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New insulin-producing cells created using Dolly-cloning method
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SPECIAL REPORT STEM CELL MEDICINE
too quickly, buying time for the genes in the egg’s new nucleus to revert to an embryonic state. Electrical pulses and chemicals fooled the cell into thinking it was A revived cloning method has turned human adult cells into stem fertilised, prompting it to divide cells that can become anything you need, from neurons to cartilage and multiply. The result was a bundle of 60 to transfer (SCNT), to transform skin debilitating diseases and injuries,” 200 cells – the first time an adult Helen Thomson cells from a 35 and a 75-year-old says Susan Solomon at the New cell has been used to make a THE dream of generating a bank man into stem cells. The other team York Stem Cell Foundation cloned human embryo. In the of stem cells to treat injury and went a step further, turning skin (NYSCF), who worked on one study. centre of the bundle were illness is a step closer. Embryonic cells from a woman with diabetes To achieve the feat, the teams – embryonic stem cells that can stem cells have been custominto insulin-producing beta cells one led by Young Gie Chung at the differentiate into any cell in the made from adult cells without that could replace those destroyed CHA University in Seoul, South body, given the right environment. manipulating the cell’s genes, a by the disease. The approach has Korea, and the other by Dieter Egli In 2013, a similar procedure was process that might trigger cancer. the potential to replace many at the NYSCF – first removed the used to convert cells from a fetus Using a similar cloning other types of tissue including nucleus of a donated human egg into embryonic stem cells. A technique to the one that created heart cells, neurons and cartilage. and replaced it with the nucleus fetus’s cells are already essentially Dolly the sheep, two teams have This could spur on treatments from an adult skin cell. Caffeine embryonic, so the latest work independently shown that it is for Parkinson’s disease, multiple was added to stop the cell dividing is a big step forward. Since the possible to turn an adult cell into sclerosis and liver disease, and incidence of stem cell-treatable “Cell replacement therapies disease increases with age, an embryonic stem cell, which can repair damaged bones. could dramatically change then become any cell in the body. “Cell replacement therapies researchers needed to figure treatments and even cure One team used the technique, could dramatically change out how to rewind adult cells, debilitating diseases” called somatic cell nuclear treatments and even cure says Robert Lanza at Advanced
Every cell, off the peg
6 | NewScientist | 3 May 2014
In this section ■ Cell-free metabolism sparked in the lab, page 8 ■ Solar wind holds clues for fusion reactor, page 12 ■ Watson: the supercomputer in your pocket, page 17
Blood of oldest woman hints at the limits of life
diabetes and turned them into stem cells. These were then made into beta cells that could theoretically replace those lost to the disease (Nature, doi.org/sjn). However, this personalised approach is unlikely to be the way forward. If the treatment was tailor-made for each patient, an embryo would have to be discarded every time. As well as the ethical objections this would raise, the procedure would be time-consuming, costly and would be limited by the small number of eggs donated. It is also unnecessary, says Lanza.
DEATH is the one certainty of life, but when will it come knocking? A pioneering analysis of blood from one of the world’s oldest and healthiest women suggests it may come down to the vigour of your body’s stem cells. Hendrikje van Andel-Schipper, born in 1890, was once the oldest woman in the world. She was also remarkable for her health, with crystal-clear cognition until she was close to death, and a circulatory system free from disease. When she died in 2005, aged 115, she bequeathed her body to science with the approval of her family. A team led by Henne Holstege of the VU University Medical Center in Amsterdam, the Netherlands, has now examined van Andel-Schipper’s blood and other tissues to see how they were affected by age. The results suggest that our lifespan might ultimately be limited by the capacity of our stem cells to keep replenishing tissues. For example, we are born with about 20,000 blood stem cells, and at any one time, roughly 1000 are simultaneously cloning themselves to replenish our blood. During life, the number of active stem cells shrinks, and their telomeres, the protective tips on their chromosomes, shorten to the point at which the cell can no longer replicate. On van Andel-Schipper’s death, about two-thirds of the white blood cells left in her body originated from
Donor cells are sometimes rejected because of our body’s human leukocyte antigen (HLA) system. This produces proteins that are recognised by immune cells. If the proteins are not recognised, rejection occurs. Luckily, most people share one of a handful of HLA systems. That means you should only need to create stem cells specific to each –No extra genes required– HLA system, rather than each individual, says Lanza. Cell Technology in Worcester, Personalised stem cells would Massachusetts, a co-author of only be needed for people with the study led by the South Korean uncommon HLA proteins. group (Cell Stem Cell, doi.org/sh2). Banks of stem cells could be The approach offers an created from just a handful of alternative to another method eggs. To make the process even used to dial back the clock on more efficient, the embryonic adult cells. Induced pluripotent stem cells could be transformed stem cells (iPS) are adult cells that into the final product in advance, have been coaxed into behaving so heart cells or neurons, say, like embryonic cells by adding could be picked “off the shelf” four extra genes. There was a lot as needed, says Lanza. of excitement when iPS cells were Ian Wilmut of the University of first created in 2006, but since Edinburgh, UK, who created Dolly then serious problems have the sheep, describes the work as emerged, involving incomplete very encouraging. He says that reprogramming of the cells and SCNT stem cells should now be the worry that the extra genes compared with iPS cells to see might trigger cancer. “We’ve which are the closest match to overcome a lot of these problems,” true embryonic stem cells created says Lanza, “but SCNT might turn from fertilised embryos. “By out to be the only way to fully contrasting these two approaches reprogram cells.” we may be able to optimise both To prove the potential of the procedures and produce the best technique, Egli’s group took skin possible cells for use in research cells from a woman with type 1 and therapy,” he says. ■
