With a leap forward that sounds like something out of a science fiction movie, researchers last week announced significant progress on perfecting an islet cell transplantation technique that could lead to a cure for Type 1 diabetes.
Researchers have cured Type 1 diabetes in mice by transplanting them with islet cells (the cells in the pancreas that actually produce insulin and which, in a type one diabetic, no longer function) wrapped in a new synthetic biomaterial that enabled the fragile cells to survive infusion, graft to the host, and function successfully. This new and novel approach of wrapping islet cells in a specially engineered biomaterial addresses several problems with islet cell transplantation that has prevented it from being developed as readily available procedure to cure the nation’s three million Type 1 diabetics.
“Islet cell transplantation is the most promising therapy that is being developed for a Type 1 diabetes cure,” said Dr. Andres Garcia, a researcher with Georgia Tech’s Petit Institute for Bioengineering and Bioscience who worked on the biomaterials project with researchers from Emory University and in conjunction with the Juvenile Diabetes Research Foundation. “However, there are several shortfalls that need to be addressed before it can be perfected.” The biomaterials, developed by Garcia and his team, are designed to address those shortfalls.
In traditional islet cell transplantation, which has been tested in clinical trials around the world for the last decade, islet cells are infused into a person’s liver. The cells then reside in the liver where they produce insulin and ostensibly “cure” a person of Type 1 diabetes.
However, more than half the islet cells die upon infusion, according to Garcia. This is problematic because the cells are harvested from cadaver pancreases and are not readily available to begin with. Because of the high loss of the cells in the procedure most subjects in clinical trials had to be infused with cells from two or sometimes three separate donors. Additionally, each subject must be matched for genetic compatibility with not one, but several donors.
The cells left alive after infusion tend to die off over time. Part of this is because of a blood clotting response by the body and also because the potent immunosuppression drugs each subject takes to keep from rejecting the cells themselves contribute to the death of the cells.
Another significant fallback regarding traditional islet cell transplantation, according to Garcia, is that the cells are not linked via the circulatory system to the body, the way they are in a person whose islet cells function normally. Islet cells require a lot of blood flow to get the insulin they produce into the system when needed. Lack of blood flow reduces the effectiveness of the cells.
The biomaterial holding the islet cells—which is completely synthetic, is 96 percent water, and which Garcia described as having the consistency of diluted Jello-O—and that was infused into the mice, however, addresses several of these problems.
The material acts as a shield to effectively prevent the death of so many islet cells immediately following infusion. This means that fewer cells are needed for a successful infusion. That not only translates to an increased availability of cells, it also means that only one donor is needed for each patient and a match is easier to find for each patient.
The biomaterial is completely synthetic so researchers have a lot of control over how it functions. For this experiment in mice, researchers engineered the material so that as it broke down over time it released a protein that created a vascular link between the islet cells and the circulatory system in mice, a process known as “vascularization.”
“Creating a working vascular system is a process, not an event,” Garcia said. “We engineered it so the biomaterial took time degrading so a system could be established by the time it broke down.”
The biomaterial was further engineered so that as it broke down it also integrated, or grafted, specifically to the surrounding tissue. This meant that the cells attached to the body without the use of staples or sutures and surgery was avoided. Garcia and his team infused the cells outside the small intestine of the mice.
“It’s a better location than the liver,” Garcia said. “It’s got a lot of blood vessels and it’s in the digestive path.”
The success in grafting the islet cells is compelling, but it’s only a first step in a long process, Garcia said. He predicted that next year researchers would be experimenting on pigs, which are more closely related biologically to humans than mice are.
And so far the team has not tackled the immune acceptance issues.
“We are exploring some strategies for that,” Garcia said. “Perhaps we can develop an ultra-thin coating that can shield the cells from immunosuppression.”
In what might be described as another breakthrough, although one of a very different type, Garcia said the Juvenile Diabetes Research Foundation is being proactive in enabling research to continue in the field. The JDRF funded a consortium of more than a dozen researchers all working toward the same goal along the same lines.
“Bringing everyone together to create some synergies is a very refreshing approach,” Garcia said. “It’s a creative way to move things forward.”