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3D vascularized pancreatic islets - for islets transplantation (Technion)

Summary

The present invention provides a unique 3D pancreatic-like model for co-culture of isolated pancreatic islets with endothelial cells on a PLLA/PLGA biodegradable polymeric scaffold.
Insulin-dependent diabetes mellitus (IDDM) is a chronic inflammatory disease in which there is autoimmune-mediated organ-specific destruction of insulin-producing beta cells in the pancreatic islets of Langerhans, resulting in glucose homeostasis abnormalities and metabolic complications that are debilitating and life-threatening. Islet transplantation is a potentially curative treatment since replacement of these cells could prevent mortality, however thus far islet cell transplantation has had poor success due mainly to the fact that the tissue grafts must establish new vasculature from the host to survive. Native islets in the pancreas have a rich microvasculature that provides efficient oxygen and nutrient delivery and ensures rapid dispersal of pancreatic hormones to the circulation, and therefore after implantation, the survival and function of islet grafts depends on reestablishment of new blood vessels. During the time required for revascularization, there is a much-increased susceptibility to loss from ischemic injury, so that rapid and adequate islet revascularization is crucial for the survival and function of transplanted islets. In both experimental and clinical islet transplantations, islets are cultured for several days between isolation and transplantation.
The present invention provides an advanced tissue-engineering technique for development of 3D co-culture systems that reconstruct vascularization of pancreatic tissue ex-vivo. In this novel engineered 3D pancreatic model, isolated pancreatic islets can be co-cultured with endothelial cells using PLLA/PLGA biodegradable polymeric scaffolds. The endothelial cells organize into 3D tubes throughout the engineered construct and form vascular network-like structures resembling in-vivo vasculature. This presence of endothelial cells forming 3D vessel-like structures was found critical for islet survival. This model can provide an important tool for therapeutic transplantation of islets, greatly increasing the success of the procedure by increasing islet survival and reducing the number of organ donors needed per transplant and the number of repeated transplants, making this procedure more available, biologically and economically. This model also provides new exciting tools for studying central problems in molecular and cell biology of the pancreas.
In the U.S, an estimated 20.8 million people (7% of the population) have diabetes mellitus. In the next five years, around US$2.5 billion will be spent worldwide on diabetes mellitus research.

ID No.

CTT-0895

Country/Region

Israel