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Category Archives: Stem Cells

Stem cells from fat used to grow blood vessels in lab, research shows

Posted: July 26, 2012 at 4:19 am

MOBILE, Alabama -- Adult stem cells extracted during liposuction can be used to grow healthy new small-diameter blood vessels for use in heart bypass surgery and other procedures, new research shows.

The findings were presented today at the American Heart Association's Basic Cardiovascular Sciences 2012 Scientific Sessions in New Orleans.

The reason that's important, health officials said, is because millions of cardiovascular disease patients are in need of small-diameter vessel grafts for procedures requiring blood to be routed around blocked arteries.

These liposuction-derived vessels, grown in a lab, could help solve major problems associated with grafting blood vessels from elsewhere in the body or from using artificial blood vessels that are not living tissue, said Matthias Nollert, Ph.D., the lead author of the study, in a written statement.

Now, Nollert said, "small-diameter vessel grafts carry an inherent risk of clotting, being rejected or otherwise failing to function normally."

Nollert said the engineered blood vessels have good mechanical properties and "we believe they will contract normally when exposed to hormones. They also appear to prevent the accumulation of blood platelets -- a component in blood that causes arteries to narrow."

Here's how it works:

In the study, according to the American Heart Association, adult stem cells derived from fat are turned into smooth muscle cells in a laboratory, and then "seeded" onto a very thin collagen membrane.

As the stem cells multiplied, the researchers rolled them into tubes matching the diameter of small blood vessels. In three to four weeks, they grew into usable blood vessels.

Creating blood vessels with this technique has the potential for "off-the-shelf" replacement vessels that can be used in graft procedures, Nollert said.

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Doctors Report Historic Transplant in Child

Posted: July 26, 2012 at 4:19 am

In a Tissue-Engineering First, Doctors Think the Boy's New Windpipe Could Grow

July 25, 2012 -- Ciaran Finn-Lynch is an accidental medical pioneer. With his life in danger, doctors used the 13-year-old's own stem cells to grow him a new windpipe, and they did it inside his body -- a feat that's never been accomplished before.

"It's a really heroic story," says Harald C. Ott, MD, an instructor of medicine at Harvard Medical School in Boston. "They really saved this kid's life."

Ott worked out some of the science that made the procedure possible but was not directly involved in Ciaran's treatment.

Two years after the surgery, doctors say Ciaran (pronounced KEER-an) is living the life of a normal teen. He's grown more than 4 inches and gone back to school. Best of all, he has no need for an expensive and complicated regimen of anti-rejection drugs.

What doctors are learning from his case could help thousands of children born each year with life-threatening birth defects.

Ciaran was born with a windpipe so small and deformed that it caused his lungs to collapse.

Doctors managed to hold his airway open using metal tubes. But eventually the tubes eroded into his aorta, the large vessel that carries blood out of the heart. He was rushed to the hospital with massive bleeding. Twice.

The second time, the bleeding stopped on its own. That gave his doctors a small window of time to look for other options.

Two years earlier, scientists had devised a new way to create organs using a patient's own stem cells. Though the technique had only been tried in adults, they thought the same method might work for Ciaran.

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Seventeenth Patient Dosed in Neuralstem ALS Stem Cell Trial

Posted: July 25, 2012 at 7:18 pm

ROCKVILLE, Md., July 25, 2012 /PRNewswire/ --Neuralstem, Inc. (NYSE MKT: CUR) announced that the seventeenth patient was treated in the ongoing Phase I trial of its spinal cord neural stem cells for the treatment of amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). This patient is also the second to return to the trial for additional injections. In this treatment, the patient received five injections in the cervical (upper back) region of the spinal cord, in addition to the ten he had previously received in the lumbar (lower back) region, for a total of 15 injections. The final previously treated patient of this cervical cohort is expected to return to the trial in August, provided the inclusion requirements continue to be met. This ground-breaking stem cell trial is taking place at Emory University Hospital in Atlanta, Georgia.

