Heart Regeneration
Our vision is to transform the treatment of childhood heart disease using stem cell technologies.
Frontline therapies for childhood heart disease have not changed in over 30 years. The Heart Regeneration and Heart Disease Team aim to transform the treatment of childhood heart disease using stem cell technologies.
Our laboratory harnesses the power of pluripotent stem cells to create human models of disease as a platform for therapeutic development. Our research pipeline spans the full spectrum from the operating theatre to the single cell, taking full advantage of the unique capacity of the Melbourne Children’s campus.
The Team are generating heart organoids from patient stem cells, which can investigate genetic causes of childhood heart disease in patients, as well as to screen for drugs that damage or regenerate heart tissue.
Finally, we are also harnessing the regenerative potential of stem cells to create bioengineered heart tissue to treat heart failure in children.
For more information about our research pipeline:
More information
- Visit our Heart Disease page
- Learn more about our Melbourne Children’s collaborations at the Heart Failure Flagship
- Visit our A-Z Child and Adolescent Health section for more information about Childhood Heart Disease
- Learn more about Stem Cell Medicine
- Our team collaborates with reNEW on several core projects
Theme Director
Team Leaders
Group Members
Our projects
CardioRegen
Using genomics and stem cell medicine to understand the causes of CHD and for the discovery of new treatments.
Read more...Treating heart failure using bioengineered heart tissue
We are evaluating the safety and efficacy of a human pluripotent stem cell-derived bioengineered heart tissue patch for heart failure patients with childhood heart disease.
We have optimised industrial-scale production of cardiac cells from human pluripotent stem cells, and developed good manufacturing practice-compatible differentiation protocols for derivation of large, bioengineered heart tissue patches. We have also developed large animal models of paediatric heart failure in sheep for pre-clinical evaluation of the bioengineered heart tissue patches.
Promoting heart regeneration in childhood heart disease using pro-proliferative therapeutics
Our team have developed protocols for generating 3D human cardiac organoids from induced pluripotent stem cells 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 induced pluripotent stem cell-derived cardiac organoids from patients alongside their genetically corrected control tissues, as well as evaluate the safety and effectiveness of putative therapeutics in these tissues.
Our group also uses human cardiac organoids to model key aspects of human heart development including regeneration and maturation. The ultimate goal of this work is to identify a drug or molecule that can stimulate heart muscle cells to divide and regenerate in children with heart disease.
Generating bioengineered heart valves to treat childhood heart disease
Current valve prosthetics used for surgery are made from animal tissue and are not compatible with the small hearts of children. We have engineered a novel stem cell-derived tissue for the fabrication of precision-made valve bioprosthetics.
We are aiming to benchmark our current prototypes to native human heart valve tissue using single-cell RNA sequencing and histology.
Funding
- National Health and Medical Research Council (NHMRC)
- Australian Research Council (ARC)
- Medical Research Future Fund (MRFF)
- RCH Foundation
- HeartKids
- Heart Foundation
- reNEW
- Loti and Victor Smorgon Family Foundation
Collaborations
- Ben Parker, The University of Melbourne
- James Hudson, QIMR Berghofer Medical Research Institute
- Paul Gregorevic, The University of Melbourne
- Igor Konstantinov, Royal Children's Hospital
- Michael Cheung, Royal Children's Hospital
- Robert Weintraub, Royal Children's Hospital
- Christian Brizard, Royal Children's Hospital
Our publications
Sim CB et al. Hudson JE, Porrello ER. Sex-specific control of human heart maturation by the progesterone receptor. Circulation. 2021 Apr 20; 143(16):1614-1628.
Mills RJ et al. Porrello ER, Hudson JE. Drug screening in human PSC-cardiac organoids identifies pro-proliferative compounds acting via the mevalonate pathway. Cell Stem Cell. 2019. 110(1): 187-92.
Quaife-Ryan GA et al. Hudson JE, Porrello ER#. Multicellular transcriptional analysis of mammalian heart regeneration. Circulation. 2017. 136 (12):1123-1139.
Mills RJ et al. Porrello ER, Hudson JE. Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest. Proc Natl Acad Sci USA. 2017.14(40):E8372-E8381.
Voges HK et al. Porrello ER, Hudson JE. Development of a human cardiac organoid injury model reveals innate regenerative potential. Development. 2017. 144 (6):1118-1127.