Editor's note: Climate Query is a semi-weekly feature offered by Daily Climate, presenting short Q&A's with players large and small in the climate arena. Read others in the series at http://wwwp.dailyclimate.org/tdc-newsroom/query/climate-queries .

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http://rss.sciam.com/sciam/topic/gene-therapy

A nearly 13-year-old skin cancer drug rapidly alleviates molecular signs of Alzheimer's diseas e and improves brain function, according to the results of a new mouse study being hailed as extremely promising. Early-stage human clinical trials could begin within months.

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http://rss.sciam.com/sciam/topic/gene-therapy

The New Medicine Service (NMS) offered by Engalnd’s  NHS community pharmacies came into effect since 1st October 2011. NMS is a patient adherene service and focuses on patients with long term conditions that have been prescribed new medicines.

It is hoped that NMS will lead to the following outcomes:

• improve medicines adherence
• increase patient engagement with their condition and medicines, which will support them in making decisions about their treatment and self management
• reduce medicines wastage
• reduce hospital admissions due to adverse events associated with medicines
• increase reporting of medicine adverse reactions by pharmacists and patients
• positive patient assessments
• provide evidence base on the effectiveness of the service
• enable the development of outcome and/or quality measures for community pharmacy

But the Service since launch has seen severe criticism from pharmacists’ over several issues, especially how the pharmacist is re-imbursed for the providing the service which also involved patient counselling.

The answer perhaps can be found by applying predictive analytics to identify patients who are more likely to deviate or other likely to exhibit non-compliance in adhering to the prescription.

Express Scripts has developed a set of proprietary computer models that predict, up to a year in advance, which patients are at risk of not following through on their prescribed drug therapy. details

FICO an analytics service provider also provides medication adherence ranking based on predictive analytics details

Source:
http://microarray.wordpress.com/feed/

The California stem cell agency today released its letter to leaders of the California legislature concerning the conflict of interest violation by the scientist who was then chairman of the panel that makes the de facto decisions on hundreds of millions of dollars in research grants.

The agency also posted the review summary of the application involved in the conflict of interest, which had been missing from its web site.

The incident occurred last April, but was not publicly disclosed by the $3 billion research enterprise until questions were raised this month by the California Stem Cell Report. The case involved John Sladek of the University of Colorado in Denver, then chairman of the CIRM grant review group, which makes decisions on the hundreds of grant applications. The CIRM board of directors has final approval but it almost never overturns a favorable recommendation from the grant panel.

Sladek resigned from the review group after CIRM staff discovered the conflict following the March 17 review session. CIRM called it a "technical violation."

The information provided today by CIRM added some details to the matter, including Sladek's statement that the conflict was inadvertent on his part.

The June 15 letter to the speaker of the state Assembly and the leader of the state Senate was labelled "confidential disclosure." Signed by then CIRM Chairman Robert Klein, it said,

"While preparing the public summary for Basic Biology III Awards Application No. RB3-02119, CIRM staff discovered that Dr. Sladek had co-authored two papers in the last three years with a researcher on the application. Although the researcher’s name was included on the CIRM conflict of interest form, Dr. Sladek did not disclose these publications to CIRM."

As reported earlier, Sladek's participation did not affect the outcome on the application, which was not recommended for funding.

As is CIRM's practice, the review summary of the grant application did not identify the scientist seeking funding. The summary listed one reviewer with an unspecified conflict, Ali Brivanlou of Rockefeller University.

The letter was provided by CIRM at the request of the California Stem Cell Report, which also asked for the review summary of the grant application after discovering it was missing. James Harrison, outside counsel to the agency, said in an email that the summary was not posted because of a "programming error."

The summary can be found here. Here is the letter.Sladek/CIRM Conflict of Interest Letter to California Legislative Leadership

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

A conflict of interest on a grant application before the $3 billion California stem cell agency last year led to the resignation of the grant review committee's longstanding chairman, John Sladek of the University of Colorado.

The incident occurred last April but was not publicly disclosed by CIRM until the California Stem Cell Report (CSCR) raised a question earlier this month.

Sladek is professor of neurology, pediatrics and neuroscience at the University of Colorado in Denver and a former president of Cal Lutheran University in the Los Angeles area. He had served on the stem cell agency's grant review group since 2005 and as its chairman from 2009 until April of last year.

Responding to an email from CSCR, James Harrison of Remcho, Johansen and Purcell of San Leandro, Ca., outside counsel to the stem cell agency, said that CIRM's staff uncovered the conflict in April after the grant review session was concluded on March 17. Harrison described it as a "technical violation."

He said,

"While preparing the public summary for Basic Biology III (grant round)applications, CIRM staff discovered that Dr. John Sladek was one of several co-authors on scientific publications with a researcher who was listed as a consultant on a CIRM grant application."

Harrison said,

"This is a technical violation of CIRM's conflict of interest rules, which prohibit a member of the Grants Working Group ("GWG") from participating in the review of an application if the member has co-authored papers with a salaried investigator listed on a CIRM application within a three year window."

Harrison said Sladek's conflict did not violate the state's political reform act nor did he have a financial interest in the application.

