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Monday 14 January 2008

RAPID ROUNDUP - Scientists create a bio-artificial heart as published in Nature Medicine – experts respond

A technique to create an artificial heart is described in Nature medicine. Using the remains of an actual full-sized adult heart that has been stripped of all its cells, the authors replanted this scaffold with neonatal heart cells. About 22 million people worldwide, live with heart failure. An artificial heart is a theoretical alternative for transplantation.



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Professor Wayne Morrison is a Professor of Microsurgery and Director of the Bernard O'Brien Institute of Microsurgery. Last year his research group successfully grew beating heart muscle from adult stem cells inside a rat.

“This is a very interesting paper in that it is the first time a whole organ has been tissue engineered outside the body. They have done this using a few important steps, 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.

One of the limitations of this research is that this work is still in the laboratory, not inside an animal, and it is not a living structure. 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.

Another limitation is that in order to add cells back to the heart they needed 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, we can’t just get access to 100 other hearts as they have done here. Both of our techniques also use someone else’s hearts which would ultimately still cause rejection if you put it into a patient, so we need another source of cells to be able to repopulate it.

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.

The significant advance is that they potentially have a circulation, that could be connected in vivo to allow you to transfer this from a product into an animal. That is where our research differs in focus as we have aimed to grow the cells in the animal right from the beginning. The next step is to see if this research can be transferred into living animals and can be upscaled beyond rats.”

Dr Anita Thomas is NHMRC CJ Martin Fellow in the Centre for Research in Vascular Biology at the Australian Institute for Bioengineering and Nanotechnology, University of Queensland.

“There is an obvious lack in the supply of hearts suitable to replace damaged or failing organs. This report outlines initial steps in designing and testing semi-biological ‘artificial’ hearts. These are hearts that have been stripped of their cells to produce a heart ‘scaffold’, which is then repopulated by cells from other sources. The function of the ‘new hearts’ was tested in a bioreactor and found to be partially restored.

There are three steps involved in the production of these artificial hearts. The first is the production of the basic heart scaffold, which is achieved by removal of all cells from the heart by detergents. This scaffold was then repopulated with a mix of cells extracted from baby rat hearts or by the cells that line the coronary arteries. These artificial hearts were then electrically stimulated (as a pacemaker stimulates a heart) and had ‘blood’ flowing through the chambers of the heart for up to 10 days, to ‘mature’ them. These matured hearts had areas with almost complete recellularisation by normal heart cells, could cope with blood flow into the large and medium-sized arteries (for a short while) and even had a partial restoration of normal function (including contraction). However, results from the studies on the re-lining of the blood vessels with endothelial cells were less convincing.

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.”