, VS -data analysis, preparation of the manuscript; AV -sample collection, critical review of the manuscript; CD -sample collection, critical review of the manuscript; CG -design of the study, preparation of the manuscript, work

, SP -design of the study

M. F. Pittenger, A. M. Mackay, S. C. Beck, R. K. Jaiswal, R. Douglas et al., Multilineage potential of adult human mesenchymal stem cells, Science, vol.284, issue.5411, pp.143-150, 1999.

A. I. Caplan, Mesenchymal Stem Cells: Time to Change the Name! Stem Cells Transl Med, vol.6, pp.1445-51, 2017.

A. I. Caplan and J. E. Dennis, Mesenchymal stem cells as trophic mediators, J Cell Biochem, vol.98, issue.5, pp.1076-84, 2006.

A. R. Derubeis and R. Cancedda, Bone marrow stromal cells (BMSCs) in bone engineering: limitations and recent advances, Ann Biomed Eng, vol.32, issue.1, pp.160-165, 2004.

P. Mark, M. Kleinsorge, R. Gaebel, C. A. Lux, A. Toelk et al., Human Mesenchymal Stem Cells Display Reduced Expression of CD105 after Culture in Serum-Free Medium, Stem Cells Int, p.698076, 2013.

A. Mirza, J. M. Hyvelin, G. Y. Rochefort, P. Lermusiaux, D. Antier et al., Undifferentiated mesenchymal stem cells seeded on a vascular prosthesis contribute to the restoration of a physiologic vascular wall, J Vasc Surg, vol.47, issue.6, pp.1313-1334, 2008.

W. R. Otto and N. A. Wright, Mesenchymal stem cells: from experiment to clinic, Fibrogenesis Tissue Repair, vol.4, issue.20, 2011.

B. Ruster, S. Gottig, R. J. Ludwig, R. Bistrian, S. Muller et al., Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells, Blood, vol.108, issue.12, pp.3938-3982, 2006.

W. Li, G. Ren, Y. Huang, J. Su, Y. Han et al., Mesenchymal stem cells: a double-edged sword in regulating immune responses, Cell Death Differ, vol.19, issue.9, pp.1505-1518, 2012.

J. R. Munoz, B. R. Stoutenger, A. P. Robinson, J. L. Spees, and D. J. Prockop, Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice, Proc Natl Acad Sci, vol.102, issue.50, pp.18171-18177, 2005.

N. Kim and S. G. Cho, New strategies for overcoming limitations of mesenchymal stem cell-based immune modulation, Int J Stem Cells, vol.8, issue.1, pp.54-68, 2015.

H. J. Kim and J. S. Park, Usage of Human Mesenchymal Stem Cells in Cell-based Therapy: Advantages and Disadvantages, Dev Reprod, vol.21, issue.1, pp.1-10, 2017.

J. Beegle, K. Lakatos, S. Kalomoiris, H. Stewart, R. R. Isseroff et al., Hypoxic preconditioning of mesenchymal stromal cells induces metabolic changes, enhances survival, and promotes cell retention in vivo, Stem Cells, vol.33, issue.6, pp.1818-1846, 2015.

C. Toma, M. F. Pittenger, K. S. Cahill, B. J. Byrne, and P. D. Kessler, Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart, Circulation, vol.105, issue.1, pp.93-101, 2002.

A. Mohyeldin, T. Garzon-muvdi, and A. Quinones-hinojosa, Oxygen in stem cell biology: a critical component of the stem cell niche, Cell Stem Cell, vol.7, issue.2, pp.150-61, 2010.

X. Huang, L. Ding, K. L. Bennewith, R. T. Tong, S. M. Welford et al., Hypoxiainducible mir-210 regulates normoxic gene expression involved in tumor initiation, Mol Cell, vol.35, issue.6, pp.856-67, 2009.

A. He, Y. Jiang, G. C. Sun, Y. Li, J. Wang et al., The antiapoptotic effect of mesenchymal stem cell transplantation on ischemic myocardium is enhanced by anoxic preconditioning, Can J Cardiol, vol.25, issue.6, pp.353-361, 2009.

I. Rosova, M. Dao, B. Capoccia, D. Link, and J. A. Nolta, Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells, Stem Cells, vol.26, issue.8, pp.2173-82, 2008.

