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Trounson Talks Stem Cells in Qatar

By Dr. Matthew Watson


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.

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California Stem Cell Agency Waiting Until April for More Cash

By Dr. Matthew Watson


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.

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Planarian genes that control stem cell biology identified

By Dr. Matthew Watson

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.

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

By Dr. Matthew Watson

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.

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Baxter Initiates Phase III Adult Stem Cell Clinical Trial for Chronic Cardiac Condition

By Dr. Matthew Watson

Study Aims to Deliver Adult’s Own Cells As Treatment for Chronic Myocardial Ischemia

DEERFIELD, Ill.--(BUSINESS WIRE)--Baxter International Inc. (NYSE:BAX) announced today that it has initiated a phase III pivotal clinical trial to evaluate the efficacy and safety of adult autologous (an individual’s own) CD34+ stem cells to increase exercise capacity in patients with chronic myocardial ischemia (CMI).

Chronic myocardial ischemia (CMI) is one of the most severe forms of coronary artery disease, causing significant long-term damage to the heart muscle and disability to the patient. It is often diagnosed based on symptoms of severe, refractory angina, which is severe chest discomfort that does not respond to conventional medical management or surgical interventions.

“The prospect of using a person’s own adult stem cells to restore and repair blood flow in CMI is a very exciting concept based on a biological regenerative approach,” said Norbert Riedel, Ph.D., Baxter’s chief science and innovation officer. “The goals of this phase III trial are aligned with Baxter’s overall mission to develop life-saving and life-sustaining therapies and it will help us determine if the therapy can make a meaningful difference for CMI patients.”

The trial will enroll approximately 450 patients across 50 clinical sites in the United States, who will be randomized to one of three arms: treatment with their own autologous CD34+ stem cells, treatment with placebo (control), or unblinded standard of care. The primary objective is to evaluate the efficacy of treatment with CD34+ stem cells to improve the functional capacity of patients with CMI, as measured by a change in total exercise capacity at 12 months following treatment. Secondary objectives include reduced frequency of angina episodes at 12 months after treatment and the safety of targeted delivery of the cells.

After stem cell mobilization, apheresis (collecting the cells from the body) and cell processing, participants will receive CD34+ stem cells or placebo in a single treatment via 10 intramyocardial injections into targeted areas of the heart tissue. Efficacy will be measured by a change in total exercise capacity during the first year following treatment and safety data will be collected for two years. Stem cell processing will be conducted in GMP facilities in the United States by Progenitor Cell Therapy (PCT), a subsidiary of NeoStem, Inc. To learn more or enroll, visit http://www.renewstudy.com or http://www.clinicaltrials.gov.

This trial is being initiated based on the phase II data, which indicated that injections of patients’ own CD34+ stem cells may improve exercise capacity and reduce reports of angina episodes in patients with chronic, severe refractory angina.

“The phase II trial provided evidence that this strategy, leveraging the body’s own natural repair mechanisms, can improve exercise capacity and reduce chest pain, the first time these endpoints have been achieved in a population of patients who have exhausted conventional treatment options,” said Douglas Losordo, MD, vice president of new therapeutic development at Baxter.

CD34+ cells, which are blood-forming stem cells derived from bone marrow, are comprised of endothelial progenitor cells (EPCs), which develop into new blood vessels. Previous preclinical studies investigating these cells have shown an increase in capillary density and improved cardiac function in models of myocardial ischemia.

About Baxter

Baxter International Inc., through its subsidiaries, develops, manufactures and markets products that save and sustain the lives of people with hemophilia, immune disorders, infectious diseases, kidney disease, trauma, and other chronic and acute medical conditions. As a global, diversified healthcare company, Baxter applies a unique combination of expertise in medical devices, pharmaceuticals and biotechnology to create products that advance patient care worldwide.

This release includes forward-looking statements concerning the use of adult autologous stem cells to treat CMI, including expectations with respect to the related phase III clinical trial. These statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: clinical results demonstrating the safety and effectiveness of the use of autologous stem cells to treat CMI; timely submission of regulatory filings; satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; the enrollment of a sufficient number of qualified participants in the phase III clinical trial; the successful provision of stem cell processing by PCT, a third party; and other risks identified in Baxter’s most recent filing on Form 10-K and other SEC filings, all of which are available on Baxter’s website. Baxter does not undertake to update its forward-looking statements.

Photos/Multimedia Gallery Available: http://www.businesswire.com/cgi-bin/mmg.cgi?eid=50183372&lang=en

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Baxter Begins Phase III Adult Stem Cell Trial For Chronic Cardiac Condition

By Dr. Matthew Watson

(RTTNews.com) - Baxter International Inc. (BAX) said it has initiated a phase III pivotal clinical trial to evaluate the efficacy and safety of adult autologous CD34+ stem cells to increase exercise capacity in patients with chronic myocardial ischemia.

