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Category Archives: Stem Cells

Exercise rescues mutated neural stem cells

Posted: July 7, 2013 at 7:49 am

Public release date: 4-Jul-2013 [ | E-mail | Share ]

Contact: Dr. Sibylle Kohlstdt s.kohlstaedt@dkfz.de Helmholtz Association of German Research Centres

CHARGE syndrome* is a severe developmental disorder affecting multiple organs. It affects 1 in 8500 newborns worldwide. The majority of patients carry a mutation in a gene called CHD7. How this single mutation leads to the broad spectrum of characteristic CHARGE symptoms has been a mystery.

CHD7 encodes a so-called chromatin remodeler, an important class of epigenetic regulators. DNA is wound around bead-like nucleosomes consisting of histone proteins. The string of beads is then twisted into a structure called chromatin. The more nucleosomes that occupy a gene, the less active it is. Chromatin remodelers like CHD7 are essential for the regulation of gene activity because they create nucleosome-free regions in the regulatory sequences of genes. Thus, a mutation in a gene coding for a chromatin remodeler may lead to a wide pattern of misregulated genes.

Dr. Haikun Liu's lab at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is interested in the regulation of adult neural stem cells. The scientists have a particular focus on the role adult neural stem cells play in human diseases, including mental retardation and brain tumors. CHARGE patients suffer from mental retardation and learning disabilities, strongly suggesting that a central nervous defect underlies the disease.

To understand the molecular role of the CHD7 mutation in the CHARGE phenotype, the researchers created a model using genetically modified mice. These animals permit the scientists to switch off the CHD7 gene uniquely in neural stem cells at specific developmental stages. This permitted the scientists to follow how CHD7-deficient cells proliferate, differentiate and mature over the entire lifespan of the animal.

The work led to an exciting finding: by switching off CHD7 in either fetal or adult neural stem cells, the scientists observed that the mutant cells behaved in a common way: They could not efficiently differentiate into mature neurons, which are the basic functional unit in the brains of humans and other animals. Mature neurons normally have a very complex morphology, allowing them to create networks in the brain which are important for processing information. Neurons with the mutant form of CHD7, however, seem to be incapable of forming networks.

Most strikingly, Liu and colleagues found that exercise fully rescued this phenotype in the hippocampus, the core region of the brain responsible for learning and memory. They allowed the CHD7 deficient animals to exercise on a running wheel, which rodents love to do. After the running exercise the CHD7 mutant neurons were fully rescued: They were able to create functioning networks.

That running causes a dramatic increase in neurogenesis in adults has been confirmed in animals and humans. "We were extremely excited to see that the CHD7 deficiency in a cell can be bypassed via an unknown mechanism provoked by exercise involving running. Now, we are eagerly working to find the underlying mechanism," says Haikun Liu. The neuroscientist believes this discovery will lead to a better understanding of the disease, possibly even pointing to a way to reactivate the CHD7 pathway and thus to attenuate CHARGE symptoms in human patients.

CHD7 is also an important cancer-related gene; many different types of human cancers, including lung cancer, colon cancer and brain tumors exhibit mutations in the molecule. The mechanism identified here provides a clear explanation: A mutation in CHD7 leads to a blockage of differentiation in stem cells, which is a major cause of tumorigenesis.

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Scientists create human liver from stem cells

Posted: July 7, 2013 at 7:49 am

Posted on July 7, 2013, Sunday

LONDON: Scientists have for the first time created a functional human liver from stem cells derived from skin and blood and say their success points to a future where much-needed livers and other transplant organs could be made in a laboratory.

While it may take another 10 years before lab-grown livers could be used to treat patients, the Japanese scientists say they now have important proof of concept that paves the way for more ambitious organ-growing experiments.

The promise of an off-the-shelf liver seems much closer than one could hope even a year ago, said Dusko Illic, a stem cell expert at Kings College London who was not directly involved in the research but praised its success.

He said however that while the technique looks very promising and represents a huge step forward, there is much unknown and it will take years before it could be applied in regenerative medicine.

Researchers around the world have been studying stem cells from various sources for more than a decade, hoping to capitalise on their ability to transform into a wide variety of other kinds of cell to treat a range of health conditions.

There are two main forms of stem cells embryonic stem cells, which are harvested from embryos, and reprogrammed induced pluripotent stem cells (iPS cells), often taken from skin or blood.

Countries across the world have a critical shortage of donor organs for treating patients with liver, kidney, heart and other organ failure.

