Mechanisms for Their Release and Function with Implications for Space Travel"],"prefix":"10.1667","volume":"202","author":[{"given":"Nicholas","family":"Dainiak","sequence":"first","affiliation":[{"name":"Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"88","doi-asserted-by":"crossref","unstructured":"J Albanese  and N Dainiak  \"Radiat Res.\"  153, \"Ionizing radiation alters Fas antigen ligand at the cell surface and on exfoliated plasma membrane-derived vesicles: implications for apoptosis and intercellular signaling.\" 49 (2000)","DOI":"10.1667\/0033-7587(2000)153[0049:IRAFAL]2.0.CO;2"},{"key":"173","unstructured":"\"Managing space radiation risk in the new era of space exploration.\"  (2008)"},{"key":"155","doi-asserted-by":"crossref","unstructured":"M Benderitter, P Gourmelon, E Bey, et al.  \"Health Phys.\"  98, \"New emerging concepts in the medical management of local radiation injury.\" 851 (2010)","DOI":"10.1097\/HP.0b013e3181c9f79a"},{"key":"158","doi-asserted-by":"crossref","unstructured":"S Flamant  and R Tamarat  \"Radiat Res.\"  186, \"Extracellular vesicles and vascular injury: new insights for radiation exposure.\" 203 (2016)","DOI":"10.1667\/RR14482.1"},{"key":"119","doi-asserted-by":"crossref","unstructured":"S Paul  and SA Amundson  \"Int J Radiat Oncol Biol Phys.\"  71, \"Development of gene expression signatures for practical radiation biodosimetry.\" 1236 (2008)","DOI":"10.1016\/j.ijrobp.2008.03.043"},{"key":"107","doi-asserted-by":"crossref","unstructured":"S Xu, J Wang, N Ding, et al.  \"RNA Biol.\"  12, \"Exosome-mediated microRNA transfer plays a role in radiation-induced bystander effect.\" 1355 (2015)","DOI":"10.1080\/15476286.2015.1100795"},{"key":"103","doi-asserted-by":"crossref","unstructured":"FM Lyng, P Maguire, B McClean, et al.  \"Radiat Res.\"  165, \"The involvement of calcium and map kinase signaling pathways in the production of radiation-induced bystander effects.\" 400 (2006)","DOI":"10.1667\/RR3527.1"},{"key":"12","doi-asserted-by":"crossref","unstructured":"EG Trams, CJ Lauter, N Salem, et al.  \"Biochim Biophys Acta.\"  645, \"Exfoliation of membrane ecto-enzymes in the form of micro-vesicles.\" 63 (1981)","DOI":"10.1016\/0005-2736(81)90512-5"},{"key":"91","doi-asserted-by":"crossref","unstructured":"A Abramowicz, A Wojakowska, L Marczak, et al.  \"J Radiat Res.\"  60, \"Ionizing radiation affects the composition of the proteome of extracellular vesicles released by head-and-neck cancer cells in vitro.\" 289 (2019)","DOI":"10.1093\/jrr\/rrz001"},{"key":"118","doi-asserted-by":"crossref","unstructured":"SA Amundson, KT Do, S Shahab, et al.  \"Radiat Res.\"  154, \"Identification of potential mRNA biomarkers in peripheral blood lymphocytes for human exposure to ionizing radiation.\" 342 (2000)","DOI":"10.1667\/0033-7587(2000)154[0342:IOPMBI]2.0.CO;2"},{"key":"104","doi-asserted-by":"crossref","unstructured":"MD Gow, CB Seymour, LA Ryan, et al.  \"Radiat Res.\"  173, \"Induction of bystander response in human glioma cells using high-energy electrons: a role for TGF-beta1.\" 769 (2010)","DOI":"10.1667\/RR1895.1"},{"key":"108","doi-asserted-by":"crossref","unstructured":"AHJ Al-Mayah, SJ Bright, DA Bowler, et al.  \"Radiat Res.\"  187, \"Exosome-mediated telomere instability in human breast epithelial cancer cells after X irradiation.\" 98 (2017)","DOI":"10.1667\/RR14201.1"},{"key":"112","doi-asserted-by":"crossref","unstructured":"NK Jacob, JV Cooley, TN Yee, et al.  \"PLoS One.\"  8, \"Identification of sensitive serum microRNA biomarkers for radiation biodosimetry.\" e57603 (2013)","DOI":"10.1371\/journal.pone.0057603"},{"key":"64","doi-asserted-by":"crossref","unstructured":"H Valadi, K Ekstrom, A Bossios, et al.  \"Nat Cell Biol.\"  9, \"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.\" 654 (2007)","DOI":"10.1038\/ncb1596"},{"key":"128","doi-asserted-by":"crossref","unstructured":"M Port, F Herodin, M Valente, et al.  \"PLoS One.\"  11, \"MicroRNA expression for early prediction of late occurring hematologic acute radiation syndrome in baboons.\" e0165307 (2016)","DOI":"10.1371\/journal.pone.0165307"},{"key":"149","doi-asserted-by":"crossref","unstructured":"N. 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