Therapeutic Peptides for Cardiovascular Disease and Cancer Cam Patterson, MD, MBA, FACC, FAHA Ernest and Hazel Craige Distinguished Professor of Cardiovascular Medicine Chief, Division of Cardiology Director, Carolina Cardiovascular Biology Center University of North Carolina at Chapel Hill Anka N. Veleva, PhD, MA Department of Chemical and Biomolecular Engineering North Carolina State University Stuart L. Cooper, PhD Department of Chemical and Biomolecular Engineering Ohio State University

Endothelial Progenitor Cells (EPC) from Biology to Treatment □ □ In 1997, EPC were first identified in adult human peripheral blood □ □ EPC are immature cells capable of differentiating into mature endothelial cells □ □ EPC can play an important role in the formation of new blood vessels - mobilization from the bone marrow - migration through the circulation - incorporation into blood vessels □ □ Clinically, the number and function of EPC have been positively linked with improved endothelial function and regeneration Rosenzweig A., NEJM, 348, 581 (2003).

Phage Display Technology to Identify Peptides Specific for Endothelial Progenitor Cells Veleva A. et al., Biotechnology and Bioengineering, 98, 306 (2007).

Peptides Immobilized on a Biomaterial Scaffold to Improve Cyto- and Blood- compatibility of Implants Veleva A. et al., Biomaterials, 29, 3656 (2008). □ Stimulating endothelialization at the implant surface will restore vascular homeostasis early in the healing process

New Functional Tools to Target Tumor Vasculature □ □ Tumor angiogenesis has a critical role in promoting the growth of most carcinomas □ □ EPC play an important role in angiogenesis-mediated tumor progression □ □ To utilize endogenous EPC as natural vectors to deliver diagnostic and therapeutic reagents to tumors

Market Potential □ □ Regenerative Medicine - cell separations - production of pure cell populations for allogeneic stem cell therapies □ □ Medical Implant Technologies to treat cardiovascular diseases, “off-the-shelf” products - innovative intravascular stent systems - small diameter vascular grafts - pacemakers - heart valve repair - arterial septal repair implants □ □ Oncology - targeting of tumor-associated blood vessels - non-invasive detection of small cancer tissue, primary tumors & metastases - targeted therapeutics, development of highly specific drug delivery systems - personalized medicine, monitoring efficacy of therapies