Combining a new hydrogel material with a protein that boosts blood vessel growth could improve the success rate for transplanting insulin–producing islet cells into persons with type 1 diabetes. In an animal model, the technique enhanced the survival rate of transplanted insulin–producing cells, restoring insulin production in response to blood glucose levels and curing these diabetic animals.

The technology could also help patients who must have their pancreas removed because of severe pancreatitis, an inflammatory disease. Using the material and protein combination, the researchers evaluated multiple locations for implanting the islet cell clusters, the first time such a direct comparison of transplant sites has been made.

“We have engineered a material that can be used to transplant islets and promote vascularization and survival of the islets to enhance their function,” said Andrés García, a Regents’ Professor in the Woodruff School of Mechanical Engineering at the Georgia Institute of Technology. “We are very excited about this because it could have immediate patient benefits if this proves successful in humans.”

The research, supported by the Juvenile Diabetes Research Foundation and the National Institutes of Health, was reported June 2 in the journal Science Advances.

Using cells from cadavers, doctors have been experimentally transplanting pancreatic islets into humans for decades, but as many as 60 percent of the transplanted islets die immediately because they are cut off from their blood supply and are killed by an immune response due to direct injection into the bloodstream, and those that survive the transplant usually die within several months. In testing done so far, the islets have been placed into the vasculature of the liver, which has significant blood supply – but might not be the ideal location because of the hostile immune environment.

So García and collaborators, including Georgia Tech postdoctoral researcher and first author Jessica Weaver, set out to engineer a new approach to transplanting the cells. They developed a new degradable polymer hydrogel material used to deliver the cells as they are injected into the body. And they incorporated into the gel a protein known as vascular endothelial growth factor (VEGF), which encourages the growth of blood vessels into the transplanted cells.

“The transplanted islets need a lot of oxygenation and a connection to the body’s circulatory system to sense the glucose levels and transport the insulin,” noted García, who is also the Rae and Frank H. Neely Endowed Chair in Mechanical Engineering. “In addition to protecting the islets, our engineered material promotes the formation of new blood vessels to nourish the cells.”

VEGF has been tried before, but in quantities too large, it stimulates the growth of leaky blood vessels that don’t provide long–term oxygenation. Too little VEGF doesn’t grow vessels rapidly enough to maintain the transplanted islets, which are clusters containing hundreds of cells. Without sufficient vasculature in the clusters, the cells in the center don’t survive.

Weaver used diabetic mice to compare locations in the body where the transplanted cells could be placed. She studied locations in the liver, under the skin, in the mesentery regions near the intestines and in an epididymal fat pad in the abdomen.

“We were able to study the transplant sites in parallel and really look at the pros and cons of each to compare the survival rates of the cells in each area,” said Weaver. “Islet cells are very precious because we get so few from each donor. We need them all to survive to help a patient with type 1 diabetes get off insulin.”