Chronic myocardial ischemia is one of the most severe forms of coronary artery disease, causing significant long-term damage to the heart muscle and disability to the patient.

The company said that the trial will enroll approximately 450 patients across 50 clinical sites in the United States, who will be randomized to one of three arms, namely treatment with their own autologous CD34+ stem cells, treatment with placebo (control), or unblinded standard of care. The primary objective is to evaluate the efficacy of treatment with CD34+ stem cells to improve the functional capacity of patients with chronic myocardial ischemia, as measured by a change in total exercise capacity at 12 months following treatment.

Efficacy will be measured by a change in total exercise capacity during the first year following treatment and safety data will be collected for two years.

The company noted that the trial is being initiated based on the phase II data, which indicated that injections of patients' own CD34+ stem cells may improve exercise capacity and reduce reports of angina episodes in patients with chronic, severe refractory angina.

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Nitkowski hoping stem cells lead to comeback

By Dr. Matthew Watson

Left-hander C.J. Nitkowski appeared in 336 games, mostly in a relief role, over parts of 10 seasons. (AP)

The last known whereabouts of C.J. Nitkowski, in regard to his Major League career, was Washington, some seven years ago. It's entirely possible -- maybe even probable -- that this career is 100 percent over and out.

Yet there was Nitkowski on a field in the Dominican Republic last month, working in setup situations for Gigantes del Cibao in the middle of the Dominican Winter League's round-robin playoffs. Hoping, perhaps against hope, that some scout would take note of his new sidearm delivery and effectiveness against lefties and upper-80s gun readings and determine that he's worth another look. Hoping, basically, for one more chance -- a chance, he believes, that would have been completely out of the question if not for the blood-and-stem-cell treatments he received last summer. "From a medical standpoint," Nitkowski says, "[the treatments have] been a success. I'm healthy." But the route he took to get to this point is, in many ways, misunderstood. Nitkowski received treatment identical to the one that picked Bartolo Colon's ailing arm and career off the scrap heap and made him a prominent member of the Yankees rotation last season. It's a treatment that, in Colon's case, caused a bit of an uproar in the headlines last summer, as such labels as "disputed" and "controversial" were used to describe it. In reality, though, the use of one's own stem cells to promote healing in an injured area is far from a new development. In fact, the microfracture procedure that is becoming more and more common in the treatment of knee injuries (it was performed on Victor Martinez last month) is, at its core, a stem-cell procedure. In microfracture, tiny holes are drilled in the bone to allow marrow to drip out and repair damaged tissue -- the mesenchymal stem cells inside the marrow provide the repairing power. In the cases of Nitkowski and Colon, the mesenchymal stem cells were extracted from bone marrow and from body fat and then injected into a blood-poor area -- Nitkowski's left shoulder and Colon's right shoulder and elbow -- to promote healing. Now, is this really a reliable way to treat an ailing athlete? That's a subject of scrutiny. Embryonic stem cells are the cause of controversy all their own, given the ethical and political debates over their use and concern by some members of the medical community that they have the potential to become cancerous tumors. With mesenchymal stem cells, on the other hand, the debate is not over morals or safety but, rather, efficacy. "There's very little evidence that bone marrow stem cells taken from one site and injected into another will do anything," Theodore Friedmann, a geneticist at the University of California at San Diego who heads the World Anti-Doping Agency's (WADA) gene doping panel, told ESPN The Magazine recently. "The most likely outcome is that if you put stem cells in places that are unfamiliar to them, like a knee or shoulder, most of them will just die." WADA initially banned all blood-spinning therapies before reversing its position in 2011 after studies failed to demonstrate that they enhance performance the way steroids do. So WADA currently has no position on the use of stem-cell treatments. In the face of skepticism, you have the case of Colon, who in the spring of 2010 was unsigned, unable to get any of his old velocity on his fastball and seemingly at the end of a once-dazzling career. Dr. James Purita, founder of the Institute of Regenerative and Molecular Orthopedics in Boca Raton, Fla., traveled to the Dominican Republic to perform platelet-rich plasma (PRP) and stem-cell treatments to help repair ligament damage in Colon's elbow and aid a torn rotator cuff. "There was a stigma that it was illegal, because we did it in the Dominican," Purita said. "But it was just because he lived there." And there was another stigma. Because Colon not only returned to the Majors but thrived in the first half of the 2011 season, some wondered if the procedure could be labeled a performance-enhancer. When Colon's story became public, Purita was questioned by Major League Baseball officials to ensure that he did not use human growth hormone in the procedure. Purita has admitted using HGH when treating non-athletes but said he knows better than to do so in these cases. MLB did a complete investigation, and no further action was taken. "We're not reinventing the wheel here," Purita said. "We've done a number of these procedures on people