(Logo: http://photos.prnewswire.com/prnh/20061221/DCTH007LOGO )

"We are pleased that this phase of the trial, in which we have been permitted by the FDA to take the unprecedented step of dosing patients for the second time, is progressing as planned," said Karl Johe, PhD, Neuralstem's Chairman and Chief Scientific Officer. "These are the first patients in the world to receive our cells in both the lumbar and cervical regions of their spinal cords, where the stem cell therapy could support both walking and breathing."

About the Trial

The Phase I trial to assess the safety of Neuralstem's spinal cord neural stem cells and intraspinal transplantation method in ALS patients has been underway since January 2010. The trial is designed to enroll up to 18 patients. The first 12 patients were each transplanted in the lumbar (lower back) region of the spine, beginning with non-ambulatory and advancing to ambulatory cohorts.

The trial then advanced to transplantation in the cervical (upper back) region of the spine. The first cohort of three was treated in the cervical region only. The current cohort of three is receiving injections in both the cervical and lumbar regions of the spinal cord. In an amendment to the trial design, The Food and Drug Administration (FDA) approved the return of previously treated patients to this cohort. The second of these returning patients was just treated. The entire 18-patient trial concludes six months after the final surgery.

About Neuralstem

Neuralstem's patented technology enables the ability to produce neural stem cells of the human brain and spinal cord in commercial quantities, and the ability to control the differentiation of these cells constitutively into mature, physiologically relevant human neurons and glia. Neuralstem is in an FDA-approved Phase I safety clinical trial for amyotrophic lateral sclerosis (ALS), often referred to as Lou Gehrig's disease, and has been awarded orphan status designation by the FDA.

In addition to ALS, the company is also targeting major central nervous system conditions with its cell therapy platform, including spinal cord injury, ischemic spastic paraplegia and chronic stroke. The company has submitted an IND (Investigational New Drug) application to the FDA for a Phase I safety trial in chronic spinal cord injury.

Neuralstem also has the ability to generate stable human neural stem cell lines suitable for the systematic screening of large chemical libraries. Through this proprietary screening technology, Neuralstem has discovered and patented compounds that may stimulate the brain's capacity to generate new neurons, possibly reversing the pathologies of some central nervous system conditions. The company is in a Phase Ib safety trial evaluating NSI-189, its first neurogenic small molecule compound, for the treatment of major depressive disorder (MDD). Additional indications could include CTE (chronic traumatic encephalopathy), Alzheimer's disease, anxiety, and memory disorders.

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Seventeenth Patient Dosed in Neuralstem ALS Stem Cell Trial

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Key function of protein discovered for obtaining blood stem cells as source for transplants

Posted: July 25, 2012 at 7:18 pm

ScienceDaily (July 25, 2012) With an eye to the future, the results will let cells be obtained in the laboratory that can be transplanted into leukemia patients with no compatible donors.

Researchers from IMIM (Hospital del Mar Medical Research Institute) have deciphered the function executed by a protein called -catenin in generating blood tissue stem cells. These cells, also called hematopoietic, are used as a source for transplants that form part of the therapies to fight different types of leukemia. The results obtained will open the doors to produce these stem cells in the laboratory and, thus, improve the quality and quantity of these surgical procedures. This will let patients with no compatible donors be able to benefit from this discovery in the future.

The study, executed jointly with the Erasmus Medical Center Stem Cell of Rotterdam and published in the Journal of Experimental Medicine, analyzed a chain of molecular reactions that are produced inside some embryonic cells and that play a role in the creation of a hematopoietic stem cells. 'Our study contributes to deciphering the code that makes a precursor cell that is only found in the embryo become a hematopoietic stem cell. In order for that to happen, the -catenin protein must be activated for a while and with a specific dosage' explains Dr Anna Bigas, head of the IMIM Stem Cells & Cancer Group and lead researcher.

This protein also plays a fundamental role in the cells that originate and maintain some types of leukemia. 'The parallelisms between normal and leukemia stem cells prove to us that the molecular pathways that regulate both populations are the same. For this reason, our work will help us understand the origin of these diseases', argues Dr Bigas.

