Researchers say they have made powerful stem cells from both young and old adults using cloning techniques, and also found clues about why it is so difficult to do this with human beings.

The team, at Massachusetts-based Advanced Cell Technology and the Institute for Stem Cell Research in Los Angeles, say they used the cloning methods to create the stem cells to match a 35-year-old man and a 75-year-old man.

They used a bit of skin from each man, took the DNA from the skin cells and inserted it into the egg cell of a female donor, and grew very early embryos called blastocysts, the team reports in the journal Cell Stem Cell. Cells from these embryos closely match the men and could, in theory, be used to make near-identical tissue, blood or organ transplants for the men.

If verified, it would be only the second confirmed time someones been able to use cloning methods to make human embryonic stem cells, considered the bodys master cells.

Therapeutic cloning has long been envisioned as a means for generating patient-specific stem cells that could be used to treat a range of age-related diseases, said Dr. Robert Lanza, chief scientific officer for Advanced Cell Technology.

However, despite cloning success in animals, the derivation of stem cells from cloned human embryos has proven elusive. Only one group has ever succeeded, and their lines were generated using fetal and infant cells.

That was last year, at Oregon Health & Science University.

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. Theyd 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 labs 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 using the cloning technique is controversial, because it involves creating, then destroying, a human embryo.

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Group Makes Stem Cells Using Clone Technique

Eighteen years ago, scientists in Scotland took the nuclear DNA from the cell of an adult sheep and put it into another sheep's egg cell that had been emptied of its own nucleus. The resulting egg was implanted in the womb of a third sheep, and the result was Dolly, the first clone of a mammal.

Dolly's birth set off a huge outpouring of ethical concern along with hope that the same techniques, applied to human cells, could be used to treat myriad diseases.

But Dolly's birth also triggered years of frustration. It's proved very difficult to do that same sort of DNA transfer into a human egg.

Last year, scientists in Oregon said they'd finally done it, using DNA taken from infants. Robert Lanza, chief scientific officer at Advanced Cell Technology, says that was an important step, but not ideal for medical purposes.

"There are many diseases, whether it's diabetes, Alzheimer's or Parkinson's disease, that usually increase with age," Lanza says. So ideally scientists would like to be able to extract DNA from the cells of older people not just cells from infants to create therapies for adult diseases.

Lanza's colleagues, including Young Gie Chung at the CHA Stem Cell Institute in Seoul, Korea (with labs in Los Angeles as well), now report success.

Writing in the journal Cell Stem Cell, they say they started with nuclear DNA extracted from the skin cells of a middle-age man and injected it into human eggs donated by four women. As with Dolly, the women's nuclear DNA had been removed from these eggs before the man's DNA was injected. They repeated the process this time starting with the genetic material extracted from the skin cells of a much older man.

"What we show for the first time is that you can actually take skin cells, from a middle-aged 35-year-old male, but also from an elderly, 75-year-old male" and use the DNA from those cells in this cloning process, Lanza says.

They injected it into 77 human egg cells, and from all those attempts, managed to create two viable cells that contained DNA from one or the other man. Each of those two cells is able to divide indefinitely, "so from a small vial of those cells we could grow up as many cells as we would ever want," Lanza says.

They look like the cells in a human embryo in fact, they're called embryonic stem cells. And with a bit of coaxing, these cells could, theoretically, be prodded to turn into any sort of human cell nerve, heart, liver and pancreas, for example. That's what makes them potentially useful for treating all sorts of diseases.

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First Embryonic Stem Cells Cloned From A Man's Skin

Several years ago, as the therapeutic potential of stem cells was first being recognized, the only way to create them was to harvest cells from an early embryo. That embryo could come from the large collection of those that weren't used during in vitro fertilization work. But to get one that was genetically matched to the person who needed the therapy, researchers had to create an embryo that's a genetic duplicate of that individualmeaning they had to clone them.

With the development of induced stem cells, work on this approach largely fell by the waysideinduced cells were easier to create and came without the ethical baggage. But there are some lingering doubts that the induced cells are truly as flexible as the ones derived from an embryo, leading a number of labs to continue exploring cloning for therapeutic purposes. Now, a collaboration of US and Korean researchers have succeeded in creating early embryos from two adult humans and converted the embryos to embryonic stem cells.

