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Category Archives: Stem Cells

Salk researchers chart epigenomics of stem cells that mimic early human development

Posted: May 9, 2013 at 1:44 pm

Public release date: 9-May-2013 [ | E-mail | Share ]

Contact: Andy Hoang ahoang@salk.edu 619-861-5811 Salk Institute

LA JOLLA, CA Scientists have long known that control mechanisms known collectively as "epigenetics" play a critical role in human development, but they did not know precisely how alterations in this extra layer of biochemical instructions in DNA contribute to development.

Now, in the first comprehensive analysis of epigenetic changes that occur during development, a multi-institutional group of scientists, including several from the Salk Institute for Biological Studies, has discovered how modifications in key epigenetic markers influence human embryonic stem cells as they differentiate into specialized cells in the body. The findings were published May 9 in Cell.

"Our findings help us to understand processes that occur during early human development and the differentiation of a stem cell into specialized cells, which ultimately form tissues in the body," says co-lead author Joseph R. Ecker, a professor and director of Salk's Plant Molecular and Cellular Biology Laboratory and holder of the Salk International Council Chair in Genetics.

Scientists have established that the gene expression program encoded in DNA is carried out by proteins that bind to regulatory genes and modulate gene expression in response to environmental cues. Growing evidence now shows that maintenance of this process depends on epigenetic marks such as DNA methylation and chromatin modifications, biochemical processes that alter gene expression as cells divide and differentiate from embryonic stem cells into specific tissues. Epigenetic modificationscollectively known as the epigenomecontrol which genes are turned on or off without changing the letters of the DNA alphabet (A-T-C-G), providing cells with an additional tool to fine-tune how genes control the cellular machinery.

In their study, the Salk researchers and their collaborators from several prominent research institutions across the United States examined the beginning state of cells, before and after they developed into specific cell types. Starting with a single cell typethe H1 human embryonic stem cell, the most widely studied stem cell line to datethe team followed the cells' epigenome from development to different cell states, looking at the dynamics in changes to epigenetic marks from one state to another. Were they methylated, an essential process for normal development, or unmethylated? What happened to the cells during development? What regulatory processes occurred in the cell lineage?

The scientists found sections of the DNA that activate regulatory genes, which in turn control the activity of other genes, tend to have different amounts of letters of the DNA alphabet, "C" and "G" specifically, depending on when these regulatory genes are turned on during development. Additionally, regulatory genes that control early development are often located on stretches of DNA called methylation valleys, or DMVs, that are generally CG rich and devoid of epigenetic chemical modifications known as methylation. Consequently, these genes have to be regulated by another epigenetic mechanism, which the authors found were chemical changes called chromatin modifications. Chromatin is the mass of materialDNA and proteinsin a cell's nucleus that helps to control gene expression.

On the other hand, genes active in more mature cells whose tissue type is already determined tend to be CG poor and regulated by DNA methylation. The results suggest that distinct epigenetic mechanisms regulate early and late states of embryonic stem cell differentiation.

"Epigenomic studies of how stem cells differentiate into distinct cell types are a great way to understand early development of animals," says Ecker, who is also a Howard Hughes Medical Institute and Gordon and Betty Moore Foundation Investigator. "If we understand how these cells' lineages originate, we can understand if something goes right or wrong during differentiation. It's a very basic study, but there are implications for being able to produce good quality cell types for various therapies."

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Stem Cells, Racist Proms, and Obama – Video

Posted: May 8, 2013 at 1:48 am


Stem Cells, Racist Proms, and Obama
Wednesday May 1st. Like, Subscribe, and Share! Links: 2013 White House Correspondents Dinner http://www.youtube.com/watch?v=SVtQ6i1jbsk Steven Spielberg #39;s "O...

By: Steven Fleming

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Health Beat: Using your own stem cells for circulation

Posted: May 6, 2013 at 9:47 pm

Poor circulation in the legs and feet can lead to the loss of limbs or even the loss of life, but hope is on the horizon. A new treatment could help millions of people get their blood flowing again.

