TORONTO, June 15 - University of Pittsburgh School of Medicine investigators have engineered artificial blood vessels from muscle-derived stem cells (MDSCs) and a biodegradable polymer that exhibit extensive remodeling and remain free of blockages when grafted into rats. The results of their study, which is being presented at the Tissue Engineering and Regenerative Medicine International Society (TERMIS) North America Chapter meeting being held June 13 to 16 at the Westin Harbor Castle conference center in Toronto, has potentially significant implications for the treatment of heart and kidney diseases, where there is a critical need for new sources of blood vessels for vascular grafts.
The saphenous vein taken from a patient's leg continues to be the most commonly used graft for coronary artery bypass grafting even though a significant percentage of vein grafts eventually fail. Arterial grafts are the preferred conduits because they are less prone to becoming obstructed. However, they are in very limited supply, as many patients require multiple grafts. Thus, there is an ongoing search for the ideal small-caliber arterial substitute for revascularization procedures.
The University of Pittsburgh team, led by David A. Vorp, Ph.D., associate professor of surgery and bioengineering and a faculty member of the McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, developed its vascular graft by "bulk seeding," or spraying, MDSCs inside a biodegradable porous, tubular polyester urethane scaffold using a rotational vacuum seeding device.
After culturing their vascular constructs for seven days, the investigators then implanted them in the abdominal aortas of rats eight weeks before performing tests to determine how well the grafts had performed. The cell-seeded constructs showed a significantly higher blockage-free rate than unseeded controls (55 percent versus 0 percent). In addition, at eight weeks, there was an extensive remodeling of the MDSC-seeded polymer by surrounding tissue, exhibiting tissue formation that is consistent with a mature artery.
According to Dr. Vorp, these findings in a rat demonstrate the feasibility of developing MDSC-seeded tissue-engineered vascular grafts for eventual human application. "The next step is to demonstrate the use of the tissue-engineered blood vessel in a larger animal model, such as a pig, which has a coagulation system more similar to that in humans. The advantage of our approach is that the graft could utilize the patient's own stem cells and be ready for implantation almost immediately or, at most, after a relatively short culture period. This suggests that we could make these available 'off-the-shelf,' which is an essential element for clinical translation," he explained.
In addition to Dr. Vorp, others involved in this research include Alejandro Nieponice, M.D., Lorenzo Soletti, Timothy M. Maul, Burhan Gharaibeh, Ph.D., Bridget M. Deasy, Ph.D., Jianjun Guan, Ph.D., Johnny Huard, Ph.D., and William R. Wagner, Ph.D., all at the University of Pittsburgh, departments of surgery, bioengineering and orthopedic surgery.
Note to Editors: The full abstract for this study can be found at www.regenerate-nline.com/abstracts/1172.pdf.