Harrison continued,

"Nonetheless, in the spirit of setting an example of strict compliance, Dr. Sladek tendered his resignation from the GWG."

Asked for comment, Sladek said that Harrison's account was accurate and that he had nothing to add. (Both Harrison's and Sladek's verbatim comments can be found here.)

In December, the CIRM board of directors approved, on a unanimous voice vote of the 21 directors present out of 29, a resolution commending Sladek for serving in "exemplary fashion."

The stem cell agency disclosed specifics of the conflict of interest violation after the California Stem Cell Report discovered a vague reference to it in the transcript of the January meeting of the Citizens Financial Oversight and Accountability Committee, the only state entity specifically charged with oversight of the agency and its directors.

Members of the committee had raised questions about conflicts of interests at CIRM. At one point, Harrison said,

"We have also had occasion where we have had a conflict of a very technical nature on the grants working group which we addressed pursuant to our procedure and reported to the legislature."

It was that remark that triggered the request for more details.

Asked about the report to the legislature, Harrison said CIRM wrote a letter to the legislative leadership about the incident. We have asked for a copy of the letter, which we will carry when we receive it.

As of this writing, the review summary for the grant application (RB3-02119) in question was not available on the CIRM web. Normally all the summaries are posted. We have queried the agency concerning its absence.

Harrison also said that in the seven-year history of CIRM no other instances exist of grant review committee members having been determined to be in a conflict of interest after participation in a review.

Our comment: CIRM is to be commended for taking care of this situation quickly last April. Sladek correctly resigned promptly. However, failure to disclose the incident at the time does not reflect well on the California stem cell agency nor does it inspire confidence in the agency's now improving openness and transparency.

CIRM is an enterprise that has substantial built-in conflicts of interests – all legal courtesy of Prop. 71, the ballot initiative that created CIRM. Institutions linked to CIRM directors have received $1.1 billion of the $1.2 billion the agency has given away. A display of reticence in this conflict-of-interest case does little to quell the suspicions of those who have criticized the agency for "cronyism," including the journal Nature and some in the biotech business community and elsewhere. As for the description of the incident as a "very technical" violation, that amounts to a bit of PR. Either it is a violation or it isn't.

Sladek's violation is the sort of thing not well understood by the public. Most public attention is focused on financial conflicts of interest in science. However, professional conflicts of interest involving scientists are among the most invidious. The California Stem Cell Report regularly hears complaints and suspicions about such dealings at CIRM: Big-name scientists receiving favored treatment, academic researchers unfairly evaluating applications from business researchers, younger researchers being shunted to background and more. All this as a billion dollars worth of applications have been evaluated behind closed doors with no public disclosure of the economic or professional interests of the reviewers. The stem cell agency would do well to improve its openness and transparency, particularly as it moves into ticklish and expensive relationships with industry. The first step would be to post on its web site the disclosure forms filed by its grant reviewers but withheld from the public by CIRM.

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

Here are the verbatim statements from James Harrison, outside counsel to the California stem cell agency, and John Sladek concerning Sladek's conflict of interest and resignation as chair of the agency's grant review group.

Harrison made these initial remarks first and provided a few other details later.

"While preparing the public summary for Basic Biology III (grant round)applications, CIRM staff discovered that Dr. John Sladek was one of several co-authors on scientific publications with a researcher who was listed as a consultant on a CIRM grant application.
"This is a technical violation of CIRM's conflict of interest rules, which prohibit a member of the Grants Working Group ("GWG") from participating in the review of an application if the member has co-authored papers with a salaried investigator listed on a CIRM application within a three year window.

"It should be noted, however, that Dr. Sladek's participation in the review of the application would not have constituted a conflict of interest under the Political Reform Act's conflict of interest standards because Dr. Sladek did not have a financial interest in the application. In addition, the amount of funding involved - approximately $3,000 of salary per year for three years, less than one percent of the total award - was not material, and Dr. Sladek did not stand to receive any financial benefit from the application. Finally, Dr. Sladek's participation in the review did not affect the outcome because the application was not recommended, or approved, for funding.

"Nonetheless, in the spirit of setting an example of strict compliance, Dr. Sladek tendered his resignation from the GWG."

Sladek's response to a question for comment:

"Mr. Harrison’s account  is accurate and there really isn’t anything to add other than I was pleased to serve CIRM and California  for several years and wish them well as they pursue such an important mission with respect to the potential for therapeutic applications to human disease and disorders. Thank you for your inquiry."

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

Qatar Conference Center

If our readers in the Middle East are looking for a first-hand assessment of the state of stem cell research, they might want to take in the four-day conference this week in Qatar, which features the president of the $3 billion California stem cell agency.

Alan Trounson is one of a number of international stem cell notables at the session at the new Qatar Conference Center in the tiny nation in the Persian Gulf. The country is putting on the conference as a means of developing its own stem cell research capabilities.

Qatar had a gross national product of $129 billion in 2010, with a per capita income of $138,000, according to the U.S. State Department. The population is about 1.7 million, more than 75 percent of whom are foreigners with temporary residence status.

