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Category Archives: Stem Cells

3D printing with stem cells could lead to printable organs

Posted: February 6, 2013 at 2:49 pm

A potentially breakthrough 3D-printing process using human stem cells could be the precursor to printing organs from a patient's own cells.

3D-printed stem cells act like ink.

Some day in the future, when you need a kidney transplant, you may get a 3D-printed organ created just for you. If scientists are able to achieve that milestone, they may look back fondly at a breakthrough printing process pioneered by researchers at Heriot-Watt University in Scotland in collaboration with Roslin Cellab, a stem cell technology company.

The printer creates 3D spheroids using delicate embryonic cell cultures floating in a "bio ink" medium. They end up looking like little bubbles. Each droplet can contain as few as five stem cells. Basically, this comes down to the printer "ink" being stem cells rather than plastic or another material.

Dr. Will Shu is part of the research team working on the project. "In the longer term, we envisage the technology being further developed to create viable 3D organs for medical implantation from a patient's own cells, eliminating the need for organ donation, immune suppression, and the problem of transplant rejection," Shu said in a release from Heriot-Watt.

Perhaps most importantly, the stem cells survived the printing process and remained viable. Shu says this is the first time human embryonic stem cells have been 3D printed. Printing out organs may be far down the line, but it's just one potential application. The method could also be used to print out human tissue for drug testing.

The research results have just been published in Biofabrication under the title "Development of a valve-based cell printer for the formation of human embryonic stem cell spheroid aggregates."

While things like 3D-printed Mobius bacon strips and crazy pointy shoes are a lot of fun, it's applications like this that could really turn 3D printing into a world changer.

(Via PopSci)

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Trigger turns muscle stem cells into brown fat: Discovery identifies potential obesity treatment

Posted: February 6, 2013 at 2:49 pm

Feb. 5, 2013 Ottawa scientists have discovered a trigger that turns muscle stem cells into brown fat, a form of good fat that could play a critical role in the fight against obesity. The findings from Dr. Michael Rudnicki's lab, based at the Ottawa Hospital Research Institute, were published today in the journal Cell Metabolism.

"This discovery significantly advances our ability to harness this good fat in the battle against bad fat and all the associated health risks that come with being overweight and obese," says Dr. Rudnicki, a senior scientist and director for the Regenerative Medicine Program and Sprott Centre for Stem Cell Research at the Ottawa Hospital Research Institute. He is also a Canada Research Chair in Molecular Genetics and professor in the Faculty of Medicine at the University of Ottawa.

Globally, obesity is the fifth leading risk for death, with an estimated 2.8 million people dying every year from the effects of being overweight or obese, according to the World Health Organization. The Public Health Agency of Canada estimates that 25% of Canadian adults are obese.

In 2007, Dr. Rudnicki led a team that was the first to prove the existence of adult skeletal muscle stem cells. In the paper published today, Dr. Rudnicki now shows (again for the first time) that these adult muscle stem cells not only have the ability to produce muscle fibres, but also to become brown fat. Brown fat is an energy-burning tissue that is important to the body's ability to keep warm and regulate temperature. In addition, more brown fat is associated with less obesity.

Perhaps more importantly, the paper identifies how adult muscle stem cells become brown fat. The key is a small gene regulator called microRNA-133, or miR-133. When miR-133 is present, the stem cells turn into muscle fibre; when reduced, the stem cells become brown fat.

Dr. Rudnicki's lab showed that adult mice injected with an agent to reduce miR-133, called an antisense oligonucleotide or ASO, produced more brown fat, were protected from obesity and had an improved ability to process glucose. In addition, the local injection into the hind leg muscle led to increased energy production throughout the body -- an effect observed after four months.

Using an ASO to treat disease by reducing the levels of specific microRNAs is a method that is already in human clinical trials. However, a potential treatment using miR-133 to combat obesity is still years away.

"While we are very excited by this breakthrough, we acknowledge that it's a first step," says Dr. Rudnicki, who is also scientific director of the Stem Cell Network. "There are still many questions to be answered, such as: Will it help adults who are already obese to lose weight? How should it be administered? How long do the effects last? Are there adverse effects we have not observed yet?"

