Pig Cells Lead the Way of Artificial Blood Vessel Engineering
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ATLANTA - Once only a dream, artificial blood vessels are on the way to becoming reality. But it is going to take possibly 10 to 20 years, and several hurdles must be overcome before patients reap the benefits, according to Laura Niklason, M.D., Ph.D., a pioneer in the field of blood vessel engineering.
Dr. Niklason is assistant professor for the departments of biomedical engineering and anesthesia at Duke University. She spoke today on the future of blood vessel engineering at an American Medical Association Science Reporters Conference in Atlanta.
"The field of tissue engineering has really gained momentum in the last 24 months with many new advances," she says. "Overall, the field is only about 10 years old. Even when I entered this field six years ago, when I told people I wanted to try and grow an artery in the laboratory, they laughed because it wasn't clear to anybody that such a thing would be possible."
Several patient populations are awaiting the development of artificial blood vessels. Many coronary artery bypass surgery patients with severe cardiovascular disease return to the hospital multiple times for bypass procedures. Surgeons use a segment of the patient's own artery or vein to create a bypass around the blockage. But sometimes, after one or more operations, there is no vein or artery to spare. Having an engineered artery would bring hope to these patients.
Also, many patients receiving hemodialysis have shunts -- vascular grafts that connect between an artery and vein. These are pierced several times a week with needles for dialysis. The shunts are prone to infection, scarring and clotting and close off for a wide variety of reasons. Some patients return to surgery every few months to have their dialysis access replaced. Artificial blood vessels would mean the world to them, according to Dr. Niklason.
Currently, Dr. Niklason is able to take a pig's blood vessel cells and grow new blood vessels from these cells that can be re-implanted in the pig and function successfully for four weeks. "It sounds like an easy process, but it's not," she explains.
"There are really two different kinds of cells we're concerning ourselves with - smooth muscle cells which are the cells that make up the wall of the blood vessel and make the protein-like collagen that gives it mechanical strength. And then there's the endothelial cell layer which is a single-layer of cells that lines the inner surface of the blood vessel. These cells function like Teflon in that they prevent blood from clotting in the vessel," she says.
The researchers have developed bioreactors consisting of a pulsatile pump, some filters, and other apparatus that gives them a way to pump fluid through the insides of the developing blood vessels and to pulse the growing blood vessels, which makes them thicker and stronger.
"In each of these bioreactors, we have secured a biodegradable scaffolding made of very thin fibers of a degradable polymer. If you looked at this scaffolding under a microscope, it would appear like scaffolding on the outside of a building. There are many empty spaces for cells to fill in. We attach the smooth muscle cells onto the scaffolding. The bioreactor is filled with a growth medium that nurtures these cells, helping them to grow and strengthen. Over a period of six to eight weeks, the cells replicate, filling in the spaces between the fibers to form a solid tissue. While that is happening, the fibers underneath the cells are degrading. At eight weeks, if you look at it with the naked eye, it looks like a blood vessel!
"After that, we inject the endothelial cells into the lumen of the blood vessel. These cells adhere to the blood vessel and form the inner lining that helps to discourage clotting. Before these blood vessels are put back in the pigs, we run a myriad of tests to determine the quality of the new blood vessels - do they contract and respond to pharmacologic stimuli? What kind of pressure can they withstand? What are their constituents?"
So far, the researchers have seen the blood vessels function well for up to two or three weeks. However, around the fourth week, clotting sometimes becomes a problem. And while the vessels are strong, the researchers would like them to be stronger. These are two challenges they are currently working on.
A natural question is: "What happens when you begin using human cells?" "It's one thing to deal with cells from healthy young pigs, but what happens when you use cells from 75-year-old end-stage, diabetic, hypertensive, atherosclerotic patients? How well can we coax these cells to grow and form a new blood vessel? We are studying this from several angles, right now," she says.
Part of making this technology viable will be the ability to store vessels once they are created, so a person could have a bank of vessels on reserve to use as needed. "Right now, we can store individual cells reliably for years. But right now, I can't store a complete engineered artery very well," she explains.
How long will it be before patients can count on small-caliber artificial vessels for their own use? Dr. Niklason says, "I'm telling everybody 10 to 20 years. I hope we can do it sooner. But 10-20 years is probably most realistic."