Using stem cells to repair and even renew damaged hearts is a potentially revolutionary treatment for heart disease. The Foundation is currently funding three research projects in this cutting-edge area of heart research.   

Damaged hearts renewed with a patient’s own stem cells

There is evidence stem cells derived from a patient’s own tissues can be ‘coaxed’ to enhance heart muscle regeneration while avoiding immune rejection. Mesenchymal stem cells (MSCs), such as those derived from adult human bone marrow or fat cells (adipocytes), have an excellent safety record and are currently at the forefront of stem cell use in orthopaedic applications such as for tendon repair.

Over the past year the research team have progressively advanced their work on the regenerative effect of MSCs that are genetically modified with the Pim-1 survival enzyme. They have used a heart damaged by heart attack where they switched to using SPECT-CT imaging to examine the extent of heart damage and its response to cell therapy. A journal article has been submitted on the success of this methodology.The studies in this model, that closely resembles human heart attack, have progressed more slowly than anticipated, but with valuable new skills in the research group and new initiatives in their experimental procedures, they are hoping to have definitive outcomes by mid 2012.

Project Title: Efficacy of genetically engineered mesenchymal stem cells for regeneration of the post infarct heart – assessed by cardiac magnetic resonance imaging.
Investigators: Prof Stephen Hunyor, Prof Mark Sussman (State University of San Diego, USA)
Funded since: 2009

Helping the heart heal itself

The previous paradigm in thinking that saw the heart inexorably losing muscle cells with ageing and progressively fading away, was overturned when the Chernobyl nuclear disaster showed that radioactive tracers can be incorporated into newly developing heart muscle. However, the sluggish rate of turn-over of these cells, resembling an idling car engine, is too slow to assist a heart that has suffered a significant insult from heart attack or coronary disease. Thus, various ways are being examined to ‘tickle up’ so called ‘resident’ cardiac stem cells that we all have in small pockets of our hearts, to fast track them for repair.

There is increasing evidence that a significant part of the action of administered stem cells acts to facilitate heart repair and regeneration via so-called paracrine effects. In this study researchers have linked skills in molecular and developmental biology to examine the combined effect of two powerful modifications to stem cells – with the Pim-1 survival enzyme and the drug diazoxide (DZ) which act on different aspects of energy production in the heart’s mitochondria. Both treatments prevent programmed cell death (apoptosis) but while Pim-1 has a drawn out effect, DZ acts powerfully in a shorter timeframe. These complementary modes of action should prove useful in the hostile ‘environment’ after a heart attack. The research team is encouraged by early studies showing that DZ does in fact enhance one of the protective molecules (GSK3ß) that affect cardiac cell death by making them more resistant to toxins released when deprived of oxygen (oxidative stress).

Project title: Effect of short and long-term stem cell pre-conditioning on heart regeneration

Investigators: Prof Stephen N Hunyor, Jason Seow

Funded since: 2011

Repairing heart muscle with adult stem cells

Recent evidence shows that cardiac stem cells do reside in the heart itself and play a role in repairing “wear and tear” as well as the effects of more significant damage, opening up new opportunities for heart regeneration.

This project is investigating the role of growth factors in normal heart development, as well as repair following damage to the heart. Results indicate that growth factors (Wnt) play a crucial role in maintaining the status quo of cardiac stem cells, as well as the generation of new heart cells. Further work is focused on an effective treatment for damaged heart tissues through balanced production of muscle and blood vessels to regenerate the damaged heart.

Project title: Repair of the damaged heart and the role of Wnt growth factors

PhD candidate: Jason Seow

Supervisor: Professor Stephen Hunyor

Funded since: 2007