Bioengineered human acellular vessels for dialysis access in patients with end-stage renal disease: two phase 2 single-arm trials

Abstract

Summary Background For patients with end-stage renal disease who are not candidates for fistula, dialysis access grafts are the best option for chronic haemodialysis. However, polytetrafluoroethylene arteriovenous grafts are prone to thrombosis, infection, and intimal hyperplasia at the venous anastomosis. We developed and tested a bioengineered human acellular vessel as a potential solution to these limitations in dialysis access. Methods We did two single-arm phase 2 trials at six centres in the USA and Poland. We enrolled adults with end-stage renal disease. A novel bioengineered human acellular vessel was implanted into the arms of patients for haemodialysis access. Primary endpoints were safety (freedom from immune response or infection, aneurysm, or mechanical failure, and incidence of adverse events), and efficacy as assessed by primary, primary assisted, and secondary patencies at 6 months. All patients were followed up for at least 1 year, or had a censoring event. These trials are registered with ClinicalTrials.gov, NCT01744418 and NCT01840956. Findings Human acellular vessels were implanted into 60 patients. Mean follow-up was 16 months (SD 7·6). One vessel became infected during 82 patient-years of follow-up. The vessels had no dilatation and rarely had post-cannulation bleeding. At 6 months, 63% (95% CI 47–72) of patients had primary patency, 73% (57–81) had primary assisted patency, and 97% (85–98) had secondary patency, with most loss of primary patency because of thrombosis. At 12 months, 28% (17–40) had primary patency, 38% (26–51) had primary assisted patency, and 89% (74–93) had secondary patency. Interpretation Bioengineered human acellular vessels seem to provide safe and functional haemodialysis access, and warrant further study in randomised controlled trials. Funding Humacyte and US National Institutes of Health.

Implantable tissue-engineered blood vessels from human induced pluripotent stem cells

“…Although human primary aortic SMCs have been shown to generate functional blood vessels that are implantable in rats, baboons and humans [3, 21, 23], they may be hampered by variation in collagen production between donors, and in the finite replication ability of differentiated cells. Human primary fibroblasts have also been used to construct vascular grafts [24, 25], but these cells similarly face the challenge of limited passaging capability.…”

Vascular smooth muscle cells derived from inbred swine induced pluripotent stem cells for vascular tissue engineering

“…Importantly, decellularization of vascular grafts can eliminate or greatly reduce cell-based immunogenicity and enable a longer-term storage, thus providing off-the-shelf product for current clinical trials [20, 35]. However, the generation of vascular grafts using human primary VSMCs is hampered not only by limited proliferation potential of donor cells, but also by batch-to-batch variations in collagen matrix production [5].…”

Utilizing the Foreign Body Response to Grow Tissue Engineered Blood Vessels in Vivo

“…In a more recent clinical trial, the group of Niklason employed human acellular vessels as vascular access in 60 patients with ESRD, showing a primary patency of 28%, and secondary patency of 89% at 12 months post implantation, underlining the potential of TEBV approaches as potential vessel replacement [77]. VA sites offer an interesting target for the clinical implementation of TEBV’s.…”