Regenerative Properties of the Newborn Heart Offers Hope for Those With Congenital Heart Disease – The Epoch Times

Researchers from the Murdochs Children Research Institute (MCRI) are developing new treatments for congenital heart disease that could enable children born with birth defects can regenerate the damaged organ.

In 2011, Prof. Enzo Porello, who is nowhead of the Heart Regeneration Laboratory at the MCRI,demonstrated the regenerative properties of newborn mouse hearts at the University of Texas Southwestern Medical Centre. Prior to this research, the capacity of mammalian hearts to regenerate was a debated topic.

This sort of changed our thinking of what was possible in terms of stimulating the human heart to regenerate itself following damage, such as a heart attack, Porrello said, reported theAustralian. And I guess this also fuelled my own interest in my subsequent career in the area of regenerative medicine.

After hearing about cases where newborns recovered from massive heart attacks, Porello began to explore the regenerative properties of human newborn hearts.

In 2017, Porello and Prof. James Hudson manufactured living and beating heart tissues from stem cells in a laboratory at the University of Queensland.

Porello said that although other scientists had grown heart muscle cells from stem cells, nobody had grown the cells as miniature complex three-dimensional tissues. Additionally, they were not able to grow such tissues in a format compliant to drug development, he said.

And thats really the technological breakthrough that we were able to make.

According to the Australian Institute of Health and Welfare, approximately 9 out of every 1,000 babies born around the world will be born with congenital heart disease. In Australia, it is estimated that 2,400 babies are born with congenital heart disease annually, while in America, nearly one percent of all babies born are estimatedby the Centre For Disease Control to have the condition.

Porello said that, at the moment, if a child develops heart failure and doesnt respond to standard frontline therapies, a heart transplant is their only option. Children in this situation are put on a transplant waiting list, and whilst waiting for a heart to become available, they are put on mechanical support.

Heart transplantation is limited by organ donor availability, and its also limited by the need for lifelong immunosuppression in those patients, Porello said.

And so if were able to develop these bioengineered heart tissues from stem cells, this could potentially prevent or delay the need for heart transplantation in these very unwell individuals with end-stage heart failure.

Porello said that the ultimate goal of his research is to harness the self-repairing capacity of the newborn heart and to develop drugs that waken the hearts dormant regenerative abilities so that the organ may repair itself after damage.

I would say that based on recent studies in the field in the past 10 years since we first made our discovery in mice, we are certainly getting closer, he said.

There is sort of proof of concept that this is possible now, at least in mice, and the question is whether or not we can now make that a therapeutic reality in humans.

The first step in creating these complex heart tissues is attaching special molecules to stem cells; these molecules trigger the cells to morph into heart muscle tissue. The heart tissues are then developed in a plastic culture dish that consists of 96 tiny wells.

The geometry of the well is designed in such a way that the heart tissues spontaneously form when the heart muscle cells are inserted into the well, Porrello said.

He said that within each well of the device are tiny elastic micropillars; the pillars function as elastic cantilevers since they are attached to the dish at only one end and extend horizontally to the dish. The heart muscle cells condense around these cantilevers to produce tiny miniature beating heart tissues that contract around the micropillar; every time the tissue contracts, the micropillar within it deflects.

Porello said that the device enables researchers to measure the force that the tissues are generating, allowing them to observe how fast the tissues are beating and whether they display any irregularities in their heartbeat. These capabilities are useful for treatment testing because the effect that medication or genetic manipulations of stem cells have on the tissues heartbeat can be seen.

And so it serves as a pretty powerful platform for looking at drug responses, but also modelling genetic forms of heart disease.

Were actually now scaling up these tissues and growing very, very large bioengineered heart tissue patches that can be implanted onto the heart.

In an email to The Epoch Times, Porello said in the future that bioengineered heart tissue patches could be used to treat adults with heart failure, and alternative approaches are already being trialled.

Our bioengineered heart tissues could also be used to support the failing heart in adults with underlying heart disease.

Further studies are required to confirm that our bioengineered heart tissue patches are safe and effective in animal models before progressing to human trials. These pre-clinical safety and efficacy studies are underway.

He noted that although significant advances and a better understanding of the hearts regenerative mechanisms have been made in recent years, using this knowledge to develop a safe and effective drug is a slow process.

It typically takes 10 years and around $1 billion dollars to develop a new heart failure drug and take it all the way through to clinical approval. We are at the beginning of that journey.

We need to gain a better understanding of the fundamental biology underlying heart regeneration before we can develop effective treatments.

Porello is now applying his discoveries in a clinical context at theMCRIto reach his goal of regenerating human hearts. The regeneration research at the institute has two branches, the first focuses on studying diseases using lab-grown models of the heart muscle. The models are made using blood and tissue samples collected from sick children at the Royal Childrens Hospital in Melbourne.

He said that this branch of the research enables the team to model the genetic basis of the disease in any individual.

Were using this technology to model childhood heart disease, trying to understand its causes, and then using those genetic models of heart disease to test and develop therapeutic approaches to treat those conditions, he said.

Porello said that the second branch of the research performed at the MCRI explores the regenerative approach to growing the very, very large bioengineered heart tissue patches. The researchers plan is to eventuallyimplant the patches into a heart to function as a biological assistance device that supports the function of the heart.

If it works, it would be transformative, Porello said.

Stem cells have been used in medicine for more than fifty years, with the most common stem cell procedure currently beingbone marrow transplantsalso known as hematopoietic stem cell transplantsused to treat patients with blood cancers such asleukemiaand blood disorders such assickle cell diseaseandthalassemia.

More recently, skin grown from stem cells has been used to treat extensive burns, and stem cells from fat (adipose tissue) have been used as tissue fillers.

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Regenerative Properties of the Newborn Heart Offers Hope for Those With Congenital Heart Disease - The Epoch Times