W. H. Huang, H. L. Chen, P. H. Huang, T. L. Yew, M. W. Lin et al., Hypoxic mesenchymal stem cells engraft and ameliorate limb ischaemia in allogeneic recipients, Cardiovasc Res, vol.101, issue.2, pp.266-76, 2014.

L. Leroux, B. Descamps, N. F. Tojais, B. Seguy, P. Oses et al., Hypoxia preconditioned mesenchymal stem cells improve vascular and skeletal muscle fiber regeneration after ischemia through a Wnt4-dependent pathway, Mol Ther, vol.18, issue.8, pp.1545-52, 2010.
URL : https://hal.archives-ouvertes.fr/inserm-00509086

H. Zhu, A. Sun, Y. Zou, and J. Ge, Inducible metabolic adaptation promotes mesenchymal stem cell therapy for ischemia: a hypoxia-induced and glycogen-based energy prestorage strategy, Arterioscler Thromb Vasc Biol, vol.34, issue.4, pp.870-876, 2014.

C. P. Chang, C. C. Chio, C. U. Cheong, C. M. Chao, B. C. Cheng et al., Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury, Clin Sci (Lond), vol.124, issue.3, pp.165-76, 2013.

I. Sandvig, I. Gadjanski, M. Vlaski-lafarge, L. Buzanska, D. Loncaric et al., Strategies to Enhance Implantation and Survival of Stem Cells After Their Injection in Ischemic Neural Tissue, Stem Cells Dev, vol.26, issue.8, pp.554-65, 2017.

F. Mohammadali, S. Abroun, and A. Atashi, Combined mild hypoxia and bone marrow mesenchymal stem cells improve expansion and HOXB4 gene expression of human cord blood CD34+ stem cells, Arch Biol Sci, vol.3, pp.433-474, 2018.

S. Varum, O. Momcilovic, C. Castro, A. Ben-yehudah, J. Ramalho-santos et al., Enhancement of human embryonic stem cell pluripotency through inhibition of the mitochondrial respiratory chain, Stem Cell Res, vol.3, issue.2-3, pp.142-56, 2009.

D. Loncaric, P. Duchez, and Z. Ivanovic, To harness stem cells by manipulation of energetic metabolism, Transfus Clin Biol, vol.24, issue.4, pp.468-71, 2017.

R. Das, H. Jahr, G. J. Van-osch, and E. Farrell, The role of hypoxia in bone marrow-derived mesenchymal stem cells: considerations for regenerative medicine approaches, Tissue Eng Part B Rev, vol.16, issue.2, pp.159-68, 2010.

C. C. Tsai, T. L. Yew, D. C. Yang, W. H. Huang, and S. C. Hung, Benefits of hypoxic culture on bone marrow multipotent stromal cells, Am J Blood Res, vol.2, issue.3, pp.148-59, 2012.

T. Ma, W. L. Grayson, M. Frohlich, and G. Vunjak-novakovic, Hypoxia and stem cell-based engineering of mesenchymal tissues, Biotechnol Prog, vol.25, issue.1, pp.32-42, 2009.

S. Djuranovic, A. Nahvi, and R. Green, miRNA-mediated gene silencing by translational repression followed by mRNA deadenylation and decay, Science, vol.336, issue.6078, pp.237-277, 2012.

S. Djuranovic, A. Nahvi, and R. Green, A parsimonious model for gene regulation by miRNAs, Science, vol.331, issue.6017, pp.550-553, 2011.

R. David, Small RNAs: miRNA machinery disposal, Nat Rev Mol Cell Biol, vol.14, issue.1, pp.4-5, 2013.

N. Li, B. Long, W. Han, S. Yuan, and K. Wang, microRNAs: important regulators of stem cells, Stem Cell Res Ther, vol.8, issue.1, p.110, 2017.

M. Ivan and X. Huang, miR-210: fine-tuning the hypoxic response, Adv Exp Med Biol, vol.772, pp.205-232, 2014.

N. Hosseinahli, M. Aghapour, P. Duijf, and B. Baradaran, Treating cancer with microRNA replacement therapy: A literature review, J Cell Physiol, vol.233, issue.8, pp.5574-88, 2018.

R. Rupaimoole, H. D. Han, G. Lopez-berestein, and A. K. Sood, MicroRNA therapeutics: principles, expectations, and challenges, Chin J Cancer, vol.30, issue.6, pp.368-70, 2011.

