Monday January 14 2008
Researchers 'rebuilt' a rat's heart
“Scientists have grown a whole beating heart in the laboratory, bringing the goal of growing replacement organs for humans a step closer”, The Guardian reported today.
Many of the major newspapers reported on the development of the “first bioartificial heart”. Most focus on the idea that developing organs in the laboratory may signal an end to a shortage of replacement tissues for people requiring heart transplants. They go on to suggest that the technology could be applied to other organs.
The news stories are based on a laboratory study that “stripped” rat hearts of their cells, leaving a “scaffold” of the heart that was used to “re-grow” a rudimentary heart around it. As with all animal studies there is limited direct application to human health. However, the discovery that muscle cells were able to “grow” around an existing tissue skeleton sheds new light on their function and has revealed a potential new method to artificially generate heart muscle cells. As mentioned in the majority of the news reports, there is still a long way to go until a practical application is possible.
Where did the story come from?
Dr Harald Ott and colleagues from Harvard Medical School and the University of Minnesota carried out the research. The study was funded by departments at the University of Minnesota and was published in the peer-reviewed medical journal: Nature Medicine.
What kind of scientific study was this?
This was a laboratory study in tissue engineering, an interdisciplinary field that applies the principles of engineering and biological sciences toward the development of functional substitutes for damaged tissue.
The researchers used hearts that had been removed from the bodies of rats for this study. They “decellularised” the hearts using special equipment (called Langendorff apparatus) to pump a detergent (sodium dodecyl sulphate) through the hearts that stripped away their cellular components (including the structural elements and the DNA). What remained was a “heart matrix” or “scaffold” (essentially the framework of the heart, that consisted of collagen and other proteins).
This scaffold did not have the cells that are capable of contracting – the action that makes a heart pump blood. The researchers found that within the scaffold, the fibres making up the main heart vessels were preserved (i.e. the vessels were open and unobstructed) and the aortic valve was also able to open and close. This meant that some components of the heart had survived the detergent and were still capable of functioning to some degree.
The researchers then put the heart scaffolds into a bioreactor (which simulated the heart’s normal environment by forcing liquids in the right directions and by applying a stimulating electrical current). The heart scaffolds were then injected with purified heart muscle cells (obtained from rat embryos) and kept in the bioreactor for eight to 28 days. During the course of their experiment, the researchers performed several investigations on the tissues that resulted. They were particularly interested in how the “growing” heart regained its ability to contract and to respond to electrical signals. They also examined sections of the heart to see how and where the new heart cells were growing.
In a separate experiment, the researchers assessed whether they could also encourage growth of the cells that line the blood vessels in the heart (endothelial cells). To do this, the researchers infused endothelial cells from rat aortas (one of the main cardiac blood vessels) into the “decellularised” rat hearts. The liquid was made to continually move through the “heart” vessels and after seven days the hearts were dissected to see whether the heart chambers and vessels were regrowing their endothelial cells.
What were the results of the study?
The study has several important findings: firstly, the researchers were able to create a scaffold of the entire heart which had its vessels intact, its valves working and retained the four chamber structure of the heart. They observed that injecting embryonic heart cells into this scaffold stimulated the growth of heart cells which visibly contracted only four days after the injections. By the eighth day, the resulting cells showed response to an electrical current and function which researchers say was equivalent to 2% that of an adult rat heart (or 25% of the function of 16 week old embryos).
The “recellularisation” of the scaffold was greatest around the injection sites. They were also able to encourage the growth of cells that line the heart’s interior and its blood vessels.
What interpretations did the researchers draw from these results?
The researchers conclude that “with sufficient maturation” and further work on its vascular cells, this new organ could potentially become transplantable. They acknowledge that their study is limited to rat hearts, but they say that the approach “holds promise for virtually any solid organ”.
What does the NHS Knowledge Service make of this study?
This laboratory study used recognised scientific methods and its findings open up a new avenue for research into the manufacture of functional heart muscle. Following a transplant, many patients face the very real possibility that the new organ will be rejected by their own body. The hope is that technologies such as that seen in this research may one day be used to manufacture a heart from the patient’s own stem cells, meaning the organ is less likely to be rejected by the patient’s body.
- Importantly, the new hearts that “re-grew” on the heart scaffolds were not transplanted into rats to see whether – even for these animals – they were functional enough to support life. Before we can draw conclusions about the value of this technology for transplantation, such studies must be conducted.
- Though the findings are exciting for the scientific community, a tissue engineering application that will directly benefit humans is some way off. The Guardian quotes an expert from the British Heart Foundation as saying, “This isn’t something we will see in man for at least a decade.”
Sir Muir Gray adds...
Using cells to regrow tissues and organs will have a contribution to make, but not for some time.