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Helper molecules to improve islet transplant

Project summary

Using the MSC secretome to improve the outcomes of islet transplantation

Professor Peter Jones and his team will find out which molecules allow a particular kind of ‘helper cell’ to improve islet transplants. Such molecules could be combined with islet transplants to improve their outcomes for people with Type 1 diabetes and make them more widely available.

Background to research

Some people with Type 1 diabetes who have a reduced awareness of hypoglycaemia can receive an islet transplantation (insulin-producing islet cells from a donor are transplanted into a recipient). The treatment can provide lasting reductions in the number of hypos and recipients often achieve normal blood glucose control, reducing the long-term risk of complications. However, in current transplants, up to 50 per cent of the transplanted islets are lost immediately, meaning that multiple transplants are required. This is a particular issue given the shortage of donors. Transplant recipients, while independent from insulin therapy at the beginning, often revert back to needing insulin within 3-5 years.  Mesenchymal Stromal Cells (MSCs) are currently being tested as potential ‘helper cells’, to try and improve islet transplantation. Professor Peter Jones and his team have recently shown that growing and co-transplanting MSCs with islets helps them to survive, improves their ability to produce insulin and thus improves blood glucose control. MSCs work by producing a range of signalling molecules, and the researchers have found several likely candidates that might be influencing islet function. They've also discovered that human islets have over 290 different types of molecules called receptors to detect these signals.

Research aims

The team aims to work out how MSCs improve the outcomes of islet transplantation and identify specific signalling molecules that improve islet survival and function. The researchers will measure the signalling molecules produced by MSCs, test their ability to influence the survival of mouse and human islets, and test their ability to produce insulin in the lab. The most effective molecules will then be used during islet transplantation in mice with diabetes. 

Potential benefit to people with diabetes

This research will help tackle one of the key problems of islet transplant: the loss of islets immediately after transplantation. If we can find out which molecules help MSCs to improve islet transplants, such molecules could be combined with islet transplants to improve outcomes for people with Type 1 diabetes. Improving islet transplants will benefit individual recipients and reduce the number of donor islets required, thus helping to make the treatment available for many more people with Type 1 diabetes. 

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