Amnion-epithelial-cell-derived exosomes demonstrate physiologic state of cell under oxidative stress

Sheller, Samantha, Papaconstantinou, John, Urrabaz-Garza, Rheanna, Richardson, Lauren, Saade, George, Salomon, Carlos and Menon, Ramkumar (2016) Amnion-epithelial-cell-derived exosomes demonstrate physiologic state of cell under oxidative stress. Plos One, 11 6: . doi:10.1371/journal.pone.0157614


Author Sheller, Samantha
Papaconstantinou, John
Urrabaz-Garza, Rheanna
Richardson, Lauren
Saade, George
Salomon, Carlos
Menon, Ramkumar
Title Amnion-epithelial-cell-derived exosomes demonstrate physiologic state of cell under oxidative stress
Journal name Plos One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2016-06-22
Year available 2016
Sub-type Article (original research)
DOI 10.1371/journal.pone.0157614
Open Access Status DOI
Volume 11
Issue 6
Total pages 25
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2017
Language eng
Formatted abstract
At term, the signals of fetal maturity and feto-placental tissue aging prompt uterine readiness for delivery by transitioning quiescent myometrium to an active stage. It is still unclear how the signals reach the distant myometrium. Exosomes are a specific type of extracellular vesicle (EVs) that transport molecular signals between cells, and are released from a wide range of cells, including the maternal and fetal cells. In this study, we hypothesize that i) exosomes act as carriers of signals in utero-placental compartments and ii) exosomes reflect the physiologic status of the origin cells. The primary aims of this study were to determine exosomal contents in exosomes derived from primary amnion epithelial cells (AEC). We also determined the effect of oxidative stress on AEC derived exosomal cargo contents. AEC were isolated from amniotic membrane obtained from normal, term, not in labor placentae at delivery, and culture under standard conditions. Oxidative stress was induced using cigarette smoke extract for 48 hours. AEC-conditioned media were collected and exosomes isolated by differential centrifugations. Both growth conditions (normal and oxidative stress induced) produced cup shaped exosomes of around 50 nm, expressed exosomes enriched markers, such as CD9, CD63, CD81 and HSC70, embryonic stem cell marker Nanog, and contained similar amounts of cell free AEC DNA. Using confocal microscopy, the colocalization of histone (H) 3, heat shock protein (HSP) 70 and activated form of prosenescence and term parturition associated marker p38 mitogen activated protein kinase (MAPK) (P-p38 MAPK) co-localized with exosome enrich marker CD9. HSP70 and P-p38MAPK were significantly higher in exosomes from AEC grown under oxidative stress conditions than standard conditions (p<0.05). Finally, mass spectrometry and bioinformatics analysis identified 221 different proteins involved in immunomodulatory response and cellto-cell communication. This study determined AEC exosome characteristics and their cargo reflected the physiologic status of the cell of origin and suggests that AEC-derived exosomal p38 MAPK plays a major role in determining the fate of pregnancy. Understanding the propagation of fetal signals and their mechanisms in normal term pregnancies can provide insights into pathologic activation of such signals associated with spontaneous preterm parturitions.
Keyword Exosomes
Extracellular vesicle (EVs)
Amnion epithelial cells (AEC)
Oxidative stress
Mitogen activated protein kinase (MAPK)
Mass spectrometry
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
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