CONTINENTAL/AFP/GETTY IMAGES
Stem cell bank
just two stem cells. Holstege says this implies that most or all of the blood stem cells van Andel-Schipper started life with had already burned out and died, diminishing her body’s capacity to keep regenerating vital tissues and cells. The telomeres on her white blood cells were also drastically worn down. This raises some big questions, says Holstege: “Is there a limit to the number of stem cell divisions, and does that imply that there’s a limit to human life?” The team worked out the number of van Andel-Schipper’s stem cells by studying the pattern of mutations in her white blood cells. It was so similar in all her cells that the researchers concluded that they all came from one of two closely related “mother” stem cells. What’s more, the mutations caused by the blood
“The findings raise the possibility of rejuvenating ageing bodies with injections of stem cells”
stem cells replicating were harmless, says Holstege. This suggests that van Andel-Schipper had a superior system for repairing or aborting harmfully mutated cells (Genome Research, doi.org/sjm). The findings raise the possibility of rejuvenating ageing bodies with injections of stem cells saved from birth or early life. Several companies already offer such storage services. “If I took a sample now and gave it back to myself when I’m older, I would have long telomeres again,” Holstege says. Thomas von Zglinicki of Newcastle University, UK, takes a more sceptical view. Just because most of van Andel-Schipper’s blood came from two stem cells doesn’t mean all the others had been wiped out, he says. What’s more, the presence of dominant stem cells could mean that injections of young stem cells may not work because the dominant cells could suppress the –Made it to 115– fresher ones. Andy Coghlan ■ 3 May 2014 | NewScientist | 7
SPECIAL REPORT STEM CELL MEDICINE
too quickly, buying time for the genes in the egg’s new nucleus to revert to an embryonic state. Electrical pulses and chemicals fooled the cell into thinking it was A revived cloning method has turned human adult cells into stem fertilised, prompting it to divide cells that can become anything you need, from neurons to cartilage and multiply. The result was a bundle of 60 to transfer (SCNT), to transform skin debilitating diseases and injuries,” 200 cells – the first time an adult Helen Thomson cells from a 35 and a 75-year-old says Susan Solomon at the New cell has been used to make a THE dream of generating a bank man into stem cells. The other team York Stem Cell Foundation cloned human embryo. In the of stem cells to treat injury and went a step further, turning skin (NYSCF), who worked on one study. centre of the bundle were illness is a step closer. Embryonic cells from a woman with diabetes To achieve the feat, the teams – embryonic stem cells that can stem cells have been custominto insulin-producing beta cells one led by Young Gie Chung at the differentiate into any cell in the made from adult cells without that could replace those destroyed CHA University in Seoul, South body, given the right environment. manipulating the cell’s genes, a by the disease. The approach has Korea, and the other by Dieter Egli In 2013, a similar procedure was process that might trigger cancer. the potential to replace many at the NYSCF – first removed the used to convert cells from a fetus Using a similar cloning other types of tissue including nucleus of a donated human egg into embryonic stem cells. A technique to the one that created heart cells, neurons and cartilage. and replaced it with the nucleus fetus’s cells are already essentially Dolly the sheep, two teams have This could spur on treatments from an adult skin cell. Caffeine embryonic, so the latest work independently shown that it is for Parkinson’s disease, multiple was added to stop the cell dividing is a big step forward. Since the possible to turn an adult cell into sclerosis and liver disease, and incidence of stem cell-treatable “Cell replacement therapies disease increases with age, an embryonic stem cell, which can repair damaged bones. could dramatically change then become any cell in the body. “Cell replacement therapies researchers needed to figure treatments and even cure One team used the technique, could dramatically change out how to rewind adult cells, debilitating diseases” called somatic cell nuclear treatments and even cure says Robert Lanza at Advanced
Every cell, off the peg
6 | NewScientist | 3 May 2014
In this section ■ Cell-free metabolism sparked in the lab, page 8 ■ Solar wind holds clues for fusion reactor, page 12 ■ Watson: the supercomputer in your pocket, page 17
Blood of oldest woman hints at the limits of life
diabetes and turned them into stem cells. These were then made into beta cells that could theoretically replace those lost to the disease (Nature, doi.org/sjn). However, this personalised approach is unlikely to be the way forward. If the treatment was tailor-made for each patient, an embryo would have to be discarded every time. As well as the ethical objections this would raise, the procedure would be time-consuming, costly and would be limited by the small number of eggs donated. It is also unnecessary, says Lanza.