Scientists are keenly aware of the need to find other ways of obtaining organs for transplant.

The Japanese team, based at the Yokohama City University Graduate School of Medicine in Japan, used iPS cells to make three different cell types that would normally combine in the natural formation of a human liver in a developing embryo hepatic endoderm cells, mesenchymal stem cells and endothelial cells and mixed them together to see if they would grow.

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First Organ Grown From Stem Cells Alone: Report

Posted: July 7, 2013 at 7:49 am

By Brenda Goodman HealthDay Reporter

WEDNESDAY, July 3 (HealthDay News) -- Japanese scientists report they've turned a cocktail of stem cells into the world's first functioning livers.

The tiny livers were created in the lab and transplanted into mice, where they grew and began to perform the same functions as human-sized livers, including metabolizing drugs and making liver-specific proteins.

Though very basic -- the experimental livers don't have all the features of full-grown organs -- it's believed to be the first time scientists have grown a three-dimensional organ in the lab using only cells.

Previously, scientists have made solid organs using stem cells that are seeded onto some kind of scaffold, either a donor organ that's been washed of all its original cells or some kind of artificial material.

But one expert said this latest approach takes the concept one step further.

"This is a different strategy to create tissues and organs," said Dr. Anthony Atala, director of the Wake Forest Institute of Regenerative Medicine, in Winston-Salem, N.C.

"The work is very important because it allows you to study how organs are created and how they give rise to more functional complex systems," Atala said. "This is a nice advance."

With further study, researchers think their technique could one day solve the critical shortage of human organs for transplantation.

"We are now assessing the applicability to other organs such as the pancreas and kidneys because they have a similar kind of developmental course as the liver. So far, we've had fascinating results," Takanori Takebe, a professor of regenerative medicine at the Yokohama City University Graduate School of Medicine, said at a press briefing.

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Challenge to WARF hESC Patents Cites Recent U.S. Supreme Court Decision

Posted: July 7, 2013 at 2:59 am

Patents on human embryonic stem cells
are being challenged in a new legal filing that cites the recent U.S.
Supreme Court
decision that barred the patenting of human genes.
The stem cell case involves the
Wisconsin Alumni Research Foundation (WARF), which holds the patents on the
much-heralded work performed by Jamie Thomson  at the University of Wisconsin. The lawsuit was filed
by the Public Patent Foundation of New York City on behalf of
Consumer Watchdog, a nonprofit group in Santa Monica, Ca. Jeanne
Loring
, director of the Center for Regenerative Medicine at the
Scripps Research Institute, is also involved along with Alan
Trounson
, president of the California stem cell agency. The agency
itself is not a party.
This week's filing follows the
so-called Myriad decision last month by the nation's highest court which said,

“Myriad did not create anything. To
be sure, it found an important and useful gene, but separating that
gene from its surrounding genetic material is not an act of
invention.”

"WARF did not create or alter the
properties inherent in stem cells any more than Myriad created or
altered the genetic information encoded in the DNA it claimed.” 

The legal filing came in an appeal of
an earlier decision by the U.S. Patent Office. The Public Patent
Foundation, which was a successful party in the Myriad case, did the earlier legal work on the challenge to the WARF patents as well as this
week's appeal.
The appeal, prepared by Dan Ravicher,
said the WARF patents have "put a severe burden on taxpayer-funded
research in California.”
Trounson released a statement saying,

“We don't want to do anything that
gets in the way of finding treatments for some of the biggest killers
today, so we feel that all patients with all kinds of diseases
deserve to have access to these kinds of cells.”

Loring was quoted in a Consumer Watchdog press release as saying,

"Human embryonic stem cells hold
great promise for advancing human health, and no one has the ethical
right to own them.”

John M. Simpson of Consumer Watchdog
said,

 “The best course if WARF truly
cares about scientific advancement would be to
simply abandon these over-reaching patent claims.”

A story by Bradley Fikes in the San
Diego U-T
cited intellectual property attorney Lisa Haile of DLA
Piper
as saying,

“A successful use of the Myriad case
as a precedent for throwing out the foundation’s patent would open
the door to similar challenges in just about any biotech product
using material derived from life.”

WARF made no immediate comment.

Other stories on the WARF challenge
appeared in the Milwaukee JournalGenomeweb and the LaCross Tribune. 

