Biologically engineered blood vessels now an option in cardiac bypass

The first-ever human use of completely biologically engineered blood vessels grown from a person's own cells could be an option for people who have vessels too damaged for heart bypass, researchers reported at the American Heart Association's Scientific Sessions 2005.

"Sheet-based tissue engineering is an opportunity for patients to have an endless supply of vessels made from their own cells for bypass or revascularization surgeries," said Todd McAllister, Ph.D., co-author of the study and president and CEO of Cytograft Tissue Engineering in Novato, Calif.

Those mostly likely to need the tissue-engineered vessels are:
  • hemodialysis patients who require shunts between arteries and veins for access to blood filtering machines that remove wastes and excess fluids;
  • lower limb bypass patients, generally amputation candidates or diabetic patients; or
  • coronary bypass patients who do not have suitable vessels for harvest.

The coronary patients make up a particularly critical group in need of options, researchers said.

In 2002, Nicolas L'Heureux, Ph.D., McAllister and Cytograft's chief scientific officer and inventor of sheet-based tissue engineering, gave a presentation on tissue-engineered blood vessels at the American Heart Association's Scientific Sessions in Chicago.

"Back then, we demonstrated the durability and clot resistance of the vessels in different animal models," McAllister said. "Now, we're reporting for the first time our results in humans. We are presenting results on the first three of nine participants in a study looking at the use of engineered blood vessels in hemodialysis patients. The major finding is that during the first five months, no failures have been noted with these first three patients and the grafts are functioning well for hemodialysis access. This is the first completely biological tissue-engineered blood vessel that has been used in human adults."

The researchers studied hemodialysis patients because the consequences of vessel failure in the arm are far less dire than heart vessel failure. The findings, however, are promising for people who need heart bypasses but can't have them due to lack of suitable veins or arteries for grafting.

"This is a dramatic clinical situation because synthetic vascular grafts cannot be used for heart bypass," L'Heureux said. "The failure rate of synthetic grafts, which can be used in hemodialysis patients, is too high for coronary applications. Patients who require coronary bypass graft surgery typically have atherosclerotic plaque blocking blood flow in one or more coronary arteries. Surgical bypass involves rerouting blood flow around blockages to deliver nutrients and oxygen to the heart. Typically, saphenous (leg) veins or internal mammary arteries are harvested from the patient and grafted into the coronary circulation to restore blood flow to the heart. Right now, if there are no suitable autologous vessels, patients have no other option."

Sheet-based tissue engineering involves taking two cell types from a small skin and vein biopsy harvested from the back of the patient's hand. "Two cell types are extracted from the biopsies: fibroblasts (cells that gives rise to connective tissue) from the skin and endothelial cells from the inner lining of the vein," McAllister said. "We then use the fibroblasts to build the mechanical backbone of our tissue-engineered vessel and use endothelial cells to provide the lining. It's that lining that prevents the vessel from clotting."

The cells are fed in a culture dish with a proprietary media that encourages the growth of extracellular matrix proteins, such as collagen. During the next six to eight weeks, the cells produce high volumes of these proteins, he said.

"At the end of that period, you end up with a robust sheet that's comprised of cells and the proteins that those cells have produced," McAllister said. "The sheet can then be detached from the cell culture substrate and rolled, stacked or molded into more complex three-dimensional organs, such as a blood vessel. This process is unique in that it is the first technology to use fibroblast-based tissues to provide mechanical strength. Historically, cardiovascular tissue engineers have focused on the role of smooth muscle cells. This is also a novel approach in that it is the first demonstration of an engineered vessel that provides adequate mechanical strength without relying upon synthetic scaffolds or exogenous biomaterials."

The researchers noted patient management issues that need to be addressed, such as trying to identify patients several months in advance to allow time to harvest tissue and grow new vessels.

"The possibilities are far-reaching -- from building vessels to heart valves to planar (flat) tissue for other vascular repair," McAllister said. "There is also an exciting potential application for pediatric coronary repair because this is a living product and can grow with the patient. Another potential benefit of the approach is that coronary bypass patients could eliminate the injury and surgical complications associated with harvesting blood vessels from the legs."


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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