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First BioArtificial Heart Created: Major Breakthrough Could End Donor Organ Shortage

By Roger Highfield, Telegraph Media Group Limited, January 13, 2008

An unprecedented feat that could signal the beginning of the end of organ shortages has been achieved by doctors who have stripped down and refurbished a dead heart so that it can beat again.

According to the American team, the shortage of replacement hearts and other organs could be overcome with the new research. The need for anti-rejection drugs could also be completely avoided.

The research, conducted by researchers at the University of Minnesota, could pave the way to a new treatment for the 22 million people worldwide who live with heart failure. The journal Nature Medicine described the the world's first beating, retooled "bioartificial heart".

To begin, cells were removed from a whole heart. The blood vessel structure, valves, chambers, and full architecture of the heart were left intact, and repopulated with new cells.

"We just took nature's own building blocks to build a new organ," says Dr. Harald Ott, a co-investigator who now works at Massachusetts General Hospital. "When we saw the first contractions we were speechless."

The work has huge implications: "The idea would be to develop transplantable blood vessels or whole organs that are made from your own cells," said Professor Doris Taylor, director of the Center for Cardiovascular Repair, Minnesota, principal investigator.

Virtually any organ with a blood supply could be created with the new method. The list includes the pancreas, lungs, kidneys, and liver.

Although costs make it prohibitive at present, Taylor is ready to grow a human heart. But she admits that the method is "years away" from being used in hospitals.

"We could begin with human cells and pig or human scaffold now but creating the larger bioreactors (the vessels in which the organs are grown) and generating the reagents and growing enough cells would cost tens of thousands of dollars for each heart at this point."

"That is just too expensive to answer basic questions. We of course want to move in that direction, but funding is limited. As we can we will go forward - perhaps one heart at a time."

Individuals face life long immunosuppression after an organ transplant. And over the long term, kidney failure, diabetes, and high blood pressure are the trade off for heart failure when using drugs to prevent rejection. Even getting to the point of performing the transplantation operation is difficult since donor organs are limited.

Researchers believe a new heart created by decellularization is much less likely to be rejected by the body since the heart is filled with the recipient's own stem cells.

And once placed in the recipient, in theory the heart would be nourished, regulated, and regenerated similar to the heart that it replaced.

"We used immature heart cells in this version, as a proof of concept. We pretty much figured heart cells in a heart matrix had to work," Professor Taylor says. "Going forward, our goal is to use a patient's stem cells to build a new heart."

As for the source of the cells from a heart patient, she says: "From muscle, bone marrow, or heart; depending on where the science leads us."

Professor Taylor says that decellularization shows potential to change how scientists think about engineering any organ, even though heart repair was the initial goal.

"It opens a door to this notion that you can make any organ: kidney, liver, lung, pancreas - you name it and we hope we can make it," she added.

According to UK Transplant, 81 people are waiting for heart transplant. Even though 28 patients died while waiting for a transplant last year, 155 patients had their lives saved or transformed by a heart transplant.

Typically, only 3,000 transplants are performed every year, despite more than 9,000 patients making up the waiting list nationally. While waiting, 1,000 people died last year.

A UK Transplant spokesman says: "These developments offer long term hope and long may they continue but the real problem now is a desperate shortage of donated hearts."

Dr. Tim Chico, Consultant Cardiologist, University of Sheffield, says: "This is an ingenious step towards solving a massive problem. Heart failure (an inability of the heart to pump sufficient blood, usually after a heart attack) is increasing in the UK."

"A chronic shortage of donors for heart transplantation makes stem cell therapy appealing. The study is very preliminary, but it does show that stem cells can regrow in the 'skeleton' of a donor heart. However, it will take a lot of further work to assess whether this will ever be a viable option for patients."

Professor Wayne Morrison, Director of the Bernard O'Brien Institute of Microsurgery, Melbourne, comments: "This is the first time a whole organ has been tissue engineered outside the body."

"They have demonstrated that they can create a heart that looks like a heart and is shaped like a heart and, most excitingly, that they can re-establish the blood vessels that were originally there. It is this 'regrowth' of the blood vessel cells that gives the potential in the future to connect this structure to a blood vessel in the body and then get circulation to go through it."

"This very exciting study," comments Dr. Jon Frampton, University of Birmingham. "Although this is only a first step requiring considerable follow-up development, the study nevertheless represents an exciting breakthrough that will eventually make the prospect of repairing damaged hearts a reality and will also be an approach that can be extended to other organs."

Dr. Anita Thomas at the Australian Institute for Bioengineering and Nanotechnology, University of Queensland, adds: "There is one more major step to achieve before we can proceed any further: we need to see what happens when these artificial hearts are placed in a recipient animal for any length of time. The authors of the article have the necessary skills and yet have not reported their results. We wait with anticipation for their next publication."

There have been advances in growing heart tissue in the laboratory but the complex architecture and intricacies of the body's primary pump have to be mimicked exactly in order to be fully successful. Until now, the problem has been how to create a 3D scaffold that could do this.

This is why "decellulariazation" became the method of choice for Professor Doris Taylor and her colleagues. The process leaves only the extracellular matrix, the framework between the cells, intact, along with the plumbing and heart valves. This is accomplished by using a detergent to remove all the cells from the organ - in this case, an animal cadaver heart.

Taking immature cells that came from newborn rat hearts, researchers injected rat hearts with this mixture and placed the structure in a sterile chamber in the lab to grow. This was done after first removing the cells from both rat and pig hearts using a detergent.

Professor Taylor said the results were very promising. Contractions were observed in the hearts four days after seeding the decellularized heart scaffolds with cells. Even though it was only at two percent of the efficiency of an adult heart, the hearts were pumping eight days later.

A study at of the hearts at the cellular level revealed that the "cells have many of the markers we associate with the heart and seem to know how to behave like heart tissue."


 

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