from all the major sports, with the exception of hockey. We've done some of the top players. But we keep it very discreet." The reason for the discretion, beyond the obvious HIPAA standards, is that some teams are leery of or reluctant to trust these stem-cell treatments. Purita said that he performed the procedure this winter on a Major League free agent who expressed an explicit desire that word not get out, because he didn't want it to affect his contract negotiations. However, the case of Colon, who signed a one-year, $2 million contract with the A's this winter, makes one wonder if biologic stem cells could be the next medical revolution, following arthroscopy and the ulnar collateral ligament replacement known as Tommy John surgery. Nitkowski, for one, hopes to find out. A member of eight Major League teams over parts of 10 seasons from 1995-2005, the left-handed Nitkowski appeared in 336 games, mostly in a relief role. In 2006 he began a five-year stint pitching for various teams in Asia -- first in the Japanese Pacific League, then in the Korean Baseball Organization. A year ago, hoping for another shot in the bigs, he began working on a sidearm delivery, only to injure his shoulder. It was around that time that Nitkowski heard about Colon. Intrigued, he made a call to Purita's office, and, within weeks he was in Boca Raton to undergo the procedure himself. Purita first drew fat from Nitkowski's waist, then drew bone marrow from the left side of Nitkowski's lower back. The liquids were spun in a centrifuge at 2,000 rotations per minute for about 15 minutes, isolating the platelets. They were then inserted into syringes and placed under an LED light for about 20 minutes -- a process that supposedly "kick starts" the cells inside. Once this process was complete, Purita injected the platelet-rich plasma and stem cells into Nitkowski's labrum and rotator cuff. This is an important distinction. Under U.S. Food and Drug Administration guidelines, mesenchymal stem cells must be "minimally manipulated," meaning they can't be harvested in a lab for days or weeks or transported elsewhere. "Everything," Purita said, "has to be used the same day, on the same patient, and everything has to be done at the point of care." In Nitkowski's case, the whole process took about four hours. Much to his amazement, he had full range of motion within 24 hours. "The rehab starts right away," he said. "You have to commit to it, like any injury. I never thought I had the mindset to do the tedious rehab work. But if you want it bad enough, you'll do it." Nitkowski's stem-cell treatment was performed in July of last year. And per the usual protocol in Purita's treatment plan, Nitkowski had a second PRP treatment four weeks later. By November he was throwing off a mound, and he was pleased with how his arm felt and how his sidearm-delivered stuff worked in the Dominican Republic last month. "I was sitting at 86, 87 [mph] and hitting 88-89," he said. "That's more than enough [velocity] from that arm angle." Though he hasn't pitched in the bigs in seven years, Nitkowski believes he could help a team, and he's hoping someone will give him a tryout in Spring Training. "I at least want to get in front of people and be told no," he said. "I can live with that. I would love the opportunity. This is either going to happen fast, or it's not going to happen at all." Nitkowski's about to turn 39. But he's left-handed, and he's healthy. And he firmly believes the latter would not have been possible without the treatment he received. "My arm feels really good," he said. "Every pitcher has little tears. It just comes with the territory. But this seems like it could be a good maintenance plan." There are skeptics, and there are critics. Nitkowski knows how some people feel when they hear about stem-cell treatments or about Alex Rodriguez flying to Germany for blood-spinning therapy to address his chronic knee and shoulder problems. They wonder if that precious line between therapy and enhancement is being straddled too closely. Having experienced it for himself, Nitkowski is a believer in the safety, the purity and the benefits of the treatment he had performed on his arm. And he thinks many other athletes will follow. "This," he said, "is going to be mainstream sooner rather than later."

Anthony Castrovince is a reporter for MLB.com. Read his columns and his blog, CastroTurf, and follow him on Twitter at @Castrovince. This story was not subject to the approval of Major League Baseball or its clubs.

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Eggs made from stem cells could treat more than just fertility

By Dr. Matthew Watson

In a new study, Harvard researchers say they have found stem cells in women that can be used to grow new eggs. Not surprisingly, this has raised much discussion about whether a woman’s biological clock can be stopped – why worry about running out of eggs if you can just make new ones whenever you  need them?

The work described in the paper, published online Sunday by the journal Nature Medicine, is still a long way from being useful to women in need of fertility treatments. And many scientists remain skeptical that these ovarian stem cells really can mature into healthy eggs.

But as long as we’re in the pie-in-the-sky realm, let’s consider another way that the ability to grow an abundant supply of eggs would be helpful: to make human embryonic stem cell lines that would be perfectly matched to patients.

This was a hot area of research in the middle of the last decade. While many scientists studied stem cells made from embryos that were no longer needed for fertility treatments, a smaller group was pursuing a derivation method called somatic cell nuclear transfer, or SCNT. It’s better known as “therapeutic cloning.”