In addition to Trounson, other California and CIRM-connected researchers are speaking at the conference in the Qatar center, which just opened in December.  They include David Baltimore, Nobel Laureate and a former director of the stem cell agency. A company Baltimore co-founded, Calimmune, of Tucson, Az., is sharing in a $20 million CIRM grant. Other CIRM grant recipients or representatives of recipient companies appearing at the conference are Irv Weissman of Stanford; Deepak Srivastava of the Gladstone Institute, and Ann Tsukamoto Weissman of Stem Cells Inc. of Newark, Ca.

Social activities at the conference include sand dune "bashing" in off-road vehicles, camel tracking along with a look at their "robot jockeys" and a visit to the original Arabic Oryx farm.

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

The state of California plans to sell $2 billion in bonds next Thursday, but the California stem cell agency, which is entirely dependent on state borrowing, will have to wait until later this spring to see more cash.

J.T. Thomas, chairman of the stem cell agency, said he expected to see CIRM benefit from the next bond sale in April. The agency currently has sufficient funds to operate until about June, plus an arrangement with the state for continued funding if a timely bond sale is not completed.

The $3 billion stem cell agency was created in 2004 through a ballot initiative that authorized its funding through the sale of state bonds over a 10-year period. The interest on the bonds raises the total cost of the agency to taxpayers to about $6 billion. Likewise, the cost of a $20 million grant is actually more like $40 million.

Financially beleaguered California's interest costs have sharply increased in recent years as the state has borrowed $53.8 billion from 2007 to 2010. This year, interest costs will come to about $5.4 billion, nearly 6 percent of the state budget. Nine years ago, it was $2.1 billion or 2.9 percent, according a piece by Randall Jensen (no relation to this writer) of the Bond Buyer newspaper.

The expense of borrowing shrinks the amount of state money available for public schools, helping the medically indigent and other state purposes.

Next Thursday's bond sale will go to refinance debt at lower rates. This year, Gov. Jerry Brown and state Treasurer Bill Lockyer plan to sell only $5.2 billion in general obligation bonds, roughly one-fourth of what the state issued in 2009.

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

Stem cell therapy is poised to become the next big thing in the treatment of major diseases. Even those extracted from dental pulp can be preserved for future use

Watching his five-year-old pull at his loose tooth, dad Shekar remembered something he had read in a dental clinic. Stem cells from teeth, called dental pulp stem cells (DPSCs) could be preserved and retrieved to treat his son if he had a major ailment in future. Stemade, a private company, would arrange to collect DPSCs through its Smile Clinics and store them in state-of-the-art labs in several cities across the country. His thought: Stem cell technology is the next big step in medical treatment. Banking SCs is medical bio-insurance for his kid.

Stem cell therapy didn't jump out of a box yesterday. We've heard of it being used in treating leukaemia. Patients with spinal cord injury have spent huge sums on it hoping to get up and walk. Some ask: If a house lizard can grow back its tail, why can't we get our systems to re-start with a million multiplying stem cells?

Kinds of cells

The best cells for banking are embryonic cells which are programmed to develop and grow. But harvesting these is banned. Ethical issues, you know. Adult SCs beyond the embryonic stage are classified as haematopoietic (from umbilical cord blood and bone marrow) and mesenchymal (tissues and organs). While haematopoietic cells are used in the treatment of blood-related diseases such as haemophilia, blood cancer and skin troubles, tissue cells are tried on all problems other than these. HSCs are collected only from the umbilical cord and bone marrow. Tissue cells are taken from many body sources such as bone marrow, placenta, menstrual blood, cornea, outer layer of the heart, liposuction waste and teeth pulp.

Among these DPSCs are perhaps the best option, says Shailesh Gadre, MD, Stemade Biotech. We all lose our milk teeth and cell extraction here is almost painless. As for the permanent teeth, we can harvest the pulp when people have to lose them for orthodontic (cosmetic) reasons, as when braces are fixed or teeth are extracted because of poor positioning. Of course, they need to be free of caries and other dental infections.

But as we age, our cells age too, so DPSCs are best extracted and preserved when we're very young, when the cells are virile and robust. DPSCs have extraordinary doubling properties that give them a huge advantage over other stem cells, says Dr. Julian Deepak, Medical Advisor, Stemade. They are derived from the same source as nerve cells, with the same capacity as neuron cells, making them a better option for treating Parkinson's, Alzheimer's and muscular dystrophy. Work is on to see their effectiveness in curing diabetes.

Back to the kid's tooth. After the dad's call, a dentist from Stemade will check if Milan's tooth is free of disease. At a Smile Clinic he will extract it and take a blood sample. The dentist will then place the tooth in a specially-designed vial of antibiotic solution. The vial will be packed in ice-gel to keep the temperature low during transport. At their lab (which I visited) in suburban Chennai, a visual inspection is done, the tooth is flooded with anti-bacterial solution and broken open. The pulp is extracted, divided into parts for quality control and sterility (aerobic/anaerobic) tests. The processing is done in zero-contamination conditions and the cells are put in 5 different vials and placed in the vapour phase of liquid nitrogen for cryo-preservation. It is complete, patented technology. The cells are stored in raw format and can be retrieved when needed. Shekar gets a certificate and a CR Management number which will be part of his son's medical records.

