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Via cloning, human stem cells

Posted: May 15, 2013 at 10:49 pm

Oregon Health&Science University

Donor egg held by pipette prior to nuclear extraction.

By Maggie Fox, Senior Writer, NBC News

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 Parkinsons 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 theyre deficient in a key way. But they admit also that they havent quite overcome ethical qualms about working with human embryos.

However, the work opens another route to treatments using human embryonic stem cells, the bodys 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. Theyd be perfect genetic matches for each patient, meaning an end to a lifetime of taking dangerous immune-suppressing drugs after an organ transplant.

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Success! Human stem cells cloned

Posted: May 15, 2013 at 10:49 pm

Stem cells viewed on a computer screen at the University of Connecticut's Stem Cell Institute.

STORY HIGHLIGHTS

(TIME.com) -- It's been 17 years since Dolly the sheep was cloned from a mammary cell. And now scientists applied the same technique to make the first embryonic stem cell lines from human skin cells.

Ever since Ian Wilmut, an unassuming embryologist working at the Roslin Institute just outside of Edinburgh stunned the world by cloning the first mammal, Dolly, scientists have been asking -- could humans be cloned in the same way?

Putting aside the ethical challenges the question raised, the query turned out to involve more wishful thinking than scientific success. Despite the fact that dozens of other species have been cloned using the technique, called nuclear transfer, human cells have remained stubbornly resistant to the process.

Until now. Shoukhrat Mitalipov, a professor at Oregon Health & Science University, and his colleagues report in the journal Cell that they have successfully reprogrammed human skin cells back to their embryonic state.

The purpose of the study, however, was not to generate human clones but to produce lines of embryonic stem cells. These can develop into muscle, nerve, or other cells that make up the body's tissues. The process, he says, took only a few months, a surprisingly short period to reach such an important milestone.

TIME.com: Stem cell scientists awarded Nobel Prize in Physiology and Medicine

Nuclear transfer involves inserting a fully developed cell -- in Mitalipov's study, the cells came from the skin of fetuses -- into the nucleus of an egg, and then manipulating the egg to start dividing, a process that normally only occurs after it has been fertilized by a sperm.

After several days, the ball of cells that results contains a blanket of embryonic stem cells endowed with the genetic material of the donor skin cell, which have the ability to generate every cell type from that donor.

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Success! Human stem cells cloned

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Stem Cells Pulled From Cloned Embryos

Posted: May 15, 2013 at 10:49 pm

Scientists have finally recovered stem cells from cloned human embryos, a longstanding goal that could lead to new treatments for such illnesses as Parkinson's disease and diabetes.

A prominent expert called the work a landmark, but noted that a different, simpler technique now under development may prove more useful.

Stem cells can turn into any cell of the body, so scientists are interested in using them to create tissue for treating disease. Transplanting brain tissue might treat Parkinson's disorder, for example, and pancreatic tissue might be used for diabetes.

But transplants run the risk of rejection, so more than a decade ago, researchers proposed a way around that: Create tissue from stem cells that bear the patient's own DNA, obtained with a process called therapeutic cloning.

If DNA from a patient is put into a human egg, which is then grown into an early embryo, the stem cells from that embryo would provide a virtual genetic match. So in theory, tissues created from them would not be rejected by the patient.

That idea was met with some ethical objections because harvesting the stem cells involved destroying human embryos.

Scientists have tried to get stem cells from cloned human embryos for about a decade, but they've failed. Generally, that's because the embryos stopped developing before producing the cells. In 2004, a South Korean scientist claimed to have gotten stem cells from cloned human embryos, but that turned out to be a fraud.

In Wednesday's edition of the journal Cell, however, scientists in Oregon report harvesting stem cells from six embryos created from donated eggs. Two embryos had been given DNA from skin cells of a child with a genetic disorder, and the others had DNA from fetal skin cells.

Shoukhrat Mitalipov of the Oregon Health & Science University, who led the research, said the success came not from a single technical innovation, but from revising a series of steps in the process. He noted it had taken six years to reach the goal after doing it with monkey embryos.

Mitalipov also said that based on monkey work, he believes human embryos made with the technique could not develop into cloned babies, and he has no interest in trying to do that. Scientists have cloned more than a dozen kinds of mammals, starting with Dolly the sheep.

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Human stem cells created by cloning

Posted: May 15, 2013 at 10:49 pm

Seeing double: human embryonic stem cells have finally been made using cloning techniques.

OHSU Photos

It was hailed some 15 years ago as the great hope for a biomedical revolution: the use of cloning techniques to create perfectly matched tissues that would someday cure ailments ranging from diabetes to Parkinsons disease. Since then, the approach has been enveloped in ethical debate, tainted by fraud and, in recent years, overshadowed by a competing technology. Most groups gave up long ago on the finicky core method production of patient-specific embryonic stem cells (ESCs) from cloning. A quieter debate followed: do we still need therapeutic cloning?