Here’s the idea: You take an egg and remove all the DNA in the cell nucleus. Then you replace it with DNA from a patient. You give the egg an electric shock so it starts dividing and growing into an early-stage embryo.

But instead of implanting this embryo into a uterus and producing a baby that’s a genetic copy of another person, you would use it to make a line of human embryonic stem cells. Then you can use those stem cells to make replacement parts – new cardiac cells for patients who suffered heart attacks, for instance, or nerve cells that would replace those lost after a spinal cord injury. In theory, the new cells would work perfectly because they’d be a perfect genetic match. This is the vision of regenerative medicine.

For a few months back in 2005, it looked like this vision was on the verge of reality. South Korean researcher Hwang Woo Suk published a landmark paper in the journal Science in which he claimed to have made 11 lines of stem cells that were genetic matches to patients with Type 1 diabetes, spinal cord injuries and the so-called Bubble Boy disease. Scientists rejoiced, as did doctors and patients. But a few months later, Hwang was accused of faking the results. The study was retracted, and Hwang was prosecuted for embezzling research money and violating ethics laws.

Since then, researchers at Oregon Health & Sciences University have managed to clone monkey embryos in order to create embryonic stem cells. But in a 2007 study in the journal Nature, they said they had to use 304 eggs to make just two viable cell lines.

It’s hard to imagine how scientists would ever get their hands on 304 human eggs, especially since they generally aren’t allowed to pay women who might be willing to donate eggs for research purposes. It’s also not clear that a few hundred eggs would be enough to guarantee at least one line of stem cells. South Korean investigators eventually discovered that Hwang used 2,236 eggs in his studies that failed to produce a single embryo.

This is one of the major reasons why SCNT studies fell by the wayside. (For more on that, read this story from 2006.) But if there were a relatively simple way to grow hundreds – or thousands – of eggs in the lab, some scientists are confident they could create stem cells through therapeutic cloning.

If so, that would make the research at Harvard relevant to a whole lot of people besides women who hear their biological clocks ticking.

A summary of the Nature Medicine study is online here.

Return to the Booster Shots blog.

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Bad breath used as stem cell tool

By Dr. Matthew Watson

27 February 2012 Last updated at 00:06 ET

Hydrogen sulphide, the gas famed for generating the stench in stink bombs, flatulence and bad breath, has been harnessed by stem cell researchers in Japan.

Their study, in the Journal of Breath Research, investigated using it to help convert stem cells from human teeth into liver cells.

The scientists claimed the gas increased the purity of the stem cells.

Small amounts of hydrogen sulphide are made by the body.

It is also produced by bacteria and is toxic in large quantities.

Therapy

A group in China has already reported using the gas to enhance the survival of mesenchymal stem cells taken from the bone marrow of rats.

Researchers at the Nippon Dental University were investigating stem cells from dental pulp - the bit in the middle of the tooth.

They said using the gas increased the proportion of stem cells which were converted to liver cells when used alongside other chemicals. The idea is that liver cells produced from stem cells could be used to repair the organ if it was damaged.

Dr Ken Yaegaki, from Nippon Dental University in Japan, said: "High purity means there are less 'wrong cells' that are being differentiated to other tissues, or remaining as stem cells."

One of the concerns with dental pulp as a source of stem cells is the number that can be harvested.

However, the study did not say how many cells were actually produced.

Prof Chris Mason, a specialist in regenerative medicine at University College London, said: "It would be interesting to see how hydrogen sulphide works with other cells types."

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Human ovarian stem cells may hold promise for treating infertility: study

By Dr. Matthew Watson

In research that could have far-reaching implications for female fertility, U.S. scientists have isolated stem cells from human ovarian tissue that give rise to what appear to be normal egg cells.

The finding, published Sunday in the journal Nature Medicine, builds on earlier landmark papers by the Boston researchers, which suggest that female mammals continue producing egg cells, known as oocytes, into adulthood.

Since 2004, the scientists at Massachusetts General Hospital have produced a series of papers based on work in laboratory mice, which challenge the long-held belief that female mammals are born with a finite number of eggs that run out at a certain point in the life cycle.

The team was able to isolate stem cells from ovarian tissue taken from mice, from which they grew fully functional egg cells in the lab, which could then be fertilized and even produce healthy offspring.

"The primary objective of the current study was to prove that oocyte-producing stem cells do, in fact, exist in the ovaries of women during reproductive life, which we feel this study demonstrates very clearly," said lead author Jonathan Tilly, director of the Vincent Center for Reproductive Biology at Massachusetts General.

In their experiments, the team isolated the stem cells from ovarian tissue that had been removed from women in their 20s and early 30s.

