Blood Vessels Grown From Patient's Skin

Article: Blood Vessels Grown From Patient’s Skin
Author: Lawrence K. Altman
Found in: The New York Times
Published: October 9, 2007

Researchers at Cytograft Tissue Engineering of Novato, California have developed a six to nine month method of growing blood vessels – taken directly from a small section of the patient’s skin – in a laboratory with the intent of implanting them to restore blood flow around a patient’s damaged arteries and veins. This is the first time that blood vessels have been created solely from a patient’s own tissues and used to make skin grafts. This is such a huge accomplishment that the findings were published in the current issue of The New England Journal of Medicine.

Since the vessels are made from the patient’s own skin, there is no need for anti-rejection drugs, which are costly and require the patient to use them throughout his entire life to avoid long-term rejection. Furthermore, there is no risk of an inflammatory response because there are no synthetic materials or scaffolding in these vessels. Engineering these vessels is a huge feat since infection is the leading cause of graft failure (the second leading cause is shearing, where the pressure causes a graft to detach from the underlying tissue).

Doctors interested in pursuing this research project went to Argentina to conduct their studies because the medical costs are significantly lower than in America, and in Argentina, they didn’t have to deal with the strict regulations of the conservative Food and Drug Administration. Eight Argentinean patients, all of whom were receiving chronic kidney dialysis, were volunteers chosen for the study because their vessels were already worn out and because the dialysis shunts allowed for an easy way to monitor the functioning of the new vessels. On those brave eight patients, doctors performed the first human tests of the vessels. So far, none of these patients have suffered any major side effects, however, because the procedure is so new, the longest follow-up has only been for thirteen months. The long-term effects and possible
complications are not yet known, thus this procedure will not be in practiced as standard medicine for quite some time.

In the study in Argentina, surgeons cut an artery and a vein from the forearm and joined them in a link, also known as a shunt, which provided access for the repeated needle punctures required to connect the patient to a dialysis machine. These shunts can last a maximum of fifteen years, but when clots and infections develop inside the shunts that reduce or stop blood flow, new shunts must be created and installed immediately.

To obtain the skin necessary for the procedure, a fifteen-minute biopsy is all that is required. The patient is then put under local anesthesia while the surgeon removes a piece of skin, including a strip of a vein about an inch long from the back of the hand or the inner wrist. Technicians take that strip of skin and vein and use enzymes to extract fibroblast cells, the most common connective tissue found in humans and animals. These cells synthesize and maintain the extracellular matrix of tissues as well as provide the structural framework for many tissues, known as stroma. Additionally, fibroblasts play a critical roll in wound healing, which is incredibly important after a patient has undergone a skin graft procedure. In the actual graft, fibroblasts provide the mechanical backbone for the sheets that are later peeled and rolled into a tube. Technicians also extract endothelial cells from the inner lining of the vein. Endothelial cells line the interior surfaces of blood vessels, control the transit of white blood cells into and out of the bloodstream, and are involved in various processes such as angiogenesis (the formation of new blood vessels), atherosclerosis, and thrombosis (blood clotting). The fibroblast and endothelial cells are then grown by the millions as sheets in a laboratory. Under a microscope, this new vessel looks like a vein, but it has the strength of an artery, which is important because over time the body will be able to remodel the cells from a vein into a vessel with the elasticity of an artery.

A vascular surgeon in Buenos Aires, Dr. Sergio Garrido, implanted the Cytograft vessels in ether the forearm or the upper arm of the patient while he was under general anesthesia in surgery that took a little over an hour (the intravenous fluid line was inserted in another area from the malfunctioning shunt). The Cytograft vessel, only five and a half to eleven and three-quarters of an inch long, feels a little more delicate than a vein.

Cytograft reported that the vessels do have great potential for patients with damaged blood vessels due to diabetes, arteriosclerosis, and birth defects. Dr. Toshiharu Shinoka, director of pediatric cardiovascular surgery at Yale, plans to conduct studies with the new vessel because of its enormous potential in the vascular surgical field. In Japan, where Dr. Shinoka has previously practiced, the vessels were grown from cells on a scaffold that degraded and were absorbed in the body. He was also particularly enthusiastic about the new types of cells because they may prove to be beneficial for infants and children with congenital heart defects; the vessels will be able to grow with the child – since they have the elasticity of an artery – eliminating the problem of repeating skin graft procedures as the child grows. Dr. Shinoko and Cytograft have agreed to start these studies within the next two years.

Vessels in the arm would be much easier to repair in an emergency than vessels implanted deeper in the body. Researchers hope that these new vessels will allow them to save the toes and lower legs of people with poor blood circulation due to arteries damaged by diabetes or arteriosclerosis, as well as use these vessels to treat patients who need coronary bypass surgery.

Since the vessels are grown in a laboratory, there are limits to the length the vessel, meaning that multiple short segments of the vein have to be sewn together in order to create longer vessels. Researchers plan to make a two-foot long graft from four shorter ones for lower limb grafts. To test the lower limb grafts, Cytograft is currently searching for willing patients in Poland and Slovakia. Cytograft realizes that in order to make these procedures more widely-used they need to experiment on humans in the United States, and has applied to the Food and Drug Administration for approval to conduct studies of the vessels in the United States provided that at least ten patients in Poland and Slovakia are healthy six months after treatment.

Because these procedures are so new and experimental, the cost of treating one patient is an astonishing $15,000-$25,000. However, these prices are expected to drop if the procedures become more common, and hopefully Medicare and private insurance companies will agree to cover the procedure!