The full article, "MicroRNA-133 Controls Brown Adipose Determination in Skeletal Muscle Satellite Cells by Targeting Prdm16," was published by Cell Metabolism online ahead of print on February 5, 2013. The article's authors are: Hang Yin, Alessandra Pasut, Vahab D. Soleimani, C. Florian Bentzinger, Ghadi Antoun, Stephanie Thorn, Patrick Seale, Pasan Fernando, Wilfred van IJcken, Frank Grosveld, Robert A. Dekemp, Robert Boushel, Mary-Ellen Harper, and Michael A. Rudnicki.

This research was funded by the Canadian Institutes of Health Research, the National Institutes of Health, the Stem Cell Network, the Ontario Research Fund and EuTRACC, a European Commission 6th Framework grant. It was a collaboration that included researchers from the Ottawa Hospital Research Institute, University of Ottawa, University of Ottawa Heart Institute, Nordion, Erasmus Medical Centre in the Netherlands and University of Copenhagen.

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Trigger turns muscle stem cells into brown fat: Discovery identifies potential obesity treatment

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How stem cells could lead to 3D-printed organs

Posted: February 6, 2013 at 2:49 pm

Forget plastic toys. Researchers want to build a 3D printer that can assemble a human heart

In the future, instead of spending monthswaiting for a life-saving heart transplant, you might be able to just print a new heart.

That's the wild new promise of a major breakthrough in 3D printing, which seeks to enlist human embryonic stem cells to produce malleable clumps of tissue.

Normally, 3D printers put together objects layer-by-layer using plastic, metal, and other materials. Space researchers want to use it to build a base on a moon, companies like MakerBot let you print out plastic toys at home, and some people have (controversially) figured out how to use 3D printers to build their own handgun parts.

According to Popular Science, this new biomedical technique would use human embryonic stem cells floating in a chemical "bio-ink." These cells have the unique ability to be coaxed into any other type of tissue in body heart cells, liver cells, bones, you name it.

The problem, until now, was that these specific type of stem cells were incredibly delicate. So delicate, in fact, that funneling them through a nozzle to form tissue clumps often left the cells dead. But researchers at Heriot-Watt University in Scotland found that by using the precision of a 3D printer, researchers could gently arrange the cells into spheroids and overlay them with bio-ink. They found that this process left close to90 percent of the human embryionic stem cells alive after three days. Repeat this process enough times, and you could, in theory, begin to build any kind of body part imaginable.

Scientists now envision printing human tissue to test drugs, patch up damaged organs, or even build entirely new body parts, although they're the first to admit that the technique has a long way to go.

But imagine: Liver failure imminent? No problem here's a new one. Patch of skin missing from a third-degree burn? Piece of cake. How about a new set of perfect eyes without annoying astigmatism? Here you go.

Welcome to the future of medicine, folks. It's going to be great.

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How stem cells could lead to 3D-printed organs

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Scientists print 3D object with stem cells

Posted: February 6, 2013 at 2:49 pm

Stem cells. Photo: Getty Images/AFP

Scientists say they have printed 3D objects using human embryonic stem cells for the first time, furthering the quest to fabricate transplantable organs.

Once fine-tuned, the technology should allow scientists to make three-dimensional human tissue in the lab, eliminating the need for organ donation or testing on animals, they reported.

Human embryonic stem cells (hESCs) can replicate indefinitely and become almost any type of cell in the human body.

They are touted as a source of replacement tissue, fixing nearly anything from malfunctioning hearts and lungs, to damaged spines, Parkinson's disease or even baldness.

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Scientists have previously tested 3D printing, which uses inkjet technology, with other types of cells, including adult stem cells.

But until now hESCs, which are more versatile than mature ones, have proven too fragile.

"This is a scientific development which we hope and believe will have immense valuable long-term implications for reliable, animal-free drug testing and in the longer term, to provide organs for transplant on demand," said Jason King from British stem cell company Roslin Cellab, which took part in the work.

