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Category Archives: Stem Cells

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

Posted: May 12, 2013 at 3:18 am

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.) 

Source:
http://feedproxy.google.com/~r/blogspot/uqpFc/~3/57qJcfMUql0/the-klein-donation-text-of-robert_5.html

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

Posted: May 12, 2013 at 3:18 am

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.”

Source:
http://feedproxy.google.com/~r/blogspot/uqpFc/~3/dQImAqKe0Ys/the-klein-donation-text-of-stem-cell.html

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

Posted: May 12, 2013 at 3:18 am

A seemingly innocuous $21,630 gift to
the California stem cell agency has kicked up new questions about a
controversial $20 million research award and generated a wave of
special favors for the donor that stretched out to include a gold
mining multimillionaire from Canada.

Robert Klein
Elie Dolgin/Nature photo

The gift was made last May by Robert
Klein, chairman of the stem cell agency from 2004 to July 2011, but has never
been publicly reported to the agency's governing board as required by
its own regulations. 

In July, two months after he donated the cash, Klein made an unusual appearance before his old board and  pitched it to override rejection by scientific grant
reviewers of a $20 million application by StemCells, Inc., of  Newark, Ca.  The board subsequently asked for a reevaluation of the proposal, which was again rejected by reviewers. Klein persisted at a September meeting, and the 29-member board decided, on a 7-5 vote,  to go along with him. It was the
first time in its eight-year history that the board has approved an
application that was rejected twice by its scientific reviewers, who scored the proposal at 61 out of 100. 
Klein's donation to the agency, formally known as the California Institute for Regenerative Medicine (CIRM), included more than the cash, which financed trips to a prestigious stem cell conference in Japan for six of the agency's science officers in June 2012. He also arranged the waiver of roughly $3000 to $4000 for their registration fees for the annual meeting of the International Society for Stem Cell Research. Nine agency executives and other staffers were already attending at taxpayer expense, but the six could not attend because of travel budget cuts at the $3 billion agency. (The total of 15 amounted nearly one-third of the agency's staff.)

Klein's donation triggered a number of
special favors from the agency, according to documents provided by CIRM to the California Stem Cell Report under a state Public Records Act request.  Klein wanted to meet with the six science officers, who have a wide range of responsibilities, including managing and developing grant and loan programs, participating in reviews of applications and evaluating research progress. CIRM President Alan Trounson obliged. At the meeting in Japan, the six science officers received a memo approved by Trounson instructing them to meet
privately “one-on-one” with their benefactor and to give him special access to their activities. The meetings were
actually scheduled to also include a third person, Rob McEwen,  who is one of the 100 richest persons in Canada, a $20 million donor to a stem
cell center in Toronto and CEO of the gold mining company bearing his name.

The memo indicated
that the science officers – all California state employees –
should be helpful by identifying areas of “special importance” to
Klein and “other donors.” The CIRM documents show no objection
from the agency to instructions from another member of the public --
Klein aide Melissa King -- to provide her and Klein with written
summaries about the science officers' activities at the convention
along with “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.

At Klein's request, Trounson also
invited McEwen to a closed-door session in Japan involving the
agency's international partners, a session at which presumably
valuable, little known scientific information might be mentioned and
future directions charted. Trounson specifically told McEwen in an
email that it was Klein who asked that the executive be invited to the
session.
Both the agency and Klein deny any
wrongdoing in connection with the donation, which was the only
private contribution to CIRM in the 2011-12 fiscal year. Both say
there was no connection between the donation last May 16 and the
StemCells, Inc., application, which was rejected by reviewers one
month earlier during closed-door meetings April 18-20, 2012.
CIRM's gift regulations bar donations
from persons who have applied for funding or who intend to apply for
funding, but the rules do not speak to gifts from persons who lobby
on behalf of funding for others. The rules require that the governing
board of the agency be informed at a public meeting of gifts accepted
by Trounson on behalf of CIRM. Trounson is required to identify the
donor and conditions imposed by acceptance of the gift. Trounson did
neither prior to Klein's appearance last July on behalf of StemCells,
Inc.
At the July meeting, Trounson
recused himself from public discussions of the StemCells, Inc.,
application, although he did not offer an explanation. However, his
action was connected to his relationship with stem cell scientist Irv Weissman of
Stanford University, who founded the publicly traded company, currently sits on its board
and holds 124,608 shares of the firm. Trounson was a guest once at
Weissman's ranch for four days in July 2011, CIRM said in response to
a question this week.
In the wake of the California Stem Cell Report's inquiries, Kevin McCormack, the agency's senior director
for public communications, said last week that the agency plans to
report the donation to the governing board at its meeting in
the San Francisco Bay Area later this month.
McCormack said the failure to report
the donation prior to the board's consideration of StemCells, Inc.'s,
application was “due to the lack of additional donations, a
transition in CIRM’s finance office and an oversight."(See thefull text of McCormack's statement here.) 
Asked whether
the agency is concerned about the appearance of Klein's donation and
the subsequent board action, McCormack replied,

“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 (board) decision to fund
a research project that they felt had promise and was important for
the people of California.”

