Research Group
- Dr. Jeffrey Schechner, Principal Investigator
- Prof. Jordan Pober, Co-Investigator
Location
- Yale University School of Medicine, New Haven, USA
Title
- Vascularization of Engineered Human Skin Equivalents
One solution to address the shortage of organs available for transplantation is to engineer synthetic living tissues. The most widely used example of such a strategy is living skin equivalents. Unfortunately, the available products do not contain blood vessels and, probably due to a resultant inadequate delivery of oxygen and nutrients, have not performed well. To overcome this deficiency, we have developed a methodology for perfusing human skin equivalents through blood vessels formed from cultured endothelial cells (the cells that normally line blood vessels). In the proposed studies, we will first optimize the formation of blood vessels in the grafts by evaluating the benefit of adding various growth supplements prior to implantation. Then, endothelial cells will be genetically altered to overexpress the gene Bcl-2, a modification that we have previously shown to improve the formation of mature blood vessels. We will also examine the relative performance of blood vessels formed with endothelial cells derived from different sources, such as skin, blood and umbilical veins, after transplantation into immunodeficient mice. This determination of optimal vessel function will include a comparison with vessels in similarly transplanted human skin grafts using the parameters of two- and three-dimensional structure and density, presence of surface marker characteristics typical of arteries, veins and capillaries, and permeability. In addition, potential adverse effects of vascularizing grafts, such as inducing immunologic rejection and the formation of vascular tumors as a result of genetically altered endothelial cells, will be evaluated. Finally, the benefit of these modifications on overall graft performance will be determined by assessing graft take, blood flow, and retention of an intact barrier, a critical function of skin. If the hypothesis that vascularizing skin equivalents enhances their performance is correct, these studies will provide a strategy for improving the clinical utility of skin equivalents and other bioengineered tissues.