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06.11>>Blood Vessels of the Future
Blood Vessels of the Future    
 

Did you know that the average adult body contains about five liters of blood? [Can you convert that to pints and quarts?] All of that blood travels from place to place in the body through an intricate series of blood vessels, of all different sizes: arteries transport blood from the heart to the rest of the body and veins bring blood from the rest of the body back to the heart. As you might imagine, in such a complex system, there is a lot that can go wrong. For example, in coronary heart disease, the blood vessels that supply blood to the heart itself may become constricted or blocked. If this condition persists, it can lead to heart attack and potential death. To open up blocked blood vessels, patients have heart surgery where new blood vessels are added to bypass the blocked or diseased ones. This surgery is called cardiac artery bypass surgery or CABG.

One Instead of Two

Generally the new blood vessels are taken from the patient's own body, typically veins found in the leg. This means that patients undergoing CABG actually undergo two separate procedures—first to find and remove a suitable vein in the leg, then to insert it into the heart—which increases time in the operating room as well as the time it takes to recover. Furthermore, there are some patients for whom surgery is not an option simply because they don't have suitable veins, or they have already had them removed for previous surgeries. New research, however, has now shown that it is possible to bioengineer blood vessels from human cells, which means that someday CABG could be performed with just one operation—on the heart.

The research that led to this most recent breakthrough began over two decades ago and has involved researchers and clinicians from a range of disciplines. Dr. Shannon Dahl, Senior Director of Scientific Operations and Co-Founder of the bioengineering company Humacyte, began working to create blood vessels from animal tissues as a graduate student with Dr. Laura Niklason at Duke University. In 1999 Dr. Niklason showed it was possible to use cow and pig cells to create cow and pig blood vessels. During her time as a graduate student, Dr. Dahl worked with Dr. Niklason to refine these techniques and to characterize the blood vessels made in the laboratory. Once Dr. Dahl received her PhD, she, Dr. Niklason, and another colleague—Juliana Blum—started a company called Humacyte, where Dr. Dahl and her team of researchers continue their work on bioengineered blood vessels.

How It Works

"The entire process," explains Dr. Dahl, "begins with a real human blood vessel and a plastic tube." The plastic tube is made of a polymer called polyglycolic acid, which provides the shape for the future bioengineered blood vessel. Cells are removed from the human blood vessel, and are grown in culture. This process of growing cells yields enough cells to create 74 bioengineered blood vessels. Cells are used to coat the polymer vessel, and the cell-coated tubes are then incubated for eight to ten weeks during which time the cells grow and secrete structural proteins such as collagen onto the tube and the polymer itself actually degrades. By the end of the eight week period, the researchers are left with a tube made only of human cells and tissues. Finally, the tube is washed with a type of detergent that kills and removes the cells, leaving only the structural proteins behind.

Because all of the cells are washed away, the immune system is not stimulated, so this tube can then be used instead of a patient's own blood vessel. "These blood vessels can be stored in hospital refrigerators for six to twelve months,' remarks Dr. Alan Kypson, a cardiac surgeon and one of Dr. Dahl's collaborators who has worked with the new technology. This means that they would be readily available for doctors to use when patients need them.

Test, Test, Test


Video courtesy of Humacyte, Inc.

Dr. Dahl and her collaborators performed many tests on the bioengineered blood vessels to make sure they could withstand the stressful environment they would be exposed to inside a living organism. Dr. Dahl worked with many doctors and surgeons like Dr. Kypson to develop criteria for what would be an appropriate strength for a bioengineered blood vessel. In one test, the researchers compared the strength of the engineered blood vessels to that of biological human arteries and veins. To do this, they put a piece of suture through the vessel tissue and measured how much weight the suture could hold before ripping. The researchers found the bioengineered blood vessels were able to hold as much weight as the biological vessels tested. In another test, flowing liquid was put through the blood vessels to simulate blood flow. The blood vessels were inflated to see how much pressure they could withstand before they burst. In this case, the researchers found that the bioengineered blood vessels could withstand pressures at least as high as biological arteries or veins. The researchers tested the bioengineered blood vessels again after 12 months and found their strength was still comparable to the biological vessels.

The integrity of bioengineered blood vessels has already been established through implantation in healthy animal models.

From the Lab to Patients

The next step, which Humacyte is currently exploring, is using the technology in initial trials in humans. The first application for this technology in humans is for people with kidney disease. The kidneys are vital organs that clean and filter the blood. In people with kidneys that don't function properly, their blood must be cleaned artificially in a process called dialysis. This requires blood flow between an artery and vein, which usually must be surgically joined with the implantation of a plastic tube known as a graft. Over time the grafts break down, and many people have to have multiple grafts surgically implanted in order to undergo dialysis. The use of these bioengineered blood vessels in place of grafts could reduce the number of surgeries needed by dialysis patients and increase the effectiveness of each treatment.

"If the technology works with dialysis patients," Dr. Kypson explains, "then we may be able to start testing them out in cardiac surgery patients." But, admittedly, that time may not be for a few more decades.

Still, this work is extremely exciting. This is the first time human blood vessels have been bioengineered from human cells in a way that would be immediately available to patients. The blood vessels can be made in all different sizes for use in a variety of procedures, and researchers are actively working together with doctors and surgeons to make sure the technology is convenient to use. "This is on the cutting edge of translational medicine," explains Dr. Dahl. "We're taking work in the laboratory and making it available to patients." Both Dr. Dahl and Dr. Kypson attribute the project's continued success to its collaborative nature. "Tissue engineering is the science of the future," comments Dr. Kypson. "To make it work, we have to do it together."

Dr. Shannon Dahl is the Senior Director of Scientific Operations and Co-founder of Humacyte, an innovative bioengineering company. She is one of the primary collaborators on this project working to develop bioengineered blood vessels from human cells. When not in the laboratory, Dr. Dahl enjoys doing pilates, swimming, and spending time with her family.

Dr. Alan Kypson is a cardiothoracic surgeon at the East Carolina Heart Institute at East Carolina University. He has been working with Dr. Dahl and the other collaborators on this project for many years. When not in the office or the operating room, Dr. Kypson enjoys photography, playing tennis, and spending time with his family.

For More Information:

  1. Dahl, S. et al. 2011. "Readily Available Tissue-Engineered Vascular Grafts."
    Science, 3(68).

To Learn More:

Bioengineering Blood Vessels:
  1. Humacyte:
    http://www.humacyte.com/index.html
Coronary Heart Disease:
  1. American Heart Association:
    http://www.americanheart.org/presenter.jhtml?identifier=4726

  2. National Heart Lung and Blood Institute:
    http://www.nhlbi.nih.gov/health/dci/Diseases/Cad/CAD_WhatIs.html
Kidney Disease:
  1. National Kidney Foundation:
    http://www.kidney.org/kidneydisease/

  2. National Kidney and Urologic Diseases Information Clearinghouse:
    http://kidney.niddk.nih.gov/

Rebecca Kranz with Andrea Gwosdow, Ph.D. Gwosdow Associates


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