When put in culture dishes in the lab, these stem cells gave rise to cells with the characteristic features of oocytes, including the physical appearance and gene expression patterns of those seen inside human ovaries.

"They spontaneously generate eggs in the dish," Tilly said in a phone interview, noting that they proliferate so well that a small number of stem cells could easily spawn a million egg cells in the lab.

The researchers next took stem cells they had genetically manipulated to glow green and injected them into snippets of human ovarian tissue. These prepared tissue bits were then grafted beneath the skin of specially bred mice, which have no immune system that can cause rejection of human tissue.

Within two weeks, researchers discovered the implanted ovarian tissue in the mice contained numerous immature human follicles with egg cells that originated from the injected stem cells. Follicles are small sacs within the ovary which contain maturing eggs.

Tilly said they knew the eggs cells had arisen from the injected stem cells "because they were all green."

Among the many potential clinical applications the researchers are exploring is whether these stem cells could produce oocytes that could play a role in in-vitro fertilization, as well as other applications to improve the outcomes of IVF and other infertility treatments.

"Can we use these cells for fertility reasons to maximize the opportunity for patients who are experiencing infertility to have different options available to them to have a genetically matched child?" asked Tilly.

"I think it's a fairly good possibility that at some point in the not-too-distant future there will be clinical protocols developed using some aspect of these cells or their properties that will have a significant impact on human reproduction."

Among them is the idea of extracting structures responsible for energy production in cells — called mitochondria — from the stem cells and injecting them into a woman's eggs at the time of in-vitro fertilization, with the hope of boosting the chances of conception and a successful birth.

But Tilly said another idea is to see whether these ovarian stem cells could be used to delay menopause — and the myriad health effects that can develop as women age.

"I've always been intrigued by the prospects of what if you could slow the rate at which the egg cell pool goes away and end up keeping an ovary functioning long past its normal time of failure," he said.

"With these egg stem cells, it raises the prospect that by harnessing the power of those cells, perhaps we can control the rate at which that precious reserve of egg cells is depleted and maybe even delay it ... And if you could achieve that, what would happen? Would we truly see a benefit or would there be unforeseen bad effects?"

More than a decade ago, Tilly's lab created a mouse through genetic manipulation that did not experience ovarian failure with age and was able to maintain an adequate reservoir of eggs.

"So it didn't undergo the equivalent of menopause," he said, or "mouseopause" as the scientists have dubbed it.

While normal mice as they reach old age experience health problems similar to those of postmenopausal women — including declining eyesight and hearing, hair loss, osteoporosis, diminished cognitive function and reduced muscle mass — these genetically modified mice did not. Nor did they have an increased risk of cancer.

So could these stem cells one day be used as the basis for an anti-aging treatment?

"There would be some pretty significant health benefits that would come out of it," said Tilly, if that were the case.

Even though every aspect of the human oocyte-producing stem cells have so far matched what the researchers have found in their mouse equivalents, Tilly conceded that "mouse is mouse — and perhaps human will be different."

"We don't know" if eggs generated from human ovarian stem cells will be normal and healthy, he said. "We will have to be very careful if and when we get to that stage."

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Human ovarian stem cells may hold promise for treating infertility: study

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Report: Stem cells may create new eggs

By Dr. Matthew Watson

WASHINGTON — For 60 years, doctors have believed women were born with all the eggs they’ll ever have. Now Harvard scientists are challenging that dogma, saying they’ve discovered the ovaries of young women harbor very rare stem cells capable of producing new eggs.

If Sunday’s report is confirmed, harnessing those stem cells might one day lead to better treatments for women left infertile because of disease — or simply because they’re getting older.

“Our current views of ovarian aging are incomplete. There’s much more to the story than simply the trickling away of a fixed pool of eggs,” said lead researcher Jonathan Tilly of Harvard’s Massachusetts General Hospital, who has long hunted these cells in a series of controversial studies.

Tilly’s previous work drew fierce skepticism, and independent experts urged caution about the latest findings.

A key next step is to see whether other laboratories can verify the work. If so, then it would take years of additional research to learn how to use the cells, said Teresa Woodruff, fertility preservation chief at Northwestern University’s Feinberg School of Medicine.

Still, even a leading critic said such research may help dispel some of the enduring mystery surrounding how human eggs are born and mature.

“This is going to spark renewed interest, and more than anything else it’s giving us some new directions to work in,” said David Albertini, director of the University of Kansas’ Center for Reproductive Sciences. While he has plenty of questions about the latest work, “I’m less skeptical,” he said.

Scientists have long taught that all female mammals are born with a finite supply of egg cells, called ooctyes, that runs out in middle age. Tilly, Mass General’s reproductive biology director, first challenged that notion in 2004, reporting that the ovaries of adult mice harbor some egg-producing stem cells. Recently, Tilly noted, a lab in China and another in the U.S. also have reported finding those rare cells in mice.

