It had long been known that endothelial cells (thin, flat cells that form the interior layer of the entire circulatory system, from the heart to the tiniest capillaries) accumulate inside prosthetic arteries, where they play a crucial role in the healing process. Microfilaments in the endothelial layer, in both natural and artificial arteries, help the vessels withstand the shear stress of blood flow.
Surgeons prefer to use a segment of vein taken from elsewhere in a patient’s body when it is necessary to create a detour around a natural artery that has become clogged with plaque. When a natural vein is not available, vessels made of synthetic fabric are used as substitute grafts. Dr. Lester R. Sauvage, founder of the Hope Heart Institute in Seattle, was a pioneer in the development of artificial vessels. The Sauvage graft, made of Dacron and patented in 1971, is still widely used in cardiovascular surgery.
Like most other researchers, Sauvage assumed that the grafts worked because the porosity of the knitted polyester fabric allowed endothelial cells to migrate easily from adjacent tissues. The "through-wall" theory was the most widely accepted explanation of the healing mechanism. The "pannus" (for flap) theory held that the cells moved into the graft from the two ends of the natural blood vessel into which it had been placed.
In the early 1990s, Hope Institute scientists Qun Shi and Moses Hong-De Wu began to look more carefully at the source of the cells. In one experiment, they covered the outer surface of artificial arteries with silicone rubber, which endothelial cells could not penetrate. The arteries were then implanted in animals. If there were no cells in the arteries after removal, it would prove that the source was outside the grafts.
But the protective cells did show up inside the rubberized arteries. That set off what medical writer Warren King called "a cellular detective hunt." Dr. Arlene Wechezak, director of cell biology at the Hope, directed the first part of the search. As King explained it: "Endothelial cells bound to plastic were exposed to flowing laboratory nutrients -- mimicking blood flow. The cells not only divided, but the new cells moved downstream and stuck to new parts of the plastic" (The Seattle Times). The researchers concluded that similar mechanics were at work in the Dacron arteries.
In an article published in the May 1995 issue of the Journal of Vascular Surgery, Wu and Shi and their colleagues at the Hope announced that they had found "definitive proof" that the cells came from the bloodstream, and not from either the surrounding tissues or from the ends of the graft. A long graft that had been implanted in the upper thigh of a 65-year-old patient had had to be removed after 26 months because of an accumulation of fluid around the graft. Examining the graft, the researchers found endothelial cells in areas far removed from natural vessels.
Dr. William P. Hammond, associate medical director of the Hope, and scientists at the Fred Hutchinson Cancer Research Center in Seattle speculated that the bone marrow, which produces other blood cells, could also be the source of the endothelial cells. Hutchinson scientists Rainer Storb and Cong Yu performed an experiment that tested the theory. Bone marrow from one dog was transplanted into another and identified by DNA typing. Eight months later, a Dacron graft (treated with silicone to make it impervious) was implanted into one dog. When the graft was removed, the scientists found that is contained endothelial cells from both animals.
"We had been talking about it for 33 years, saying they were coming through the wall," said Sauvage. "But we proved ourselves wrong, and that was a great accomplishment" (The Seattle Times).