Heart beats in the laboratory

Scientists from the University of Minnesota have grown functioning heart tissue by taking the extracellular matrix of rat hearts and reseeding them with neonatal cardiac or aortic endothelial cells.

Doris Taylor and colleagues decellularised the adult hearts by bathing them with detergents, leaving the underlying scaffold - including blood vessels, valves and chamber geometry - intact.

They then reseeded the scaffolds with progenitor cells and maintained the 'constructs' for 28 days in a bioreactor that simulated cardiac physiology.

Four days after seeding the decellularised heart scaffolds, the team observed contractions. By day eight, the constructs could generate pump function.

"Take a section of this 'new heart' and slice it, and cells are back in there," Taylor said.

"The cells have many of the markers we associate with the heart and seem to know how to behave like heart tissue."

The work was described in a paper published online in Nature Medicine.

It is hoped that the decellularisation process could be used to make new donor organs. Because a new heart could be filled with the recipient's cells, researchers hypothesise it's much less likely to be rejected by the body.

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," Taylor said. "We pretty much figured heart cells in a heart matrix had to work. Going forward, our goal is to use a patient's stem cells to build a new heart."

Although heart repair was the first goal during research, decellularisation shows promising potential to change how scientists think about engineering organs, Taylor said.

"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."

Professor Wayne Morrison, director of the Bernard O'Brien Institute of Microsurgery at Melbourne's St Vincent's Hospital, said the paper was very interesting as it was the first time a whole organ had been tissued engineered outside the body.

Last year, Morrison's research group successfully grew beating heart muscle from adult stem cells inside a rat.

"They have done this using a few important steps," he said. "One is that they have decellularised the whole heart, essentially killing all the cells in it but preserving all the essential architecture of the organ, keeping the chambers the valves and the blood vessel structure intact.

"They then repopulated the architectural structure with new cells by injecting it with cells taken from other rat hearts and pulsing nutrient rich media over the heart structure to mimic circulation.

"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."

Morrison said one of the limitations of the research was that it was still done in vitro, not in vivo.

"Our group conducted similar research a year ago and made similar thicknesses of heart muscle inside an animal, however what we was made heart tissue. Unlike this research it wasn't a heart, which is what makes this development novel and interesting."

He said another limitation was that in order to add cells back to the heart, the team had to inject the structure with 50-75 million cells.

"Now to get 75 million cells you would need at least 100 rat hearts to make a one artificial heart. This was also a criticism of our own research which needed about 10 hearts. I think there is a long way to go for all of us in terms of where we go to get the cells that ultimately would make a real human heart."