Source:
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California Legislation, Human Egg Sales and Profits

Posted: July 7, 2013 at 2:59 am

California legislation to allow women
to be paid for their eggs for scientific research is sailing toward
final passage literally swaddled in motherhood and apple pie
arguments. Missing from the debate is a key reason behind
the bill – building profits for what some call the “baby
business.”

The legislation is touted as providing
equal treatment for women, permitting them to be paid for supplying
eggs for stem cell and other research, much as men are paid for
sperm. It also would put women who sell their eggs for research on an
equal economic footing with women who sell their eggs for fertility
treatments, which is currently permitted under state law. Payments to
those women range from an average of $9,000 to as much as $50,000,
according to a legislative analysis of the bill.

 Assemblywoman Susan Bonillla,
D-Concord, author of the bill(AB926), says,

“It is time to let women, just as any
other research subject, make an informed decision as to
participation, and justly compensate them for doing so.”

She also says that the ban on payments
has had serious impact on fertility research. In a legislative bill analysis, she says,

“It has led to a de facto prohibition
on women’s reproductive research in California, adversely
impacting the same women that the ban intended to protect. With few
oocytes donated, fertility research and fertility preservation
research has been at a standstill. This greatly affects women
suffering from fertility issues and women facing cancer who would
like to preserve their oocytes.”

Bonilla is carrying the measure on
behalf of an industry group, the American Society for Reproductive Medicine of Alabama. The fertility or baby business, which is largely
unregulated, brings in about $5 billion annually in the United
States from something like 500 clinics. It has grown rapidly over the
last couple of decades, but is likely heading for a soft spot.
Little public information is available
on the Internet discussing the industry's economic challenges.
However, demographic studies show that the size of the key market
for fertility services is stagnating. A 2012 report by the federal
government projects that the number of women in the 35 to 44 age
group, prime consumers of fertility services, is likely to grow only
0.5 percent from 2010 to 2020. And since that forecast was made, the
Census Bureau has downgraded its projections for total population
growth.
Bonilla's legislation effectively adds
a new, potential revenue stream for the industry. Fertility clinics
would be able to buy the eggs and then resell them to researchers,
adding premiums for eggs from women with special characteristics. The bill would also add a tool for bringing down the cost of fertility
treatments, which can run as much as $12,000 to $17,000 a round or
more and require several rounds, according to the NIH. Clinics could discount those prices for some women, bringing in
new customers, if they agree to authorize the use of excess eggs for
scientific research.
None of this appears necessarily
pernicious. What is pernicious is the absence of discussion of the
economics of the legislation. Without a full understanding of all
that is at stake, including economic issues and motivations,
legislators, the governor and the public are hard-pressed to make
good decisions about a significant change in California law.
Opponents of the legislation have
raised serious questions about the treatment of women by fertility
clinics, noting that the bill would turn egg providers into “vendors”
– not patients of the clinics. The Center for Genetics and Society
in Berkeley has captured the arguments in opposition including
testimony before a Senate committee hearing early in June.
Jennifer Schneider, a physician who
lost a 31-year-old daughter to cancer seven years after the younger
woman sold her eggs three times, told lawmakers,

“Unlike infertile women who are
considered patients, egg donors are treated as vendors( (her italics).
When they walk out of the IVF clinic, no one keeps track of them. 
My daughter’s death was not reported. The long-term risks of egg
donation are unknown."

Sindy Wei, a former egg provider and
now a physician with a Ph.D. in biology, testified that she wound up
in an intensive care unit after 60 eggs were extracted from her in
2001. She said,

“I fear that cases like mine are
buried deep by fertility centers concerned about their image. An
industry thriving on profits and reputation has little incentive to
report adverse events, or protect the health and medical rights of
donors.”

Where is the $3 billion California stem
cell agency on all this? The agency has not taken a position on the
bill nor have any major research organizations. The measure does not
change the law affecting agency-funded research, which bans the use of
compensation for eggs in its research. Enactment of the law, however, would
create a two-tier stem cell research standard in California, one for
scientists not constrained by the payment ban and another for those
who could use the full range of research tools. Some stem cell
researchers may well think that they have become disadvantaged as a
result.

(Editor's note: An earlier version of this article said the IVF business generated $4 billion in revenues annually. More recent estimates place it at $5 billion.)

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A First: Human Liver Created from Stem Cells

Posted: July 5, 2013 at 7:48 pm

Scientists in Japan said they had grown human liver tissue from stem cells in a first that holds promise for alleviating the critical shortage of donor organs.