But do they exist in women? Enter the new work, reported Sunday in the journal Nature Medicine.

First, Tilly had to find healthy human ovaries to study. He collaborated with scientists at Japan’s Saitama Medical University, who were freezing ovaries donated for research by healthy 20-somethings who underwent a sex-change operation. Continued...

Tilly also had to address a criticism: How to tell if he was finding true stem cells or just very immature eggs. His team latched onto a protein believed to sit on the surface of only those purported stem cells and fished them out. To track what happened next, the researchers inserted a gene that makes some jellyfish glow green into those cells. If the cells made eggs, those would glow, too.

“Bang, it worked — cells popped right out” of the human tissue, Tilly said.

Researchers watched through a microscope as new eggs grew in a lab dish. Then came the pivotal experiment: They injected the stem cells into pieces of human ovary. They transplanted the human tissue under the skin of mice, to provide it a nourishing blood supply. Within two weeks, they reported telltale green-tinged egg cells forming.

That’s still a long way from showing they’ll mature into usable, quality eggs, Albertini said.

And more work is needed to tell exactly what these cells are, cautioned reproductive biologist Kyle Orwig of the University of Pittsburgh Medical Center, who has watched Tilly’s work with great interest.

But if they’re really competent stem cells, Orwig asked, then why would women undergo menopause? Indeed, something so rare wouldn’t contribute much to a woman’s natural reproductive capacity, added Northwestern’s Woodruff.

Tilly argues that using stem cells to grow eggs in lab dishes might one day help preserve cancer patients’ fertility. Today, Woodruff’s lab and others freeze pieces of girls’ ovaries before they undergo fertility-destroying chemotherapy or radiation. They’re studying how to coax the immature eggs inside to mature so they could be used for in vitro fertilization years later when the girls are grown. If that eventually works, Tilly says stem cells might offer a better egg supply.

Further down the road, he wonders if it also might be possible to recharge an aging woman’s ovaries.

The new research was funded largely by the National Institutes of Health. Tilly co-founded a company, OvaScience Inc., to try to develop the findings into fertility treatments.

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Ovarian Stem Cells Produce Eggs in Method That May Aid Fertility Therapy

By Dr. Matthew Watson

By Ryan Flinn - Mon Feb 27 05:00:01 GMT 2012

Stem cells taken from human ovaries were used to produce early-stage eggs by scientists in Boston who may have created a new method to help infertile women.

Females have a fixed number of eggs from birth that are depleted by the time of menopause. The finding, published today in the journal Nature Medicine, challenges the belief that their ovaries can’t make more. The research was led by Jonathan Tilly, the director of Massachusetts General Hospital’s Vincent Center for Reproductive Biology.

Tilly reported in 2004 that ovarian stem cells in mice create new eggs, or oocytes, in a way similar to how stem cells in male testes produce sperm throughout a man’s life. His latest work, if reproduced, would suggest the same is true for human ovaries, potentially pointing at new ways to aid fertility by delaying when the ovaries stop functioning.

“The 50-year-old belief in our field wasn’t actually based on data proving it was impossible, or not ongoing,” Tilly said in a telephone interview. “It was simply an assumption made because there was no evidence indicating otherwise. We have human cells that can produce new oocytes.”

In the study, healthy ovaries were obtained from consenting patients undergoing sex reassignment surgery. The researchers were able to identify ovarian stem cells because they express a rare protein that’s only seen in reproductive cells.

The stem cells from the ovaries were injected into human ovarian tissue that was then grafted under the skin of mice, which provided the blood supply that enabled growth. Within two weeks, early stage human follicles with oocytes had formed.

7-Million Eggs

A female is most endowed with oocytes, or eggs, as a fetus, when she has about 7 million. That number that drops to 1 million by birth, and around 300,000 by puberty. By menopause, the number is zero. Since the 1950’s, scientists thought that ovarian stem cells capable of producing new eggs are only active during fetal development.

“This paper essentially opens the door to the ability to control oocyte development in human ovaries,” Tilly said.

About 10 percent of women of child-bearing age in the U.S., or 6.1 million, have difficulty getting pregnant or staying pregnant, according to the Centers for Disease Control and Prevention. Most cases of female infertility are caused by problems with ovulation, hormone imbalance or age.

The study by Tilley and his colleagues offers “a new model system for understanding the human egg cell,” said David F. Albertini, director of the Center for Reproductive Services and professor in the department of molecular and integrative physiology at Kansas University, in a telephone interview.

‘Practical Applications”

Still, “there’s a long way to go before this has real practical applications. I’ve spent 35 years of my life studying egg cells and this is a cell that is at least as complicated as a neuron in the brain, if not more,” Albertini said.

