Exosomal Signaling during Hypoxia Mediates Microvascular Endothelial Cell Migration and Vasculogenesis

Salomon, Carlos, Ryan, Jennifer, Sobrevia, Luis, Kobayashi, Miharu, Ashman, Keith, Mitchell, Murray and Rice, Gregory E. (2013) Exosomal Signaling during Hypoxia Mediates Microvascular Endothelial Cell Migration and Vasculogenesis. Plos One, 8 7: e68451.1-e68451.24. doi:10.1371/journal.pone.0068451


Author Salomon, Carlos
Ryan, Jennifer
Sobrevia, Luis
Kobayashi, Miharu
Ashman, Keith
Mitchell, Murray
Rice, Gregory E.
Title Exosomal Signaling during Hypoxia Mediates Microvascular Endothelial Cell Migration and Vasculogenesis
Journal name Plos One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-07
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0068451
Open Access Status DOI
Volume 8
Issue 7
Start page e68451.1
End page e68451.24
Total pages 24
Place of publication San Francisco, United States
Publisher Public Library of Science (PLoS)
Collection year 2014
Language eng
Formatted abstract
Vasculogenesis and angiogenesis are critical processes in fetal circulation and placental vasculature development. Placental mesenchymal stem cells (pMSC) are known to release paracrine factors (some of which are contained within exosomes) that promote angiogenesis and cell migration. The aims of this study were: to determine the effects of oxygen tension on the release of exosomes from pMSC; and to establish the effects of pMSC-derived exosomes on the migration and angiogenic tube formation of placental microvascular endothelial cells (hPMEC). pMSC were isolated from placental villi (8–12 weeks of gestation, n = 6) and cultured under an atmosphere of 1%, 3% or 8% O2. Cell-conditioned media were collected and exosomes (exo-pMSC) isolated by differential and buoyant density centrifugation. The dose effect (5–20 µg exosomal protein/ml) of pMSC-derived exosomes on hPMEC migration and tube formation were established using a real-time, live-cell imaging system (Incucyte™). The exosome pellet was resuspended in PBS and protein content was established by mass spectrometry (MS). Protein function and canonical pathways were identified using the PANTHER program and Ingenuity Pathway Analysis, respectively. Exo-pMSC were identified, by electron microscopy, as spherical vesicles, with a typical cup-shape and diameters around of 100 nm and positive for exosome markers: CD63, CD9 and CD81. Under hypoxic conditions (1% and 3% O2) exo-pMSC released increased by 3.3 and 6.7 folds, respectively, when compared to the controls (8% O2; p<0.01). Exo-pMSC increased hPMEC migration by 1.6 fold compared to the control (p<0.05) and increased hPMEC tube formation by 7.2 fold (p<0.05). MS analysis identified 390 different proteins involved in cytoskeleton organization, development, immunomodulatory, and cell-to-cell communication. The data obtained support the hypothesis that pMSC-derived exosomes may contribute to placental vascular adaptation to low oxygen tension under both physiological and pathological conditions.
Keyword Mesenchymal stem-cells
Src family kinases
Urinary exosomes
Cancer
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 55 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 60 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 15 Sep 2013, 00:13:47 EST by System User on behalf of UQ Centre for Clinical Research