Until recently, Derrick Blount was unable to ride his bike. He said the problem was that "being in a sitting position would greatly restrict the blood flow to my left leg.

Blount has Buergers disease, a form of poor circulation brought on by smoking. He quit the habit and almost had to quit his art gallery job because of his leg limitations. Where as tasks like hanging a picture should take no more than 20 minutes, it was taking him and hour-and-a-half.

So, Blount took part in Dr. Omaida Velazquezs clinical trial at the University of Miami. The doctor is taking stem cells from patients hip bones and injecting them into their legs and feet to help restore circulation.

"It is believed that these cells release some growth factors and proteins that help in regeneration of blood vessels," explained Velazquez, chief of the Division of Vascular and Endovascular Surgery at the University of Miami Miller School of Medicine.

Velazquez said the treatment could help millions of people with dangerous circulation problems, like peripheral arterial disease.

Blounts not sure if hes getting the stem cells in the double blind study, but said, "These blood pressures are very significantly improved on his left toes, and clinically, almost to a miraculous level.

Right now, the trial is recruiting participants across the country. See the research summary for information about the trials.

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Cash and Favors: Robert Klein Gives $21,630 to the California Stem Cell Agency

Posted: May 5, 2013 at 10:33 pm

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The Klein Donation: Text of Stem Cell Agency's Key Responses

Posted: May 5, 2013 at 10:26 pm

Here is the text of the key comments
from the California stem cell agency in response to questions from
the California Stem Cell Report (CSCR) concerning the $21,630
contribution by Robert Klein. Here is a link to the full story on the matter.

CSCR to CIRM:

“Is CIRM concerned about the
appearance created by the donation from Bob Klein to enable scientific
staff to attend the ISSCR meeting in Yokohoma, coming one
month after the GWG (the review group) rejected StemCells Inc's Alzheimer's application
and one month before the July Board meeting that led to the approval
of the award?”(Editor's note: It was actually two months before the board meeting.)

CIRM's response:

“No, the two items are entirely
separate with no connection. Item 1  involved Bob Klein making a
donation to allow science officers to attend a critically important
scientific meeting on stem cell research.  The science officers
 had originally planned on attending but then were told they
could not because of cuts in our out-of-state travel budget – Bob
Klein’s donation, without using state funds, enabled the science
officers to attend.  Item 2 is an ICOC decision to fund a
research project that they felt had promise and was important for the
people of California.”

CSCR to CIRM:
"Please explain why the agency
could not finance the trip itself ."
CIRM's response:
"During the financial year 2011/12  the
Governor's Office issued an Executive Order requiring state agencies,
under the Governor's direct authority, to reduce out-of-state travel.
 Although CIRM was not required to participate, we nevertheless
imposed restrictions on out-of-state travel to meet the intent/spirit
of the Governor's request.  Accordingly, we made a decision to
reduce the number of our science staff who would be attending the
 conference.  Bob Klein's donation made it possible
for those staff to go." 

CSCR asked several questions re the
failure to report the Klein donation to the board as required by
agency rules.
CIRM's response:

“Under the Gift Policy, the President
had the authority to accept Mr. Klein’s generous offer as a 'Direct
payment or reimbursement by third parties for the costs of general
operation or grant management administrative activities.' (Gift
Policy, Sec. III(A)(2).)  Because CIRM receives gifts only
infrequently, CIRM staff determined that it would be more efficient
to report gifts to the Board on a semi-annual basis.  Mr.
Klein’s donation was the first gift CIRM had received in some
years.  Due to the lack of additional donations, a transition in
CIRM’s finance office, and an oversight, CIRM staff has not yet
presented a report including Mr. Klein’s gift.  Staff plans to
report Mr. Klein’s gift as part of the finance report at the May
Board meeting.  Because the President had the authority to
accept the gift pursuant to section III(A)(2) of the Gift Policy, it
did not require a commitment letter.  (See Gift Policy, Sec.
III(C)(1) ['A Commitment Letter is not required for gifts described
under III.A.2., 3. and 4.'].)  However, consistent with the
policy, Dr. Trounson sent Mr. Klein a letter of appreciation, a copy
of which we have already provided you.”