A paper published this week1 by Shoukhrat Mitalipov, a reproductive biology specialist at the Oregon Health and Science University in Beaverton, and his colleagues is sure to rekindle that debate. Mitalipov and his team have finally created patient-specific ESCs through cloning, and they are keen to prove that the technology is worth pursuing.

Therapeutic cloning, or somatic-cell nuclear transfer (SCNT), begins with the same process used to create Dolly, the famous cloned sheep, in 1996. A donor cell from a body tissue such as skin is fused with an unfertilized egg from which the nucleus has been removed. The egg reprograms the DNA in the donor cell to an embryonic state and divides until it has reached the early, blastocyst stage. The cells are then harvested and cultured to create a stable cell line that is genetically matched to the donor and that can become almost any cell type in the human body.

Many scientists have tried to create human SCNT cell lines; none had succeeded until now. Most infamously, Woo Suk Hwang of Seoul National University in South Korea used hundreds of human eggs to report two successes, in 2004 and 2005. Both turned out to be fabricated. Other researchers made some headway. Mitalipov created SCNT lines in monkeys2 in 2007. And Dieter Egli, a regenerative medicine specialist at the New York Stem Cell Foundation, successfully produced human SCNT lines3, but only when the eggs nucleus was left in the cell. As a result, the cells had abnormal numbers of chromosomes, limiting their use.

Mitalipov and his group began work on their new study last September, using eggs from young donors recruited through a university advertising campaign. In December, after some false starts, cells from four cloned embryos that Mitalipov had engineered began to grow. It looks like colonies, it looks like colonies, he kept thinking. Masahito Tachibana, a fertility specialist from Sendai, Japan, who is finishing a 5-year stint in Mitalipovs laboratory, nervously sectioned the 1-millimetre-wide clumps of cells and transferred them to new culture plates, where they continued to grow evidence of success. Mitalipov cancelled his holiday plans. I was happy to spend Christmas culturing cells, he says. My family understood.

The success came through minor technical tweaks. The researchers used inactivated Sendai virus (known to induce fusion of cells) to unite the egg and body cells, and an electric jolt to activate embryo development. When their first attempts produced six blastocysts but no stable cell lines, they added caffeine, which protects the egg from premature activation.

None of these techniques is new, but the researchers tested them in various combinations in more than 1,000 monkey eggs before moving on to human cells. They made the right improvements to the protocol, says Egli. Its big news. Its convincing. I believe it.

The experiments took only a few months, Mitalipov says. People say, you did it in monkeys in 2007. Why did it take six years in humans? Most of the time, he says, was spent navigating US regulations on embryo research.

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Stem Cells Made From Cloned Human Embryos

Posted: May 15, 2013 at 10:49 pm

Scientists in the United States have hailed a major breakthrough after recovering stem cells from cloned human embryos for the first time.

Researchers described the use of skin to generate embryonic stem cells - which removes one of the obstacles to human cloning - as a "milestone".

The cells could potentially be used to make newbrain tissue for Parkinson's sufferers, new heart muscle for people with cardiovascularproblems or pancreatic tissue to treat diabetes.

But while the breakthrough will help the development of stem cell therapies that avoid fertilised human embryos, the cloning technique used in the process is expected to fuel controversy and claims of Brave New World-style science.

The scientists dismissed such criticism, saying they were not interested in cloning humans and did not believe their methods could successfully be used in this way.

Lead researcher Professor Shoukhrat Mitalipov said: "While nuclear transfer breakthroughs often lead to a public discussion about the ethics of human cloning, this is not our focus, nor do we believe our findings might be used by others to advance the possibility of human reproductive cloning.

"Our finding offers new ways of generating stem cells for patients with dysfunctional or damaged tissues and organs," he explained in the journal Cell.

"Such stem cells can regenerate and replace those damaged cells and tissues and alleviate diseases that affect millions of people."

The stem cells demonstrated an ability to convert into several different cell types, including nerve, liver and heart cells.

"While there is much work to be done in developing safe and effective stem cell treatments, we believe this is a significant step forward in developing the cells that could be used in regenerative medicine," MrMitalipovadded.

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Breakthrough: stem cells from a cloned embryo

Posted: May 15, 2013 at 10:49 pm

Scientists have used caffeine to achieve a stem cell breakthrough that many researchers thought impossible but that could lead to new therapies for many crippling diseases.

A US team used a human skin cell to create a cloned human embryo from which they were able to extract embryonic stem cells, a world first.

The technique, known as somatic cell nuclear transfer, or therapeutic cloning, is ethically controversial because it involves the production, and subsequent destruction, of a human embryo.

Its medical promise is that the embryonic stem cells obtained which can turn into all cell types in the body for possible organ repair and transplant are genetically matched to the person who donated the skin cell.

