A purely biological spare part
For the first time it has been possible to create a blood vessel entirely from human cells. No synthetic scaffolds were required for the mold. Such replacement blood vessels could be used for patients requiring bypass surgery. "The blood vessel performs, looks and feels the same functions as real tissue," said Nicolas L'Heureux, a research associate at the University of California, San Diego School of Engineering (UC San Diego). The investigations were carried out at the Laboratoire d'Organogenese Experimentale (LOEX) at the Laval University School of Medicine in Quebec by L'Heureux, Lucie Germain, Raymond Labbe and Francois Auger. Although researchers have tried to create fully biological blood vessels in the past, their work failed because the engineered blood vessels were too weak to withstand the blood pressure in the body and would rupture once implanted. The Canadian researchers made a blood vessel from human cells and implanted it in a dog for a week. The graft proved strong enough and allowed blood to flow through it. The studies showed that the all-natural tissue was tough enough to withstand nearly 20 times normal human blood pressure (Magazine of the Federation of American Societies for Experimental Biology January 1998).
"We believe this represents a fundamental breakthrough that could lead to the engineering of a variety of tissues," said John Frangos, professor of bioengineering at UC San Diego.
Currently, most engineered tissues for skin, blood vessels and cartilage are built on scaffolds made from synthetic materials or animal products. This extracellular matrix gives shape and form to tissue. Human cells such as fibroblasts and muscle cells are placed in the artificial casing. Finally, the human cells grow into the biodegradable artificial material and cover it with extracellular matrix proteins.
Tissue made entirely from the patient's own cells offers some key advantages. "We avoid immune responses that lead to complete rejection, and we reduce the risk of the body responding to the transplant with chronic inflammation that leads to scar tissue formation," said L'Heureux. "As a result, we may one day be able to create smaller functional vascular grafts that more closely match natural blood vessel diameters, thereby improving blood flow behavior within the vessel."
Bypass surgery involves replacing the blocked section of the artery with a graft from another artery or a vein in the patient's leg. However, this technique has certain disadvantages. A vein graft, in order to do the work of an artery, must grow additional muscle, which can eventually clog the graft. As a result, patients often require repeat bypass surgery, and in many cases the patient does not have enough he althy tissue for further grafts. In addition, atherosclerosis can clog peripheral blood vessels, such as the blood vessels in major arteries in the legs. In all of these cases, engineered vascular grafts could be used.
The key to the engineering of fully biological tissue is the design of the bioreactor. The LOEX technique works by harvesting fibroblasts from the recipient's skin and smooth muscle cells from a near-surface vein. These cellular building blocks create collagen and other proteins that intertwine to form a strong and flexible cloth-like matrix. The "cloth" is then wrapped around a tube to give it the shape of a blood vessel. The tube is placed in a bioreactor, where a nutrient fluid made of amino acids and vitamins flows through and around the tubes. Temperature, pH, atmosphere and nutrient mix are carefully controlled. Finally, endothelial cells that make up the blood vessel wall are incorporated into the protein matrix and the tube is removed.
"The biochemical and mechanical environment can affect gene expression and fundamentally alter cell behavior," said L'Heureux. "Through the bioreactor, we mimic the body environment and transform the skin cells into blood vessel cells."
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