The work needs to be reproduced and expanded by other scientists “to make it into something that will make us confident the cells are safe to use and we could actually use them to repopulate an egg-depleted ovary,” he said.

Tilly’s team is exploring the development of an ovarian stem-cell bank that can be cryogenically frozen and thawed without damage, unlike human eggs, he said. The researchers are also working to identify hormones and other growth factors for accelerating production of eggs from human ovarian stem cells and ways to improve in-vitro fertilization.

“The problem we face with IVF is we don’t have many eggs to work with,” he said. “These cells are renewable. If we are successful -- and it’s a big if -- in generating functioning eggs from these cells, we can generate as many eggs as we need to on a per patient basis.”

Tilly is also collaborating with researchers at the University of Edinburgh in the U.K. to determine whether the oocytes can be developed into fully mature human eggs for fertilizing. The U.S bans creating or fertilizing embryos for experimental purposes, he said.

A company Tilly co-founded, Boston-based OvaScience Inc., has licensed the technology for potential commercial applications.

To contact the reporter on this story: Ryan Flinn in San Francisco at rflinn@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

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Ovarian Stem Cells Produce Eggs in Method That May Aid Fertility Therapy

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Regular vitamin and mineral supplementation lowers colon can

By Dr. Matthew Watson

by: John Phillip

Researchers publishing in the Canadian Journal of Physiology and Pharmacology (CJPP) have found that a diet enhanced with vitamin and mineral supplementation can lower the risk of developing precancerous colon cancer lesions by up to 84%. Colon cancer is the second most common form of the disease affecting men and women in the US, with nearly 150,000 new diagnoses each year.

Nutrition experts and alternative practitioners understand that cancer is largely a disease caused by poor lifestyle behaviors including a diet lacking an optimal intake of vitamins and minerals. Chronic illnesses including colon cancer are the result of many years and decades of low nutritional status, as support for a healthy immune response is suppressed. Scientists now provide compelling evidence in support of whole-food based vitamin and mineral supplementation to dramatically lower the risk of colorectal cancer. Read more...

AyurGold for Healthy Blood

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The GMO Debate, Food For Thought Part 1 – KITV Honolulu

By Dr. Matthew Watson


DigitalJournal.com
The GMO Debate, Food For Thought Part 1
KITV Honolulu
Genetic Engineering has entered our food chain in a big way. In 2012, more than half of the crops grown in the United States are GMOs. According to the USDA, 88% of all corn crops, 90% of cotton crops, and 94% of soybean crops are GMO crops.
GMO LabelingManila Bulletin

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My decision on Bt brinjal was not influenced by NGOs: Jairam – Expressindia.com

By Dr. Matthew Watson


Hindu Business Line
My decision on Bt brinjal was not influenced by NGOs: Jairam
Expressindia.com
New Delhi Days after Prime Minister Manmohan Singh spoke of the role of foreign-funded NGOs in instigating protests against genetic engineering in agriculture, Rural Development Minister Jairam Ramesh has asserted that his controversial decision to put ...
Decision on Bt. Brinjal not influenced by NGOs: JairamTwoCircles.net
No NGO pressure in Bt Brinjal moratorium: JairamDaily Bhaskar
Jairam differs with PM, says no NGO forced Bt Brinjal banHindustan Times

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of bio-technology – Coastweek

By Dr. Matthew Watson


Coastweek
of bio-technology
Coastweek
NAIROBI (Xinhua) -- Kenya is among countries in Africa that has made steady progress in adoption and regulation of biotechnology to boost crop production and enhance food sufficiency, an expert said in Nairobi on Wednesday.
Use GMOS to Increase Food, Expert AdvisesAllAfrica.com
Kenyan MPs demand GM crop products urgentlyAfrica Science News Service
'Emulate Brazil, China, not Europe'Truth about Trade & Technology

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Patient Adherence Investments by Pharma Companies Current Scenario

By Dr. Matthew Watson

Source: Data Sneak Peek: Groups Involved in Patient Adherence Teams

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Pharma looks to mobile strategies to effectively reach prescribers | mHIMSS

