2006 - UZ Leuven

VERMEULEN P., DICKENS S., VRANCKX J.J.: Expansion ofhematopoetic stem cells as a model for vascularized tissue constructs:the facts, the myths, the promises. J. Plast. Reconstr. & Aesth. Surg.,2006; 59: S5.In order to maintain bulk and function of tissue engineered constructs,vascular networks are essential for delivery of oxygen and nutrients.Different strategies are studied thus far to achieve this goal. 1) Theuse of angiogenic growth factors (VEGF, bFGF, PDGF, HGF,Angiopoietin) releasing polymers. These gels create a microenvironmentwhere cytokines promote the in situ formation of capillarbeds. 2) Prevascularization allows vascular ingrowth into an in vivoimplanted (biodegradable) matrix and seeding of cells of choiceafterwards. The peritoneal cavity is mostly used for this purpose. 3)Genetic modifcation of the in vivo environment or ex vivo expandedcells with an angiogenic growth factor. 4) Transplantation of“angiogenic stem cells” like endothelial progenitor cells (EPCs) orhematopoietic stem cells (HSCs) which can sprout from alreadyformed vessel walls (angiogenesis) or create tubular conduits withendothelial lining (vasculogenesis). Recent insights in the last decadehave shown that the biological behavior of bone marrow derivedendothelial progenitor cells (EPCs) and (HSCs) is complex andintertweened. These cells have the possibility to integrate intodamaged endothelium (smoking, atherosclerosis, trauma…) or createcollateral blood vessels in vivo. From their release out off the bonemarrow sinsoids to the final homing and differentiation, they undergo adynamic functional and morphological profiling. Culture of EPCsallows to expand and purify these CD34+/KDR+/AC133+ cells ex vivoand apply them to morphological defects, ischemic tissue or use themas cellular components for ex vivo tissue engineering. We present ourstrategy for understanding the behavior and integration of ex vivoexpanded EPCs in a pathological wound healing model. The coreelements of this strategy are 1) ex vivo expansion of EPCs ; 2)Tetracyclin regulated expression of VEGF165 by means of lipofectinmediated transfection; 3) establishment of a diabetic porcine fullthickness wound healing model.VRANCKX J.J., STEINSTRAESSER L., MOHAMMADI-TABRISI A.,JACOBSEN F., MITTLER D., LEHNHARDT M., LANGER S., STEINAUH.U., ERIKSSON E.: A novel titanium wound chamber for the study ofwound infections in pigs. Comp. Med., 2006; 56: 279-285.In the face of emerging multidrug-resistant microbes, reliable animalmodels are needed to study potential new therapies in infectedwounds. To this end, we implanted screw-top titanium chambers91