The team used a specially-designed "valve-based" printer that deposited a "bio ink" of liquid containing laboratory-cultivated hESCs.

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Stem cells is no hype but it is a better hope: Experts

Posted: February 6, 2013 at 2:49 pm

One day 2 of Bangalore India Bio (BIB) Indias premier Biotech Show organised by the department of Information Technology, Bio-Technology and Science & Technology, Government of Karnataka and the Vision Group on Biotechnology, featured another TRACK ON REGENERATIVE MEDICINE, the topic was THE PROMISES AND CHALLENGES OF REGENERATIVE MEDICINE. The session was Chaired by B.N. Manohar Chief Executive Officer, Stempeutics Research Pvt. Ltd. and the Speakers were Prof. Ravi Bellamkonda Associate Vice President for Research, Carol Ann and David D. Flanagan Chair in Biomedical Engineering & GCC Distinguished Scholar, Georgia Institute of Technology, USA, Dr. N.K. Venkataramana - Director of Advanced Neuro-Science Institute and Vice-Chairman of BGS-Global Hospitals and Dr. Suresh Babu - Application Scientist, Life Science Centre (R&D), Agilent Technologies.

Opening the session B.N. Manohar, said, Today regenerative medicine, stem cells, neurology have tremendous potential. Bio Pharma can change the present US$5bn to US$100billion by 2025. Globally US$150bn revenue is made by Biotechnology industries in which 15% is from Pharma industries. In which India contributes 10% to pharma revenue. Stem cells will become a major benchmark for medical treatment. They can be utilized in many ways, which will be shared by the Panel.

Prof. Ravi Bellamkonda, said, the concept of damaged cells to regenerate the cells in the nerve gap, the polymer drug for the cell therapy to grow organwhich is to be viable but need investments. When the nerve gaps are more than 10mm they dont heal fast on their own, Surgeons use pseudo nerve for nervegrafting. Nerve grafting has many disadvantages like second surgery, rate multiple grafting etc 40% success rate, to overcome this is designing the ideal bridge inthe nerve gaps. We are working in our lab to design a pseudo nerve which has genetic approach which has the capacity for bridging for auto grafting and alsodeveloping a gel. This was developed directly in the tissues but it did not work so we tried to work with the embryonic cells (rat), fiber cells with polymer whichallows the gel formation which allows the nerve growth. The Schwann cells which migrated to the glial cells for the growth of nerve cells. This takes nearly 10years for the treatment so trying to concentrate for the short term a treatment which promotes the nerve bridge. We worked on Peripheral nerve submerges withmacrophage which responds to the M2 phenotype for the auto grafting, the Schwann cells migrates quickly regenerating the cells, the study is still under process.We will be able to provide more jobs as we expand.

Dr. N. K. Venkataramana, in his talk said, Started with advancement in medicine from past 3decades and the UN met medical needs in neurological disorders alone we have more than 15 million people adding on every year and their accounts to 300 million which is a huge burden. For this burden stem cells was a boon in the field. We thought that the fundamental property and its cell repairing capacity can be exploited by the scientists and a way to meet the medical needs. Our main goal is to inject the stem cells into the body, so the natural power of regeneration can be enhanced and supported. All stem cells are not equal, majority of us use adult stem cells, embryonic stem cells for the research. Use of Mesenchymal stem cells a multipotent, hypo neurogenic in large scale production is possible. Bone marrow transplantation was known because of stem cells, till then we never saw. With the advancement we can distinguish the cells and utilize for the purpose. In past 30 years I have never seen a recovery of spinal cord injury but now the stem cells giving hope that even in the case of head injury, Parkinsons disease recovery is possible. Understanding the mechanism of action is difficult, follows few postulates they are activation of stem cells, regeneration of cells, Immunomodulation, secretion of growth factors. Mesenchymal cells are Immunomodulatory, secrete many bio active molecules, which has anti apocratic effect, Immunomodulatory, angiogenesis, antifibrotic effect, these can be exploited in many ways for the medical purpose. Different sources of stem cells give different genetic expressions and can be used for different purpose. Concluding with all this data available today, stem cells is no longer a hype but it is a better hope.