Creating lab-grown tissue to replenish organs damaged by accident or disease is a Holy Grail for the pioneering field of research into the premature cells known as stem cells.

Now Takanori Takebe of the Yokohama City University Graduate School of Medicine and a team reported Wednesday in the journal Nature that they grew tissue "resembling the (human) adult liver" in a lab mouse.

They first created induced pluripotent stem (iPS) cells which they mixed with other cell types and coaxed into "liver buds" -- the precursor clusters that develop into a liver. The buds, each about five millimeters (0.2 inches) big, were then transplanted onto a mouse brain, where they were observed transforming into a "functional human liver" complete with blood vessels, the scientists wrote.

"To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells," said the report.

The technique has yet to be tested in humans, but serves as an important proof of concept, it added.

Stem cells are infant cells that can develop into any part of the body. Until a few years ago, when iPS cells were created, the only way to obtain stem cells was to harvest them from human embryos. This is controversial because it requires the destruction of the embryo, a process to which religious conservatives and others object.

But iPS cells are easily obtainable mature cells that are "reprogrammed" into a versatile, primitive state from where they can develop into any kind of cell in the body. Takebe told a press conference ahead of the report's release that the man-made liver was observed through a replacement glass skull that was fitted around the mouse's brain.

The liver developed blood vessels which fused with those of the animal. It also performed certain human-specific liver functions -- producing proteins and processing specific drugs. "We have concluded that this liver is functioning," the scientist said. "We think this is enough for improving the survival after liver failure."

Scientists commenting on the research described it as promising.

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A First: Human Liver Created from Stem Cells

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Scientists produce functional human livers from stem cells

Posted: July 5, 2013 at 7:48 pm

New research is paving the way towards 'off-the-shelf' human organs for transplantFor the very first time, scientists have succeeded in creating a functional, three-dimensional human liver from stem cells, bringing medicine one step closer towards having 'off-the-shelf' transplant organs.

The scientists created tiny liver 'buds', roughly 4 millimetres wide, by bringing together the same types of human cells that combine when the liver starts to grow in the human embryo. Rather than using embryonic stem cells as their 'base', though, the scientists reprogrammed mature human skin cells back into an embryonic state producing 'induced pluripotent stem cells' or iPSCs. They then added cells taken from umbilical cord blood called endothelial cells which create the lining of blood vessels, and another type called mesenchymal stem cells, which go into producing bone, cartilage and fat tissues.

[ Related: Stem-cell therapy wipes out HIV in two patients ]

The buds that grew from this combination of cells not only formed liver tissue, but they also formed a network of blood vessels throughout the tissue. When these buds were transplanted into mice that were suffering from liver failure, they took over various liver functions, keeping the mice alive, and the buds even connected up with the surrounding blood vessels and kept growing.

The most amazing part about this entire discovery is that it essentially happened as an unexpected result. One of the study leaders, Takanori Takebe, from Yokohama City University in Japan, was simply working on a way to create 'vascularized' liver tissue that is, tissue with blood vessels running through it which has, so far, been very difficult to do. Some trials have used artificial scaffolding to form the growing cells into the right shape, and others have just grown pure cultures of cells, but Takebe tried combining different types of cells together at the same time. He found that, as they grew, they organized themselves into three-dimensional structures.

"We just simply mixed three cell types and found that they unexpectedly self-organize to form a three-dimensional liver bud this is a rudimentary liver," Takebe told BBC News. "And finally we proved that liver bud transplantation could offer therapeutic potential against liver failure."

After that discovery, it took hundreds of tries to get up to the stage of making these tiny liver buds.

"The strategy is very promising, and represents a huge step forward," said Dr Dusko Ilic, a stem cell scientist at King's College London, according to BBC News.

"Although the promise of an off-the-shelf-liver seems much closer than one could hope even a year ago, the paper is only a proof of concept. There is much unknown and it will take years before it could be applied in regenerative medicine."

[ More Geekquinox: Astronomers detect strange radio signals from deep space ]

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Stem cells give woman her life back

Posted: July 4, 2013 at 4:45 pm

Megan Strachan, with her dog Ollie, suffers from scleroderma - a rare disease in which the immune system attacks the body. Picture: Norm Oorloff Source: Herald Sun

AS Megan Strachan strolls near her Drouin home, it is difficult to believe that a year ago she was crippled by an incurable disease causing her body to harden and consume itself.

She believes an experimental stem cell transplant has freed up her limbs from the effects of scleroderma - when the immune system attacks victims' skin so it hardens and cannot move.

