Abstract 14292: Toll-Like Receptor 2/6-Dependent Stimulation of Mesenchymal Stem Cells Promotes Angiogenesis in vitro and in vivo
Background: Toll-like receptors (TLR) play a crucial role in the recognition of exogenous as well as endogenous ligands in order to initiate inflammatory pathways of the immune defense. However, even regenerative aspects of TLR stimulation have been described. In this regard, we recently identified the TLR2/6 ligand MALP-2 as a potent inducer of angiogenesis. Since mesenchymal stem cells (MSCs) have been already successfully used for therapeutic angiogenesis and tissue regeneration we here investigated if MALP-2 may enhance the potential of MSCs to promote angiogenesis in vitro and in an experimental sheep model in vivo.
Methods and Results: Human MSCs from the iliac crest of healthy subjects were isolated, cultured and expanded in vitro and were shown to be positive for the mesenchymal stem cells markers CD73 and CD271 as well as for the MALP-2 receptors TLR2 and TLR6. MALP-2 stimulation did not induce proliferation or migration of MSCs. However, conditioned medium from MALP-2 stimulated MSCs significantly increased proliferation, migration and tube formation of endothelial cells as compared to conditioned medium from untreated cells. Analysis of the conditioned medium from MSCs revealed that MALP-2 stimulation enhanced the secretion of several chemokines and growth factors including the vascular endothelial growth factors (VEGF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Finally, MSCs were isolated from the iliac crest of black head sheep and co-cultivated with MALP-2 ex vivo. Autogenic implantation of these cells within a scaffold cylinder into the M. latissimus dorsi significantly enhanced the capillary density of these constructs after 6 month.
Conclusions: We here present first evidence that TLR2/6-dependent stimulation of MSCs promotes angiogenesis in vitro and in vivo offering novel therapeutic strategies for therapeutic angiogenesis and tissue regeneration.
- © 2012 by American Heart Association, Inc.