Oxygen Tension Regulates Human Mesenchymal Stem Cell Paracrine Functions

• Published in: Stem cells translational medicine Vol. 4; no. 7; pp. 809 - 821
• Main Authors: Paquet, Joseph, Deschepper, Mickael, Moya, Adrien, Logeart-Avramoglou, Delphine, Boisson-Vidal, Catherine, Petite, Hervé
• Format: Journal Article
• Language: English
• Published: Durham, NC, USA AlphaMed Press 01.07.2015; Oxford University Press; Wiley
• Subjects: Angiogenesis; Anoxia; Biological activity; Bone marrow; Cell culture; Cell cycle; Cellular Biology; Chemotaxis; Cytokines; Data analysis; Enabling Technologies for Cell-Based Clinical Translation; Experiments; Human mesenchymal stem cells; Hypoxia; Immunomodulation; Inflammation; Life Sciences; Mesenchymal stem cells; Mesenchyme; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; Near anoxia and hypoxia; Oxygen tension; Paracrine signalling; RANTES; Regenerative medicine; Secretome; Stem cells; Vascular endothelial growth factor; France; Angiogenesis; Human mesenchymal stem cells; Secretome; Cytokines; Near anoxia and hypoxia; Chemotaxis
• ISSN: 2157-6564; 2157-6580
• DOI: 10.5966/sctm.2014-0180

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. This study examined the shift of the human mesenchymal stem cell (hMSC) cytokine signature induced by oxygen tension. 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 results elucidate important aspects of using MSCs in regenerative medicine, contribute to improving the efficacy of such therapies, and highlight the interest in using conditioned media in therapeutic modalities.