It can affects joints and lead to organ failure.

The jury is out on whether controversial stem cell treatments can impact the disease that affects up to 5000 Australians, but Ms Strachan is thrilled to have her life back.

"At the time of the transplant I was bedridden. All my joints had contracted, so they were all bent and I couldn't stand up straight because my skin was hard from head to toe," Ms Strachan said.

"Slowly, but surely, over the course of the two years, my skin started softening and I was able to straighten my arms."

Diagnosed just before turning 30, within four months Ms Strachan had to give up her job as a nurse and then moved in with her parents to be looked after.

With no frontline treatment, Ms Strachan talked to an expert in Switzerland, who put her on to haematologist Dr John Moore. He was pioneering autologous stem cell transplants at Sydney's St Vincent's Hospital.

Dr Moore's process involves returning a patient's stem cells in conjunction with chemotherapy, with the toxic drugs responsible for killing off the immune system's attack while stem cells offset the treatment's side-effects.

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First Functioning Human Organ Made of Induced Stem Cells

Posted: July 4, 2013 at 4:45 pm

Proto-livers in dishes in the lab. Credit: Takanori Takebe

A team of Japanese researchers has created the first functioning human organ, a liver, from induced pluripotent stem cells. While the technology is at least a decade from clinical application, it opens the door to using stem cells to solve the shortage of donor organs.

The organ precursors were grown in the lab using iPS cells. When these early organs, called liver buds, were transplanted into mice, they matured into tissue resembling the adult human liver. After just four to six days, the cells had self-organized into a functioning organ with a healthy blood supply.

The team of researchers at Yokohama City University began with human skin cells, which they genetically reverted to an embryonic stem-cell state and then coaxed into liver-precursor cells. They then exposed these cells to environments similar to what the developing liver experiences in a fetus, adding to the dish stem cells that line blood vessels and form tissues. Within 48 hours the cells had amassed into tiny proto-organs visible to the naked eye.

Once the liver buds were about 4 or 5 millimeters, the team implanted 12 liver buds into either the brain or abdomen of each mousesites chosen for their ease of access. The researchers had labeled the cells with fluorescent proteins, which helped them monitor the buds for formation of blood vessels.

They found that the organ developed a vascular system almost immediately and performed liver-specific functions within weeks. By day ten the transplanted liver buds were producing albumin, a key protein produced by the liver. After 60 days the gene expression of cells in the liver bud had significantly shifted from its precursor cells.

As further proof, the mice were given drugs that mice livers cannot normally metabolize but human livers can. The mice successfully broke down these drugs into the same components that humans do.

The results are published today in Nature.

The technique is unlikely to produce whole replacement livers, but could be used to grow mini-livers that supplement a failing organ. Such transplants wouldnt even need to be located near the existing liver. Lead researcher Takanori Takebe hopes to reduce the size of the liver buds to 100 micrometers, so they can be injected into the bloodstream of mice.

Takebe estimates that with an infusion of hundreds of thousands of liver buds, about 30 percent of a persons liver function could be restored. The limitation at the moment is to create enough suitable liver buds in sufficient quantity to create a viable clinical therapy, he said.

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Human Liver Created From Stem Cells In Mouse

Posted: July 4, 2013 at 4:45 pm

Scientists have for the first time created a functional human liver from stem cells derived from skin and blood - suggesting organs could be grown in labs in another 10 years.

The research could alleviate an acute shortage of donor organs across the world for patients with liver, heart, kidney and other organ failure.

Japanese scientists, based at the Yokohama City University Graduate School of Medicine, said they grew tissue "resembling the (human) adult liver" in a lab mouse.

The team used induced pluripotent stem (iPS) cells, which are often taken from blood and skin, to make three different cell types that would normally combine in the natural formation of a human liver.

These were then mixed to see if they would grow into three-dimensional structures called "liver buds" - the precursor clusters that develop into a full liver organ.

The buds were then transplanted onto a mouse brain, where they were observed transforming into a "functional human liver" complete with blood vessels, the scientists wrote in the journal Nature.

"To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells," said the report.

Takanori Takebe, who led the study, said the liver also performed certain human-specific liver functions - producing proteins and processing specific drugs.

He was so encouraged by the success of this work that he plans similar research on other organs such as the pancreas and lungs.

The technique has yet to be tested in humans, but serves as an important proof of concept, the report added.

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Human Liver Created From Stem Cells In Mouse

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