More than 25 million people in Western societies are currently affected by vascular diseases, diseases that affect the body’s blood vessel network, but current treatment options are limited and often include lifelong supervision and immunosuppression. A team of scientists and doctors at the University of Gothenburg has discovered a possible solution: a transplantable vascular graft created from the patient’s own blood to assure that their body accepts the graft.
Vascular diseases are a wide-ranging and include heart disease, strokes, atherosclerosis and blood clots. The risk of vascular disease increases with age, and factors such as smoking, high cholesterol, diabetes or long periods of sitting or standing still. However, some infants, children and adolescents face these afflictions as well.
Currently, doctors use synthetic grafts or vessels from organ donors to treat blockage or narrowing of blood vessels. However, these allogeneic transplants can cause issues such as blood vessel narrowing, clot formation, infection and immune-related rejection among others. Graft healing, or the growth of normal endothelial cells surrounding the blood vessel linings is severely limited in humans, especially when dealing with synthetic grafts.
While previous methods to obtain stem cells from bone marrow or by cell separation have resulted in successful transplants, a research team, headed by Suchitra Sumitran-Holgersson, a professor of transplantation biology at the University of Gothenburg, has found that autologous whole blood can serve the same purpose with fewer procedural complications.
They began their process by decellularizing the veins, which means getting rid of the cells in the tissue. Collagen, fibronectin, laminin and other important matrix proteins remained. After this procedure, they began the recellularization process to add cells back into the tissue by perfusing the vein with the patient’s blood for two days.
After the initial blood addition, a special endothelial cell medium was added, and four days later, a layer of cells was already visible on the previously decellularized vein. Within six days, cell growth plateaued and the researchers could test the vein for different parameters to assess the success of the procedure.
After performing the various analyses, the researchers found no significant difference between the recellularized and normal sample, which indicates that they created a functionally replaceable vein.
The novel approach was then tested in two pediatric patients: a four-year old with an absent portal vein, and a two-year old with a lack of portal circulation. The portal vein is responsible for the liver’s processing and filtering of large amounts of nutrient-rich blood drained from the digestive system. Their symptoms were fatigue, elevated body temperatures, anemia, low clotting abilities, lowered immunity and pain associated with food intake.
Twenty-one months after the procedure, the first patient has had no complications and now has normal clinical laboratory parameters. The second patient had an identical second graft made after seven months to replace the first because of a reduced diameter at the two ends of the implanted vein. Nineteen months after this procedure, the patient appears as well as the first.
With these two successful cases, there are high hopes for the procedure on a larger scale. There may no longer be a need to treat patients using risky embryonic cell separation, immunosuppression measures or painful bone-marrow techniques.
“I have been working in the field of organ transplantation for nearly 30 years now, and one of the critical problems we face is the lack of organ donors,” study author Suchitra Sumitran-Holgersson wrote in an email to The News-Letter. “This problem has therefore instigated us to explore other alternatives to increasing the pool of donor organs, and one way would be to work on organ regeneration.”
This method will benefit patients with chronic vein deficiency or the need for heart valves or bypass surgery. Not all organs are created equal, however.
“More complicated organs such as the liver, heart, kidney, etc. will be more of a challenge since these organs are vascularized and composed of several different cell types,” Sumitran-Holgersson wrote. “This would then mean that a different type of approach is required for regeneration of these complicated organs.“