The method used is called somatic cell nuclear transplant. It involves taking an unfertilized egg and removing its nucleus, thereby deleting the DNA of the egg donor. At the same time, a nucleus from the cell of a donor is carefully removed and injected into the egg. After some time, during which the environment of the egg resets the developmental status of the donor's DNA, cell division is activated. If the process is successful, the end result is a small cluster of cells that starts along the path of forming an embryo.

This technique was recently used to create embryonic stem cells from an infant donor. But the new team managed to perform the technique successfully with two male donors, one 35 years old and the second 75. The primary change needed was simply to extend the period in which the donor DNA is reset by the proteins present in the egg.

After the resulting cells divided long enough to form a blastocyst (an early stage of embryonic development), they were harvested and converted to embryonic stem cells. The researchers showed that the resulting stem cells could form all of the major tissues of a mature embryo, as close as you can come to demonstrated stem-cellness with human samples.

In mice and many other animals, however, it's possible to simply allow the cells to keep growing and implant them into a female at the appropriate stage. And that's what's striking about this research: there doesn't appear to be anything keeping it from being done in humans. The efficiency in many other mammals is low and sometimes results in aberrant growth. But, given enough attempts, there are no obvious barriers between this work and a cloned human.

The authors avoid discussing this implication completely, focusing instead on its therapeutic potential.

Cell Stem Cell, 2014. DOI: 10.1016/j.cell.2013.05.006 (About DOIs).

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75-year-old human cloned for the production of stem cells

Released: 4/16/2014 10:00 AM EDT Embargo expired: 4/17/2014 12:00 PM EDT Source Newsroom: Johns Hopkins Medicine Contact Information

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Newswise Johns Hopkins researchers have discovered an unexpected phenomenon in the organs that produce sperm in fruit flies: When a certain kind of stem cell is killed off experimentally, another group of non-stem cells can come out of retirement to replace them.

The discovery sheds light on the tiny environments that stem cells occupy in animal bodies and may help explain how stem cells in tumors replenish themselves, the researchers report in the May 8 issue of the journal Cell Reports. Damage of the kind duplicated in the laboratory occurs naturally after exposure to radiation and perhaps also after ingestion of toxic chemicals such as those used in chemotherapy.

The research group, led by Erika Matunis, Ph.D., a professor of cell biology at the Johns Hopkins University School of Medicine, has been using the fruit fly as a model living system in which to study stem cells in their natural state. Most stem cell research is done on cells grown in the laboratory, but in real life, stem cells reside in tissues, where they are sequestered in tiny spaces known as niches. Adult stem cells keep dividing throughout life to make various kinds of cells, like new blood cells and germ cells.

Matuniss group studies such niches in fruit fly testes, the sperm-producing organs shaped like a coiled tube whose end houses a niche. In the niche are three kinds of cells: germ line stem cells, which divide to produce sperm; somatic cyst stem cells, which make a kind of cell that helps the sperm-producing cells out; and hub cells, which make signals that keep the other two kinds of cells going.

The hub cells are not stem cells; they have settled on their final form, incapable of dividing further or changing their function or so everyone thought.

However, in a bid to figure out what happens when the somatic cyst stem cells are killed off, Matunis suggested that graduate student Phylis Hti figure out how to best do away with them, thinking the task would be straightforward.

Instead, she says, it took a lot of heroic, patient combinations of different genes working together to kill the somatic cyst cells, Matunis says.

When we finally figured out a way to kill all of the somatic stem cells, we thought that the rest of the tissue would probably just empty out, she says. In 35 percent of testes, thats just what happened. But in the rest, the somatic stem cells grew back. This was a surprise, Matunis says, and left a puzzle: Where were the new somatic stem cells coming from?

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Surprise: Lost Stem Cells Naturally Replaced By Non-Stem Cells, Fly Research Suggests

However a team at the Research Institute for Stem Cell Research at CHA Health Systems in Los Angeles and the University of Seoul said they had achieved the same result with two men, one aged 35 and one 75.

