Optimising islet transplantation with vascularized tissue engineering chambers

Funded Activity Summary

Diabetics have high blood sugar levels because cells in the pancreas known as islets produce too little of the hormone insulin. Most diabetics need daily insulin injections to maintain normal blood sugar levels. Transplanting islets is the most promising way to treat type 1 diabetes, but, apart from the obvious difficulty of rejection of foreign islets, several major problems remain: (1) there are insufficient pancreata (and therefore islets) for transplantation; and (2) the efficiency of delivery of surviving islet transplants is too low. In pilot studies we have grown a new living pancreatic organ in mice by inserting islets from genetically-related mice together with a structural protein matrix, growth factors and blood vessels inside a plastic chamber. The blood vessels maintain nutrition to the islet cells and simultaneously allow insulin to be released into the bloodstream, thus normalising the high blood sugar in diabetics. In Aim 1 of these experiments we will find the optimal way to grow mature islets in blood vessel-containing chambers in diabetic mice, focusing on (a) the best time to add islets to the chamber - 0, 1 or 2 weeks after establishment, (b) the minimum number of islets to effectively normalise blood sugar and (c) how long we can keep islets alive and functional in chambers, examining periods up to 12 months. In Aim 2 we will test the ability of islet stem cells (provided by our co-investigators at Walter and Eliza Hall Institute, Melbourne) to survive in the chambers and to produce sufficient insulin to effectively lower blood sugar levels to normal in diabetic mice. In Aim 3 we will grow human islets in chambers in special diabetic mice that do not reject foreign tissue, in order to confirm similar behaviour of human islets in this controlled environment. Using this data, we hope to create a research model of functioning islets, that is accessible, retrievable and manipulable, for the further study of diabetes and transplantation.

Funded Activity Details

Start Date: 01-01-2006

End Date: 01-01-2008

Funding Scheme: NHMRC Project Grants

Funding Amount: $451,651.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Surgery

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

cell growth/differentiation | diabetes | extracellular matrix | growth factor | islet transplantation | organogenesis | reconstructive surgery | tissue regeneration | type 1 diabetes | vascular graft

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