By Dr. Matthew Watson

Via Scoop.itinPharmatics

Companies on the forward edge are putting a heavy emphasis on digital in their commercial models — but how can mobile technologies assist pharmaceutical and biotech firms in this transition?   Tablets to support the sales force – While sales forces are shrinking, they still play a vital role in educating prescribers on new medications. The pharma industry, taking the lead of companies like GSK, is starting to incent sales reps based on quality of service versus amount of sales (read more here in the WSJ). One of the tools that is helping deliver better service is the tablet. Reps with an iPad can deliver more interactive and engaging product information, capture signatures for compliance and make the most of a few quick minutes with a doctor in the time it would take a laptop to boot up.   Online and mobile drug sampling programs – Companies now have the ability to leverage PDMA-compliant mobile apps and websites that allow physicians to request free product samples that they can distribute to their patients to gauge efficacy and assist with adherence. Because the Internet never sleeps, physicians can do this no matter what shifts they are working, independent of time zone or location, 24 hours a day.   Direct-to-HCP mobile advertising – It used to be that most online and mobile advertisements for drugs were placed only in industry magazines, blogs and online communities geared toward healthcare professionals and general consumer websites. We see this changing, with emergence of mobile networks focused on healthcare such as Tomorrow Networks, which is comprised of more than 50 medical apps. Pharma companies can now buy ad placements in mobile apps made exclusively for physicians and other healthcare professionals. A physician can be looking up treatment information at the point of care and see an ad for a medication that is relevant to their patient’s ailment. That’s incredibly powerful for the physician and advantageous for the advertiser.   mDetails – Physicians want to learn about the best drugs and treatments for their patients. mDetails are multimedia mobile product presentations that provide information about drugs in a way that allows physicians to absorb detailed information at their own pace — and in their own time. Because mDetails are distributed on smartphones – it lets physicians fit pharma product education into ‘found time’ at any point during their day that’s convenient for them.   By employing a multi-channel approach and by helping healthcare professionals do their jobs better instead of just selling to them, pharmaceutical companies can reach their target audiences and develop deeper value-based relationships. The aforementioned examples are just a few of the ways that pharmaceutical companies can leverage the ever-growing mobile channel; there are many more evolving every day.
Via http://www.mhimss.org

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British Government launches Government Cloud Store with 257 Cloud Computing Suppliers

By Dr. Matthew Watson

Via Scoop.itinPharmatics
UK Government launches G-Cloud store with 257 cloud computing suppliers. Offering the public sector around 1,700 cloud computing services for year-long contracts. The G-Cloud initiative, dubbed CloudStore, aims to bring a broader range of cloud computing suppliers to the government market and increase the flexibility in procurement contracts
Via http://www.govstore.net

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IOM’s Lagging Effort for Comments on the $3 Billion California Stem Cell Agency

By Dr. Matthew Watson


With the $700,000 Institute of Medicine inquiry into the performance of the California stem cell agency half complete – at least publicly – the blue-ribbon panel seems to be coming up short on comments from outside of the agency itself.

The major public effort by the IOM to secure comments is the passive posting of forms to be filled out on the IOM web site.

How many responses has the IOM received on those forms? The IOM has not disclosed that information despite two inquiries earlier this month by the California Stem Cell Report.

The prestigious institute is undertaking the study of $3 billion agency under contract with CIRM, which is paying the IOM $700,000. Some CIRM directors have expressed hope that the IOM findings will help build support for another multi-billion dollar state bond measure to renew financing for CIRM. It is scheduled to run out of money for new grants in five years.

So far, the IOM panel has held two public meetings, one in Washington, D.C., and one in the San Francisco area. The final California hearing is scheduled for April 10 in Irvine with the last public meetings scheduled for later this year in Washington.

So far, the panel has heard only from CIRM employees or directors as well as researchers who have received tens of millions of dollars in CIRM grants. The IOM has not heard publicly from a single independent witness.

The IOM has posted on its web site forms seeking comments from the public, grant recipients, beneficiary institutions and businesses. However, passive postings of forms are unlikely to generate more than a relative handful of responses. To produce significant numbers requires aggressive and targeted follow-up.

It is also unclear exactly what the IOM is doing to seek information from biotech businesses and unsuccessful grant applicants. Some businesses have complained publicly about the tiny share of funding that industry has received. And some CIRM directors have expressed concern for several years about the inadequacies of business funding.

On Feb. 12, the California Stem Cell Report queried the IOM about its efforts at outreach, asking for specifics on what is being done. Christine Stencel, a spokeswoman for the IOM, replied,

"The IOM has been obtaining and compiling lists of organizations and people to circulate the questionnaires as widely as possible among target groups. For example, IOM has sent a notice to some 300 stakeholder groups encouraging participation."

Other specifics were not forthcoming. (The full text of the questions and responses can be found here.)

On Feb. 15, the California Stem Cell Report followed up with these additional questions,

"Regarding the 300 stakeholder groups, how are those defined? Please give me a few examples.

"Based on your response, is it correct to say that the IOM is not sending out questionnaires directly to all CIRM grant applicants, including those who were rejected?

"Is it correct to say that no special effort -- other than that described in your response -- is being made to seek responses from stem cell businesses?

"The failure to provide numbers on the responses so far would indicate that the numbers are so small that the IOM is choosing not to disclose them. If that is not the case, please email me the numbers."

As of this writing, the IOM has not responded to those questions. We will carry its response verbatim when we receive it.

Source:
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