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Journal Articles Stem Cells Translational Medicine Year : 2015

Oxygen Tension Regulates Human Mesenchymal Stem Cell Paracrine Functions

la tension d'oxygène régule les fonctions paracrines des cellules souches mésenchymateuses

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Abstract

Mesenchymal stem cells (MSCs) have captured the attention and research endeavors of the scientific world because of their differentiation potential. However, there is accumulating evidence suggesting that the beneficial effects of MSCs are predominantly due to the multitude of bioactive mediators secreted by these cells. Because the paracrine potential of MSCs is closely related to their microenvironment, the present study investigated and characterized select aspects of the human MSC (hMSC) secretome and assessed its in vitro and in vivo bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. In contrast to supernatant conditioned media (CM) obtained from hMSCs cultured at either 5% or 21% of O2, CM from hMSCs cultured under near anoxia exhibited significantly (p < .05) enhanced chemotactic and proangiogenic properties and a significant (p < .05) decrease in the inflammatory mediator content. An analysis of the hMSC secretome revealed a specific profile under near anoxia: hMSCs increase their paracrine expression of the angiogenic mediators vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, RANTES, and monocyte chemoattractant protein 1 but significantly decrease expression of several inflammatory/immunomodulatory mediators. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine and could contribute to improving the efficacy of such therapies. SIGNIFICANCE: The present study investigated and characterized select aspects of the human mesenchymal stem cell (hMSC) secretome and assessed its in vitro and in vivo biological bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. The present study provided the first evidence of a shift of the hMSC cytokine signature induced by oxygen tension, particularly near anoxia (0.1% O2). Conditioned media obtained from hMSCs cultured under near anoxia exhibited significantly enhanced chemotactic and proangiogenic properties and a significant decrease in the inflammatory mediator content. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine, could contribute to improving the efficacy of such therapies, and most importantly highlighted the interest in using conditioned media in therapeutic modalities.
Les cellules souches mésenchymateuses (CSM) sont très attractives pour la thérapie cellulaire en raison de leur potentiel de différenciation. Cependant, de nombreuses preuves suggèrent que les effets bénéfiques des CSM sont principalement dus à la multitude de médiateurs bioactifs sécrétés par ces cellules. Parce que le potentiel paracrine des CSM est étroitement lié à leur microenvironnement, la présente étude a examiné et caractérisé certains aspects du sécrétome du CSM humain (CSMh) et évalué sa bioactivité in vitro et in vivo en fonction de la tension en oxygène, en particulier près de l'anoxie. (0,1% O 2) et l’hypoxie (5% O 2), conditions qui reflètent l’environnement auquel les MSC sont exposés au cours de traitements in vivo à base de MSC. Contrairement aux milieux conditionnés (MC) obtenus à partir de CSM cultivées à 5% ou à 21% d'oxygène, les MC provenant de CSM cultivées presque en anoxie présentaient des propriétés chimiotactiques et proangiogéniques renforcées de manière significative (p <0,05) et une diminution significative du contenu en médiateur inflammatoire p<0,05). Une analyse du sécrétome des CSM a révélé un profil spécifique dans l'anoxie proche: les CSM accroissent leur expression paracrine du facteur de croissance endothélial vasculaire (VEGF)-A, VEGF-C, l'interleukine-8, RANTES et la protéine 1 de monocyte, un agent chimioattractant monocytaire mais diminue de façon significative l'expression de plusieurs médiateurs inflammatoires / immomodulateurs. Ces résultats fournissent de nouvelles preuves qui élucident des aspects d'une grande importance pour l'utilisation des CSM en médecine régénérative et pourraient contribuer à améliorer l'efficacité de tels traitements.
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Dates and versions

inserm-01973949 , version 1 (08-01-2019)

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Joseph Paquet, Mickael Deschepper, Adrien Moya, Delphine Logeart-Avramoglou, Catherine Boisson-Vidal, et al.. Oxygen Tension Regulates Human Mesenchymal Stem Cell Paracrine Functions. Stem Cells Translational Medicine, 2015, 4 (7), pp.809-821. ⟨10.5966/sctm.2014-0180⟩. ⟨inserm-01973949⟩
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