These are your own (autologous) cells and will need no matching should you need them for treatment of tissue-and-organ-related diseases such as spinal cord/bone/liver/cartilage regeneration, diabetes, eye-care, etc., says Shailesh. Adds Dr. Julian, Now for most diseases we just do maintenance therapy. With their regenerative property, stem cells will cure diseases in the future.

Fine, but for a few details. One, is the banking fee? Yes, you have to pay for the banking facility, but we can help you with EMIs, says Shailesh. Subsidies are given to the poor as part of CSR. We want to reach as many households as possible. Others are the right to will it and fool-proof identification of the cells. We may store DPSCs at six and may need them at sixty.

Go here to read the rest:
It's not pulp fiction

To read Hard Cell by Mayrav Saar (PostScript, Feb. 26), one would think the only form of stem-cell therapy is the embryo-destroying kind. There wasnt a single mention of non-embryonic adult stem cells.

One attraction of embryonic versus non-embryonic research for some is political the chance to stick it to pro-lifers. But it grieves me to see ailing people used as pawns in this culture war and being denied the possible benefits of adult stem-cell research.

Flushing such an idea down the memory hole, as you help do with this article, is against the spirit of scientific inquiry.

Bob Hunt, Hillsborough, NJ

Wrong on the right

If social conservatives had won out in history, women would not be able to vote and we would still have slavery (Why Social Issues Matter, Jeffrey Bell, PostScript, Feb. 26).

Their thinking denigrates the role of science and promotes antiquated religious beliefs. Many of the causes taken up by social conservatives have been seen to be wrong in light of later progressive thought.

While social conservatives say some good things, history has shown that their views work against American freedoms an obscurantism that continues today.

Jeffrey Bell should balance his thought with facts and not be led blindly by evangelicals.

Eduardo Rodriguez, Corona

Continue reading here:
Stem-cell pawns

Cardiac cellular therapies are undergoing global clinical trials with "encouraging early results" and these economical options will soon be available in India which could bring relief to patients who cannot afford the currently available expensive surgical treatments, says Indian American cardiac surgeon Dr Mukesh Hariawala.

Delivering a special invited plenary lecture on the "Novel Cellular Therapies for Heart Disease" at the recently concluded Healthcare India 2012 convention in New Delhi, the renowned cardiac surgeon asserted that the new developments in cardiac cellular therapies would bring down the alarming healthcare costs globally.

Dr Hariawala is internationally acclaimed as a pioneer of cardiovascular surgical techniques using Therapeutic Angiogenesis. He said Therapeutic Angiogenesis is a fast emerging science of stimulating growth of new blood vessels in the heart which acts as natural bypasses to areas lacking in blood supply.

Dr Hariawala demonstrated angiogenesis along with bypass surgery, lasers and stem cell injections as a novel "Combo Therapy."

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The laser energy acts by creating channels in the diseased heart muscle which also triggers Angiogenesis. Stem cells are then injected directly into coronary arteries feeding the diseased territory or in the stimulated lasered muscle during the open heart surgery. This option could be very helpful in Indian patients with diffused distal small caliber coronary arteries and diabetes, who are not amicable to routinely offered current interventions, he said.

Dr Hariawala acknowledged that only a combination of these four therapies could give it the "Therapeutic Threshold Power" and bring about optimum results and relief of patients symptoms. Standalone, each of these therapies is weak to treat a large muscular pumping organ like the heart.

Stem cells have a therapeutic role and hold enormous promise for the future as they are harvested from the patient's own tissues. Currently, adult stem cell extraction is done from one's own hip bone and patients do not have to worry about rejection phenomenon occurring as they are native cells unlike transplanted from another donor. In the future, stem cell banks could proliferate allowing donors to freeze and store cells for family members who could be treated for many diseases, he added.

Harvard-trained Dr Hariawala's studies have been published in several scientific surgical journals and medical text books.

To report problems or to leave feedback about this article, e-mail: To contact the editor, e-mail:

Read more:
Angiogenesis and Stem Cell Therapy Key to Treating Heart Patients: Dr Mukesh Hariawala

ScienceDaily (Mar. 1, 2012) Despite their unassuming appearance, the planarian flatworms in Whitehead Institute Member Peter Reddien's lab are revealing powerful new insights into the biology of stem cells -- insights that may eventually help such cells deliver on a promising role in regenerative medicine.

In this week's issue of the journal Cell Stem Cell, Reddien and scientists in his lab report on their development of a novel approach to identify and study the genes that control stem cell behavior in planarians. Intriguingly, at least one class of these genes has a counterpart in human embryonic stem cells.

"This is a huge step forward in establishing planarians as an in vivo system for which the roles of stem cell regulators can be dissected," says Reddien, who is also an associate professor of biology at MIT and a Howard Hughes Medical Institute (HHMI) Early Career Scientist. "In the grand scheme of things for understanding stem cell biology, I think this is a beginning foray into seeking general principles that all animals utilize. I'd say we're at the beginning of that process."

