Novel approach to create liver organoids

Posted: 12th August 2017

The 1982 classic film ‘Blade Runner’, set in Los Angeles in 2019, brought to life a world in which artificial humans could be engineered entirely in a lab.

While the real world hasn’t quite caught up with Ridley Scott’s imagination, researchers in SVI’s O’Brien Institute Department are working to develop lab-grown liver ‘organoids’ to help those affected by liver disease.

In 2016, Dr Geraldine Mitchell and her long-time colleague Professor Wayne Morrison were awarded an NHMRC Project Grant to fund the development of what they call a ‘liver in a dish.’ The ultimate aim of their work is to grow an ‘organoid’ derived from a patient’s own cells, to be used as a source of tissue for liver transplantation.

Geraldine says that liver disease is more common than is generally recognised in Australia. It is associated with common conditions such as obesity, diabetes, viral hepatitis, excessive alcohol intake and cancer.

“The only current treatment for advanced liver disease is transplantation and because there are not enough organs to meet demand, many patients die before they can get a transplant,” says Geraldine.

Geraldine’s research involves a multi-disciplinary team, including researchers and surgeons, whose focus is on using human cells to ‘grow’ a liver that could be up-scaled in the future to be used for transplantation, or as a platform on which to test drugs to treat the disease

Geraldine explains that without the involvement of surgeons at St Vincent’s Hospital, and in particular, her PhD student, Surgical Fellow, Dr Kiryu Yap, the project would not be viable.

“Kiryu is often called, both in and out of hours, to collect liver tissue from patients having surgery who have agreed to us using very small segments of their liver for our experiments. For this project, access to human cells is paramount.”

Kiryu says that one of the major hurdles is the need for cells in the organoid to get enough oxygen. The team are approaching this problem by engineering a vascular system for the tissue, derived from human support cells that can form blood vessels and secrete growth factors to help liver development.

Other components include a porous scaffold that provides a physical support upon which the cells can grow and a special gel, which provides other factors that promote the cells’ survival.

Ultimately, the team intend to use stem cells from a person with liver disease to grow liver tissue for transplantation. Geraldine says that this is the most clinically feasible method to generate the millions of liver cells that would be required for personalised organoid generation.

Even though the promise of genetically identical replacement body parts remains the stuff of science fiction, the way is being paved by Geraldine and her team.

For more information please see: Vascular biology