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The Klein Donation: Text of Robert Klein's Comments on Special Treatment by CIRM

Posted: May 5, 2013 at 10:25 pm

Here is the text of comments from
Robert Klein, former chairman of the California stem cell agency,
concerning his $21,630 donation to the agency and subsequent actions
by the agency. Klein's comments May 1 came in response to questions
from the California Stem Cell Report(CSCR) on April 30. The text of
the inquiry from CSCR precedes Klein's response. Here is a link to the story on the matter.

CSCR to Klein:

"I have sent the following to CIRM
asking for their response and am offering the same opportunity to
you. Here is what I sent the agency:
'The documents that I have received so
far show that after Klein gave CIRM $21,000 the agency instructed six
of its science officers to give him special access to their
activities and apparently did not object to additional instructions
from another member of the public, Melissa King, to provide Klein and
her with written summaries about their activities at the ISSCR
convention and “details” about their work at CIRM. Email
addresses of the six were also provided to Klein, who may have
additionally received their cell phone numbers although that is not
entirely clear. The CIRM documents show that the six were told to
engage in one-on-one sessions with Klein, which actually included a
third person, a wealthy Canadian mining company executive. One
document indicates that the science officers should assist in
fundraising for CIRM by identifying areas of “special importance”
to Klein and 'other donors.'
"'Additionally, Alan Trounson, at
Klein's request, invited the mining executive to a closed door
session involving the agency's international partners, a session at
which presumably valuable, little known scientific information would
be discussed and future directions charted. Trounson specifically
told the executive that it was Klein who asked that executive be
invited to the session, adding to Klein's clout in any business or
other dealings that Klein might have with the executive.'

My questions to CIRM deal with the
special treatment that was provided in connection with your donation.
I would ask you if you think that state agencies should provide this
sort of extraordinary treatment for individuals who donate to the
agency. At the very least, doesn't this raise questions about the
integrity of the agency and doubts in the public mind about whether
it can be fair and even-handed in its activities?

Klein's response:

"In April or May of 2012 I committed
to contribute a charitable donation to CIRM to cover the travel costs
for 5-7 additional science officers to attend the International Stem
Cell Conference in Japan.  It is important to CIRM that their
science officers understand the cutting edge research being developed
around the world so that CIRM does not fund redundant research; but,
to the contrary, the science officers understand how to create
networks between California scientists and scientists in other
foreign countries who are doing complementary research that can
potentially accelerate the advancements of therapies for patients. I
do not hold any financial interest in biotech companies. I have
historically been involved in encouraging international collaboration
to advance medical therapies; for patients, every day of delay in the
development of a therapy is a delay they cannot afford. To
conceptually document the value of additional scientists traveling to
these meetings, it was discussed that there should be conceptual,
bullet point summaries about the value for CIRM obtained through the
scientists discussions at the international conference.  The
idea was to create bullet points of information about a few of the
most meaningful scientific concepts and contacts the science officers
benefitted from each day of attendance at the conference. I did not
participate in the selection of the science officers who attended and
I did not play any part in determining what activities they
participated in. There were two fundamental goals to the very short
one-on-one sessions that were arranged at "down time" that
would not conflict with their other activities. The first goal was to
conceptually understand if each of the science officers believed that
the benefit to the agency was sufficient to justify the cost of their
attending, when considering the learning and contacts they had gained
which might accelerate research and therapies for patients. The
second goal was to assist universities and non-profits, principally
in Canada - a research partner of CIRM - in advancing their
contributions from an existing donor or donors.

