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Home > About JDRF & Our Impact > Our research > Research projects > Growing beta cells in the lab from stem cells
Dr. Fiona Docherty from the University of Birmingham
In this project, Fiona will investigate if turning on a specific gene called GLIS3, which has been shown to increase insulin levels, produces better beta cells in the lab. Ultimately, improving the quality of lab-grown beta cells will reduce the number of cells needed for transplants and maximise their ability to precisely control blood sugar levels in patients.
Transplanting islets (clusters of cells containing the beta cells) has had positive outcomes in the clinic but is severely limited by a lack of organ donors. An alternative to transplanting donor islets is to transplant beta cells grown from stem cells. Already, clinical trials are underway in the US where several people with type 1 have received transplants of lab-grown beta cells.
While these trials are exciting and will help us understand how well the cells survive in humans, we need to make them closer to natural adult human beta cells. So far, the beta cells researchers can make in the lab make a hundred times less insulin than those from donor islets. We are funding Fiona’s project to improve the quality of beta cells in the hope they can be used in future clinical trials.
Fiona has previously found that the GLIS3 gene regulates the function of the insulin gene (which makes insulin when turned on) in human beta cells. GLIS3 also controls several other genes that are needed for beta cells to carry out their function of producing and releasing insulin. However, she has found that there isn’t much GLIS3 in the beta cells her team has been making in the lab.
So, Fiona will increase the level of GLIS3 at different stages in the development of beta cells from stem cells. She thinks this will produce beta cells that contain significantly higher levels of insulin.
To switch the GLIS3 gene on, Fiona will add a chemical called tamoxifen to the mixture that her beta cells are growing in. She will compare how functional her beta cells are compared to the standard beta cells that her lab grows. Their functionality will be assessed by the amount of C-peptide in the population of beta cells, indicating how much insulin they contain. Fiona will also measure how much insulin the beta cells release when they are exposed to glucose.
As this is only a small year-long project, Fiona aims to determine the optimum levels of GLIS3 at key stages in beta cell development to produce better functioning beta cells. After she has established this – and if her project proves successful – she will apply for a larger grant to develop more of these improved beta cells.
Transplantation of donor islets has shown us that cell therapy could be an effective treatment – and possibly even a cure – for type 1. Patients who receive islets from donors experience around 35 months without needing to give themselves insulin, but then the transplant starts to lose its effectiveness. Generating an abundant and high functioning source of beta cells could lead to transplants of lab-grown beta cells becoming a routine treatment for people with type 1. For this potential treatment to become a reality, studies like Fiona’s are vital to create cells of the highest quality in terms of function, purity and of course, safety.
We are funding another research team who are trying to improve the quality of lab-grown beta cells. Based at Kings College London, this team is led by Dr Rocio Sancho and is tweaking the mixture in which the beta cells are grown. The researchers are adding different proteins to a water-based gel to more accurately mimic the conditions that beta cells grow in in humans.
This award will help to fund the next generation of immunotherapy research, enabling more efficient clinical trials, in more locations, so that promising treatments can reach people sooner.
This project aims to overcome two major roadblocks to developing and licensing immunotherapies for people newly diagnosed with type 1 diabetes.
Dr Bewick is exploring ways to improve the health, performance and number of beta cells in the body, so that people with type 1 can be less reliant on insulin pumps and injections – or even, one day, live without them completely.
This project is looking at a new way to turn stem cells into beta cells in the lab, to better understand what conditions make this process happen efficiently.