Leading the way

Murdoch Children's Research Institute (MCRI) is one of few institutes globally with the in-house capacity to complete the end-to-end process of inducing, editing and utilising induced pluripotent stem cells for high-throughput drug-disease modelling and discovery.

The advancements will hopefully help patients like James. Now 10, James was born with the serious and rare condition hypoplastic left heart syndrome (HLHS). Only half his heart functions properly.

His mum Nikki says the team caring for James has been amazing, and they are now looking to research that could find a treatment or cure for HLHS.

"My family needs options," she says. "To get those options we need research by people who have the drive, the vision and the knowledge to find the answers we so desperately need."

MCRI Cardiac Regeneration Laboratory Head Associate Professor Enzo Porrello says patients like James inspire the research and underline its importance. "By recreating heart tissue with a patient's stem cells, we hope to eventually treat these serious conditions."

Scientific discovery pairs deep, insightful thinking with good old-fashioned elbow grease.

The extraordinary vision and indomitable working spirit of the team behind the MCRI Stem Cell Medicine program is taking us into areas only dreamed of a few years ago.

Our researchers are creating, manipulating and screening stem cells to develop personalised and novel treatments for rare and serious diseases.

MCRI's workhorse of the lab is induced Pluripotent Stem Cells (iPSC). These are created in the lab from a patient's blood and skin cells, which are turned back into stem cells. These redeveloped stem cells can be transformed into specialised cells and miniorgans to test and study in the laboratory.

Our iPSC expertise now encompasses a range of tissues, including kidney, heart, brain, blood, muscle, bones and immune cells. With the support of our in-house iPSC Derivation and Gene Editing team, MCRI researchers have access to bespoke iPSCs in the quest to find new treatments for currently incurable diseases.

Professor Melissa Little, Stem Cell Medicine Program Leader, says: "Our Stem Cell Medicine program is opening a door to a whole new world of treatment possibilities. With the advent of disease modelling, drug screening and cellular therapy technologies, we hope to deliver more effective and targeted treatments for patients.

"Ultimately we aim to deliver more effective and personalised treatments or cures for every child."

A model solution

The multi million dollar Stafford Fox Medical Research Foundation Stem Cell Medicine Disease Modelling and Drug Screening Facility will scale up and streamline disease modelling and drug screening to identify safe and effective treatments for childhood diseases and disorders. Targets include asthma, genetic heart and kidney disease, and Type 1 diabetes.

The fully integrated facility is the first of its kind in Australia to combine a $3 million dollar, four-in-one robotic system with advanced stem cell production facilities.

Its key pieces of equipment were installed in 2019, making the facility one of only a handful in the world able to create, grow and differentiate patient stem cells, perform high-throughput drug screens and then visualise the cellular outcomes in 3D.

Dr Alejandro Hidalgo-Gonzalez heads the facility and says its ability to conduct experiments faster and with even greater accuracy will enable his team to perform 4000 drug screens on human samples in the time it would take to process 100 manually.

This means faster answers for patients, improved treatment choices and more time for researchers to search for their next big breakthrough.

The flexibility, support and generosity of the Stafford Fox Medical Research Foundation (SFMRF) over many years has been crucial to establish MCRI's Stem Cell Medicine program.

"We're so proud to have been supporters of the Stem Cell Medicine program at MCRI since its origin in 2012. It is extraordinary to see the heights the program has already reached, and astonishing to think what's to come," says SFMRF Trustee Ken Wallace.

Alejandro, whose appointment was possible thanks to the SFMRF, says MCRI's location on the Melbourne Children's campus provides invaluable opportunities to rapidly translate his team's work into real-world outcomes. "We have built a world-class facility, open to researchers across a range of childhood diseases," he says, referring to the way that stem cell modelling is now part of a wide range of research into conditions including autism and speech disorders.

Outside MCRI, the facility has the capacity and ability to support the work of research groups within the Parkville Precinct and beyond.

"In 2019 we moved closer to our goal of making it standard practice to model the disease of a patient with a serious genetic condition so that we can create an effective treatment designed personally for them," says Alejandro. "This will be life-changing for many patients and their families. For some it may mean better treatment results, and for others possibly even a cure."

Generating new therapies

Organ regeneration, cell therapies and tissue engineering all show immense potential.

This ground-breaking work could ultimately treat thousands of children like James. It includes:

  • Revolutionising congenital kidney disease research by growing mini-kidneys to model patient disease and seek targeted therapies
  • Improving outcomes for children who need bone marrow transplants because of leukaemia, the most common childhood cancer
  • Using patient stem cells to create models to better understand how the brain develops and how it can misdevelop, leading to rare but devastating conditions such as leukodystrophies, RETT syndrome, autism and mitochondrial diseases
  • Searching for cures for congenital heart disease by recreating human heart tissue derived from patients' own stem cells to understand how the heart could regenerate. In Australia, congenital heart diseases affect up to 10 of every 1000 babies born. Our mini-hearts, grown in the laboratory, allow us to investigate the causes of these heart diseases, test heart drug toxicity and eventually bioengineer heart tissues for transplantation.