Desferrioxamine-driven upregulation of angiogenic factor expression by human bone marrow stromal cells

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 TGFbeta1 were similar in BMSCs, whether they were exposed to DFX (50 microM) 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-1alpha 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.