Dr. Suresh Babu, an Application Scientist, extensively with proteins and has presented 25 papers till date said, Proteins can undergo various kinds ofmodifications. This is the reason for the different characterizations of proteins. Thus, for different characterizations, new technology is required. The AgilentToolbox for Biologic Characterization is a product of Agilent Technologies. It is used for Intact mAb (Monoclonal Antibodies) Analysis, i.e. to analyze inactiveantibodies. A new chip known as the HPLC Chip is used, which is used in 4 steps Setup, Insert, Click (on the software) and Spray the sample. The chip hasbeen elemental in deconvulating the MS Spectrum of intact mAbs. To do this, PNGase F treatment is done. The Glycons show a missing peak. To show aclear spectrum, the number of antibodies are reduced. This same process can be done on Fc fragments as well. It has practical significance as well, because only1 nanogram of the sample is required, as opposed to over 200 nanograms in conventional methods.

Another application this technology is used in is Peptide Mapping. The peptides are subjected to the data. 94% Heavy Chains and 84% Light Chains are reported. Peptide mapping can also be done by using U.V rays.

Another new detector has been developed to increase sensitivity. About 10% increase has been reported. Size Exclusion Chromatography(SEC) is performedto show the aggregation of mAb. All the systems devised by Agilent technologies are metal and Iron free so that they do not react with the biomolecules. HeatStress has also been done to degrade the antibodies. Aggregates of the protein molecules have been by pH Stress. A linearity curve was plotted whichshowed the concentration of the sample to be 12.5-2000 micrograms per milliliter. For charged varients, Ion Exchange Chromatography(IEC) is widelyused.he added.

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Riverside Newspaper: 'Ethical Minefield' Still Not Cleared at Stem Cell Agency

Posted: February 5, 2013 at 4:21 pm

The California stem cell agency's
attempts to deal with the conflict of interest problems at the $3
billion research program amount to a minor fix that is not a “serious solution,” the Riverside Press-Enterprise editorialized yesterday.

The editorial came as the agency
launches a road trip campaign to convince newspaper editorial boards around
the state that the agency is worthy of continued financial support.
The agency will run out of money for new grants in less than four
years.
The Riverside editorial pointed to the blue-ribbon Institute of Medicine report in December that called for creation of a
new, independent majority on the 29-member board. None of the current
members are independent. The ballot measure that created the
agency required board members to be appointed from various
constituencies.
The newspaper said,

“That arrangement is hardly a model
of objective decision making. The agency so far has distributed about
$1.7 billion in grants, with about 90 percent of that money going to
institutions represented on the governing board. 

“Voluntary abstentions are not a
serious solution to that ethical minefield. Nor would that approach
eliminate potential conflicts, because the agency would still allow
the abstaining members to take part in the discussions and debate
about who should get the grants. 

“The Institute of Medicine instead
recommended remaking the board with truly independent members who
have no stake in grant awards. The stem-cell agency rejected that
step because it would require changing Prop. 71, either through a
super-majority in the Legislature or another ballot measure. That
excuse should be a vivid warning to Californians about the dangers of
passing complex, costly and inflexible initiatives. 

“Agencies handling billions of
taxpayers’ dollars should not avoid good government practice or
basic fiscal safeguards. The stem-cell institute offers minor fixes
when it needs substantial changes — and legislators should not
accept that cavalier approach.”

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Debunking California Stem Cell Agency Claims of 'No Actual Conflicts'

Posted: February 4, 2013 at 1:08 pm

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Los Angeles Times Columnist: Stem Cell Agency Still Saddled with Conflict of Interest Problems

Posted: February 3, 2013 at 8:11 am

The governing board of the $3 billion
California stem cell agency will remain dominated by “special
interests” even with the adoption of a plan last week responding to
the far-reaching recommendations of a blue-ribbon Institute of
Medicine (IOM)
study, a columnist for the Los Angeles Times said today.

