UCSF School of Pharmacy faculty member Shuvo Roy, PhD, has received a three-year $1 million grant to create surgically implantable capsules of donor pancreas cells to assist in curing type 1 diabetes patients of daily insulin injections and the disease’s potentially life-threatening complications.
The goal of the project is a successful animal demonstration of a postage-stamp-sized silicon capsule with semipermeable membranes, designed to allow the passage of nutrients and oxygen needed to keep the pancreas cells alive so they can secrete insulin in a precise, rapid response to the body’s needs while simultaneously protecting them from destruction by the recipient’s immune system.
Roy’s Biodesign Laboratory, which focuses on medical device development, is based in the Department of Bioengineering and Therapeutic Sciences, a joint department of the UCSF Schools of Pharmacy and Medicine.
In type 1 diabetes, the body’s own immune system destroys the beta cells in the pancreas that secrete insulin—the vital hormone that, generally speaking, provides energy from food and, more specifically, regulates levels of blood sugar (glucose) by promoting its uptake into muscles and fat and inhibiting its production by the liver.
This autoimmune disease randomly strikes 1.25 million Americans, and is associated with lost life expectancy of up to 13 years.
Currently, treatment for most patients is a daily regimen of multiple insulin injections that must be constantly balanced – via blood-draw glucose monitoring – with stress, diet, and exercise levels. Even so, less than a third of those with type 1 diabetes (formerly known as insulin-dependent or juvenile diabetes) are able to achieve target blood glucose levels, thus risking complications that include kidney failure, blindness, nerve damage, heart attacks, and strokes.
For nearly two decades, some patients with type 1 diabetes have been treated with transplants of pancreatic islets – tiny clusters of hormone-producing cells (there are about a million islets in the adult pancreas) – from deceased organ donors. The goal is for patients to become insulin-independent and to achieve more naturally responsive, healthy blood glucose levels.
But the application of such treatment is limited by the need for long-term use of immunosuppressant drugs to prevent rejection of the donor cells. This can leave patients “vulnerable to other debilitating and life-threatening diseases, including cancer,” notes JDRF. In addition, statistical analysis by the National Institutes of Health of 571 such islet transplants done from 1999 to 2009 found that “eventually most recipients need to start taking insulin again.”
The experimental solution of encapsulating insulin-secreting cells for implantation has been attempted, but it too has faced long-term limitations: Encapsulated cells have died off either due to their imperfect isolation from immune system cells, or due to localized immune reactions that cause scarring around the capsules, cutting off oxygen to the islet cells. In addition, there can be delays in the insulin secreted by the encapsulated cells reaching the bloodstream, thus distorting their response to blood glucose levels.
Roy’s JDRF-funded project seeks to overcome those transplantation and encapsulation challenges by using a new class of semipermeable silicon membranes developed in his lab, which are fabricated using production techniques adapted from the semiconductor and microchip industry.
The thin membranes have precisely defined pores ranging from five to fifteen nanometers (billionths of meters) in width—immune system cells and antibodies are larger, while glucose and insulin are smaller. In addition, these silicon nanopore membranes can be grafted with biocompatible polymer films that are only a few molecular-layers thick to reduce scarring around the capsules and thus ensure their performance in the body for extended time periods.
The goal is to load such a capsule with the pancreatic islets and surgically implant it between an artery and a vein. The pressure difference will drive blood filtrate through the membranes’ nanopores, carrying in nutrients (including oxygen and glucose) to the encapsulated cells, and carrying away waste products and insulin.
“Islet cell implantation has the potential to revolutionize treatment of type 1 diabetes by replacing the cells that can automatically respond to and manage blood glucose levels,” said JDRF Director of Discovery Research Albert Hwa, PhD. “Dr. Roy’s research could be an important step towards finding a way to nourish and protect implanted islet cells and creating a therapy that frees people living with the disease from the constant burden of blood-glucose monitoring, carbohydrate counting, and insulin dosing.”
Health-e-Solutions comment: Islet cell implantation has the potential to transform the treatment of type 1 diabetes, provided the encapsulation can stop the autoimmune attack and keep the blood supply strong to the encapsulated cells. So far, it has not proven to be a cure, but research like this continues to push the limits of islet transplantation, to assist in #CuringType1Diabetes.
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