Pioneering technology will help overcome the limited supply of insulin-producing cells
A trio of scientists at the Diabetes Research Institute and the University of Miami’s Biomedical Nanotechnology Institute (BioNIUM) has received a $4.9 million grant from the National Institutes of Health to further understanding of pancreatic islet cells with the goal of developing enough of these insulin-producing cells to treat millions with diabetes. The grant, one of only four awarded, is a part of the Consortium on Human Islet Biomimetics, a group under the newly formed Human Islet Research Network.
Over the next five years, the three scientists will engineer a human physiomimetic islet microsystem — or, simply put, an “organ on a chip” — that they believe will help them learn more about many of the still-unexplained workings of islets and the insulin-producing beta cells they contain. The team hopes to use the microchips to increase the current supply of islets available to transplant into patients with diabetes, screen pharmaceuticals for patients with diabetes and/or create beta cells from stem cells.
“The idea is to fabricate a microchip capable of mimicking the native islet,” said Cherie Stabler, Ph.D., associate professor of biomedical engineering and surgery, and Director of the Tissue Engineering Program at the DRI, who is one of the researchers who received the grant. “These platforms can then serve as a screening tool to understand drugs that may impair or enhance islet function, as well as to identify conditions that can help islets survive better.”
In a healthy person, beta cells sense rising levels of glucose in the blood — such as after a meal — and produce insulin to bring the glucose back down to normal levels. In people with type 1 diabetes, however, the beta cells are mistakenly destroyed by the body’s immune system.
Beta cells are clustered — 3,000 to 4,000 strong — in pancreatic structures known as islets; it is estimated that a healthy, adult pancreas contains approximately one million islets. DRI researchers have already demonstrated that islets transplanted into patients with diabetes can function for more than 12 years. The challenges are that the only source of islets for transplantation is human cadavers, making supply very limited; scientists are still searching for the optimal site in the body in which to transplant islets; and transplant patients must currently take anti-rejection drugs for the rest of their lives.
“The goal of my research laboratory is to duplicate the organ level functionality and complexity outside the human body and within fluidic microsystems,” said another of the researchers, Ashutosh Agarwal, Ph.D., assistant professor of biomedical engineering and pathology. “These organs on chips can serve as powerful tools in the hands of clinicians and bioengineers.”
The platform itself, he explained, is a structure about the size of a cell phone and is made of specialty glass, polymers and plastics. Its features — channels, valves, pumps and multiple wells — are in the size of microns, hence the microchip analogy. Each well, which will house islet cells embedded within coatings being tested, can be connected to its own plumbing line to receive nutrients and can have its own oxygen supply.
“A muffin pan on a micro scale is a good analogy, but think of each cup as having its own automated supply of ingredients instead of having to be filled manually,” said Agarwal. “This approach also will give us the opportunity to conduct experiments without using animal models. If we have a platform that successfully mimics human physiology and fools the cells into thinking they are still inside the body, then we can replace animal models and make our preclinical trials cheaper, better and more predictive of human outcomes.”
“If we take islets out of the pancreas, we can only culture them for a few days; they have to be put into a patient,” said Stabler. “We still don’t know how to culture islets properly. In fact, it’s one of the few primary cells we cannot effectively culture. Once we identify the parameters that will support islet culture, we will have an efficient, high-content approach to maintaining islets or even generating new ones from stem cells.”
“The key is to create and support an environment that keeps the islets healthy,” said Camillo Ricordi, M.D., Stacy Joy Goodman Professor of Surgery and director of the Diabetes Research Institute He is the physician-scientist of the trio, and he will head up the project’s screening efforts with human insulin-producing cells.
“The proposed technologies will help us develop novel strategies to optimize survival, function and regeneration of insulin-producing cells, and will also help us define improved methods of producing islets from stem cells,” he said. “That capability would enable us to overcome the supply problem and help millions of people we cannot help now. This project exemplifies the benefits of team science and the very productive efforts of the DRI and the Department of Biomedical Engineering. This type of collaborative, interdisciplinary strategy has always been central to the DRI’s cure-focused mission.”
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Source: University of Miami; Diabetes Research Institute