DEATH is the one certainty of life, but when will it come knocking? A pioneering analysis of blood from one of the world’s oldest and healthiest women suggests it may come down to the vigour of your body’s stem cells. Hendrikje van Andel-Schipper, born in 1890, was once the oldest woman in the world. She was also remarkable for her health, with crystal-clear cognition until she was close to death, and a circulatory system free from disease. When she died in 2005, aged 115, she bequeathed her body to science with the approval of her family. A team led by Henne Holstege of the VU University Medical Center in Amsterdam, the Netherlands, has now examined van Andel-Schipper’s blood and other tissues to see how they were affected by age. The results suggest that our lifespan might ultimately be limited by the capacity of our stem cells to keep replenishing tissues. For example, we are born with about 20,000 blood stem cells, and at any one time, roughly 1000 are simultaneously cloning themselves to replenish our blood. During life, the number of active stem cells shrinks, and their telomeres, the protective tips on their chromosomes, shorten to the point at which the cell can no longer replicate. On van Andel-Schipper’s death, about two-thirds of the white blood cells left in her body originated from
Donor cells are sometimes rejected because of our body’s human leukocyte antigen (HLA) system. This produces proteins that are recognised by immune cells. If the proteins are not recognised, rejection occurs. Luckily, most people share one of a handful of HLA systems. That means you should only need to create stem cells specific to each –No extra genes required– HLA system, rather than each individual, says Lanza. Cell Technology in Worcester, Personalised stem cells would Massachusetts, a co-author of only be needed for people with the study led by the South Korean uncommon HLA proteins. group (Cell Stem Cell, doi.org/sh2). Banks of stem cells could be The approach offers an created from just a handful of alternative to another method eggs. To make the process even used to dial back the clock on more efficient, the embryonic adult cells. Induced pluripotent stem cells could be transformed stem cells (iPS) are adult cells that into the final product in advance, have been coaxed into behaving so heart cells or neurons, say, like embryonic cells by adding could be picked “off the shelf” four extra genes. There was a lot as needed, says Lanza. of excitement when iPS cells were Ian Wilmut of the University of first created in 2006, but since Edinburgh, UK, who created Dolly then serious problems have the sheep, describes the work as emerged, involving incomplete very encouraging. He says that reprogramming of the cells and SCNT stem cells should now be the worry that the extra genes compared with iPS cells to see might trigger cancer. “We’ve which are the closest match to overcome a lot of these problems,” true embryonic stem cells created says Lanza, “but SCNT might turn from fertilised embryos. “By out to be the only way to fully contrasting these two approaches reprogram cells.” we may be able to optimise both To prove the potential of the procedures and produce the best technique, Egli’s group took skin possible cells for use in research cells from a woman with type 1 and therapy,” he says. ■
CONTINENTAL/AFP/GETTY IMAGES
Stem cell bank
just two stem cells. Holstege says this implies that most or all of the blood stem cells van Andel-Schipper started life with had already burned out and died, diminishing her body’s capacity to keep regenerating vital tissues and cells. The telomeres on her white blood cells were also drastically worn down. This raises some big questions, says Holstege: “Is there a limit to the number of stem cell divisions, and does that imply that there’s a limit to human life?” The team worked out the number of van Andel-Schipper’s stem cells by studying the pattern of mutations in her white blood cells. It was so similar in all her cells that the researchers concluded that they all came from one of two closely related “mother” stem cells. What’s more, the mutations caused by the blood
“The findings raise the possibility of rejuvenating ageing bodies with injections of stem cells”
stem cells replicating were harmless, says Holstege. This suggests that van Andel-Schipper had a superior system for repairing or aborting harmfully mutated cells (Genome Research, doi.org/sjm). The findings raise the possibility of rejuvenating ageing bodies with injections of stem cells saved from birth or early life. Several companies already offer such storage services. “If I took a sample now and gave it back to myself when I’m older, I would have long telomeres again,” Holstege says. Thomas von Zglinicki of Newcastle University, UK, takes a more sceptical view. Just because most of van Andel-Schipper’s blood came from two stem cells doesn’t mean all the others had been wiped out, he says. What’s more, the presence of dominant stem cells could mean that injections of young stem cells may not work because the dominant cells could suppress the –Made it to 115– fresher ones. Andy Coghlan ■ 3 May 2014 | NewScientist | 7