Brighter futures for heart disease patients

From creating pulsing heart cells in petri dishes to developing bioengineered heart patches made from stem cells, discover the incredible ways that researchers at the RCH and MCRI are using tissue samples to change health outcomes for childhood heart disease (CHD).

Each year, one in every 100 children born are impacted by CHD. As CHD continues to be the leading cause of death and disability in children across Australia, cardiology patients at the RCH aren’t just receiving the best care, they’re also helping to shape breakthroughs for future generations.

Thanks to generous support from Shine On Foundation and the Loti and Victor Smorgon Family Foundation, the Melbourne Centre for Cardiovascular Genomic and Regenerative Medicine (CardioRegen) research program is using genomics and stem cell medicine to help deliver better outcomes for children diagnosed with CHD.

Despite the many incredible medical advancements across the past 20 years which have helped to dramatically increase the survival rate of CHD conditions, the number of children being diagnosed with each year continues to rise.

“As the National Centre for Paediatric Heart Failure and Heart Transplantation, the RCH is seeing a sharp rise in the number of children with CHD hospitalised due to heart failure, a condition whereby the heart is unable to pump enough blood to meet the needs of the body. There are only a few ways to treat heart failure. In mild cases, you can look at drugs or put the child on a ventricular assist device (VAD) which is a machine that breaths and pumps blood for them. However, a large majority of cases require a heart transplant,” said Dr Adam Piers, Program Manager of CardioRegen.

“Sadly, the gap between the number of donors and the number of children with heart failure requiring transplantation is growing. Even if a child does get a transplant, only 50 per cent of them are alive in five years after it, so the transplant is in no way a cure. That’s why CardioRegen is working to come up with therapies that will hopefully stop children needing a transplant, but if they do, will improve their outcomes.”

Led by Professor Igor Konstantinov and Associate Professor Enzo Porrello, CardioRegen brings together a dedicated team of clinicians and researchers from across the hospital and the MCRI to understand the causes of CHD and to help discover new treatments.

The first phase of the CardioRegen project was to establish the Melbourne Children’s Heart Tissue Bank, also referred to as the biobank, which is a repository of heart tissue and blood samples which the team have collected from consenting RCH patients who have received treatment for CHD over the past three years.

“Using biobank samples, we’ve been able to model CHD in a dish and use genomic diagnosis and stem cell modelling to come up with three new future therapies for CHD, which all have the opportunity to improve the clinical outcomes for children with diagnosed with heart conditions”, said Adam.

“The first therapy we’re looking at is developing a bioengineered heart tissue patch. Made of millions of heart cells, which are derived from biobank stem cells, the patch will be attached to the exterior wall of the heart and grow with the patient. The end goal is to improve the function of the heart, potentially removing the need for a heart transplant. If the child does need a transplant, the patch may buy them much needed time.”

“The second therapy is centred around drug development. Again, we will use the stem cells from the biobank to create heart cells. From there we will be able to look for pre- existing medications or drug compounds that can promote better outcomes for children. This might be heart regeneration for certain conditions, or the identification of specific drugs to treat cardiomyopathies for other patients.”

“The final therapy involves creating a new diagnostic screening tool for heart transplant rejection, which is something Igor is incredibly passionate about. Currently, when a child has a heart transplant, they are required to have frequent diagnostic tests to ensure the heart isn’t rejecting. This requires them to come to the hospital every month for the first six months, and then every few months for two years after that for a biopsy. Not only is it expensive, but it is awful for the child. Plus, for families who live interstate, it often means relocating to Melbourne for a period of time after the transplant.”

“Through the biobank, we’ve been taking blood samples from patients at each biopsy and looking at the immune cells in the blood. We have then been able to link back to their rejection score to see if there are patterns that emerge. While we’re only in the research stage, we are seeing some promising patterns, and ideally, down the track we will be able to replace the biopsy with a blood sample that would be taken at their local pathology centre. While it isn’t stopping the heart rejecting, we hope that it will improve their quality of life as they won’t need to have invasive surgeries or even relocate.”

Thanks to philanthropic funding, the CardioRegen team is well positioned for phase two of the project, which will see an expansion of pre-clinical testing for the patch. They will also enter pre-clinical work for the drug therapy and diagnostic testing projects, again with the aim of entering clinical trials in the next five to 10 years.

“The support that we have received from both Shine On Foundation and the Loti and Victor Smorgon Family Foundation have been integral to the project. Not only did this funding allow us to establish the Melbourne Children’s Heart Tissue Bank, but we have also been able to leverage it to secure other project grants,” said Adam.

“We hope that within the next five to 10 years, we will be well on the way to delivering cardiac regenerative medicine on campus.”