US scientists have for the first time made a beating heart in a laboratory using heart tissue from dead rats and pigs to make a framework and seeding it with live cells.
The research is the work of scientists at the University of Minnesota and is published in the January 13th early online issue of Nature Medicine.
The researchers used a process known as whole organ decellularization, where essentially all the cells of a heart are removed, leaving only those that constitute the physical framework, the extracellular matrix or “scaffolding” between cells.
Principal investigator, Dr Doris Taylor, who is director of the Center for Cardiovascular Repair, Medtronic Bakken professor of medicine and physiology at the University of Minnesota, said:
“The idea would be to develop transplantable blood vessels or whole organs that are made from your own cells.”
Every year, over half a million Americans are diagnosed with heart failure, and 5 million are living with the disease. A shortage of donor hearts means that 50,000 people die every year in the US.
The idea of providing transplant patients with a “bioartificial” heart, or replacing part of a diseased heart with a working component grown in the lab, has been considered theoretically possible for some time, and this study has taken a first step into turning theory into practice.
Before this study, scientists had managed to generate heart tissue in the lab, but making a three-dimensional scaffold that imitates the complex architecture, had been somewhat of a mystery, explained Taylor.
There are three parts to the challenge of growing a bioartificial heart: engineering the architecture of the organ, making and mimicking the cell composition, and activating the pumping action.
Taylor and colleagues “cleaned” the cells off the hearts of dead rats and pigs using detergents. This process, called decellularization, removed all but the underlying extracellular matrix, leaving enough scaffolding parts, such as blood vessels (vascular architecture), valves, and heart chambers, to create the framework of a heart.
To mimic the heart cells, they then reseeded the framework with progenitor cardiac and endothelial cells from newborn rat hearts and put it in a sterile environment to grow.
They kept 8 of the “constructs” for up to 28 days in a bioreactor that simulated heart physiology.
After four days, contractions started, and after 8 days, using physiological load and electrical stimulation, the hearts were pumping at around 2 per cent of adult strength, or around 25 per cent of the strength of a 16 week fetus.
“Take a section of this “new heart” and slice it, and cells are back in there,” said Taylor.
“The cells have many of the markers we associate with the heart and seem to know how to behave like heart tissue,” she explained.
Co-investigator of the study and a former research associate in the center for cardiovascular repair, now working at Massachusetts General Hospital, Dr Harald C. Ott, said:
“We just took nature’s own building blocks to build a new organ.”
“When we saw the first contractions we were speechless,” he added.
The research team is optimistic about their results, which they believe will help to increase availability of donor organs.
As Taylor explained, not only is there a shortage of donor organs, once they receive a new heart, patients face a lifetime on drugs to to stop their immune system rejecting the new organ. They also have a higher risk of high blood pressure, diabetes, and kidney failure.
Using this new decellularization process, a new heart could be filled with cells from the recipient, thus reducing the likelihood that their immune system would try to reject it, and their body might instead look after it by nourishing it, regenerating it, and regulating it said the researchers.
Taylor explained that their study had proved the concept, taken the first step to showing it was possible to create a working heart in three dimensions:
“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,” said Taylor.
Their next goal, she explained, will be to “use a patient’s stem cells to build a new heart”.
Although the aim of the study was to look at the heart, the process of decellularization has the potential to engineer other organs too.
“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,” said Taylor.
A professor from Imperial College London who is working on making heart tissue patches to replace failing human hearts, told BBC News this new research was a real step forward. One of the challenges to making a human heart is making sure there is enough oxygen supply. The architecture is critical, because nearly every cell needs to be near a blood vessel to get enough oxygen, and it seems that in this study they have solved that part of the problem.
“Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart.”
Harald C Ott, Thomas S Matthiesen, Saik-Kia Goh, Lauren D Black, Stefan M Kren, Theoden I Netoff & Doris A Taylor.
Nature Medicine, Published online: 13 January 2008.
Sources: journal article, Nature Medicine press release, BBC News.
Written by: Catharine Paddock