Michael Hiltzik, Pulitzer Prize winning
writer and author, wrote that IOM study showed the agency “the path
to cleansing itself of its aura of connivance and influence trading.
That the board can't even bring itself to place the proposals before
the voters or their elected representatives only shows how much money
it's willing to waste to keep living in its own little world.”
Hiltzik's column in California'slargest circulation newspaper included fresh comments from both
Harold Shapiro, who chaired 17-month IOM study, which was
commissioned by CIRM, and Jonathan Thomas, the chairman of CIRM and
who drew up the response.
Hiltzik wrote that the study “concluded
that the CIRM board members were saddled with 'almost unavoidable
conflicts of interest, whether actual or perceived.'” He continued,

“That's because by law, 23 of the 29
members must be representatives of California institutions eligible
for CIRM grants or of disease advocacy groups with their own interest
in steering money toward their particular concerns. 

“As a remedy, the panel proposed
eliminating some board slots reserved for grant-receiving
institutions by Proposition
71,
 the 2004 initiative that created the agency. The idea
was to fill those slots with truly independent members free of any
stake in CIRM funding, even indirectly.”

 Hiltzik wrote,

 "Thomas told me his proposal dealt
with even perceived conflicts of interest on the board in such
"definitive fashion" that it won't be necessary to bother
the Legislature, much less the voters, with such big changes as
remaking the board with a majority of independent members. He pointed
out, not without some pride, that one board member called his
proposed changes 'draconian.'"

Hiltzik had some praise for Thomas.

“Let's stipulate that Thomas has, in
CIRM terms, moved a mountain by jostling the board even this far.
Since its inception, the board has set records for arrogance. That's
a direct legacy from Proposition 71, which exempted the stem cell
program, uniquely among California government bodies, from any
practical oversight by the Legislature or elected officials.”

The Times columnist continued,

“Shapiro told me from his Princeton
office that Thomas' proposals were 'a significant step in the right
direction, which at least indicates that they haven't ignored the
report.' But he doesn't share Thomas' view that voluntary recusals
solve the conflict of interest problem. That can be done, Shapiro
said, only by replacing stake-holding board members with
independents.

"'The more you can reduce the
inherent conflicts, the better off everyone is going to be,' he said.
The board will 'have to go further over time, in my view.'"

Hiltzik wrote,

“The Shapiro panel said it didn't
find any instances of inappropriate behavior by board members or
specific conflicts, but there are two reasons for that: It didn't
search for any, and Proposition 71 defined certain conflicts out of
existence. The measure states that it's no conflict for a board
member to also be an officer of an academic institution or private
corporation that might be applying for grants.

“One of the CIRM board's enduring
self-delusions is that its conflicts of interest are purely a matter
of 'perception.' But there have been documented instances
of favoritism shown to well-connected grant or loan applicants, and
at least one overt attempt by a board member to overturn a rejection
of his institution's project. So much of the board's discussion takes
place behind closed doors or informally that the opportunities for
mutual back scratching are incalculable.

“Thomas' 'draconian' proposals won't
change this state of affairs. Special interests will still dominate
the board. Will barring 13 members from voting on grants while giving
them full rein to participate in discussions really eradicate even
the perception of conflicts? You'd have to be terminally naive to
think so.”

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Hyping the Economic Impact of the California Stem Cell Agency

Posted: February 3, 2013 at 8:11 am

The $3 billion California stem cell agency today served up a warmed-over version of a study that would have the
public believe that the research program has had a major economic
impact on the state.