Planarians (Schmidtea mediterranea) are tiny freshwater flatworms with the ability to reproduce through fission. After literally tearing themselves in half, the worms use stem cells, called cNeoblasts, to regrow any missing tissues and organs, ultimately forming two complete planarians in about a week.

Unlike muscle, nerve, or skin cells that are fully differentiated, certain stem cells, such as cNeoblasts and embryonic stem cells are pluripotent, having the ability to become almost cell type in the body. Researchers have long been interested in harnessing this capability to regrow damaged, diseased, or missing tissues in humans, such as insulin-producing cells for diabetics or nerve cells for patients with spinal cord injuries.

Several problems currently confound the therapeutic use of stem cells, including getting the stem cells to differentiate into the desired cell type in the appropriate location and having such cells successfully integrate with surrounding tissues, all without forming tumors. To solve these issues, researchers need a better understanding of how stem cells tick at the molecular level, particularly within the environment of a living organism. To date, a considerable amount of embryonic stem cell research has been conducted in the highly artificial environment of the Petri dish.

With its renowned powers of regeneration and more than half of its genes having human homologs, the planarian seems like a logical choice for this line of research. Yet, until now, scientists have been unable to efficiently find the genes that regulate the planarian stem cell system.

Postdoctoral researcher Dan Wagner, first author of the Cell Stem Cell paper, and Reddien devised a clever method to identify potential genetic regulators and then determine if those genes affect the two main functions of stem cells: differentiation and renewal of the stem cell population.

After identifying genes active in cNeoblasts, Wagner irradiated the planarians, leaving a single surviving cNeoblast in each planarian. Left alone, each cNeoblast can form colonies of new cells at very specific rates of differentiation and stem cell renewal.

The researchers knocked down each of the active genes, one per planarian, and observed how the surviving cNeoblasts responded. By comparing the rate of differentiation and stem cell renewal to that of normal cNeoblasts, they could determine the role of each gene. Thus, if a colony containing a certain knocked down gene were observed to have fewer stem cells than the controls, it could be concluded that gene in question plays a role in the process of stem cell renewal. And if the colony had fewer differentiated cells than normal, the knocked down gene could be associated with differentiation.

Here is the original post:
Planarian genes that control stem cell biology identified

29-02-2012 17:57 Learn more at http://www.cordblood.com CBR's team of dedicated professionals is prepared to guide you through every step of the banking process and beyond. Meet Sherry, CBR's transplant coordinator. As Sherry says, her employer is CBR, but she works for the families who need newborn stem cell medicine. She is the voice parents hear over the phone when they need to use their stored cord blood stem cells. Sherry's dedication and passion to deliver exceptional customer service to clients is one example of the many people at Cord Blood Registry who are committed to helping families live longer, healthier lives.

Read this article:
Cord Blood Registery Helps Families Use Stem Cells - Video

Newswise UCLA stem cell researchers have discovered a critical placental niche cell and signaling pathway that prevent blood precursors from premature differentiation in the placenta, a process necessary for ensuring proper blood supply for an individuals lifetime.

The placental niche, a stem cell safe zone, supports blood stem cell generation and expansion without promoting differentiation into mature blood cells, allowing the establishment of a pool of precursor cells that provide blood cells for later fetal and post-natal life, said study senior author Dr. Hanna Mikkola, an associate professor of molecular cell and developmental biology and a researcher at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Mikkola and her team found that PDGF-B signaling in trophoblasts, specialized cells of the placenta that facilitate embryo implantation and gas and nutrient exchanges between mother and fetus, is vital to maintaining the unique microenvironment needed for the blood precursors. When PDGF-B signaling is halted, the blood precursors differentiate prematurely, creating red blood cells in the placenta, Mikkola said.

The study, done in mouse models, appears March 1, 2012, in the peer-reviewed journal Developmental Cell.

We had previously discovered that the placenta provides a home for a large supply of blood stem cells that are maintained in an undifferentiated state. We now found that, by switching off one signaling pathway, the blood precursors in the placenta start to differentiate into red blood cells, Mikkola said. We learned that the trophoblasts act as powerful signaling centers that govern the niche safe zone.

The study found that the PDGF-B signaling in the trophoblasts is suppressing production of Erythropoietin (EPO), a cytokine that controls red blood cell differentiation.

When PDGF-B signaling is lost, excessive amounts of EPO are produced in the placenta, which triggers differentiation of red blood cells in the placental vasculature, said Akanksha Chhabra, study first author and a post-doctoral fellow in Mikkolas lab.

Mikkola and Chhabra used mouse models in which the placental structure was disrupted so they could observe what cells and signaling pathways were important components of the niche.

The idea was, if we mess up the home where the blood stem cells live, how do these cells respond to the altered environment, Chhabra said. We found that it was important to suppress EPO where blood stem cell expansion is desired and to restrict its expression to areas where red blood cell differentiation should occur.

The finding, Chhabra said, was exciting in that one single molecular change was enough to change the function of an important blood stem cell niche.