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"This study is a breakthrough development that overcomes a major scientific hurdle with significant implications for potentially treating a range of diseases," said Bryce Vissel, the head of the Neurodegeneration Research Program at the Garvan Institute of Medical Research.

Scientists, including Australian researchers, have spent years attempting to create embryonic stems cells from cloned human embryos. "Our finding offers new ways of generating stem cells for patients with dysfunctional or damaged tissues and organs," said the study leader, Shoukhrat Mitalipov, from the Oregon Health & Science University.

"Such stem cells can regenerate and replace those damaged cells and tissues and alleviate diseases that affect millions of people," said Professor Mitalipov.

The chair of stem cell sciences at the University of Melbourne, Martin Pera, said the new method also offered a unique approach to preventing inherited mitochondrial diseases, which cause debilitating degeneration in the brain and heart of affected individuals.

The discovery is published in the prestigious journal Cell.

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Embryonic stem cells made from skin

Posted: May 15, 2013 at 10:49 pm

US researchers have reported a breakthrough in stem cell research, describing how they have turned human skin cells into embyronic stem cells for the first time.

The method described by Oregon State University scientists on Wednesday in the journal Cell, would not likely be able to create human clones, said Shoukhrat Mitalipov, senior scientist at the Oregon National Primate Research Centre.

But it is an important step in research because it does not require the use of embryos in creating the type of stem cell capable of transforming into any other type of cell in the body.

The technique involves transplanting an individual's DNA into an egg cell that has been stripped of genetic material, a variation of a method called somatic cell nuclear transfer.

'A thorough examination of the stem cells derived through this technique demonstrated their ability to convert just like normal embryonic stem cells, into several different cell types, including nerve cells, liver cells and heart cells,' said Mitalipov.

He added that since the reprogrammed cells use genetic material from the patient, there is no concern about transplant rejection.

'While there is much work to be done in developing safe and effective stem cell treatments, we believe this is a significant step forward in developing the cells that could be used in regenerative medicine,' Mitalipov said.

Years of research on monkey cells using the same technique have not successfully produced any monkey clones.

Since the human cells used in the study appeared even more fragile, researchers said it was unlikely clones could be made.

'While nuclear transfer breakthroughs often lead to a public discussion about the ethics of human cloning, this is not our focus, nor do we believe our findings might be used by others to advance the possibility of human reproductive cloning,' they said.

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Embryonic Stem Cells: Advance In Medical Human Cloning

Posted: May 15, 2013 at 10:49 pm

Human cloning has been used to produce early embryos, marking a "significant step" for medicine, say US scientists.

The cloned embryos were used as a source of stem cells, which can make new heart muscle, bone, brain tissue or any other type of cell in the body.

The study, published in the journal Cell, used methods like those that produced Dolly the sheep in the UK.

However, researchers say other sources of stem cells may be easier, cheaper and less controversial.

Opponents say it is unethical to experiment on human embryos and have called for a ban.

Stem cells are one of the great hopes for medicine. Being able to create new tissue might be able to heal the damage caused by a heart attack or repair a severed spinal cord.

There are already trials taking place using stem cells taken from donated embryos to restore people's sight.

However, these donated cells do not match the patient so they would be rejected by the body. Cloning bypasses this problem.

The technique used - somatic cell nuclear transfer - has been well-known since Dolly the sheep became the first mammal to be cloned, in 1996.

Skin cells were taken from an adult and the genetic information was placed inside a donor egg which had been stripped of its own DNA. Electricity was used to encourage the egg to develop into an embryo.

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Stem cells recovered from cloned human embryos

Posted: May 15, 2013 at 10:49 pm

NEW YORK Scientists have finally recovered stem cells from cloned human embryos, a longstanding goal that could lead to new treatments for such illnesses as Parkinsons disease and diabetes.

A prominent expert called the work a landmark but noted that a different, simpler technique under development may prove more useful.

Stem cells can turn into any cell of the body, so scientists are interested in using them to create tissue for treating disease. Transplanting brain tissue might treat Parkinsons disorder, for example, and pancreatic tissue might be used for diabetes.

But transplants run the risk of rejection, so more than a decade ago researchers proposed a way around that: Create tissue from stem cells that bear the patients own DNA, obtained with a process called therapeutic cloning.

If DNA from a patient is put into a human egg, which is then grown into an early embryo, the stem cells from that embryo would provide a virtual genetic match. So in theory, tissues created from them would not be rejected by the patient.

That idea was met with some ethical objections because harvesting the stem cells involved destroying human embryos.

Scientists have tried to get stem cells from cloned human embryos for about a decade, but theyve failed. Generally, thats because the embryos stopped developing before producing the cells.

In 2004, a South Korean scientist claimed to have gotten stem cells from cloned human embryos, but that turned out to be a fraud.

