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Cloning technique produces human stem cells for the first time

Oregon Health&Science University

Donor egg held by pipette prior to nuclear extraction.

Researchers say they have finally managed to use cloning technology to make human embryos and grow stem cells from them in the hopes of making perfectly matched grow-your-own tissue transplants.

They used a human egg cell and parts of a human skin cell to grow a very early human embryo, then transformed cells from this ball of cells into beating heart cells and skin cells. The process may eventually help treat a range of diseases, from Parkinson’s to rare inherited conditions, they reported Wednesday in the journal Cell.

The researchers, at Oregon Health & Science University, say their embryos almost certainly could not grow into living human babies or even start a pregnancy – they’re deficient in a key way. But they admit also that they haven’t quite overcome ethical qualms about working with human embryos.

However, the work opens another route to treatments using human embryonic stem cells, the body’s master cells. “These stem cells are kind of very early unprogrammed cells but they have the capacity to become any other cell type,” says Shoukhrat Mitalipov, who led the research.

These cells are very different from so-called adult stem cells, like those taken from bone marrow. Adult stem cells cannot give rise to cells of other tissue types -- blood cells cannot be used to make brain cells, for instance.

Dr. George Daley, a stem cell expert at Harvard Medical School, called it a "beautiful piece of work".

When human embryonic stem cells were first discovered in 1998, scientists immediately dreamed of using cloning technology to help people grow their own organ and tissue transplants, and to use them to study disease. They’d be perfect genetic matches for each patient, meaning an end to a lifetime of taking dangerous immune-suppressing drugs after an organ transplant.

But in the many years since, no lab’s been able to do the work easily. It seems it is much harder to clone a human being than it is to clone a sheep, a frog or a mouse. And then there are the ethical concerns, not only concerns about cloning human beings but over working with human embryos. A federal court has only just ruled in the past year that government funds may be used in the research.

Scientists have found several other routes to harnessing the power of these master cells, which can give rise to any tissue type in the body, from nerve cells to muscle, bone and skin. There are cells taken from embryos left over at fertility clinics – currently being tested as treatments for blindness by a company, Advanced Cell Technology of Massachusetts.

Oregon Health & Science University

Researchers at Oregon Health & Science University have successfully developed a method for converting human skin cells into embryonic stem cells.

Other groups have learned how to “trick” ordinary skin cells into re-modeling themselves into different tissues. These so-called induced pluripotent stem cells, iPS cells for short, might also some day be used to grow transplants perfectly matched to a patient. But again, the technique isn’t easy and there have been many stumbling blocks.

Several other scientists said the science was sound, but said the field had mostly moved on from the pursuit of cloning technology. "IPS cells are easier to produce and have wide applications in research and regenerative medicine, and it remains to be shown whether (cloned embryonic stem cells) have advantages over iPS cells," Daley said by e-mail.

Cloning almost got left in the dust with the work on the other techniques. But the team at OHSU had been perfecting the technique in monkeys, and now they’ve managed to make it work with human cells. The advantage, they say, is that the donated human egg provides fresh and rejuvenating DNA.

The technique they use is called somatic cell nuclear transfer – the same method used to make Dolly, the sheep who was the first mammal cloned from the cell of another adult mammal, in 1996. Scientists remove the nucleus from a normal cell, usually a type of skin cell. They do the same with a human egg cell, then inject the nucleus from the skin cell into the egg.

Various chemical or electrical tricks can be used to start the egg growing as if it had been fertilized by sperm. The method’s been used to make sheep, dogs, horses, and mice – but never human beings.

None of these clones are precise copies because the egg contains an important source of DNA, called mitochondrial DNA. And defects in this DNA cause many diseases, including diabetes and a condition called Leigh syndrome, which causes seizures and dementia.

Mitalipov hopes that replacing the mitochondrial DNA as part of the cloning process might help make tissue that could correct these diseases. His team tested cells taken from a patient with Leigh syndrome, a neurological disorder, and made stem cells using the technique.

“It allows you to produce genetically corrected cells,” he said. “There are a variety of age-related diseases that we believe are caused by acquired mitochondrial mutations.”

Lots of testing lies ahead and because of laws banning the use of federal money to directly make human embryos, Mitalipov’s lab uses private funds instead. But he believes the method cannot be used to make human babies.

“We have been doing it for years in primates and the embryos never implant,” he said. The blastocysts appear to lack a key layer of cells, he said, that give rise to the placenta and that are needed for a normal pregnancy.

Nonetheless, he admits that is unlikely to reassure people who object to experimenting on human embryos. “They’ll say ‘oh, you are just creating a disabled embryo’,” he said.

O. Carter Snead, a bioethicist and professor of law at the University of Notre Dame, called it sad news. “The use and destruction of living human beings – at any stage of biological development – for scientific research is a terrible injustice.  Human cloning for biomedical research is a particularly aggravated form of this harm," Snead said in a statement.

Another barrier --- human eggs are not easy to come by and there are also ethical questions about whether women should be paid to donate their eggs for this kind of research.

The work will almost certainly be used to study diseases in lab dishes at first. But Daley, who heads the bone marrow transplant program at Boston Children's Hospital, said using a patient's own cells offers potentially huge advantages. "A lot of patients don't have an optimal donor," he said. So bone marrow transplants are done only for the patients in the most dire need.

"If we could make every patient their own donor ... we would bypass the transplant barrier," he said. "Everyone could be a donor for themselves."

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