As for the special treatment of Klein
in the wake of his donation, the agency did not respond to inquiries
asking for an explanation.
Klein said in
an email that his donation was not connected to StemCells, Inc. He said that as late as June he had “no idea”
that the its application had been rejected by reviewers. Klein said that he committed to the donation
in “April or May.”  (The full text of Klein's comments re the application can be found here and here.)

Prior to leaving CIRM in 2011, Klein was a non-voting  member of the CIRM grant review committee, which consists of out-of-state scientists and seven CIRM board members. His service on the committee included the period when it approved a planning grant for StemCells, Inc., to prepare its application for the $20 million.

Klein noted that he did not pick the six science officers for the Japan trip. One of them was the lead science officer on the award round involving StemCells, Inc. A second was also heavily involved, according to  the transcript of the July 2012 board meeting. Science officers, however, do not vote on or score applications. Klein characterized the CIRM staff as recommending against approval of the grant so “they were clearly not influenced” by his donation.

Klein said his meetings with the six
science officers were aimed at determining whether they believed the
cost of attending the stem cell convention justified what they
learned at the meeting. He said a second goal was to aid universities
and other researchers, mainly in Canada, “in advancing their
contributions from an existing donor or donors.” Canada is one of
CIRM's research partners.

Klein defended the involvement of
McEwen, who Klein said has contributed to the stem cell group conducting the meeting. Klein said McEwen does not engage in technical
discussions and added,

“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.”

Private funding of activities by state
employees has stirred up controversy over the years in California.
The most recent example was Gov. Jerry Brown's much-reported trip to
China this spring, which was financed by private donations. Articles
in the Los Angeles Times and The Sacramento Bee both noted that
private funding arrangements have plenty of critics.
Columnist George Skelton of the Times
wrote,

 “It just looks unseemly — a pack of lobbyists and other
favor-seekers paying big bucks to traipse after the governor,
schmoozing and gaining invaluable access.”

Reporter David Siders carried a quote in The Bee
from Jock
O'Connell, international trade adviser for the economics
consulting firm Beacon Economics, who said,

“They're donating because they want
to curry favor with the incumbent administration."

Asked whether CIRM planned to accept
donations for trips in the future, McCormack replied that the agency
is “always open to donations from generous supporters” provided
they meet the state's legal requirements.

Source:
http://feedproxy.google.com/~r/blogspot/uqpFc/~3/FefPhO0IEiY/cash-and-favors-robert-klein-gives.html

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

Posted: May 12, 2013 at 3:18 am

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."

Source:
http://feedproxy.google.com/~r/blogspot/uqpFc/~3/SBGFem2qPWo/the-klein-donation-text-of-robert.html

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

Posted: May 12, 2013 at 3:18 am

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.

Source:
http://feedproxy.google.com/~r/blogspot/uqpFc/~3/4fqob6pGa2A/the-klein-donation-memo-from-klein-aide.html

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cerebral palsy 6 weeks after stem cells – Video

Posted: May 10, 2013 at 7:51 pm


cerebral palsy 6 weeks after stem cells

By: Rejuvaa

Originally posted here:
cerebral palsy 6 weeks after stem cells - Video

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Epigenomics of stem cells that mimic early human development charted

Posted: May 10, 2013 at 7:51 pm

May 9, 2013 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 modifications -- collectively known as the epigenome -- control 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 type -- the H1 human embryonic stem cell, the most widely studied stem cell line to date -- the 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 material -- DNA and proteins -- in 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."

For example, says Matthew Schultz, a graduate student in Ecker's lab, "understanding how development plays out normally could give us clues about how to reverse the process and turn normal adult cells into stem cells to regenerate tissues."

See original here:
Epigenomics of stem cells that mimic early human development charted

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Multiple sclerosis hope ‘lie in stem cells’

Posted: May 10, 2013 at 7:51 pm

Professor Shaun McColl says new treatment for multiple sclerosis lies within modified adult stem cells. Picture: Dean Martin Source: adelaidenow

A POTENTIAL new treatment for multiple sclerosis lies within modified adult stem cells, University of Adelaide researchers say.

The researchers hope using stem cells from fat tissue - to send cells with anti-inflammatory properties directly to the damaged site in the central nervous system - will be able to treat the autoimmune disease.

Director of the Centre for Molecular Pathology, Professor Shaun McColl, said treatments for MS needed to control the immune response and repair the damage caused to the fatty myelin sheaths that protect the nerves.

