Westmead professor’s remarkable study could cure diabetes

A man checks his blood sugar levels – a daily reality for people living with type 1 diabetes.

Groundbreaking new research from Westmead Hospital clinician Professor Chris Liddle has discovered that human stem cells can be used to create insulin-producing pancreatic islets, paving the way to a cure for type 1 diabetes.

Type 1 diabetes is an auto-immune condition in which the immune system destroys the cells in the pancreas which produce insulin — the hormone that allows your body to use sugar.

It affects more than 120,000 Australians and there is no cure. The condition is managed for life with insulin injections several times a day or the use of an insulin pump.

But a study published today in the the world’s leading multidisciplinary science journal Nature has shown that islets grown from human stem cells can control blood glucose levels when injected into diabetic mice.

Professor Chris Liddle

Professor Chris Liddle — a principal investigator at The Westmead Institute for Medical Research’s Storr Liver Centre and University of Sydney — co-authored the study, which was led by researchers from the Salk Institute for Biological Studies in La Jolla, California.

According to Prof Liddle, this study used stem cells derived from human umbilical vein and human fat that were re-programmed to generate ‘human islet-like organoids’ (HILOs).

“Pancreatic islets contain multiple cell types, not just insulin-producing beta cells. The research team created three-dimensional HILOs that not only include beta-like cells [the cells that produce, store and release insulin in the islets of the pancreas], but also other supporting cell types found in normal islets,” said Prof Liddle.   

“Under the microscope, and using gene sequencing analysis, we are able to show that the three-dimensional HILOs are very similar to human islets. When the HILOs are transplanted into diabetic mice, they secrete insulin when blood glucose levels are high, just as normal islets would.”

While human pancreatic islet transplantation has been a major advancement in treating severe cases of type 1 diabetes, the availability, quality and limited cellular longevity of this approach limits its application.

Human islet-like organoids. Picture provided by the Salk Institute

Pancreatic islet transplantation currently involves implanting insulin-producing islet cells from a deceased human donor into the liver of a person with type 1 diabetes. When successful, the procedure can control blood glucose levels, reduce the frequency and severity of hypoglycaemic (low blood sugar) episodes and potentially eliminate the need for regular insulin injections.

A number of transplants are usually needed, and immunosuppressant drugs to prevent the immune system from attacking the transplanted cells are also required.

While the procedure is now funded by the Australian Government, pancreatic islet transplantation is currently limited to people with severely unstable type 1 diabetes, particularly those for whom insulin therapy alone is not effective and who experience recurrent and severe hypoglycaemic episodes.

Professor Philip O’Connell is executive director at The Westmead Institute for Medical Research and pioneered pancreatic islet transplantation in Australia.

Almost 20-years ago, he led Australia’s first pancreatic islet transplantation trials at Westmead Hospital and The Westmead Institute for Medical Research.

Today, he continues his research, aiming to improve this procedure and develop islet transplantation as a mainstream treatment for type 1 diabetes.

Professor O’Connell, who was not involved in this research study, said: “Pancreatic islet transplantation has saved hundreds of lives around the globe however, it has its limitations.  For example, pancreatic islets are taken from deceased donors, and the wait for donor islets can be lengthy. Once donor islets are obtained, not all are suitable for transplantation.

“This research indicates the potential to alleviate some of these issues.  Stem cells derived from readily available human tissues can be expanded then re-programmed into potentially unlimited numbers of islets that are suitable for transplantation.”

The Westmead Health Precinct is one of the largest health, education, research and training precincts in Australia and a key provider of jobs for the greater Parramatta and Western Sydney region.  It includes four major hospitals, three world-leading medical research institutes and the state’s largest research-intensive pathology service.