"The Canadian mining executive had an
important history in contributing to the International Stem Cell
Society and to Canadian non-profit research institutions. This
individual has an expert background in mining and a passionate
personal commitment to medical research; but, he does not engage in
technical discussions of research. On a conceptual basis it was
important for him to understand the spectrum of medical advances
towards therapies. His additional contributions to Canadian
non-profits could assist Canada in collaborating with California on
more international research, with California only funding the
research done in California and the donor helping to fund the
research done in Canada. No specific grant applications were
discussed. Finally, the discussion with the international partners
focuses on the funding process and funding collaboration it does not
discuss any individual grants. The value of international
collaboration and the benefits of collaborating with new
international partners is discussed. Scientific theories and
individual grants are not discussed and new scientific information is
not presented. I attended this session of international partners to
support international collaboration; again, I do not hold any
financial interest in any biotech organizations. Additionally, I do
not have any business or financial relationship with the Canadian
mining executive. The Canadian executive, based upon family and
friends who have had chronic disease, is a significant donor to
non-profit research institutions in Canada. All of my activities, the
donation and the encouragement to develop information to validate the
future benefits of science officers traveling to international stem
cell conferences were focused on benefitting California patients with
chronic illness or injury and the agency formed through Proposition
71."

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The Klein Donation: Text of Robert Klein's Response re StemCells, Inc.

Posted: May 5, 2013 at 10:25 pm

Here is the text of the initial
response from Robert Klein, chairman of the California stem
cell agency until July 2011, to questions from the California Stem Cell Report (CSCR)
concerning his $21,630 donation to the agency. The questions posed by
CSCR on precede the response by Klein. Here is a link to a story on
the matter.


CSCR to Klein:

“Why did you give the agency the
money?
“Did you place on conditions on its
use?
“Did anyone connected with the agency
indicate in advance  that your donation would be desired? If so
who? Who did you deal with primarily on the donation -- Trounson,
Thomas or...?
“The donation came one month after
grant reviewers rejected StemCells Inc.'s Alzheimer's application. Do
you think it was appropriate to make the donation and then ask the
board twice to override its reviewers?
“Do you think the donation and
subsequent action on StemCells, Inc.'s Alzheimer's application will
negatively color the perception of future efforts by CIRM at private
fundraising?”

Klein's response:
“In April or May of 2012 I committed
approximately $20,000 as a contribution to CIRM to cover the travel
expenses of staff to the International Stem Cell Society
meeting in Japan. My commitment to ensure scientific staff can
participate in international meetings dates back many years. In 2011
I wrote the following explanation of its importance in obtaining the
knowledge to accelerate the drive of scientific research to reach
patients with chronic disease.
            Leverage
Leading Edge Science
           