"The proportion of diseases you can treat with lab-made tissue increases with age. So if you cant do this with adult cells it is of limited value, said Robert Lanza, co-author of the research which published in the journal Cell Stem Cell

The technique works by removing the nucleus from an unfertilised egg and replacing it with the nucleus of a skin cell. An electric shock causes the cells to begin dividing until they form a blastocyst a small ball of a few hundred cells.

In IVF it is a blastocyst which is implanted into the womb, but with this technique the cells would be harvested to be used to create other organs or tissues.

However, the breakthrough is likely to reignite the debate about the ethics of creating human embryos for medical purposes and the possible use of the same technique to produce cloned babies which is illegal in Britain.

Although the embryos created may not give rise to a human clone even if implanted in a womb, the prospect is now scientifically closer.

However scientists have been trying for years to clone monkeys and have yet to succeed.

Dr Lanza admitted that without strong regulations, the early embryos produced in therapeutic cloning could also be used for human reproductive cloning, although this would be unsafe and grossly unethical.

However, he said it was important for the future of regenerative medicine that research into therapeutic cloning should continue.

Reproductive biologist Shoukhrat Mitalipov of Oregon Health and Science University, who developed the technique last year said: "The advance here is showing that (nuclear transfer) looks like it will work with people of all ages.

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Breakthrough in human cloning offers new transplant hope

Stem cells in bone marrow need to produce hydrogen sulfide in order to properly multiply and form bone tissue, according to a new study from the Center for Craniofacial Molecular Biology at the Ostrow School of Dentistry.

Professor Songtao Shi, principal investigator on the project, said the presence of hydrogen sulfide produced by the cells governs the flow of calcium ions. The essential ions activate a chain of cellular signals that results in osteogenesis, or the creation of new bone tissue, and keeps the breakdown of old bone tissue at a proper level.

Conversely, having a hydrogen sulfide deficiency disrupted bone homeostasis and resulted in a condition similar to osteoporosis -- weakened, brittle bones -- in experimental mice. In humans, osteoporosis can cause serious problems such as bone fractures, mobility limitations and spinal problems; more than 52 million Americans have or are at risk for the disease.

However, Shi and his team demonstrated that the mice's condition could be rescued by administering small molecules that release hydrogen sulfide inside the body. The results indicate that a similar treatment may have potential to help human patients, Shi said.

"These results demonstrate hydrogen sulfide regulates bone marrow mesenchymal stem cells, and restoring hydrogen sulfide levels via non-toxic donors may provide treatments for diseases such as osteoporosis, which can arise from hydrogen sulfide deficiencies," Shi said.

Story Source:

The above story is based on materials provided by University of Southern California. The original article was written by Beth Newcomb. Note: Materials may be edited for content and length.

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Proper stem cell function requires hydrogen sulfide

LONDON Human cloning has been used to create stem cells from adults for the first time, in a breakthrough which could lead to tissue and organs being regrown.

Using the cloning technique that produced Dolly the sheep in 1996, researchers were able to turn adult human skin cells into stem cells, which can grow into any type of tissue in the body.

They even used the cells of a 75-year-old man, raising the prospect of body parts being regenerated in old age.

The advance could lead to new tissue-transplant operations for a range of debilitating disorders, such as Parkinsons disease, multiple sclerosis, heart disease and spinal cord injuries.

Last year, a team created stem cells from the skin cells of babies, but it was unclear whether it would work in adults.

However, a team of scientists from the Research Institute for Stem Cell Research at CHA Health Systems in Los Angeles and the University of Seoul said they had achieved the same result with two men, one aged 35, the other the 75-year-old.

The proportion of diseases you can treat with lab-made tissue increases with age. So if you cant do this with adult cells it is of limited value, said Robert Lanza, co-author of the research, which was published in the journal Cell Stem Cell.

The technique works by removing the nucleus from an unfertilised egg and replacing it with the nucleus of a skin cell. An electric shock causes the cells to divide until they form a blastocyst, a small ball of a few hundred cells.

In IVF, a blastocyst is implanted into the womb, but with the new technique the cells would be harvested to create other organs or tissues.

The breakthrough is likely to reignite the debate about the ethics of creating human embryos for medical purposes and the possible use of the same technique to produce cloned babies which is illegal in Britain.

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In human cloning first, scientists create stem cells from adults