New paradigm in arteriovenous grafts opens up possibility of novel cure for diabetes

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Mohamed Zayed

A novel twist to arteriovenous graft platforms—traditionally the preserve of hemodialysis—has the ability to open up a new paradigm of treatment across a host of metabolic disorders like diabetes, a study to be presented at a scientific session on June 27 will demonstrate.

For initial in vivo trials, performed on adult pigs, researchers constructed a multilayered arteriovenous graft with specific biomaterials made of polytetrafluoroethylene (PTFE). The multilayered graft, modified in order that it could be implanted with pancreatic beta cells, would then function in vivo, releasing insulin inside the implanted host. The researchers would then be able to demonstrate the treatment of diabetes without ex vivo insulin.

The investigators were able to demonstrate that their novel arteriovenous graft platform can be used—sans immunosuppression— in a large animal with good beta cell survival, observed Mohamed Zayed, MD, an assistant professor at Washington University School of Medicine in St. Louis, who will present data from the study during the scientific session.

“We used an age-old idea where arteriovenous grafts, typically used for hemodialysis purposes, can be re-appropriated for the purpose of cellular transplantation,” he tells Vascular Connections. “We constructed a multilayered arteriovenous graft with specifications that allow for easy cellular implantation. For our proof of concept experiments, we implanted insulin-producing beta cells in the graft to determine if this can be a novel platform for treatment of diabetes.”

The results of the study, Zayed goes on, showed that “porous layers in the arteriovenous graft allowed for efficient diffusion of glucose and insulin and had good biocompatibility. In vivo, we observed successfully surgical implantation of the arteriovenous graft, 100% survival of implanted pigs, and good graft patency as monitored by serial ultrasound.”

Zayed, also a vascular surgeon at the St Louis Veterans Affairs Medical Center, set out to develop an alternative to ex vivo insulin administration in patients with diabetes who don’t have a functional capacity to produce enough insulin. His quest to produce an alternative through cell transplantation, he explains, exists in a field that has been stagnating “due to the heavy reliance on immunosuppression in patients that require pancreatic or islet cell transplants.”

But Zayed et al made strides on immunosuppression. “What’s remarkable about this study is that, with the current designs we’ve iterated, the host does not need any immunosuppression,” Zayed says. “So, without having to administer any immunosuppression, we’re able to maintain high cell survival and sustained insulin-production from the cells placed in the arteriovenous graft. And this has been confirmed in a large animal model. Our proof of concept has been successful, and we hope to translate this eventually into humans who need a host of these types of metabolic therapies.”

WHEN: Saturday, June 27, 2020, 9:32 a.m.–9:42 a.m. Scientific Session 5

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