In addition to embryonic stem cells, each of our body's organs has another type of stem cell that has the capacity to regenerate all the cells for the tissue in question. However, they are only formed in the embryonic stage and are maintained for the rest of our lives. hematopoietic stem cells are part of the blood and, when they are transplanted, they are the inception for all of this tissue's cells.

At present, transplanting these cells is dependent on the availability of compatible donors. Nonetheless, there is still a high percentage of patients with no donors and that, therefore, cannot be submitted to this procedure. The results of this article lay the foundations so that, in the future, these patients can benefit from a source of laboratory-generated hematopoietic stem cells created from compatible embryonic cells or other types of expressly transformed cells.

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The above story is reprinted from materials provided by IMIM (Hospital del Mar Research Institute).

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Key function of protein discovered for obtaining blood stem cells as source for transplants

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Driver of breast cancer stem cell metastasis found

Posted: July 24, 2012 at 11:18 pm

ScienceDaily (July 24, 2012) Researchers at the University of Michigan Comprehensive Cancer Center have found that a cancer gene linked to aggressive spread of the disease promotes breast cancer stem cells. The finding implies a new way to target the behavior of these lethal cells.

The finding involves the cancer gene RhoC, which has previously been shown to promote metastasis of many types of cancer. RhoC levels increase as breast cancer progresses and high levels of RhoC are associated with worse patient survival.

Cancer stem cells are the small number of cells within a tumor that are believed to fuel the tumor's growth and spread. Researchers believe traditional chemotherapy and radiation treatments often become ineffective because they do not kill the cancer stem cells, and that the key to future treatments is to develop drugs that target and kill these cells.

This new study, which appears online in PLoS ONE, suggests a new way to get at the cancer stem cells.

"Targeting the specific molecular cogs driving the cancer stem cell machinery responsible for the cancer spreading has potential for future treatments. Eliminating cancer stem cells may ultimately be necessary to cure certain cancers, but in the meantime, we may be able to manage the cancer stem cell population and the invasive behaviors of these cells by disrupting the molecular machinery, using RhoC as a target," says senior study author Sofia D. Merajver, M.D., Ph.D., professor of internal medicine and epidemiology at the University of Michigan and scientific director of the breast oncology program at the U-M Comprehensive Cancer Center.

The researchers looked at breast cancer cell lines that were highly metastatic and cell lines from normal breast tissue. By inhibiting or overexpressing RhoC, they found that RhoC expression is necessary to cause metastasis in both cell lines, and that RhoC overexpression alone can cause metastasis. The researchers also tested this in mice and had similar results.

Merajver's lab, in conjunction with other U-M researchers, is studying a novel small molecule drug to inhibit RhoC, which has shown promising initial results in the laboratory. The researchers are continuing to develop this inhibitor, which will require several years of additional testing in the laboratory before potentially advancing to clinical trials.

Breast cancer statistics: 229,060 Americans will be diagnosed with breast cancer this year and 39,920 will die from the disease, according to the American Cancer Society

Additional authors: Devin T. Rosenthal, Jie Zhang, Liwei Bao, Lian Zhu, Zhifen Wu, Kathy Toy and Celina G. Kleer, all from U-M

Funding: Department of Defense Breast Cancer Research Program (BC083262); National Institutes of Health (T32-GM07315); Burroughs Wellcome Fund; Breast Cancer Research Foundation

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Driver of breast cancer stem cell metastasis found

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Companies selectively targeting cancer stem cells

Posted: July 22, 2012 at 3:54 pm

Today, I posted this to Twitter:

3 Innovative Cancer Treatments...But Which Is The Best Bet? seekingalpha.com/a/fjed $GSK $IMUC $VSTM #cancerSC via @seekingalpha — Jim Till (@jimtill) July 17, 2012

The article is about three companies that are working on treatments designed to target cancer stem cells (CSCs). The companies are OncoMed, Verastem and ImmunoCellular Therapeutics. The article is interesting.

