JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE RESEARCH ARTICLE J Tissue Eng Regen Med 2008; 2: 272–278. Published online 30 May 2008 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/term.92 Desferrioxamine-driven upregulation of angiogenic factor expression by human bone marrow stromal cells Esther Potier 1 * , Elisabeth Ferreira 1 , Sylviane Dennler 2 , Alain Mauviel 2 , Karim Oudina 1 , Delphine Logeart-Avramoglou 1 and Herv´ e Petite 1 1 Universit´ e Denis Diderot Paris VII, Laboratoire de Recherches Orthop´ ediques (B2OA), UMR CNRS 7052, Paris, France 2 Universit´ e Denis Diderot Paris VII, INSERM U697, Paris, France Abstract Bone marrow stromal cells (BMSCs) are the subject of intense research because of their biological properties and potential use for the repair of damaged tissues. Success of BMSC-based therapies, however, relies on a number of methodological improvements, including the establishment of a vascular network providing nutrients and oxygen to the transplanted cells and ensuring their immediate survival and long-term functionality. We described a method to enhance the autocrine expression of angiogenic factors by BMSCs. For this purpose, human BMSCs were treated with desferrioxamine (DFX). No PDGF-BB, VEGF-R1 or -R2 mRNA expression was detected under any of the conditions tested. mRNA and protein expression levels of TGFβ 1 were similar in BMSCs, whether they were exposed to DFX (50 μM) or to control conditions under normoxia for 48 h. In comparison with the results obtained with control conditions under normoxia, exposure of BMSCs to DFX for 48 h resulted in upregulation of bFGF at the protein (26-fold) but not at the mRNA levels and VEGF at both the mRNA (1.5-fold) and protein levels (4.5-fold). In comparison with the results obtained with control conditions under hypoxia, DFX induced a 50% increase in VEGF secretion but led to the same level of hypoxia inducible factor-1α protein expression (a transduction factor involved in angiogenic factor expression and known to be activated by DFX). Exposure of BMSCs to DFX resulted in oversecretion of angiogenic factors, suggesting that DFX-treated BMSCs could be used to supply angiogenic factors. Copyright  2008 John Wiley & Sons, Ltd. Received 15 October 2007; Revised 20 March 2008; Accepted 3 April 2008 Keywords bone marrow stromal cells; desferrioxamine; angiogenic factors; HIF-1; hypoxia, VEGF 1. Introduction The possibility of isolating and expanding autologous bone marrow stromal cells (BMSCs) and driving them towards the osteogenic (Friedenstein et al., 1968; Pit- tenger et al., 1999; Prockop, 1997), neural (Sanchez- Ramos et al., 2000; Woodbury et al., 2000) or cardiomy- ocytic (Toma et al., 2002) phenotypes presents a high potential for numerous applications of cell therapy (Bang et al., 2005; Quarto et al., 2001; Shyu et al., 2006; Tomita *Correspondence to: Esther Potier, Laboratoire de Recherches Orthop´ ediques (B2OA), UMR CNRS 7052, Facult´ e de M´ edecine Lariboisi` ere-Saint-Louis, 10 Avenue de Verdun, 75010 Paris, France. E-mail: esther.potier@gmail.com et al., 1999). However, when transplanted in vivo, either as cell suspension after tissue ischaemia to restore cardiac (Dai et al., 2005; Jiang et al., 2006; Toma et al., 2002) or cerebral (Bang et al., 2005; Zhao et al., 2002) function, or in association with a scaffold for repairing large bone defects (Bruder et al., 1998; Cancedda et al., 2003; Petite et al., 2000), BMSCs undergo oxygen and nutrient depri- vation due to the disruption of the host vascular system and/or the lack of pre-existing vascular networks within scaffolds. This initial absence of vascular networks, affect- ing BMSC survival and functionality, constitutes one of the main limitations of cell therapy and calls for the develop- ment of strategies promoting a rapid (re)vascularization. In the present study, a method that has the potential to stimulate the expression of angiogenic factors by BMSCs Copyright  2008 John Wiley & Sons, Ltd.