Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis.

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 th...

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Autores principales:	Carlos Salomon, Jennifer Ryan, Luis Sobrevia, Miharu Kobayashi, Keith Ashman, Murray Mitchell, Gregory E Rice
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1e943efee7f041869cdd2592de91055d
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spelling	oai:doaj.org-article:1e943efee7f041869cdd2592de91055d2021-11-18T07:38:18ZExosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis.1932-620310.1371/journal.pone.0068451https://doaj.org/article/1e943efee7f041869cdd2592de91055d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23861904/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Vasculogenesis 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.Carlos SalomonJennifer RyanLuis SobreviaMiharu KobayashiKeith AshmanMurray MitchellGregory E RicePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e68451 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carlos Salomon Jennifer Ryan Luis Sobrevia Miharu Kobayashi Keith Ashman Murray Mitchell Gregory E Rice Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis.
description	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.
format	article
author	Carlos Salomon Jennifer Ryan Luis Sobrevia Miharu Kobayashi Keith Ashman Murray Mitchell Gregory E Rice
author_facet	Carlos Salomon Jennifer Ryan Luis Sobrevia Miharu Kobayashi Keith Ashman Murray Mitchell Gregory E Rice
author_sort	Carlos Salomon
title	Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis.
title_short	Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis.
title_full	Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis.
title_fullStr	Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis.
title_full_unstemmed	Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis.
title_sort	exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/1e943efee7f041869cdd2592de91055d
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_version_	1718423146600595456

Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis.

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