Read more from the original source:
UCLA Scientists Identify Cell and Signaling Pathway that Regulates the Placental Blood Stem Cell Niche

Public release date: 1-Mar-2012 [ | E-mail | Share ]

Contact: Kim Irwin kirwin@mednet.ucla.edu 310-206-2805 University of California - Los Angeles Health Sciences

UCLA stem cell researchers have discovered a critical placental niche cell and signaling pathway that prevent blood precursors from premature differentiation in the placenta, a process necessary for ensuring proper blood supply for an individual's lifetime.

The placental niche, a stem cell "safe zone," supports blood stem cell generation and expansion without promoting differentiation into mature blood cells, allowing the establishment of a pool of precursor cells that provide blood cells for later fetal and post-natal life, said study senior author Dr. Hanna Mikkola, an associate professor of molecular cell and developmental biology and a researcher at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Mikkola and her team found that PDGF-B signaling in trophoblasts, specialized cells of the placenta that facilitate embryo implantation and gas and nutrient exchanges between mother and fetus, is vital to maintaining the unique microenvironment needed for the blood precursors. When PDGF-B signaling is halted, the blood precursors differentiate prematurely, creating red blood cells in the placenta, Mikkola said.

The study, done in mouse models, appears March 1, 2012, in the peer-reviewed journal Developmental Cell.

"We had previously discovered that the placenta provides a home for a large supply of blood stem cells that are maintained in an undifferentiated state. We now found that, by switching off one signaling pathway, the blood precursors in the placenta start to differentiate into red blood cells," Mikkola said. "We learned that the trophoblasts act as powerful signaling centers that govern the niche safe zone."

The study found that the PDGF-B signaling in the trophoblasts is suppressing production of Erythropoietin (EPO), a cytokine that controls red blood cell differentiation.

"When PDGF-B signaling is lost, excessive amounts of EPO are produced in the placenta, which triggers differentiation of red blood cells in the placental vasculature," said Akanksha Chhabra, study first author and a post-doctoral fellow in Mikkola's lab.

Mikkola and Chhabra used mouse models in which the placental structure was disrupted so they could observe what cells and signaling pathways were important components of the niche.

Read more:
UCLA scientists identify crucial cell and signaling pathway in placental blood stem cell niche

ScienceDaily (Mar. 1, 2012) UCLA stem cell researchers have discovered a critical placental niche cell and signaling pathway that prevent blood precursors from premature differentiation in the placenta, a process necessary for ensuring proper blood supply for an individual's lifetime.

The placental niche, a stem cell "safe zone," supports blood stem cell generation and expansion without promoting differentiation into mature blood cells, allowing the establishment of a pool of precursor cells that provide blood cells for later fetal and post-natal life, said study senior author Dr. Hanna Mikkola, an associate professor of molecular cell and developmental biology and a researcher at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Mikkola and her team found that PDGF-B signaling in trophoblasts, specialized cells of the placenta that facilitate embryo implantation and gas and nutrient exchanges between mother and fetus, is vital to maintaining the unique microenvironment needed for the blood precursors. When PDGF-B signaling is halted, the blood precursors differentiate prematurely, creating red blood cells in the placenta, Mikkola said.

The study, done in mouse models, appears March 1, 2012, in the peer-reviewed journal Developmental Cell.

"We had previously discovered that the placenta provides a home for a large supply of blood stem cells that are maintained in an undifferentiated state. We now found that, by switching off one signaling pathway, the blood precursors in the placenta start to differentiate into red blood cells," Mikkola said. "We learned that the trophoblasts act as powerful signaling centers that govern the niche safe zone."

The study found that the PDGF-B signaling in the trophoblasts is suppressing production of Erythropoietin (EPO), a cytokine that controls red blood cell differentiation.

"When PDGF-B signaling is lost, excessive amounts of EPO are produced in the placenta, which triggers differentiation of red blood cells in the placental vasculature," said Akanksha Chhabra, study first author and a post-doctoral fellow in Mikkola's lab.

Mikkola and Chhabra used mouse models in which the placental structure was disrupted so they could observe what cells and signaling pathways were important components of the niche.

"The idea was, if we mess up the home where the blood stem cells live, how do these cells respond to the altered environment," Chhabra said. "We found that it was important to suppress EPO where blood stem cell expansion is desired and to restrict its expression to areas where red blood cell differentiation should occur."

The finding, Chhabra said, was exciting in that one single molecular change "was enough to change the function of an important blood stem cell niche."

See more here:
Cell and signaling pathway that regulates the placental blood stem cell niche identified

MARLBOROUGH, Mass.--(BUSINESS WIRE)--

Advanced Cell Technology, Inc. (ACT, OTCBB: ACTC), a leader in the field of regenerative medicine, today announced year-end results for the year ended December 31, 2011. The Company utilized $13.6 million in cash for operations during the year, compared to $8.8 million in the year-earlier period. The increase in cash utilization resulted primarily from ACTs ongoing clinical activities in the US and Europe. ACT ended the year with cash and cash equivalents of $13.1 million, compared to $15.9 million in cash and cash equivalents in the year-earlier period.