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Royalty Rules at the California Stem Cell Agency: Business Friendly Changes Proposed

Posted: July 22, 2012 at 3:54 pm


If you are looking to follow the money
trail at the $3 billion California stem cell agency, next Thursday's meeting of its 29-member board of directors is a good place to start.


On the agenda are revisions in its
intellectual property rules, which are all about who gets paid and how much and when – should an agency-financed product generate
significant cash.

The key question about the proposed changes is whether they will generate an appropriate return for the state, given its $6 billion investment, including interest on the bonds that finance CIRM. The impact of the changes is not crystal clear. And the staff memo does not mention two important definition changes that appear to be quite business friendly.

During the 2004 ballot campaign that
created the stem cell agency, California voters were told that the
state would share as much as $1 billion or more in royalties. Eight
years later, no royalties have materialized since CIRM research has
not yet resulted in a commercial therapy. 
At next week's meeting in Burlingame,
directors will be asked to modify CIRM rules for royalties that CIRM
staff said "could be a disincentive" for business. A staff memo said the proposals would alter provisions that create "administrative challenges and uncertainty." The memo asserted
the proposed changes would ensure "a comparable economic
return to California" equal to the existing provisions.
However, the memo provided no explanation or evidence for how that
result would come about. The proposed changes could also be applied
retroactively with the agreement of CIRM and the grantee.
Currently CIRM grantees and
collaborators must share as much as 25 percent of their licensing
revenue in excess of $500,000, depending on the proportion of agency
funding for the product. The IP rules also contain a provision for
payments in the event of development of a "blockbuster" therapy.
The staff memo described how that would work.

“It provides that grantees and
collaborators must share revenues resulting from CIRM funded research
as follows: after revenues exceed $500,000, three times the grant
award, paid at a rate of 3% per year, plus upon earning
$250M(million) in a single calendar year, a onetime payment of three
times the award, plus upon earning revenues of $500M in a single
calendar year, an additional onetime payment of three times the award
and, finally, in the instance where a patented CIRM funded invention
or CIRM funded technology contributed to the creation of net
commercial revenue greater than $500M in a single calendar year, and
where CIRM awarded $5 million or more, an additional 1% royalty on
revenues in excess of $500 million annually over the life of the
patents.”

The proposed changes would exempt "pre-commercial revenues" from the state's revenue sharing, the
memo said, in order to maximize the amount businesses can "re-invest
in product development." 
The proportionality payment provision
would be changed to require only 15 percent of licensing revenues if
CIRM's investment is less than 50 percent and 25 percent if it is
more than 50 percent. 
Revenue sharing would be extended to "commercializing entities." No definition of "commercializing entities" was provided in the board agenda material, but a June version of the changes defined them as "A For-Profit Grantee and its Collaborator or Licensee that sells, offers for sale or transfers a Drug, product(s) or services resulting in whole or in part from CIRM-Funded Research."

Not mentioned in the CIRM staff memo were two new provisions in the rules involving the definition of licensing revenue and the sale of a therapy. Both could be construed as quite favorable to businesses. According to the June version of the changes, licensing revenues are defined as a figure minus "a proportion of expenses reasonably incurred in prosecuting, defending and enforcing related patent rights equal to CIRM’s percentage of support for development."  The sale provision says that royalties on "net commercial revenue" are not due until received from sales in the United States or Europe. That provision would appear to exclude California from receiving royalties on product sales in most of the world, where it is easier to receive regulatory approval for sale of new therapies and drugs. (See here -- page 2 -- for royalty provision and here for definition of "first commercial sale"-- page 3.)

The existing IP regulations are
enshrined in a 2011 state law. However, the law also provided that
they can be altered by the agency, the CIRM memo said, “if it
determined that it was necessary to do so either to ensure that
research and therapy development are not unreasonably hindered as a
result of CIRM’s regulations or to ensure that the State of
California has an opportunity to share in the revenues derived from
such research and therapy development.”

