Anales RANF

S4-02 ENHANCED OSTEOGENESIS AND ANGIOGENESIS FOR PUTATIVE BONE GRAFTS BY ACTIVATING PURINERGIC RECEPTOR SIGNALING DURING MESENCHYMAL STEM CELL DIFFERENTIATION Edda Tobiasch, Vanessa Bröker, Sarah Shoushrah, Margit Schulze Bonn-Rhine-Sieg University of Applied Sciences, Rheinbach, Germany Critical size bone defects are an incapacitating clinical condition which remains a challenge in reconstructive orthopedic surgery. Bone restoration is of growing interest due to an increasing number of elderly, which might need reconstruction after tumor surgery. But the need for bone replacement also concerns the young after traffic or sports accident. Since the sources for autografts are limited and their access is associated with infection risks and donor site morbidity, much hope is placed in tissue engineering strategies using stem cells. Next to scaffolds which should provide substrate for cell growth and mechanical integrity, bioactive molecules are needed to induce or enhance differentiation of these cells. One approach which is following this strategy is using mesenchymal stem cells and artificial ligands for purinergic receptors. Human mesenchymal stem cells (MSCs) were isolated from liposuction material after plastic surgery. Their stem cell character was confirmed by specific stains after three lineage differentiations and the validation of a defined set of positive and negative markers. The purinergic (P) receptors pattern before and after differentiation of MSCs towards osteoblast, endothelial and smooth muscle cells was unraveled. Several P2 receptor subtypes were altered during the maturation of MSCs towards the respective cell types. These alterations are functional and artificial ligands of the individual receptors can influence the differentiation process. In detail, expression level regulation of P2Y4 and P2Y14 seems to influence the onset of osteogenesis at the branching point to adipogenesis. Administration of a selective P2X7 antagonist led to enhanced matrix mineralization, confirming the role of P2X7 during late osteogenesis. Some specific P2 receptors such as P2Y1 also play a significant role in angiogenesis. Since vessel formation is a prerequisite for a successful treatment of critical size bone defects, artificial P2 receptor ligands are promising bioactive molecules for functionalized scaffolds with MScs in future bone tissue engineering.