Heart of rat rebuilt in lab to give hope of 'tailored' human organs
Scientists have brought a dead heart back to life by rebuilding it from a bare framework of tissue filled with stem cells in a study that promises to provide a new source of "reconditioned" organs for transplant operations.
It is believed to be the first time that researchers have in effect created a whole organ in a test tube, and the breakthrough could lead to ways of synthesising bespoke tissues, such as kidney, liver or pancreas, tailored to patients.
The technique, which is still experimental, involved dissolving the muscle cells of a dead rat's heart to produce an empty scaffolding of connective tissue which was then repopulated with stem cells taken from younger rats.
After several days of being cultured in the laboratory, the cells started to beat rhythmically and a few days later the reconditioned heart began to pump blood again, to the astonishment of the scientists involved.
"Initially we thought this was just a good idea, but when we saw the first heartbeats we were speechless," said Harald Ott of the Massachusetts General Hospital, a member of the research team.
It is hoped that the technique could be developed into a reliable method of building human hearts and other organs from a patient's own stem cells, which would mean that the transplanted tissue was unlikely to be rejected by the immune system, Dr Ott said.
"I see the need for more donor organs by simply working in a hospital setting on a day-to-day basis. If our work becomes applicable to humans, which we think it may, it has the potential to save millions of lives," he said.
The research team, led by Professor Doris Taylor of the University of Minnesota, has pioneered the technique of dissolving the cardiac muscle cells of the heart to produce an empty scaffold called a decellularised matrix.
"You can think of it as a bare, wooden frame for a house. We inject the scaffold with cells, we leave it in the lab for about a week and after that the cells begin to contract, and the heart starts to pump," Professor Taylor said.
"In theory the decellularised organ, now with cells, is on the way to becoming a new heart. It opens the notion that we can make any organ. At first we focused on the heart but our hope is that if you need it, we can make it," she said.
"We believe in giving nature the tools and getting out of the way, so we took nature's building blocks to build a new organ. We are not there yet, but this is a good first step," she added.
The study, which is published today in the journal Nature Medicine, shows that it is possible to strip down an organ as complex as the heart and rebuild it using stem cells taken from the immature hearts of about 100 young rats.
If the technique is to be applied in humans it would be necessary to find an equally plentiful supply of stem cells from, for instance, the skin of the patient – which may be possible using a breakthrough reported last year by Japanese scientists who created embryonic-like stem cells from human skin using genetic engineering.
"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. Going forward, our goal is to use a patient's stem cells to build a new heart," Professor Taylor said. "It opens a door to this notion that you can make any organ – kidney, liver, lung or pancreas," she said.
Other scientists have welcomed the breakthrough. "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," said Professor Wayne Morrison, director of the Bernard O'Brien Institute of Microsurgery in Melbourne, who last year grew beating heart muscles from adult stem cells inside a rat.
Jon Frampton, a Wellcome Trust senior fellow at Birmingham University, said: "Although this is only a first step requiring considerable follow-up development, the study nevertheless represents an exciting breakthrough."
The process
The muscle cells of a dead heart were dissolved using a form of detergent to produce a framework of connective tissue, right. The thickest part of the heart wall is marked on the middle picture. After this process living stem cells from young rats were introduced into the framework of the heart, which started to pump blood
By Steve Connor, Science Editor
Published: 14 January 2008
© 2008 Independent News and Media Limited
Scientists have brought a dead heart back to life by rebuilding it from a bare framework of tissue filled with stem cells in a study that promises to provide a new source of "reconditioned" organs for transplant operations.
It is believed to be the first time that researchers have in effect created a whole organ in a test tube, and the breakthrough could lead to ways of synthesising bespoke tissues, such as kidney, liver or pancreas, tailored to patients.
The technique, which is still experimental, involved dissolving the muscle cells of a dead rat's heart to produce an empty scaffolding of connective tissue which was then repopulated with stem cells taken from younger rats.
After several days of being cultured in the laboratory, the cells started to beat rhythmically and a few days later the reconditioned heart began to pump blood again, to the astonishment of the scientists involved.
"Initially we thought this was just a good idea, but when we saw the first heartbeats we were speechless," said Harald Ott of the Massachusetts General Hospital, a member of the research team.
It is hoped that the technique could be developed into a reliable method of building human hearts and other organs from a patient's own stem cells, which would mean that the transplanted tissue was unlikely to be rejected by the immune system, Dr Ott said.
"I see the need for more donor organs by simply working in a hospital setting on a day-to-day basis. If our work becomes applicable to humans, which we think it may, it has the potential to save millions of lives," he said.
The research team, led by Professor Doris Taylor of the University of Minnesota, has pioneered the technique of dissolving the cardiac muscle cells of the heart to produce an empty scaffold called a decellularised matrix.
"You can think of it as a bare, wooden frame for a house. We inject the scaffold with cells, we leave it in the lab for about a week and after that the cells begin to contract, and the heart starts to pump," Professor Taylor said.
"In theory the decellularised organ, now with cells, is on the way to becoming a new heart. It opens the notion that we can make any organ. At first we focused on the heart but our hope is that if you need it, we can make it," she said.
"We believe in giving nature the tools and getting out of the way, so we took nature's building blocks to build a new organ. We are not there yet, but this is a good first step," she added.
The study, which is published today in the journal Nature Medicine, shows that it is possible to strip down an organ as complex as the heart and rebuild it using stem cells taken from the immature hearts of about 100 young rats.
If the technique is to be applied in humans it would be necessary to find an equally plentiful supply of stem cells from, for instance, the skin of the patient – which may be possible using a breakthrough reported last year by Japanese scientists who created embryonic-like stem cells from human skin using genetic engineering.
"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. Going forward, our goal is to use a patient's stem cells to build a new heart," Professor Taylor said. "It opens a door to this notion that you can make any organ – kidney, liver, lung or pancreas," she said.
Other scientists have welcomed the breakthrough. "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," said Professor Wayne Morrison, director of the Bernard O'Brien Institute of Microsurgery in Melbourne, who last year grew beating heart muscles from adult stem cells inside a rat.
Jon Frampton, a Wellcome Trust senior fellow at Birmingham University, said: "Although this is only a first step requiring considerable follow-up development, the study nevertheless represents an exciting breakthrough."
The process
The muscle cells of a dead heart were dissolved using a form of detergent to produce a framework of connective tissue, right. The thickest part of the heart wall is marked on the middle picture. After this process living stem cells from young rats were introduced into the framework of the heart, which started to pump blood
By Steve Connor, Science Editor
Published: 14 January 2008
© 2008 Independent News and Media Limited