The memo continued,

"The proposed amendments re-strike
the balance both to ensure that industry will partner with CIRM and
to ensure that the State has the opportunity to benefit from
successful therapy development."

Board action next week will give the
go-ahead for posting the proposals as part of the official state
administrative rules process. They are subject to additional changes
in that process. 
The agenda originally contained the full text of the changes. However, that material has been dropped from the board agenda. An earlier version can be found here and here. We have queried the agency about the reason for dropping the text in the board agenda.

(Editor's note: The agency has now reposted the version of the text of the changes that was on the agenda earlier, saying that it was having problems with its web site. For the definitions of terms, however, it is still necessary to refer to the June documents.)

Source:
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California’s $12.4 Million Stem Cell Recruitment Lure

Posted: July 22, 2012 at 3:54 pm


Directors of the California stem cell
agency next Thursday are likely to approve spending $12.4 million to
lure a couple of stem cell stars to the Golden State.

It is part of a $44 million recruitment
program that has brought three highly regarded scientists to three
California research institutions, all of which have representatives
on the CIRM board. (See here, here and here.)
As usual, the $3 billion stem cell agency does not
identify the potential recipients in advance of the meeting or the
institutions that are recruiting them. However, if you have a modicum
of knowledge about the specific fields involved, it is likely that
you can identify them based on the information in CIRM's review summaries and some Internet searching.
One of the proposed research grants–a
$5.7 million award--would go a scientist who won raves from CIRM's
reviewers. The researcher was described as an “exceptional
scientist and one of the leading young developmental biologists.”
Reviewers gave his proposal a score of 90 and, in summary, said,

“Major strengths include the
candidate's exceptional productivity and contributions to the fields
of mammalian embryology and kidney development, the significance and
potential of the research program, the PI's proven leadership
capabilities, and the outstanding institutional commitment.”

 The other grant was larger–$6.7
million–but reviewers raised a number of questions about the
candidate although they recommended it for funding. The
review summary ranked the application at 57 and said,

“In summary, this is an application
from an established leader in NSC biology to pursue research focused
on disease mechanisms in PD. Strengths of the proposal include the
quality of the PI, the focus of the project on an interesting
hypothesis, and the leadership in basic science that the candidate
would bring to the applicant institution. Weaknesses included
deficiencies in the research plan, the limited track-record of the PI
in PD research and an institutional environment lacking adequate
support for basic science investigations.“

Last January, in a rare move, CIRM
directors rejected a $6.3 million recruitment grant with a score of
76 sought by the Buck Institute, which is not represented on the
board.
The proposals are scheduled to be acted
on at a public CIRM board meeting in Burlingame, Ca.

(Editor's note: an earlier version of this item incorrectly said the total of both grants was $13.4 million.)

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UC Davis Researchers Score Big in $113 Million Stem Cell Award Round

Posted: July 22, 2012 at 3:54 pm


Scientists at the University of
California at Davis
are set to win nearly half of $113 million
expected to be awarded next week by the California stem cell agency
as it pushes aggressively to turn research into marketplace cures.