“Travel by CIRM staff members and leadership permits CIRM to stay
in contact with, and understand, the leading edge advances of
scientists all over the world, and to leverage those advances by
creating a platform for collaborations between these leading
scientists and their peers in California. Currently, CIRM has
collaboration agreements with 15 foreign governments pursuant to
which these governments have pledged $134,380,000 in commitments to
fund the work of their scientists on join teams with California
scientists to develop therapy candidates and to advance therapies to
human trials. Although a significant amount of this commitment is
currently pending scientific peer review and not all of it will be
awarded as part of a successful application, every dollar in
funding by a foreign government magnifies the scientific impact of
California’s taxpayer dollars. If just $40 million is awarded each
year over ten years, it would provide California with $400 million of
scientific leverage.
  •     It
    is critical to understand that there are unpublished scientific
    discoveries in progress in each of these nations. Often, publication
    may trail a scientific discovery by nine months or more.
  •     The
    travel requested by CIRM provides a critical link for the timely
    transmission of valuable new information. California cannot afford to
    lose the opportunity to harness discoveries in other countries to
    advance the development of therapies in California and to capture the
    opportunity to advance therapies for patients instead of using
    California taxpayer dollars to duplicate discoveries already mastered
    in other countries.
  •      While
    CIRM’s scientific staff works with scientists in other countries to
    capture the scientific knowledge for the benefit of California’s
    therapy development teams, the Chairman’s Office works with
    international finance ministers, the premiers of international
    states, and foreign funding agencies to ensure funding allocations
    for these bilateral funding agreements. These discussions often
    involve face-to-face negotiations in foreign nations and states, in
    addition to meetings at international conferences, all of which are
    supported by extensive staff work in California.
  •      CIRM
    issued its first co-funding awards early in 2009. Over the last two
    years, these agreements have yielded $57 million in international
    funds actually approved through peer review. This $57 million
    represents participation by only the first five countries and one
    international state with which CIRM established a collaboration. Now,
    CIRM has agreements with nine countries and two international states
    and an additional three countries will be added in the near future.
  •     Even
    if CIRM were only to obtain $30 million per year in international
    matching funds, the ratio of return on CIRM’s $206,920 travel
    expenditures would be approximately 145 to 1.
  •    Proposition 71 specifically anticipated
    and directs CIRM to develop leverage and global leadership to capture
    the benefit for patients.
Keeping on the Cutting Edge of Stem
Cell Science
"CIRM’s over 20 MDs and/or PhDs
science officers on the grant review staff at CIRM reach out
nationally and internationally through conferences that may include
10-20 meetings per day and workshops of 8-12 hours per day to grasp
the leading edge of this pre-publication, dynamic
revolution in medical knowledge. In order to ensure that the
every research dollar is optimally deployed to advance therapies to
save lives or rescue the quality of life for patients, it is critical
that CIRM staff remain on the cutting edge of new discoveries.
International conferences and workshops provide a critical
opportunity for massive and decisive transfers of information, which
ensures that California is funding the right research.
“I principally corresponded with Dr.
Trounson on the issue covering the travel expenses for the staff for the reasons stated above. I had no input into the selection
of scientific staff. In May and even in June when the conference
occurred I had no idea that there would be any disagreement on the
Alzheimer’s application of Stem Cells Inc. in August. At the Board
meeting I asked that there be consideration for the fact that three
other peer reviews had found the work leading up to this application
to be outstanding and they had ranked it highly. In addition, the
current peer review had not been briefed on the fact that they
downgraded the applicant for following the directions on material
points by the prior peer reviews. Finally, the standard deviation on
the 2012 peer review was extremely high and the re-review by the
three member committee resulted in a split decision. It is
particularly appropriate with a huge standard deviation,
demonstrating both strong support and opposition within the peer
review group, for the Board to make its own independent decision. 
Please recall that the staff recommended against approval so that
they clearly were not influenced by my commitment to a contribution
to the Agency, months before, for the benefit of scientific staff to
be able to attend an international science conference. Additionally,
Dr. Trounson, I believe, recused himself from the review of the Stem
Cells Inc. application, for unrelated reasons, so he was not
involved. I personally had served on the three prior peer reviews,
including one in the prior year that recommended this application for
a Disease Team approval. I know how strongly the scientists on those
three prior peer reviews supported funding this scientific research,
with the 2011 review specifically recommending this Disease Team for
approval. I believe it was extremely important for me to provide a
voice to those three scientific panels who disagreed with a portion
of the scientists on the 2012 scientific panel. Supporting the
scientific movement to human trials for Alzheimer’s has to be
eventually approved by the FDA; but, this loan will move the science
and the potential for clinical trials forward significantly and
hopefully obtain FDA approval. I believe all three of the Board’s
overrides of the peer review recommendations on the Disease Team
round in 2008 are leading directly to human trials in the United
States and/or United Kingdom. 92% of the all of the funds awarded by
CIRM have followed the recommendations of the peer review committee;
but, in those significant cases where the Board has made an
independent decision, there has been an extremely high success rate
particularly when there has been a high level of disagreement within
the Peer Review Board that was overridden and prior peer reviews
recommended and/or approved the scientific approach and concepts of
the applicant.”

(Editor's note:  The applications in this round were reviewed once in April 2012 by CIRM's full grant review group. StemCells, Inc.'s application was subject to a reevaluation after Klein's appeal in July 2012 and rejected again, but it was not a full review.  Klein may be referring also an earlier round that provided grants for planning to apply for the full $20 million.) 