E. Van-rooij, A. L. Purcell, and A. A. Levin, Developing microRNA therapeutics, Circ Res, vol.110, issue.3, pp.496-507, 2012.

P. Fasanaro, D. 'alessandra, Y. , D. Stefano, V. Melchionna et al., MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3, J Biol Chem, vol.283, issue.23, pp.15878-83, 2008.

R. Hu, H. Li, W. Liu, L. Yang, Y. F. Tan et al., Targeting miRNAs in osteoblast differentiation and bone formation, Expert Opin Ther Targets, vol.14, issue.10, pp.1109-1129, 2010.

X. Huang, Q. T. Le, and A. J. Giaccia, MiR-210--micromanager of the hypoxia pathway, Trends Mol Med, vol.16, issue.5, pp.230-237, 2010.

W. Chang, C. Y. Lee, J. H. Park, M. S. Park, L. S. Maeng et al., Survival of hypoxic human mesenchymal stem cells is enhanced by a positive feedback loop involving miR-210 and hypoxia-inducible factor 1, J Vet Sci, vol.14, issue.1, pp.69-76, 2013.

R. I. Mccormick, C. Blick, J. Ragoussis, J. Schoedel, D. R. Mole et al., miR-210 is a target of hypoxia-inducible factors 1 and 2 in renal cancer, regulates ISCU and correlates with good prognosis, Br J Cancer, vol.108, issue.5, pp.1133-1175, 2013.

Z. Chen, Y. Li, H. Zhang, P. Huang, and R. Luthra, Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression, Oncogene, vol.29, issue.30, pp.4362-4370, 2010.

S. Y. Chan, Y. Y. Zhang, C. Hemann, C. E. Mahoney, J. L. Zweier et al., MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2, Cell Metab, vol.10, issue.4, pp.273-84, 2009.

Z. Zhang, H. Sun, H. Dai, R. M. Walsh, M. Imakura et al., MicroRNA miR-210 modulates cellular response to hypoxia through the MYC antagonist MNT, Cell Cycle, vol.8, issue.17, pp.2756-68, 2009.

H. W. Kim, H. K. Haider, S. Jiang, and M. Ashraf, Ischemic preconditioning augments survival of stem cells via miR-210 expression by targeting caspase-8-associated protein 2, J Biol Chem, vol.284, issue.48, pp.33161-33169, 2009.

L. B. Buravkova, E. R. Andreeva, V. Gogvadze, and B. Zhivotovsky, Mesenchymal stem cells and hypoxia: where are we? Mitochondrion, vol.19, pp.105-117, 2014.

M. Dominici, L. Blanc, K. Mueller, I. Slaper-cortenbach, I. Marini et al., Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement, Cytotherapy, vol.8, issue.4, pp.315-322, 2006.

. Brahimi-horn, P. J. Mc, and . Oxygen, FEBS Lett, vol.581, pp.3582-91, 2007.

G. L. Semenza, Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1, Biochem J, vol.405, issue.1, pp.1-9, 2007.

V. L. Dengler, M. Galbraith, and J. M. Espinosa, Transcriptional regulation by hypoxia inducible factors, Crit Rev Biochem Mol Biol, vol.49, issue.1, pp.1-15, 2014.

P. J. Ratcliffe, HIF-1 and HIF-2: working alone or together in hypoxia?, J Clin Invest, vol.117, issue.4, pp.862-867, 2007.

K. Tamama, H. Kawasaki, S. S. Kerpedjieva, J. Guan, R. K. Ganju et al., Differential roles of hypoxia inducible factor subunits in multipotential stromal cells under hypoxic condition, J Cell Biochem, vol.112, issue.3, pp.804-821, 2011.

T. Uchida, F. Rossignol, M. A. Matthay, R. Mounier, S. Couette et al., Prolonged hypoxia differentially regulates hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha expression in lung epithelial cells: implication of natural antisense HIF-1alpha, J Biol Chem, vol.279, issue.15, pp.14871-14879, 2004.

M. Y. Koh, R. Lemos, X. Liu, and G. Powis, The hypoxia-associated factor switches cells from HIF-1alpha-to HIF-2alpha-dependent signaling promoting stem cell characteristics, aggressive tumor growth and invasion, Cancer Res, vol.71, issue.11, pp.4015-4042, 2011.

M. Y. Koh and G. Powis, Passing the baton: the HIF switch, Trends Biochem Sci, vol.37, issue.9, pp.364-72, 2012.