Some of the 2011 highlights included:

2011 was a very important and successful year for ACT as we began our Phase 1/2 trials for the treatment of macular degeneration, said Gary Rabin, chairman and CEO of ACT. We are very excited about the preliminary Phase 1/2 clinical data from our dry-AMD and Stargardts disease trials, which were published in The Lancet earlier this year. The data demonstrated the safety of ACTs human embryonic stem cell (hESC)-derived retinal pigment epithelium (RPE) cells for the treatment of both diseases. The vision of both patients appears to have improved after transplantation, and no adverse safety issues have been observed. We look forward to validating these early findings as we expand these clinical activities throughout this year. Additionally, we made significant progress in advancing our scientific platform, expanding our board of directors and management team and strengthening our balance sheet.

The Company also announced today that it expects to shortly file a preliminary proxy statement with the Securities and Exchange Commission in which it will seek shareholder approval for a reverse split of between 1-for 20 and 1-for 80 shares. The Company is pursuing the reverse split for the sole purpose of meeting the requirements necessary for a listing on the Nasdaq Global Market. The Company believes that a listing on a national change will allow it to expand its shareholder base and improve the marketability of its common stock by attracting a broader range of investors.

Conference Call

The Company will hold a conference call at 9:00 a.m. EST tomorrow, during which it will discuss 2011 results and provide an update on clinical activities. Interested parties should dial (888)264-3177 followed by the reference conference ID number: 57426004. The call will be available live and for replay by webcast at: http://us.meeting-stream.com/advancedcelltechnology030212

About Advanced Cell Technology, Inc.

Advanced Cell Technology, Inc., is a biotechnology company applying cellular technology in the field of regenerative medicine. For more information, visitwww.advancedcell.com.

Forward-Looking Statements

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Advanced Cell Technology Announces 2011 Financial Results

SEATTLE, Feb. 29, 2012 /PRNewswire/ -- Omeros Corporation (NASDAQ: OMER - News) today announced that it has identified compounds that functionally interact with each of the following six orphan G protein-coupled receptors (GPCRs): GPR17, GPR153, CCRL2, LGR4, LGR6 and OPN5. Without compounds that functionally interact with orphan GPCRs, developing drugs targeting those receptors is extremely difficult. Omeros has now unlocked 33 of them, representing over 40 percent of the Class A orphan GPCRs. There are approximately 120 orphan GPCRs and Omeros expects to unlock a large percentage of them, focusing first on Class A orphan GPCRs.

GPR17 is a novel target tied to multiple sclerosis. GPR153 is associated with schizophrenia, and CCRL2 is connected to immunological disorders, such as rheumatoid arthritis. LGR4 is linked to cancer stem cells and the self-renewal and maintenance of adult stem cells. LGR4 is also tied to bone disorders, such as osteoporosis. LGR6 is expressed in the hair follicle stem cells and is involved in long-term wound repair, including the formation of new hair follicles. OPN5 is a recently discovered photoreceptor for ultraviolet light, but its physiological role is currently unknown. Omeros is in the process of filing broad patent applications around its unlocked orphan GPCRs and compound optimization efforts are in progress.

"We continue to advance rapidly through the Class A orphans and, by the end of 2012, we plan to have screened them all using our proprietary Cellular Redistribution Assay," said Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros. "For each of these receptors, the compounds uniquely identified by Omeros represent keys to drug development, and we believe that Omeros exclusively controls those keys. In parallel with our successful screening efforts, we are building our patent position for each of our unlocked orphans with the goal of protecting and capitalizing on our discoveries."

Ongoing GPCR Program

Omeros is screening orphan GPCRs against its small-molecule chemical libraries using its proprietary, high-throughput cellular redistribution assay (CRA). The CRA detects receptor antagonists, agonists and inverse agonists. Omeros has announced that it has identified and confirmed sets of compounds that interact selectively with 33 orphan receptors linked to metastatic melanoma (GPR19), esophageal squamous cell carcinoma and obesity-related type-2 diabetes (GPR39), hepatocellular carcinoma (GPR80), squamous cell carcinoma (GPR87), pancreatic cancer (GPR182), acute lymphoblastic leukemia (P2Y8/P2RY8), ovarian and prostate cancer (OGR1), arterial stiffness (GPR25), sleep disorders (OPN4), cognitive disorders (GPR12), torpor or "suspended animation" (GPR50), anxiety disorders (GPR31), schizophrenia (GPR52, GPR153), bipolar disorder and schizophrenia (GPR78), psychotic and metabolic disorders (GPR27, GPR85, GPR173), cognitive impairments (MAS1), inflammatory responses (GPR32), obesity and diabetes (GPR21), appetite control (GPR101), immunological disorders (CCRL2), rheumatoid arthritis and HIV-mediated enteropathy (GPR15), respiratory and immune disorders (GPR141), multiple sclerosis (GPR17), motor control (GPR139), congenital cataracts and birth defects of the brain and spinal cord (GPR161), cancer stem cells and the self-renewal and maintenance of adult stem cells (LGR4) and long-term wound repair, including the formation of new hair follicles (LGR6). In addition, Omeros has unlocked GPR20, GPR135 and OPN5, which have not yet been tied to any indications but are expressed preferentially in the gastrointestinal tract (GPR20), brain (GPR135) and eye, brain, testes and spinal cord (OPN5).

