Proangiogenic and Prosurvival Functions of Glucose in Human Mesenchymal Stem Cells upon Transplantation

A major limitation in the development of cellular therapies using human mesenchymal stem cells (hMSCs) is cell survival post‐transplantation. In this study, we challenged the current paradigm of hMSC survival, which assigned a pivotal role to oxygen, by testing the hypothesis that exogenous glucose...

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Bibliographic Details
Published in:	Stem cells (Dayton, Ohio) Vol. 31; no. 3; pp. 526 - 535
Main Authors:	Deschepper, Mickael, Manassero, Mathieu, Oudina, Karim, Paquet, Joseph, Monfoulet, Laurent‐Emmanuel, Bensidhoum, Morad, Logeart‐Avramoglou, Delphine, Petite, Herve
Format:	Journal Article
Language:	English
Published:	Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-03-2013 Oxford University Press AlphaMed Press
Subjects:	Angiogenesis Animals Anoxia Bioengineering Biomaterials Biotechnology Bone marrow Cell Differentiation - drug effects Cell Differentiation - physiology Cell Growth Processes - drug effects Cell Growth Processes - physiology Cell Hypoxia - drug effects Cell Hypoxia - physiology Cell Survival - drug effects Cell Survival - physiology Cellular Biology Female Glucose Glucose - metabolism Glucose - pharmacology Human mesenchymal stem cells Humans Ischemia Life Sciences Marrow stromal cells Medical research Mesenchymal Stem Cell Transplantation - methods Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - drug effects Mesenchymal Stromal Cells - metabolism Mesenchymal Stromal Cells - physiology Mice Mice, Nude Stem cells Subcellular Processes
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Summary:	A major limitation in the development of cellular therapies using human mesenchymal stem cells (hMSCs) is cell survival post‐transplantation. In this study, we challenged the current paradigm of hMSC survival, which assigned a pivotal role to oxygen, by testing the hypothesis that exogenous glucose may be key to hMSC survival. We demonstrated that hMSCs could endure sustained near‐anoxia conditions only in the presence of glucose. In this in vitro cell model, the protein expressions of Hif‐1α and angiogenic factors were upregulated by the presence of glucose. Ectopically implanted tissue constructs supplemented with glucose exhibited four‐ to fivefold higher viability and were more vascularized compared to those without glucose at day 14. These findings provided the first direct in vitro and in vivo demonstration of the proangiogenic and prosurvival functions of glucose in hMSC upon transplantation and identified glucose as an essential component of the ideal scaffold for transplanting stem cells. STEM CELLS2013;31:526–535
Bibliography:	First published online in S Disclosure of potential conflicts of interest is found at the end of this article. C XPRESS E Author contributions: M.D.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; M.M. and K.O.: collection and/or assembly of data; J.P. and L.E.M.: conception and design and data analysis and interpretation; M.B.: provision of study material or patients; D.L‐A.: data analysis and interpretation and financial support; H.P.: conception and design, data analysis and interpretation, financial support, manuscript writing, and final approval of manuscript. Telephone: 0157278533; Fax: 0157278533 December 7, 2012. TEM ELLS ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	1066-5099 1549-4918
DOI:	10.1002/stem.1299