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BookmarkScienceDaily (Oct. 23, 2003) — ANN ARBOR, Mich. – Surgeons at the University of Michigan Health System report that they have been able to strip tiny blood vessels from rats and re-engineer them to be more effective when implanted in a new animal. The findings could benefit people who have already had vascular bypass surgery and need new blood vessels for subsequent procedures.
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Essentially, the researchers take these hair-width arterial grafts from a donor rat, remove all living cells from the rest of the tissue, insert vascular cells from the new host and then reimplant the graft. Using the host's own cells increases the likelihood of success by reducing the chance of rejection.
"Small blood vessels are needed all the time for grafts to use in heart bypass surgery, lower extremity bypasses and tissue transfer. The biggest problem is finding a source for these vessels. A typical source is some other blood vessel in the patient's body. To be able to have something that we can manufacture ahead of time or be able to take off the shelf, would be advantageous to many patients," says lead researcher David L. Brown, M.D., assistant professor in the Division of Plastic Surgery at the U-M Medical School.
Previous research has used similar techniques with larger blood vessels, like those used in cardiac bypass surgery. This is the first study to look at these very small blood vessels.
"You'd expect that the smaller the vessel is, the greater the chance that it would clot. But in our study, the blood vessels stayed open, despite being only 1 millimeter in diameter," says Gregory Borschel, M.D., a resident surgeon in the Division of Plastic Surgery at the U-M Medical School. Clotting becomes a problem when reattaching the vessels.
"Tissue engineered blood vessels may provide further options for patients who need vascular bypass procedures yet have no suitable donor vessels of their own," says Borschel, who will present his findings Wednesday, Oct. 22, at the American College of Surgeons 89th Annual Clinical Congress in Chicago.
Though Borschel and Brown are plastic surgeons, perhaps the widest applications for this technique are in cardiac surgery. For example, patients undergoing coronary artery bypass might benefit from tissue engineered donor vessels. For people receiving bypass surgery or a tissue transfer after an injury, surgeons often harvest blood vessels from the leg, sternum or arm. But taking tissue from these areas can cause problems in that location.
Donor tissue is not an option because the body would reject the foreign cells. The engineered tissue would be injected with the host's own cells, reducing the risk of rejection.
In this study, researchers harvested the iliac (groin) grafts from rats. They then stripped this tissue of its cells using a detergent solution. The acellular tissue was injected with endothelial cells from genetically identical rats before being grafted into the rat's femoral artery. A control group of rats received grafts of acellular tissue not re-engineered with the new rat's cells.
The resulting blood vessels were monitored every 48 hours and examined closely after four weeks and again at three months. At four weeks, eight of the nine recellularized grafts remained open and functioning, while three of the five acellularized control grafts had clotted. One group of recellularized grafts was viable at three months. The recellularized grafts also demonstrated structural characteristics similar to normal vessels.
"This is a very close collaboration between three areas: clinical, engineering and basic biology," says study co-author Robert G. Dennis, Ph.D., assistant professor of biomedical engineering at U-M.
Researchers are now looking at ways to use this technology. In one application, researchers have created a biochamber that contracts like a heart. The pressure stimulates the endothelial cells into the chamber, helping new cells to grow and take root.
U-M is applying for a patent for this technique and is in negotiations with a company that wishes to use the technology commercially. The study was funded by the Plastic Surgery Educational Foundation, the U.S. Department of Defense's Defense Advanced Research Projects Agency (DARPA), and the Ethel C. Coller Fellowship in the UMHS Department of Surgery.
In addition to Brown, Borschel and Dennis, study authors include U-M researchers Yen-Chih Huang, Douglas E. Dow, J.B. Lynch and William M. Kuzon.