The latest study was prepared last
August by a firm that was hired under an RFP in 2010 that said it must execute "a vibrant and aggressive strategy to support the goals and initiatives of CIRM.” 
The agency paid $300,000 for the
original study but contends the report is “independent” of CIRM.
According to the CIRM press release
today, the latest version of the study by Jose Alberro of the
Berkeley Research Group claims creation of 38,000 “job years” and
$286 million in “new tax revenue” from the award of $1.5 billion. Those awards actually cost something in the neighborhood of $3 billion, given that state taxpayers must pay interest the borrowed funds that finance the agency. 
The Institute of Medicine's recent
blue-ribbon report on the stem cell agency carried remarkably different
information than the economic figures reported today. The institute's study was also financed by CIRM but at a cost of
$700,000. The report said,

“In the short term, CIRM’s
expenditures are supporting approximately 3,400 jobs and their
innovative efforts have also attracted substantial additional private
and institutional resources to this research arena in California
CIRM’s long-term impact on such critical aspects of the California
economy as state tax revenues and health care costs beyond the
shorter-term and temporary impact of its direct expenditures cannot
be reliably estimated at this point in CIRM’s history."

Here is what the California Stem Cell Report wrote in 2011 when the first study was released:

“No doubt exists that the stem cell
spending has had a beneficial economic impact. But whether it has had
a 'significant' impact on the California economy is in the eye of the
beholder. The state's economy runs to something like $1.7 trillion a
year. If California were a nation, it would rank among one of the
larger economies in the world. The workforce totals around 18
million, making 25,000 jobs statistically less than a hiccup. Keep in
mind as well that CIRM, until 2009,  paid the interest on its
borrowing with more borrowed funds, all of which adds to the total
cost of the borrowing, which is about $3 billion on top of the $3
billion CIRM is handing out.”

By ballyhooing economic impact reports
the stem cell agency would seem to be inviting assessment of its
efforts as an industrial development enterprise, which involve
criteria significantly different than that of a research enterprise.
A few years ago, we asked the agency's then Chairman Robert Klein
whether he wanted to have CIRM assessed as industrial development
effort. His quick response was a very emphatic no. Klein nonetheless
frequently touted the figures produced under the contract with the
agency.
The latest figures are undoubtedly
likely to be cited as the agency begins a road trip around the state
to meet with newspaper editorial boards to trumpet CIRM's reponse to
the Institute of Medicine study.
See below for a full copy of the
report. We have asked CIRM for a copy of the contract with the group
that prepared it. We will carry it when we receive it.
   

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Sacramento Bee: Stem Cell Agency Falling Short on IOM Recommendations

Posted: February 3, 2013 at 8:11 am

It's exceedingly rare when the
California stem cell agency makes the front page of any newspaper.

So it is worthy of note that The
Sacramento Bee
this morning carried a lengthy piece on its page one
about the agency and its response to the blue-ribbon Institute of
Medicine
(IOM) report.
The headline said,

 “Analyst: Stem
cell agency reforms fall short.”

The analyst is the Institute of
Medicine, more specifically Harold Shapiro, chairman of the panel that
studied California's $3 billion research effort for 17 months at
a cost of $700,000 to the agency.
Bee reporter Cynthia Craft wrote that
Shapiro said the stem cell agency is “falling short” in its
response to the IOM recommendation.
Craft wrote,

"'There certainly is a gap between
what we recommended and what they responded with,' said Shapiro,
president emeritus at Princeton
University
. ' I wish they had moved closer to our
recommendations.'"

Craft said the IOM made sweeping recommendations “emphasizing the need for new blood on a governing
board that has been plagued by the appearance of conflicts of
interest, cronyism and sluggishness in getting stem-cell products to
market.”
Craft also interviewed Jonathan
Thomas
, chairman of the stem cell agency, who said some of the IOM
recommendations would take legislative action. But Thomas said that
was “out of the question.”
Craft wrote,

“The process would take years, he
said. The first opportunity to get on the ballot, for instance, would
be in the fall of 2014.”

The agency will run out of cash for new
grants in less than four years.
Craft's story was the first major news
article in years about the agency in the Bee, the only daily
newspaper in the state's capital. She reviewed a bit of the history
of the agency and concerns about conflicts of interest. She
concluded,

“Shapiro said he stands firmly behind
his committee's report. 

"'I think our recommendations sit
together and interrelate to each other well – and should have been
moved along as quickly as possible,' Shapiro said. 

"'It might have been helpful if
they indicated to us what they were willing to do and what they
weren't,' he said."

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