Directors of the $3 billion agency are
virtually certain to approve awards to three researchers at UC Davis,
which operates its medical school and other research facilities in
nearby Sacramento. The other three expected winners are from UCLA,
Stanford
and StemCells, Inc., of Newark, Ca., a publicly traded firm.
The $113 million round is the second largest research round in CIRM's history, surpassed only by an
another, earlier $211 million “disease team” round. The latest
effort is aimed at bringing proposed clinical trials to the FDA for approval or possibly starting trials within four years. That deadline
is close to the time when CIRM is scheduled to run out of cash unless
new funding sources are developed.
CIRM is currently exploring seeking
private financing. It could also ask voters to approve another state
bond issue. (Bonds currently provide the only real source of cash for
CIRM.)  In either case, the agency needs strong, positive results from
its grantees to support a bid for continued funding.
The CIRM board is scheduled to approve
the latest awards one week from tomorrow at a public meeting in Burlingame in the San Francisco area. The agency's policy is to
withhold the identities of applicants and winners until after formal
board action. The California Stem Cell Report, however, has pieced
together their identities from public records.
Here are the winners and links to the
grant review summaries, listed in order of the CIRM scientific
scores:
  • Vicki Wheelock, UC Davis, $19 million,
    for development of a genetically modified cell therapy for
    Huntington's disease, an inherited neurodegenerative disorder.
    Scientific score 87.
  • Antoni Ribas, UCLA, $20 million, for
    genetic reprogramming of cells to fight cancer. Scientific score 84.
  • Nancy Lane, UC Davis, $20 million, for
    development of a small molecule to promote bone growth for the
    treatment of osteoporosis. Scientific score 80.
  • John Laird, UC Davis, $14.2 million,
    for development of mesenchymal stem cells genetically modified for
    treatment of critical limb ischemia, which restricts blood flow in
    the lower leg and can lead to amputation. Scientific score 79.
  • StemCells, Inc., (principal
    investigator not yet known), $20 million, for development of human
    neural stem cells to treat chronic cervical spinal cord injury. The
    company, founded by Stanford scientist Irv Weissman, who serves on
    its board, said earlier this year that it had filed two applications
    in this round, one of which dealt with cervical cord spinal injury.
    No other applicants filed a proposal for such research. Scientific score 79.
  • Robert Robbins, Stanford, $20 million,
    development of a human embryonic stem cell treatment for end-stage
    heart failure.
    Scientific score 68.

In the case of businesses, the awards
come in the form of loans. Grants go to nonprofits. One of the
reasons behind the varying mechanisms is the difference in CIRM's
intellectual property rules for businesses and nonprofits.

CIRM's Grant Working Group earlier this
year approved the applications during closed door sessions. The full
CIRM board has ultimate authority on the applications, but it has
almost never rejected a positive action by the grant reviewers.
The board originally allotted $243 million for this round. Directors could reach into the 15
applications rejected by reviewers and approve any of them, which the
board has done in other rounds. In this round, three rejected
applications scored within seven points of the lowest rated
application approved by reviewers, which could lead some directors
to argue that the scores are not significantly different. One of the
three came from Alexandra Capela of StemCells, Inc., and was scored at 61. The other two and their scores are Clive Svendsen of
Cedars-Sinai, score 64, for ALS research, and Roberta Brinton of
USC, score 63, for an Alzheimer's project.
Rejected applicants also can appeal
reviewer decisions to the full CIRM board in writing and in public
appearances before directors.
Twenty-three researchers were eligible
to apply for funding, CIRM told the California Stem Cell Report.
Applicants qualified by either winning a related planning grant from
CIRM last year or by being granted an exception to that requirement
by CIRM staff. Of the 22 researchers who ultimately applied(one
nonprofit dropped out), six came from biotech businesses. Three of
those qualified through exceptions. Three other businesses won
planning grants last year out of the eight businesses that applied.
CIRM has come under fire for its
negligible funding of stem cell firms and is moving to embrace
industry more warmly.
Only one of the grants approved by
reviewers involves research with human embryonic stem cells, which
was the critical key to creation of the California stem cell agency.
California voters established the agency in 2004 on the basis that it
was needed because the Bush Administration had restricted federal
funding of human embryonic stem cell research.  

Source:
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Companies selectively targeting cancer stem cells

Posted: July 22, 2012 at 3:53 pm

Today, I posted this to Twitter:

3 Innovative Cancer Treatments...But Which Is The Best Bet? seekingalpha.com/a/fjed $GSK $IMUC $VSTM #cancerSC via @seekingalpha — Jim Till (@jimtill) July 17, 2012

The article is about three companies that are working on treatments designed to target cancer stem cells (CSCs). The companies are OncoMed, Verastem and ImmunoCellular Therapeutics. The article is interesting.

Source:
http://cancerstemcellnews.blogspot.com/feeds/posts/default?alt=rss

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