"We've already shown that adult stem cells have great potential to both control the immune response and promote repair of the central nervous system. It also prevents further damage," Prof McColl said.

"But the trick is getting the stem cells to the right location where they can perform this function."

MS is a progressive disease in which the body attacks the central nervous system, causing nerve inflammation and scarring. It results in the impairment of motor, sensory and cognitive function. When stem cells are injected into theblood system, very few cross the blood/brain barrier into the central nervous system.

Lead investigator Dr Iain Comerford said it was hoped the manipulated adult stem cells could cross that barrier, targeting the inflammation site and repairing the damaged myelin.

"It involves promoting stem-cell migration to the central nervous system by manipulating receptors on the surface of the stem cells that control cell movement," Dr Comerford said.

"We are also modifying the stem cells to suppress the immune response by introducing molecules that regulate inflammation," Dr Comerford added.

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Multiple sclerosis hope 'lie in stem cells'

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Stem cells show promise for treating rare nerve disease

Posted: May 10, 2013 at 7:51 pm

Led by Dr. Peiyee Lee and Dr. Richard Gatti, researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have used induced pluripotent stem (iPS) cells to advance disease-in-a-dish modeling of a rare genetic disorder, ataxia telangiectasia (A-T).

Their discovery shows the positive effects of drugs that may lead to effective new treatments for the neurodegenerative disease. iPS cells are made from patients' skin cells, rather than from embryos, and they can become any type of cells, including brain cells, in the laboratory. The study appears online ahead of print in the journal Nature Communications.

People with A-T begin life with neurological deficits that become devastating through progressive loss of function in a part of the brain called the cerebellum, which leads to severe difficulty with movement and coordination. A-T patients also suffer frequent infections due to their weakened immune systems and have an increased risk for cancer. The disease is caused by lost function in a gene, ATM, that normally repairs damaged DNA in the cells and preserves normal function.

Developing a human neural cell model to understand A-T's neurodegenerative process and create a platform for testing new treatments was critical because the disease presents differently in humans and laboratory animals. Scientists commonly use mouse models to study A-T, but mice with the disease do not experience the more debilitating effects that humans do. In mice with A-T, the cerebellum appears normal and they do not exhibit the obvious degeneration seen in the human brain.

Lee and colleagues used iPS cell-derived neural cells developed from skin cells of A-T patients with a specific type of genetic mutation to create a disease-in-a-dish model. In the laboratory, researchers were able to model the characteristics of A-T, such as the cell's lack of ATM protein and its inability to repair DNA damage. The model also allowed the researchers to identify potential new therapeutic drugs, called small molecule read-through (SMRT) compounds, that increase ATM protein activity and improve the model cells' ability to repair damaged DNA.

"A-T patients with no ATM activity have severe disease but patients with some ATM activity do much better," Lee said. "This makes our discovery promising, because even a small increase in the ATM activity induced by the SMRT drug can potentially translate to positive effects for patients, slowing disease progression and hopefully improving their quality of life."

These studies suggest that SMRT compounds may have positive effects on all other cell types in the body, potentially improving A-T patients' immune function and decreasing their susceptibility to cancer.

Additionally, the patient-specific iPS cell-derived neural cells in this study combined with the SMRT compounds can be an invaluable tool for understanding the development and progression of A-T. This iPS cell-neural cell A-T disease model also can be a platform to identify more potent SMRT drugs. The SMRT drugs identified using this model can potentially be applied to most other genetic diseases with the same type of mutations.

This research was supported by training and research grants from the California Institute of Regenerative Medicine, the National Institutes of Health, APRAT, A-T Ease and Scott Richards Foundation.

The Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research: UCLA's stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Broad Stem Cell Research Center is committed to a multidisciplinary, integrated collaboration among scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed toward future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine at UCLA, UCLA's Jonsson Cancer Center, the UCLA Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science.

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Stem cells show promise for treating rare nerve disease

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Priority Health: Stem Cells

Posted: May 10, 2013 at 7:51 pm

Recently, doctors in Illinois implanted a windpipe into a 2-year-old girl.

Hanna Warren's new trachea is made of plastic fibers and her own stem cells.

Stem cells are cells that have the potential to develop into some or many different cell types in the body.

They usually serve as a repair system.

Theoretically, they can also divide without limit to replenish other cells for as long as the person or animal is still alive.

When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell - muscle cell, red blood cell, brain cell, etc.

Stem cells have potential in many different areas of health and medical research.

They help scientists understand how cells transform into the many different types of cells needed to live.

Some of the most serious medical conditions, such as cancer and birth defects, are due to problems that occur somewhere in this transforming process.

There are several sources of stem cells.

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Priority Health: Stem Cells

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