Researchers Prove it Possible to Grow Functional Arteries from Cells

A team of researchers has successfully "grown" functional arteries from animal cells by re-creating the nurturing environment native arteries experience.

The scientists, including vascular cell biologist Dr. Karen Hirschi from Baylor College of Medicine, found that when the engineered arteries were implanted back into the donor animals, they functioned much like the native arteries. The results of the research effort, led by Dr. Laura Niklason from Duke University and Dr. Robert Langer from MIT, were published in the April 16 issue of the journal Science.

The researchers began by removing endothelial cells and smooth muscle cells from blood vessels of an adult pig. After culturing, the smooth muscle cells were shaped around a biodegradable polymer to form vessels. The structure was then placed in an innovative "bioreactor" system, created by Dr. Niklason, that simulates fetal blood circulation.

"One of the novelties of this research was the fact that this graft was autologous [grown from the animal's own cells]," says Dr. Hirschi. "That was an advancement as well as the innovative technology used to create the grafts and institute a pulsatile flow in the bioreactor."

Inside the bioreactor, the vessels were "bathed" in a nutrient medium on the outside while a specific mix of nutrients, including vitamin C and copper, was pumped through the developing vessels, similar to the way the heart circulates blood through the body. Dr. Hirschi, who studies the role of nutrients in controlling blood vessel cell differentiation and growth at the USDA's Children's Nutrition Research Center, played a role in determining which nutrients would maximize the strength of the vessels.

"Vitamin C and copper are two nutrients that are required for the production of extracellular matrix in blood vessel cells," says Dr. Hirschi. "The matrix is like a glue that holds all the cells together and keeps them strong and in a formed structure. By providing the nutrients, which enhance the formation of this matrix, it makes the blood vessel stronger and able to be sewn into the animal and withstand the blood flow inside the body."

The polymer scaffolding dissolved over an eight-to-10-week period, leaving a tube of vascular smooth muscle cells. The endothelial cells were then added to the inside of the tube and several days later, the arteries were ready for implantation back into the donor pigs where they remained for four weeks.

"Four weeks is considered to be a short-term implantation relative to the whole lifespan of the animal, but it was long enough for us to see how the vessel graft adapted," says Dr. Hirschi.

When the vessels were implanted, the researchers observed that their creations in fact were as strong as native vessels. The implanted vessels also held surgical sutures without tearing and responded to drugs similar to how the native vessels would.

Much more research is needed to determine when this type of tissue engineering can be done in a clinical setting. If it is possible, this technique could be used to treat patients with cardiovascular or peripheral vascular disease.

"Our hope is to be able to create blood vessel grafts from a patient's own cells that could be implanted back into the patient to bypass diseased vessels," says Dr. Hirschi. "There's no way we can predict when that would be an option right now. We really need to learn a whole lot about culturing the human cells and creating the human grafts first."

Some obstacles face the researchers when considering engineered arteries in humans.

"We need to understand how the grafts behave over a longer term implantation and we also need to learn how to culture cells from human blood vessels," says Dr. Hirschi.

The researchers are now working on optimizing the conditions under which the cells are exposed in the bioreactor.

Other researchers involved in the project were: Dr. Jinming Gao, Case Western Reserve University in Cleveland; Dr. William Abbott and Dr. Stuart Houser, Massachusetts General Hospital in Boston; and Dr. Robert Marini from MIT. The research was funded by grants from the National Institutes of Health and the Foundation for Anesthesia Education and Research.

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©2006 Texas Medical Center

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