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JDRF-funded scientists at Harvard University have provided new insights into to how stem cells develop to become insulin-producing beta cells.

The team, lead by Professor Doug Melton, have identified a marker which allows them to distinguish mature beta cells (which can produce insulin) from immature beta cells (which cannot).  The study is published in this month’s issue of the prestigious journal Nature Biotechnology.

Many scientists are working on ways to turn stem cells into beta cells. So far, they have managed to turn stem cells into immature beta cells in the lab, that when transplanted into mice will become mature beta cells that release insulin in response to glucose.  Although this is excellent progress, transplanting immature beta cells into humans is not ideal as there is a chance that some of the immature beta cells may not develop as expected, and instead begin multiplying out of control, causing cancer. For this reason, scientists want to be able to make fully mature beta cells in the laboratory which would then be much more suitable for transplantation.

Professor Melton’s work takes us a step further towards making mature beta cells in the lab. They have identified a protein that is found in mature beta cells but not in immature non- insulin producing ones. The protein, called urocortin-3, can now be used as a marker of mature insulin producing cells and will help scientists identify mature beta cells more easily when testing out new  ways to make them from stem cells. 

Rachel Connor, Head of Research Communication at JDRF said ‘Stem cells provide exciting possibilities for studying type 1 diabetes and potentially treating the condition in the future. Professor Melton’s study helps us understand more about how beta cells develop and crucially, also provides a way to efficiently test if new techniques for making mature beta cells from stem cells are working effectively’.

Could tiny packets of stem cells help people with type 1 diabetes to produce their own insulin again? JDRF has joined forces with Viacyte, a US based biotechnology company, and the California Institute for Regenerative Medicine (CIRM) to help answer this question.

The organisations have come together to conduct preclinical testing of a first-of-its-kind cell therapy for type 1. The potential treatment is an innovative combination of cells and a special ‘packaging’ material. One of the unusual things about the therapy is that the cells, derived from embryonic stem cells, are not mature when they are packaged – rather they are immature human pancreatic hormone cells.

Initial tests have shown that once implanted, within their protective packaging, these immature cells develop into mature hormone producing cells, including the vital insulin producing beta cells that are missing in people with type 1. Tests in rodents have shown that once mature, these packets of cells are capable of regulating blood glucose levels.

Existing cell therapies such as islet and pancreas transplantation have the potential to cure type 1 by restoring normal islet function in people with the condition. But because there is a huge shortage of pancreatic islets from organ donors, it is important to find a replenishable supply of functional insulin-producing cells. This product, by using stem cells rather than tissue form organ donors could overcome this hurdle. Furthermore, packaging the cells in a device that creates a physical barrier around the cells (a process called "encapsulation") has the potential to protect the transplanted cells from immune rejection, and may eliminate the need for chronic immunosuppressive drugs.

The three-year series of preclinical studies being co-funded by JDRF will help prepare the information necessary to apply for regulatory approvals to study the system for safety and efficacy in people with type 1 diabetes.

Rachel Connor, Head of Research Communication at JDRF said ‘JDRF is excited to be working with Viacyte and CIRM on this pioneering project. Encapsulation technologies and stem cell therapies have fantastic potential in treating type 1 diabetes, so this type of innovation could be a huge step forward for people living with the condition.’

JDRF-funded researchers in Israel have found that stem cells made from beta cells in the pancreas of adults have a ‘memory’ that makes them better able to produce insulin than other types of stem cell.

The team from Tel Aviv University, led by Shimon Efrat, published their discovery in the July issue of the journal Cell Stem Cell.

Stem cells can be taken from either embryos or adults. Both types have the potential to turn into many different types of cell, including insulin-producing beta cells. However this latest study suggests that the source of the stem cells has more influence than previously thought. The genetic ‘memory’ of stem cells derived from the pancreas means the cells find it easier to turn into insulin-producing beta cells, making them a better option for treating for type 1 diabetes.

Scientists hope to be able to use these stem cells to grow new beta cells to replace those destroyed in people with type 1 diabetes. When coupled with therapies to prevent or block the immune system from attacking the newly introduced beta cells, this research offers a possible route to a cure for type 1. 

This project forms part of the JDRF research programme aiming to find ways to replace or regenerate insulin-producing beta cells in people with type 1 diabetes. You can read more here.