Diabetes Research and Vascular Networks

Technion Researchers Construct a Polymeric Scaffold Array with Pancreatic Islets Surrounded by a Vascular Network. This heralds the potential for the fabrication of transplantable "islets"

The scientific journal PLoS ONE reports that Technion researchers have succeeded in constructing a three-dimensional polymeric scaffold array with pancreatic islets surrounded by a vascular network.

"We have shown that the three-dimensional environment and the engineered blood vessels support the islets – and this support is important for the survival of the islets and for their insulin secretion activity", says Prof. Shulamit Levenberg of the Department of Biomedical Engineering. "We have shown that these laboratory-made polymeric scaffolds can be transplanted subcutaneously and can heal a diabetic mouse. The ability to increase the islets' vasculature and to support their post-transplant survival could allow the transplant of four times less islets than is customary in transplants in mice, while still achieving decreased blood sugar levels and diabetes relief". 

The mechanism which causes the failure of pancreatic islet transplants is as yet not entirely clear, but the prevailing opinion is that it has to do with ischemic damage – and a delay in the creation of new blood vessels.

The Technion researchers hypothesize that blood vessels also have an active role in inter-cellular communication that supports the survival and function of pancreatic islets. To test this hypothesis, the researchers developed a three-dimensional network of endothelial blood vessels in engineered pancreatic tissues produced from islets, fibroblasts and endothelial cells. This triple array, which was seeded on highly porous polymeric scaffolds, mimics the natural anatomical context of pancreatic vasculature.

"We have shown that the increase in islet survival is correlated with creation of surrounding endothelial tubes", says Prof. Levenberg. "Adding fibroblasts to pancreatic islet and endothelial cell cultures encouraged the creation of the vascular network, which supported islet survival as well as insulin secretion. Significant differences were seen in many variables – gene expressions, profiles of the growth factors of endothelial cells, ECM, morphogens and screening markers – between two-dimensional culture systems and three-dimensional culture systems that allow an endothelial network, and such differences were even greater after fibroblasts were added that support the creation of the engineered blood vessels."

Transplanting the vascularized engineered islet tissue has improved the survival and acceptance of such islets in diabetic mice, and has even improved their function in decreasing blood glucose. The Technion researchers hope that these findings herald potential strategies for the fabrication of transplantable islets with improved survivability.

The work was done by research student Keren Francis in Prof. Levenberg's laboratory and in cooperation with Yuval Dor from the Hebrew university, under a joint research grant provided by Juvenile Diabetes Research Foundation International.

The laboratory is now researching the effect of the vascular network and the three-dimensional growth on human islets, under joint finance of the Juvenile Diabetes Research Foundation International and the Israel Science Foundation.