This proposal describes a five-year training program for the development of an academic career in vascular tissue engineering. The principal investigator is an accomplished vascular surgeon who has begun a basic science effort centered around the creation of a small-caliber vascular graft. Now, through a unique integration of interdepartmental resources, the principal investigator will expand his scientific skills to yield translational research. The program focuses on the creation and in vivo testing of a novel vascular graft. Irving Shapiro, PhD, Director of Jefferson's Cell and Tissue Engineering Program, will sponsor the principal investigator's scientific development along with Thomas Tulenko, PhD, Director of Jefferson's Cardiovascular Biology Research Program. Dr. Shapiro is a leader in the field of bone and cartilage tissue engineering, while Dr. Tulenko's expertise resides in vascular cell biology and cardiovascular disease. Both have extensive experience in training postdoctoral fellows and graduate students. To enhance the program, the investigator will work with Christopher Adams, PhD, an expert in electron and laser confocal microscopic analysis of tissue-engineered constructs;James San Antonio, PhD, an authority in endothelial cell-matrix interactions;and Yi Shi, MD, PhD, an expert in vascular graft remodeling. Keith Danielson, PhD, and Ronald Weigel, MD, PhD, scientists in stem cell engineering and cancer biology, respectively, will further advise and direct the investigator's educational program. The scientific goal of the project is to construct and test a novel small-caliber vascular bypass graft, created by seeding a natural vascular tissue scaffold (decellularized cadaver vein) with autologous microvessel endothelial cells derived from adipose tissue.
The specific aims i nclude determining: 1) the optimal scaffold design and media conditions for endothelial cell seeding, 2) the optimal paradigm for graft creation, and 3) the durability and healing characteristics of the seeded graft in vivo. Resources from the Jefferson's Cell and Tissue Engineering and Cardiovascular Research Laboratories provide the ideal setting for training physician-scientists in the field of vascular tissue engineering. This environment maximizes the potential for the principal investigator to achieve independence in a field with translational applicability.
|McIlhenny, Stephen; Zhang, Ping; Tulenko, Thomas et al. (2015) eNOS transfection of adipose-derived stem cells yields bioactive nitric oxide production and improved results in vascular tissue engineering. J Tissue Eng Regen Med 9:1277-85|
|Zhang, Ping; Moudgill, Neil; Hager, Eric et al. (2011) Endothelial differentiation of adipose-derived stem cells from elderly patients with cardiovascular disease. Stem Cells Dev 20:977-88|
|Abdollahi, Hamid; Harris, Lisa J; Zhang, Ping et al. (2011) The role of hypoxia in stem cell differentiation and therapeutics. J Surg Res 165:112-7|
|Harris, Lisa J; Abdollahi, Hamid; Zhang, Ping et al. (2011) Differentiation of adult stem cells into smooth muscle for vascular tissue engineering. J Surg Res 168:306-14|
|McIlhenny, Stephen E; Hager, Eric S; Grabo, Daniel J et al. (2010) Linear shear conditioning improves vascular graft retention of adipose-derived stem cells by upregulation of the alpha5beta1 integrin. Tissue Eng Part A 16:245-55|
|Harris, Lisa J; Zhang, Ping; Abdollahi, Hamid et al. (2010) Availability of adipose-derived stem cells in patients undergoing vascularýýsurgical procedures. J Surg Res 163:e105-12|
|Fischer, Lauren J; McIlhenny, Stephen; Tulenko, Thomas et al. (2009) Endothelial differentiation of adipose-derived stem cells: effects of endothelial cell growth supplement and shear force. J Surg Res 152:157-66|
|Zhang, Ping; Baxter, Jason; Vinod, Kateki et al. (2009) Endothelial differentiation of amniotic fluid-derived stem cells: synergism of biochemical and shear force stimuli. Stem Cells Dev 18:1299-308|
|DiMuzio, Paul; Tulenko, Thomas (2007) Tissue engineering applications to vascular bypass graft development: the use of adipose-derived stem cells. J Vasc Surg 45 Suppl A:A99-103|