In Wednesdays edition of the journal Cell, however, scientists in Oregon report harvesting stem cells from six embryos created from donated eggs. Two embryos received DNA from skin cells of a child with a genetic disorder, and the others had DNA from fetal skin cells.

Shoukhrat Mitalipov of the Oregon Health & Science University, who led the research, said the success came not from a single technical innovation, but from revising a series of steps in the process. He noted it had taken six years to reach the goal after doing it with monkey embryos.

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Klein, StemCells, Inc., and $31,000 in Consulting Fees for Torres

Posted: May 15, 2013 at 8:33 am

The Robert Klein-StemCells, Inc.,
affair has taken another turn with the disclosure that a vice
chairman of the California stem cell agency was paid at least $31,000
over a two-year period by Klein and also voted on behalf of Klein's
effort to win approval of a $20 million award for StemCells, Inc.

Art Torres received what he reported were
consulting fees during 2011 and 2012 from firms controlled by Klein, former chairman of
the agency. In 2012, Torres backed Klein's
efforts to override grant reviewers' rejection of the $20 million
application from the Newark, Ca., publicly traded firm.
Art Torres, center, with Bob Klein, left, at Klein's last meeting in
2011 as chairman of the California stem cell agency.
 Incoming chairman Jonathan Thomas is at right. 

The 29-member board of the California
Institute for Regenerative Medicine (CIRM)
, as the agency is formally
known, narrowly voted 7-5 last September for the award. It was the
first time that the board has approved an application rejected twice
by its scientific reviewers. It was also the first time that Klein
has lobbied the board on behalf of a specific application since
stepping down in June 2011. He was elected chairman in 2005 as the
agency was just beginning its work and is an iconic figure to many in
the California stem cell community.

Asked for comment last week by the
California Stem Cell Report, Torres said,

"My decision to support an award
to StemCells, Inc. to explore the use of neural stem cell
transplantation to treat Alzheimer's disease was based on the merits
of the application and the hope it offers to patients who suffer from
Alzheimer's, a disease that affects millions, including Bob Klein's
late mother. I have no financial interest in StemCells, Inc. nor does
Bob Klein, and my decision to support the award has no connection
whatsoever to the work I do with Bob Klein."

Kevin McCormack, senior director for
public communications at CIRM, said that Torres' statement would be
the only comment on the matter from the agency.
Klein did not respond to questions,
declaring that personal issues were occupying his time.
The California Stem Cell Report's
questions to all three dealt with the propriety of Torres' employment
by both CIRM and Klein while Klein was asking the board to award a
business $20 million. The governing board has a code of conduct that
declares members should “maintain the highest standards of
integrity and professionalism.” However, it does not speak to
questions of appropriate employment by CIRM directors outside of the
agency.
In January 2012, Torres authored a document discussing CIRM's conflict of interest rules. He said they
are intended “to eliminate even the appearance of impropriety.”
He also referred to CIRM's policy on “incompatible activities”
for employees. It deals with activities that could “discredit”
the agency or that are “inimical” to it. However, it does not
specifically deal with the type of situation involving Torres and
Klein, who is a real estate investment banker and attorney. The policy additionally does not address cases where a
governing board member is also an employee of the agency.
Torres' economic disclosure statements,
which are required by state law, contain only broad ranges for compensation, and the amount could be significantly higher than
$31,000. Torres reported that in 2011 he was paid between $10,001 and
$100,000 by both Klein Financial Corp. and K CP Cal, which share the
same address as Klein's offices in Palo Alto. In 2012, Torres reported receiving between $10,001 and $100,000 from K CP Cal and
between $1,001 and $10,000 from Klein Ventures LLC, which also has
the same address.
Torres reported that the payments were
consulting fees and that the firms dealt with real estate. He did not
respond to requests for more details.
Torres earns $225,000 a year in his part-time role as one of two vice chairmen for the agency. Under the
arrangement, he works four days a week.
Torres was chairman of the state
Democratic Party and a longtime state legislator. He was nominated
for vice chairman in 2009 by state Treasurer Bill Lockyer, among
others.
Last week, another financial
arrangement involving Klein surfaced in connection with the
StemCells, Inc., application. Klein gave the agency $21,000 last May,two months before he pitched the board on the StemCells, Inc.,application. The donation was not reported to the board prior to
Klein's appearances before the panel. The agency's regulations
require such gifts to be reported to the board but do not specify a
time frame. Following inquiries from the California Stem Cell Report,
the agency said it would report the donation at the agency board
meeting next week.
Klein's donation financed a trip by six
CIRM science officers to Japan for an international stem cell
conference. The agency directed the officers to give special access
to Klein. Two of the officers were heavily involved in the grant
round that included the StemCells, Inc., application, which scientific reviewers scored at 61 on a scale of 100.

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