Influence of hypoxia on the domiciliation of Mesenchymal Stem Cells after infusion into rats: possibilities of targeting pulmonary artery remodeling via cells therapies?

<p>Abstract</p> <p>Background</p> <p>Bone marrow (BM) cells are promising tools for vascular therapies. Here, we focused on the possibility of targeting the hypoxia-induced pulmonary artery hypertension remodeling with systemic delivery of BM-derived mesenchymal stem ce...

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Main Authors: Domenech Jorge, Pages Jean-Christophe, Bonnet Nicolas, Vaudin Pascal, Rochefort Gaël Y, Charbord Pierre, Eder Véronique
Format: Article
Language:English
Published: BMC 2005-10-01
Series:Respiratory Research
Subjects:
Online Access:http://respiratory-research.com/content/6/1/125
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author Domenech Jorge
Pages Jean-Christophe
Bonnet Nicolas
Vaudin Pascal
Rochefort Gaël Y
Charbord Pierre
Eder Véronique
author_facet Domenech Jorge
Pages Jean-Christophe
Bonnet Nicolas
Vaudin Pascal
Rochefort Gaël Y
Charbord Pierre
Eder Véronique
author_sort Domenech Jorge
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Bone marrow (BM) cells are promising tools for vascular therapies. Here, we focused on the possibility of targeting the hypoxia-induced pulmonary artery hypertension remodeling with systemic delivery of BM-derived mesenchymal stem cells (MSCs) into non-irradiated rats.</p> <p>Methods</p> <p>Six-week-old Wistar rats were exposed to 3-week chronic hypoxia leading to pulmonary artery wall remodeling. Domiciliation of adhesive BM-derived CD45<sup>- </sup>CD73<sup>+ </sup>CD90<sup>+ </sup>MSCs was first studied after a single intravenous infusion of Indium-111-labeled MSCs followed by whole body scintigraphies and autoradiographies of different harvested organs. In a second set of experiments, enhanced-GFP labeling allowed to observe distribution at later times using sequential infusions during the 3-week hypoxia exposure.</p> <p>Results</p> <p>A 30% pulmonary retention was observed by scintigraphies and no differences were observed in the global repartition between hypoxic and control groups. Intrapulmonary radioactivity repartition was homogenous in both groups, as shown by autoradiographies. BM-derived GFP-labeled MSCs were observed with a global repartition in liver, in spleen, in lung parenchyma and rarely in the adventitial layer of remodeled vessels. Furthermore this global repartition was not modified by hypoxia. Interestingly, these cells displayed <it>in vivo </it>bone marrow homing, proving a preservation of their viability and function. Bone marrow homing of GFP-labeled MSCs was increased in the hypoxic group.</p> <p>Conclusion</p> <p>Adhesive BM-derived CD45<sup>- </sup>CD73<sup>+ </sup>CD90<sup>+ </sup>MSCs are not integrated in the pulmonary arteries remodeled media after repeated intravenous infusions in contrast to previously described in systemic vascular remodeling or with endothelial progenitor cells infusions.</p>
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spelling doaj.art-928af943a46340eeb8b71266af20e0c92022-12-22T03:20:23ZengBMCRespiratory Research1465-99212005-10-016112510.1186/1465-9921-6-125Influence of hypoxia on the domiciliation of Mesenchymal Stem Cells after infusion into rats: possibilities of targeting pulmonary artery remodeling via cells therapies?Domenech JorgePages Jean-ChristopheBonnet NicolasVaudin PascalRochefort Gaël YCharbord PierreEder Véronique<p>Abstract</p> <p>Background</p> <p>Bone marrow (BM) cells are promising tools for vascular therapies. Here, we focused on the possibility of targeting the hypoxia-induced pulmonary artery hypertension remodeling with systemic delivery of BM-derived mesenchymal stem cells (MSCs) into non-irradiated rats.</p> <p>Methods</p> <p>Six-week-old Wistar rats were exposed to 3-week chronic hypoxia leading to pulmonary artery wall remodeling. Domiciliation of adhesive BM-derived CD45<sup>- </sup>CD73<sup>+ </sup>CD90<sup>+ </sup>MSCs was first studied after a single intravenous infusion of Indium-111-labeled MSCs followed by whole body scintigraphies and autoradiographies of different harvested organs. In a second set of experiments, enhanced-GFP labeling allowed to observe distribution at later times using sequential infusions during the 3-week hypoxia exposure.</p> <p>Results</p> <p>A 30% pulmonary retention was observed by scintigraphies and no differences were observed in the global repartition between hypoxic and control groups. Intrapulmonary radioactivity repartition was homogenous in both groups, as shown by autoradiographies. BM-derived GFP-labeled MSCs were observed with a global repartition in liver, in spleen, in lung parenchyma and rarely in the adventitial layer of remodeled vessels. Furthermore this global repartition was not modified by hypoxia. Interestingly, these cells displayed <it>in vivo </it>bone marrow homing, proving a preservation of their viability and function. Bone marrow homing of GFP-labeled MSCs was increased in the hypoxic group.</p> <p>Conclusion</p> <p>Adhesive BM-derived CD45<sup>- </sup>CD73<sup>+ </sup>CD90<sup>+ </sup>MSCs are not integrated in the pulmonary arteries remodeled media after repeated intravenous infusions in contrast to previously described in systemic vascular remodeling or with endothelial progenitor cells infusions.</p>http://respiratory-research.com/content/6/1/125arterieshypertension, pulmonaryhypoxialungremodelingmesenchymal stem cells.
spellingShingle Domenech Jorge
Pages Jean-Christophe
Bonnet Nicolas
Vaudin Pascal
Rochefort Gaël Y
Charbord Pierre
Eder Véronique
Influence of hypoxia on the domiciliation of Mesenchymal Stem Cells after infusion into rats: possibilities of targeting pulmonary artery remodeling via cells therapies?
Respiratory Research
arteries
hypertension, pulmonary
hypoxia
lung
remodeling
mesenchymal stem cells.
title Influence of hypoxia on the domiciliation of Mesenchymal Stem Cells after infusion into rats: possibilities of targeting pulmonary artery remodeling via cells therapies?
title_full Influence of hypoxia on the domiciliation of Mesenchymal Stem Cells after infusion into rats: possibilities of targeting pulmonary artery remodeling via cells therapies?
title_fullStr Influence of hypoxia on the domiciliation of Mesenchymal Stem Cells after infusion into rats: possibilities of targeting pulmonary artery remodeling via cells therapies?
title_full_unstemmed Influence of hypoxia on the domiciliation of Mesenchymal Stem Cells after infusion into rats: possibilities of targeting pulmonary artery remodeling via cells therapies?
title_short Influence of hypoxia on the domiciliation of Mesenchymal Stem Cells after infusion into rats: possibilities of targeting pulmonary artery remodeling via cells therapies?
title_sort influence of hypoxia on the domiciliation of mesenchymal stem cells after infusion into rats possibilities of targeting pulmonary artery remodeling via cells therapies
topic arteries
hypertension, pulmonary
hypoxia
lung
remodeling
mesenchymal stem cells.
url http://respiratory-research.com/content/6/1/125
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