CardioRegen

Overview

Childhood heart disease (CHD) is a life-long condition that affects up to one in 100 live births. As a result, there are around 65,000 children and young adults currently living with childhood heart diseases such as cardiomyopathy, congenital or acquired heart disease. CHD is the leading cause of death and disability in children.

Over the last 20 years, research and surgical advances have resulted in an increased CHD survival rate, with more than 85 per cent of children with CHD living into adulthood.

In recent years there has been a sharp increase in the number of children with CHD hospitalised due to heart failure. Heart failure is currently resolved through a heart transplant, but there are fewer donors compared to children needing a transplant.

Current treatment involves disease management instead of treating the underlying cause.

Melbourne Centre for Cardiovascular Genomics and Regenerative Medicine (CardioRegen)

CardioRegen is made up of researchers and clinicians from Murdoch Children’s Research Institute (MCRI), The Royal Children’s Hospital (RCH), the University of Melbourne, Alfred Health and Monash University.

Our researchers are studying whether we can use stem cells (cells that self-renew) to improve the lives of people living with childhood heart disease. These regenerative stem cell technologies may be able to repair and replace damaged heart tissue to improve clinical care for patients with childhood heart disease.

Our research

Melbourne Children’s Heart Tissue Bank

Since 2018, the Melbourne Children’s Heart Tissue Bank (MCHTB) has collected over 2,000 samples from RCH patients across the departments of Cardiac Surgery, Cardiology, ICU, Anaesthetics, Pathology and Neurology. The MCHTB is a key enabler in the CardioRegen pipeline that drives several CardioRegen projects that aim to understand CHD pathogenesis by providing samples at the whole organ, cellular and DNA levels with direct links to high-quality patient data in our clinical database.

Development of bioengineered heart tissue for children with heart failure

This project aims to evaluate the safety and efficacy of a human pluripotent stem cell-derived bioengineered heart tissue patch (BHTP) for heart failure patients with CHD. We have optimised industrial-scale production of cardiac cells from human pluripotent stem cells, GMP-compatible differentiation protocols for derivation of large BHTPs and developed large animal models of paediatric heart failure in sheep for pre-clinical evaluation of BHTPs.

Drug development in stem cell models of childhood heart disease

Our team has developed protocols for generating 3D human cardiac organoids (hCO) from induced pluripotent stem cells (iPSCs) which more closely recapitulate the native tissue architecture, cellular composition, and physiology of the heart. Using this model system, we have been able to functionally test iPSC-derived cardiac organoids from CHD patients alongside their genetically corrected (i.e. isogenic) control tissues, as well as evaluate the safety and effectiveness of putative therapeutics in these tissues. Our drug screening pipeline will focus on identifying new compounds or repurposing existing drugs to promote heart regeneration in children with cardiomyopathies that culminate in heart failure.

Translation of a new diagnostic test for rejection after heart transplantation

Current care for heart failure patients requiring transplantation involves obtaining a cardiac biopsy, which is invasive and costly. We have previously developed (and patented) a transcriptomic blood test to predict low-grade transplantation rejection. The current program builds on this transcriptomic work by using flow cytometry as an accurate and non-invasive method to detect immune cell markers in heart transplant recipient blood samples. Importantly, changes to immune cell composition in paediatric heart transplant recipients will be compared to the blood of age-matched patients from the MCHTB. The aim of this work is to replace or reduce the need for cardiac biopsies in heart transplant patients.

Research team

• Professor Igor Konstantinov
• Professor Enzo Porrello
• Dr Adam Piers
• Associate Professor Mirana Ramialison
• Professor Michael Cheung
• Professor Christian Brizard
• Dr Melissa Lee
• Associate Professor Kelly Smith
• Associate Professor David Elliott
• Professor Robert Weintraub
• Professor Lea Delbridge
• Professor David McGiffin
• Professor Stephen Harrap
• Associate Professor Dan Pellicci
• Associate Professor Kim Dalziel
• Dr Li Huang
• Ms Kim An

Funding and collaborators

Funding

• The Royal Children’s Hospital Foundation
• Shine On Foundation
• Foundation for Children
• Heart Foundation
• The Kids’ Cancer Project
• Stem Cells Australia
• National Health and Medical Research Council (NHMRC)
• Australian Research Council (ARC)
• Medical Research Future Fund (MRFF)

Collaborators

• The Royal Children’s Hospital Foundation
• University of Melbourne
• Alfred Health
• Monash University

Publications

Sadek, H. A., & Porrello, E. R. (2020). Neonatal heart regeneration: Moving from phenomenology to regenerative medicine. The Journal of thoracic and cardiovascular surgery, 159(6), 2451–2455.

Lock, M. C., Tellam, R. L., Darby, J. R. T., Soo, J. Y., Brooks, D. A., Macgowan, C. K., Selvanayagam, J. B., Porrello, E. R., Seed, M., Keller-Wood, M., & Morrison, J. L. (2020). Differential gene responses 3 days following infarction in the fetal and adolescent sheep heart. Physiological genomics, 52(3), 143–159.

Sreejit, G., Abdel-Latif, A., Athmanathan, B., Annabathula, R., Dhyani, A., Noothi, S. K., Quaife-Ryan, G. A., Al-Sharea, A., Pernes, G., Dragoljevic, D., Lal, H., Schroder, K., Hanaoka, B. Y., Raman, C., Grant, M. B., Hudson, J. E., Smyth, S. S., Porrello, E. R., Murphy, A. J., & Nagareddy, P. R. (2020). Neutrophil-Derived S100A8/A9 Amplify Granulopoiesis After Myocardial Infarction. Circulation, 141(13), 1080–1094.

Konstantinov, I. E., Naimo, P. S., & Buratto, E. (2021). Commentary: Ozaki valve reconstruction in children: Is it still a valve replacement?. The Journal of thoracic and cardiovascular surgery, 161(5), 1579–1581.

Naimo, P. S., Buratto, E., & Konstantinov, I. E. (2020). Commentary: Surgery for an anomalous aortic origin of a coronary artery: To do, or not to do? That is the question. The Journal of thoracic and cardiovascular surgery, 160(3), 772–773.

View the full publication list

Contact us

CardioRegen
Murdoch Children's Research Institute
50 Flemington Road, Parkville
Victoria 3052 Australia
Email:  show email address