Miami, FL (May, 2006) — Scientists at the Diabetes Research Institute (DRI) at the University of Miami Leonard M. Miller School of Medicine have successfully tested a new biomechanical device to treat diabetes in the laboratory.
It may mark a fundamental change in how islet cell transplantation will be done in the future. The results of the study are published in the May 15 issue of the journal Transplantation. Islet cell transplantation is a technique that replaces the cells that are destroyed in patients with type 1 diabetes.
This method was pioneered by the Diabetes Research Institute investigators. “We have unequivocally demonstrated for the first time, that insulin producing cells can survive and function long term after transplantation within a pre-vascularized device with a 5 mm diameter,” said Camillo Ricordi, M.D., scientific director and chief academic officer of the DRI. “Unlike previous models, the geometry of this device could easily be scaled up for clinical trials.
“Successful reversal of diabetes with this device is quite exciting. It opens the possibility of creating a bio-artificial organ that could replace the current practice of injecting islets into the liver.”
In patients with type 1 diabetes, the immune system mistakenly attacks islet cells in the pancreas – the cells that produce insulin to regulate the body’s levels of blood sugar. In islet cell transplantation, insulin-producing cells are harvested from donor pancreata and injected into the liver through that organ’s portal vein – the main blood supply into the liver.
While the DRI has had great success with that method for decades, there are problems. “The injection of islet cells into the blood in the portal vein results in the generation of inflammation that compromises their viability,” said Luca Inverardi, M.D., director of immunobiology of islet transplantation at the DRI. “Many of those cells fail.”
Islet cells may lodge in tiny capillaries inside the liver, blocking blood flow. Also, islet cells become essentially “invisible” once they’re implanted in the liver, so they are difficult to image or monitor with biopsies. And relatively elevated levels of immune system suppressing drugs, which are necessary after any transplant, can damage islet cells over time.
“It would be highly desirable to replace the liver as the site of these transplants,” said Antonello Pileggi, M.D., research professor of surgery at the DRI. “This device is very promising and seems to have long-term reliability in these initial experimental models.”
In the study, investigators implanted a 2 centimeter-long device (about one inch) with a diameter of approximately half-a-centimeter into an animal model. The device is made of biocompatible stainless steel mesh and polytetrafluoroethylene (PTFE) plastic caps and a plug (see photo) .
The device was left implanted for 40 days during which tissue and new blood vessels proliferated around and inside it. The plug retains space inside the mesh. After 40 days, through a small incision, the plug is removed and islet cells in a saline solution are injected into the space.
The device is capped and the incision closed.Insulin production was measured within days of islet cell transplantation and proper blood sugar was quickly achieved and maintained. Scientists found no adverse effects even 180 days after transplantation. In laboratory models where the device was removed the diabetic condition quickly returned.
“This alternative to transplanting islet cells into the liver is easy to perform, easy to evaluate and provides an ideal new site for islet transplantation,” said Pileggi. The next step is a larger study to repeat these results and generate more data to present to the Food and Drug Administration.
The eventual objective is to test a similar approach in clinical trials to treat patients with type 1 diabetes, as an alternative to intrahepatic islet transplantation.
UM Leonard M. Miller School of Medicine
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