About G Protein-Coupled Receptors

GPCRs, which mediate key physiological processes in the body, are one of the most valuable families of drug targets. According to Insight Pharma Reports, GPCR-targeting drugs represent 30 to 40 percent of marketed pharmaceuticals. Examples include Claritin (allergy), Zantac (ulcers and reflux), OxyContin (pain), Lopressor (high blood pressure), Imitrex (migraine headache), Reglan (nausea) and Abilify (schizophrenia, bipolar disease and depression) as well as all other antihistamines, opioids, alpha and beta blockers, serotonergics and dopaminergics.

The industry focuses its GPCR drug discovery efforts mostly on non-sensory GPCRs. Of the 363 total non-sensory GPCRs, approximately 240 have known ligands (molecules that bind the receptors) with nearly half of those targeted either by marketed drugs (46 GPCRs) or by drugs in development (about 70 GPCRs). There are approximately 120 GPCRs with no known ligands, which are termed "orphan GPCRs." Without a known ligand, drug development for a given receptor is extremely difficult.

Omeros uses its proprietary high-throughput CRA to identify small-molecule agonists and antagonists for orphan GPCRs, unlocking them to drug development. Omeros believes that it is the first to possess the capability to unlock orphan GPCRs in high-throughput, and that currently there is no other comparable technology. Unlocking these receptors could lead to the development of drugs that act at these new targets. There is a broad range of indications linked to orphan GPCRs including cardiovascular disease, asthma, diabetes, pain, obesity, Alzheimer's disease, Parkinson's disease, multiple sclerosis, schizophrenia, learning and cognitive disorders, autism, osteoporosis, osteoarthritis and several forms of cancer.

About Omeros Corporation

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Adding Six More, Omeros Now Has a Total of 33 Unlocked Orphan GPCRs in its Portfolio

London, Feb 29 (IANS) Children shot with their own stem cells, for the very first time in a rare immune disorder, have shown improvement.

The condition, known as X-CGD, is caused by faulty genes. Doctors were able to take a sample of the children's stem cells, manipulate them in the lab and reintroduce them. This gave the children a working copy of the faulty gene and their condition improved, enabling them to temporarily fight off infections.

It is the third immune disorder that doctors at Great Ormond Street Hospital have successfully tackled. The others were the life-threatening conditions, X-SCID and ada-SCID, and 90 percent of treated children have improved, with some showing signs that their immune system has been normalised for good.

Remy Helbawi, 16, from South London, was the first child with X-CGD to be treated. The condition only affects boys and means that while his body produces the white blood cells to fight viruses it does not have the correct cells to fight off bacterial or fungal infections, The Telegraph reports.

The resulting infections can be life-threatening. Up until now the only treatment has been a bone marrow transplant which would offer a permanent cure.

Remy's brother who also had the disease was found a bone marrow match and was successfully treated that way but no match has been found for Remy and a serious lung infection was threatening his life.

Remy said: "Until I was 10 I had the same life as anyone else, except I had eczema a lot of the time. I didn't have a fungal infection until about ten, but when I got my first fungal infection my life changed. I missed a lot of school, I had lots of tests and was in hospital. I would get exhausted after climbing stairs."

Before undergoing the gene therapy, Remy had to have chemotherapy which made his hair fall out and he was kept in isolation for a month.

Remy's nurse Helen Braggins said: "Remy had been unwell for last two years and began to miss school. He had significant fungal lung disease in January of last year, which was getting worse. Without some radical treatment intervention, Remy would not have survived and was becoming increasingly short of breath."

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Children improve in rare disorder with own stem cells

Scientists are growing living brain cells from skin samples which could help research into treatments for schizophrenia and bipolar disorder.

Scientists at the University of Edinburgh are growing the cells from skin samples taken from families known to carry faulty genes, which are believed to cause mental illness.

The project, which has received 1 million in funding from the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), aims to develop brain stem cells that could be used to test and screen drugs.

Scientists said it is not easy to understand the diseases using animal models and it is difficult to predict if possible new treatments will work.

They hope using cell-based systems derived from the skin or hair of affected patients will enable researchers to create tests that are more relevant to the disease in humans, and will reduce the dependence on animal models.

Andrew McIntosh, professor of biological psychiatry, said: "We are making different types of brain cells out of skin samples from people with bipolar disorder and schizophrenia.

"Once we have grown these in the laboratory we can then study the cells' neurological function and see how they respond to standard psychiatric treatments. Following this, we hope to be able to screen new medicines."

In the past, researchers used brain tissue from people with schizophrenia and bipolar depression from deceased donors to gain insight into these brain conditions. Scientists said that access to the living brain cells is an exciting development in studying mental illness.

The university said that between 1% and 4% of the world's population is diagnosed with bipolar disorder or schizophrenia, for which there are few highly effective treatments. Little is known about the causes of these conditions but a genetic component is involved as it can run in families.

Well over a million people in the UK are said to be affected by these conditions.

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Living brain cells used in research