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The Klein Donation: Memo from Klein Aide to Six Stem Cell Agency Science Officers

Posted: May 5, 2013 at 10:24 pm

Here is the email that Melissa King, an aide to Robert Klein, sent to the six science officers from the California stem cell agency. King was executive director of the CIRM governing board when Klein was chairman of the agency from 2004 to July 2011. Here is link to the story involving Klein's $21,630 gift to the agency.

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Stem cells may help Mumbai acid attack victim regain vision: doctors

Posted: May 5, 2013 at 4:45 pm

India, May 5 -- Ophthalmologists are hoping that Preeti Rathi, 25, who lost vision in her right eye after an unknown man threw acid on her face at Bandra Terminus, may be able to regain her vision after undergoing stem cell therapy.

On Saturday morning, Rathi, who was admitted inside the burns intensive care unit at Masina Hospital at Byculla, scribbled a note pleading her ophthalmologist Dr Yasmin Bhagat to help her see with both eyes again.

"We have helped patients of acid attack to regain vision by using stem cell therapy in the past. Once she (Rathi) recovers fully we can look at harvesting stem cells from her parents' eye and transplanting them in her right eye as the cornea is damaged by the acid," said Dr Bhagat.

Doctors said that her condition is stable and she was put on ventilator support for a few hours to give her rest. According to doctors, Rathi's face is fully bandaged while her eyes are stil shut. "She cannot see but her left eye is showing improvement." added Bhagat who has treated numerous such acid attack victims in the past.

Rathi's father Amarsingh is planning to meet officials from INHS Asvini, where Preeti was supposed join as a nurse, to postpone her joining date. "If they postpone her joining, she would be very happy," said Amarsingh

Meanwhile, The Bandra Government Railway Police (GRP), who are probing the acid attack, have scanned the passenger list of train in which the accused was travelling. Further probe is underway.

Published by HT Syndication with permission from Hindustan Times.

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Divide and Define: Clues to Understanding How Stem Cells Produce Different Kinds of Cells

Posted: May 5, 2013 at 4:45 pm

Newswise ANN ARBORThe human body contains trillions of cells, all derived from a single cell, or zygote, made by the fusion of an egg and a sperm. That single cell contains all the genetic information needed to develop into a human, and passes identical copies of that information to each new cell as it divides into the many diverse types of cells that make up a complex organism like a human being.

If each cell is genetically identical, however, how does it grow to be a skin, blood, nerve, bone or other type of cell? How do stem cells read the same genetic code but divide into very different types?

Researchers at the University of Michigan have found the first direct evidence that cells can distinguish between seemingly identical copies of chromosomes during stem cell division, pointing to the possibility that distinct information on the chromosome copies might underlie the diversification of cell types.

Scientists in the lab of Life Sciences Institute researcher Yukiko Yamashita explained how stem cells can distinguish between two identical copies of chromosomes and distribute them to the daughter cells in a process called nonrandom chromosome segregation. They also described the genes responsible. Their work is scheduled to be published online May 5 in Nature.

"If we can figure out how and why cells are dividing this way, we might be able to get a glimpse of how we develop into a complete human, starting from a single cell," Yamashita said. "It is very basic science, but understanding fundamental biological processes always has wide-ranging implications that could be exploited in therapeutics and drug discovery."

During the cell division cycle, the mother cell duplicates its chromosomes, generating two identical sets. When the cell divides to become two cells, each cell inherits one set of chromosome copies. In many divisions, the daughter cells are identical to the motherone skin cell becomes two, for instance.

But in a process called asymmetric division, a cell divides into two daughters that are not identicala skin stem cell divides into another skin stem cell and a regular skin cell, for example. In that case, the genetic information within the chromosome copies remains the same, but the type of cell, or "cell fate," is different.

The Yamashita lab used stem cells from the testes of the fruit fly Drosophila to study the process of cell division.

"The Drosophila germ line stem cell can be identified at a single-cell resolution, so they are an ideal model," Yamashita said.

The stem cells cluster and are easy to identify; they divide to produce another germ line stem cell and a differentiating cell called a gonialblast, which goes on to eventually become a sperm cell.

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