Tissue-engineered blood vessels show promise for dialysis

[kkmalaysia]

Blood vessels grown from human cells can successfully function as access grafts for hemodialysis, according to a study hailed as “a revolutionary milestone” in tissue engineering.
 
In a series of 10 end-stage renal disease patients, the new vessels performed comparably to short-term standards set for conventional access grafts, US researchers report.
 
Primary patency was maintained in 78 percent of grafts at 1 month, and 60 percent at 6 months.
 
Long-term intervention rates also appear lower than with conventional grafts, which are typically prone to failure.
 
Recruitment for phase III trials has already begun, and the technology is expected to be commercially available within 3 to 5 years.
 
“This is the first structurally functioning tissue-engineered organ that’s been built without using synthetic scaffolds or exogenous materials,” said lead author Dr. Todd McAllister of Cytograft Tissue Engineering Inc., California, US.
 
“To come in and demonstrate essentially equivalent to, or better than, the standard of care on your first try is a pretty remarkable achievement. We have to take these results with a grain of caution because it’s such a small patient cohort, but the results seem encouraging,” he said.
 
The vessels, which overcome the issues of rejection and infection associated with synthetic grafts, are grown using a technique called sheet-based tissue engineering. Fibroblasts are taken from biopsy samples and grown around a 4.8 mm diameter stainless steel rod using bovine serum-enriched culture. Each graft takes 6 to 9 months to produce.
 
The grafts were implanted as arteriovenous shunts into patients with advanced disease, a previous access graft failure and a high probability of repeat failure – an extremely challenging population for a clinical trial, according to McAllister. Patients were enrolled at centers in Poland and Argentina, between September 2004 and April 2007. [Lancet 2009 Apr 25;373(9673):1440-6]
 
One patient withdrew before graft implantation, and another died shortly after of unrelated causes. Three of the remaining grafts failed within the first 3 months – an outcome consistent with predicted failure rates in such a high-risk population, the authors say.
 
The grafts in the remaining five patients all functioned for 6 to 20 months of hemodialysis. Just one surgical intervention was required to maintain patency – an intervention rate of 0.015 per patient-month.
 
McAllister acknowledged that the tissue-engineered grafts would be expensive in the short term, costing around US$15,000 to $17,000 more than synthetic equivalents. However with conventional grafts typically needing one to three interventions a year, costing around US$10,000 each time, he said that he expects the new grafts to become cost-effective over time.
 
An accompanying commentary notes that further refinements to the technology could open “realistic opportunities” for reducing production times and costs, and could lead to the grafts becoming more widely available in future.
 
“The successful clinical testing of the first commercial tissue-engineered vascular graft is a revolutionary milestone, manifesting the emergence of clinical vascular tissue engineering,” wrote Drs. Vladimir Mironov and Vladimir Kasyanov, of the Medical University of South Carolina, US, and Riga Stradins University, Latvia. [Lancet 2009 Apr 25;373(9673):1402-4]
 
McAllister et al. defined graft success against the objectives of the US National Kidney Foundation Dialysis Outcomes Quality Initiative, which target 76 percent patency at 3 months for native vein fistula implantations.
 
The study has generated considerable attention since early results were published for the first six patients. [N Engl J Med 2007 Oct 4;357(14):1451-3]