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"Ghost" hearts from a pig and the patient's stem cells will replace the need for heart donations

Today, patients needing a heart transplant have to join a waiting list, and hearts become available when someone else dies. Because there are not enough hearts, only critically ill patients are put on the waiting list

By: Doris Taylor, Professor of Regenerative Medicine, University of New Hampshire

A "ghost" heart is a pig heart that has been prepared so that it can be transplanted into humans. Provided by Doris Taylor
A "ghost" heart is a pig's heart that has been prepared so that it can be transplanted into humans. Provided by Doris Taylor

Heart disease is the leading cause of death in the world. The World Health Organization estimates that 17.9 million people die from heart disease each year, 32% of global deaths.

Doris Taylor is a scientist working in the field of regenerative medicine and tissue engineering. Her work focused on creating customized functional human hearts in the lab that could eliminate the need for donors. Taylor called these hearts "ghost hearts".

In March 2023, Taylor spoke at the Amazing Solutions 2023 conference in Naples, Florida, about Ghost Heart and her journey to create it. Below are edited answers to questions from The Conversation. Taylor also appeared on Guy Kawasaki's Remarkable People podcast.

What are the biggest challenges facing organ donation today?

Today, patients needing a heart transplant have to join a waiting list, and hearts become available when someone else dies. Because there are not enough hearts, only critically ill patients are put on the waiting list. The US performs about 11 heart transplants a day, and every day there are more than 3,000 people waiting for a heart.

Even when organs are successfully transplanted, it is not a Hollywood fairy tale. A person who receives an organ transplant actually replaces one disease with medical complications and other diseases. Medicines needed to prevent rejection can cause high blood pressure, diabetes, cancer and kidney failure. These are serious medical problems that also affect people emotionally, financially and physically.

About 18% of people die in the first year after a transplant.

Doris Taylor lectures at the Amazing Solutions Conference 2023

What is the so-called "ghost heart"? How It Works?

A ghost heart is a heart that has had its cells removed. All that remains is the heart frame, or skeleton. It is called a ghost heart because the removal of the cells causes the heart to turn from red to white. It is not possible to work with a human heart as a skeleton, as there is a low availability of human hearts for research purposes.

So my team and I turned to the closest thing: pork heart. Pig hearts are similar to human hearts in terms of their size and structure. Both have four chambers - two atria and two ventricles - responsible for pumping blood. Already today structures from pig hearts, such as valves, are safely used for transplantation into humans.

To remove the cells, the pig's heart is gently flushed through its blood vessels with a mild detergent to remove the cells. This process is called cell removal by perfusion. A cell-free heart can then be re-infused with new cells – in this case, the patient's cells – thus creating a personalized heart.

What role do stem cells play in heart formation?

If we were to arrange the cells necessary for an average 350 gram human heart, they would stretch for 66,000 km. If we stacked them on top of each other, they would add up to 2 billion rows of cells, or enough to fill seven movie screens. But heart cells do not divide. If they were, hearts would probably be able to repair themselves.

In contrast, stem cells do divide. They can also differentiate into special cells - in this case, heart cells. Nobel laureate Dr. Shinya Yamaneka discovered a method to create stem cells from blood or skin cells of an adult. My team and I used this method to obtain stem cells, and then grew billions of such cells. The team then used chemicals to make them turn into heart cells. We used this method to obtain billions and billions of heart cells.

The first time I saw heart cells beating in a plate - my life changed. But although the cells are alive and beating, they are not a heart. To be a heart, these cells have to be placed in a way that allows them to become a unified organ, mature and be able to pump blood. In a human body, this happens during embryonic development. We had to reproduce this ability in the laboratory.

In 2022, a pig's heart that underwent genetic engineering to reduce rejection and improve the reception of the organ - was transplanted into a human. Why is it better to build a heart from scratch using a pig skeleton?

Let me be clear: any heart is better than no heart at all. And intersex organ transplantation – the process by which non-human animal organs are transplanted into humans – has opened doors for all scientists in this field.

The patient received a genetically edited pig heart. Human genes were added, and some of the pig genes were removed, but the heart still consisted mostly of pig cells within the pericardium. As a result, the person had to take anti-rejection drugs that suppressed the immune system. And unbeknownst to the doctors, the heart carried a virus found in pigs that finally killed the patient two months after the transplant.

I believe that these kinds of problems are avoided with the ghost heart. My team removes the porcine cellular material from the skeleton, leaving only the protein structure and vascular channels behind. The proteins are so similar to human skeletal proteins that they do not seem to cause rejection.

What are the biggest challenges facing Ghostheart's development efforts?

My team and I encountered two main obstacles. The first is the time and cost of growing the cells. The second is to allow the heart to mature after the cells are inserted into it - all while maintaining sterility without antibiotics. My lab and our partners had to actually reconstruct a heart outside the body and build a kind of artificial human body that provides food, temperature control, oxygen and other foods as well as blood pressure and artificial blood flow - we call it a bio-heart cradle, in which the heart is placed. We need to train the immature heart cells to work together and grow them to be strong enough to pump blood, we need to figure out how to feed them and provide them with oxygen without lungs, and maintain sterility without an immune system. This is a huge task.

I liken it to a symphony where each part has to come in at exactly the right time to create a complex and beautiful song - but if one part is not ready in time, everything falls apart. My job is to be the conductor of the orchestra.

Where do you see the future of organ donation in 30 years?

Today, organ donation lags behind the needs. Scientists aim to change this by increasing the number of donors, making more organs available by regenerating them where possible and building new technology – as my team and I are doing with the ghost heart. All to satisfy demand. But access to treatment is not equal. In fact, organ transplantation is a huge issue of health inequality. Today, the organ transplant system is failing non-white people. For example, African Americans have a higher rate of heart failure but are less likely to receive hearts.

As science advances, scientists have the opportunity to make organs accessible and provide organs that do not require toxic and expensive drugs. I look forward to that day and work on it every day to help create it.

Most people know months to years in advance that they need a transplant. Generally, the current wait time for a heart is about a year for white Americans but longer for African Americans, while the data for Latinos and Asians is less clear. In other organs, the wait can be 3 to 5 years. Not only is this a long period - it is an unfair waiting period that needs to change.

Building a heart is a 24/7, 365 days a year endeavor. The team and I are committed, together with our supporters, to take advantage of the opportunity to build hearts earlier and to change the field of heart transplants from emergency surgeries to planned surgeries in hospitals, and to do so in an equitable manner.

For the article in THE CONVERSATION

More of the topic in Hayadan:

2 תגובות

  1. Why not print the skeleton in XNUMXD, but, each time build another section and another section, and then in each section you deal with a small part (the size of the small heart they developed in Tel Aviv) this will simplify the problem to something that you know how to deal with.

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