Initial results from human clinical trials involving the use of bioengineered blood vessels could point the way to cost-effective alternative therapies for hemodialysis patients with end-stage renal disease.
Current synthetic vascular graft technology is associated with low patency rates, high rates of stenosis, and high intervention rates, producing one-year failure rates of up to 50%. This poor performance means the only viable options for patients with chronic kidney disease whose condition deteriorates to end-stage renal disease (ESRD) are hemodialysis or kidney transplant.
However, promising initial results from human clinical trials involving the use of bioengineered blood vessels presented by Jeffrey H. Lawson, MD, PhD, vascular surgeon at Duke University Medical Center, in Durham, NC, and colleagues at the 2013 American Heart Association Scientific Sessions could point the way to cost-effective alternative therapies for hemodialysis patients with end-stage renal disease (ESRD).
According to the study abstract, this “tissue-engineered vascular graft” is comprised of “human extracellular matrix and is similar in strength to native human vein and artery.” Further, the graft “may be stored in a regular refrigerator, making it readily available for off-the-shelf surgical use.”
During the process prior to implantation, human vascular cells were isolated, screened, and banked. The cells were used to grow bioengineered vessels in bioreactors. A decellularization process was used to remove cellular antigens and render the graft non-immunogenic. The bioengineered vessels are 6mm in diameter and 40 cm in length and are mechanically similar to natural vascular material.
During phase I clinical trials in which the vessels were implanted in non-human primates, researchers reported the vessels had no infections and no indications for immune response. Researchers reported evidence of cellular repopulation, meaning the vessels repopulated with the primate’s own vascular cells. The vessels achieved 100 percent overall patency and have had some related thrombosis and no evidence of structural disintegration or aneurysms.
Based on these promising pre-clinical results, trials in humans were initiated in late 2012 to study safety, tolerability, patency, and other issues.
Lawson and colleagues presented interim data from 28 patients who had received the vascular grafts at study sites in Poland. He said that the initial performance of the investigational bioengineered vessels is encouraging, and that these vessels may one day offer an alternate option for dialysis access for the growing population of patients with ESRD.
Patients were monitored by monthly clinical and ultrasound monitoring within the first six months following implantation of the graft, with follow-up evaluations every six months thereafter. Patients will be followed for up to two years.
A news release accompanying the announcement of the preliminary results at AHA 2013 said the investigational bioengineered vessels “may potentially be associated with low rates of vessel clotting, low infection rates, and low rates of surgical interventions.” So far, researchers report that the vessels have “remained open to blood flow (patent), with no indication of an immune response in recipients, no aneurysms (abnormal widening or ballooning of part of an artery due to weakness in the blood vessel wall), and flow rates and durability suitable for dialysis.”
Clinical trials that will enroll up to 20 patients who will receive the bioengineered vessels began in May 2013 in the US.