PI David A. Vorp

Co-PI William Wagner and J. Peter Rubin

Title Autologous Stem Cell-Based Tissue Engineered Vascular Grafts

Summary: There are nearly one million aortocoronary bypass, peripheral arterial bypass and arterio-venous access graft procedures performed each year in the US. The limitations of current options, which include fully-synthetic grafts and autologous vein or artery, are well-documented3-5. Readily-available, biocompatible, tissue engineered vascular grafts (TEVGs) have great potential as suitable alternatives. However, to date, only a small number of TEVG approaches have been attempted clinically due to a number of barriers. Our laboratory has developed TEVGs constructed from a novel biodegradable elastomeric scaffold seeded with rat or human adult mesenchymal stem cells (MSCs). While we have demonstrated effectiveness with MSCs from bone marrow and muscle, this exploratory proposal will focus on use of human adult adipose derived stem cells (ADSCs), given their relative ease of isolation and the availability of fat in the patient population in need.

Our approach in this proposal will consist of our novel methodology to create TEVGs by rapidly and efficiently bulk-seeding a biomimetic scaffold with adult human ADSCs. The TEVGs will be tested in a cost-effective, reliable and hardy rat model which is not immune compromised or immunosuppressed, but yet does not exhibit marked immunological response to xenotransplanted tissue or cells.

In summary, the significance of this work is the identification of what factors affect the successful performance of a human stem cell based TEVG, which would move this technology significantly closer to clinical translation. The primary innovation in this proposal lies in three areas: our unique method of creating a TEVG; the use of a rich and easily obtained source of autologous ADSCs; and the recognition that either too
few ADSCs may be available from a given patient, or that patient age and/or sex may be confounding factors, either of which will affect clinical translation of an ADSC-based TEVG. No other study, to our knowledge, has addressed these critical issues of clinical practicality in the development of a human, stem cell-based TEVG.

Source: Department of Health and Human Services
National Institutes of Health (R21)
National Institute of Biomedical Imaging and Bioengineering

Term Budget Period: 01/15/2013 – 12/31/2013
Project Period: 01/15/2013 – 12/31/2014

Amount Year 01      Year 02      TOTAL
TOTAL $190,625    $229,875    $420,500