Mouse stem cells used to produce eggs, Japanese scientists say

Reaching a long-sought milestone, Japanese researchers have demonstrated in mice that eggs and sperm can be grown from stem cells and combined to produce healthy offspring, pointing the new treatments for infertility.

If the achievement can be repeated in humans and experts said they are optimistic that such efforts will ultimately succeed the technique could make it easier for women in their 30s or 40s to become mothers. It could also help men and women whose reproductive organs have been damaged by cancer treatments or other causes.

About one in 10 American women of childbearing age have trouble becoming or staying pregnant, and more than one-third of infertile couples must contend with a medical problem related to the prospective father, according to the national Centers for Disease Control and Prevention in Atlanta.

Using current technology, only about one-third of attempts at assisted reproduction result in live births, CDC data show. Scientists, doctors and patients would like to boost that percentage.

"These studies provide that next level of evidence that in the future fertility could be managed with stem cell intervention," said Teresa Woodruff, chief of fertility preservation at Northwestern University Feinberg School of Medicine.

The prospect of using stem cells to grow new eggs is particularly tantalizing, since women are born with a set number and don't make more once they are gone. In a sense, the therapy would allow them to turn back their biological clocks, said Stanford stem cell researcher Renee A. Reijo Pera, who studies reproduction.

"This is a get-them-back strategy," she said.

Dr. Mitinori Saitou and colleagues at Kyoto University detailed how they generated the functional mouse eggs in a report published online Thursday by the journal Science. Last year, the researchers reported in the journal Cell that they had done the same thing with mouse sperm.

In both cases, the team started with embryonic stem cells, which have the potential to develop into all of the different types of cells in the body.

The scientists exposed the embryonic stem cells to stimuli that coaxed them to become egg and sperm precursors.

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Mouse stem cells used to produce eggs, Japanese scientists say

Stem cells could lead to future fertility treatments, study says

In a long-sought achievement, Japanese researchers have demonstrated in mice that both eggs and sperm can be grown from stem cells and combined to produce healthy offspring, pointing the way to a new avenue for fertility treatments.

If the milestone accomplishment can be repeated in humans -- and experts said they are optimistic that such efforts will ultimately succeed -- the technique could make it easier for women in their 30s or 40s to become mothers. It could also help men and women whose reproductive organs have been damaged by cancer treatments or other causes.

About 10% of American women of childbearing age have trouble becoming or staying pregnant, and more than one-third of infertile couples must contend with a medical problem related to the prospective father, according to the U.S. Centers for Disease Control and Prevention in Atlanta.

Using current technology, only about one-third of attempts at assisted reproduction result in live births, CDC data show. Scientists, doctors and patients would like to boost that percentage.

"These studies provide that next level of evidence that in the future fertility could be managed with stem cell intervention," said Teresa Woodruff, chief of fertility preservation at Northwestern University's Feinberg School of Medicine.

The prospect of using stem cells to grow new eggs is particularly tantalizing, because women are born with a set amount and don't make more once they are lost. In a sense, the therapy would allow them to turn back their biological clocks, said Stanford stem cell researcher Renee A. Reijo Pera, who studies reproduction.

"This is a get-them-back strategy," she said.

Using stem cells to create sperm and eggs in mice is a feat researchers have attempted, without much success, for more than a decade, said Dr. George Q. Daley, a leading stem cell researcher at Children's Hospital in Boston.

Dr. Mitinori Saitou and colleagues at Kyoto University detailed how they generated the functional mouse eggs in a report published online Thursday by the journal Science. Last year, the researchers reported in the journal Cell that they had done the same thing with mouse sperm.

In both cases, the team started with embryonic stem cells, which have the potential to develop into all of the different types of cells in the body. The scientists exposed the embryonic stem cells to stimuli that coaxed them to become egg and sperm precursors.

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Stem cells could lead to future fertility treatments, study says

Bernard Siegel to Deliver Keynote Addresses at Midwest Conference on Stem Cell Biology and Therapy and BioFlorida …

PALM BEACH, Fla.--(BUSINESS WIRE)--

Genetics Policy Institute (GPI) announced today that Bernard Siegel, Executive Director of GPI, will make two keynote presentations this month at regional conferences: Midwest Conference on Stem Cell Biology and Therapy October 5-7 in Rochester, Michigan and BioFlorida Conference 2012 October 7-9 in Miami, Florida.

Siegel will present a keynote address titled The Power of Advocacy at the Midwest Conference on Stem Cell Biology and Therapy. The Genetics Policy Institute joined with the Oakland University William Beaumont Institute for Stem Cell and Regenerative Medicine (ISCRM) as a collaborating partner for the event. Researchers from hospitals, medical organizations, academic institutions and the business community throughout the Midwest will discuss not only the latest advances in this rapidly expanding field of medical science, but the ethical and moral issues that surround it.

"I am pleased to participate in these important conferences, which showcase the latest scientific developments in their respective regions and beyond. ISCRM and the World Stem Cell Summit have a strong connection, as the Institute was officially launched at our 2010 Summit in Detroit, said Bernard Siegel, GPI's Executive Director and founder of the annual World Stem Cell Summit.

BioFloridas 15th annual Conference is the premier event for Floridas bioscience community. This years meeting will bring together more than 500 professionals from across Florida, the Southeast and the nation to discuss major trends and issues, including topics related to product development, scientific research, business development, financing and public policy.

Siegels keynote address at BioFlorida is titled: The Mandate to Deliver Cures: Aligning Patient Advocacy, Industry and Science. Former Governor Jeb Bush will deliver the second keynote at BioFloridas annual Conference.

The 2012 World Stem Cell Summit is in West Palm Beach, Florida this December, so we have been working closely with the biotechnology community here. I am delighted to partner with BioFlorida as they advance Floridas bioscience industry," said Siegel, who also serves on the Executive Committee of the Alliance for Regenerative Medicine and Board of the Coalition for Advancement of Medical Research. He serves as spokesperson for the Stem Cell Action Coalition.

ABOUT GPI:The Genetics Policy Institute (GPI) supports stem cell research to develop therapeutics and cures. GPI pursues its mission by honoring leadership through the Stem Cell Action Awards, producing the World Stem Cell Summit, publishing theWorld Stem Cell Report, organizing educational initiatives and fostering strategic collaborations. For more information, visitwww.genpol.org.

ABOUT THE WORLD STEM CELL SUMMIT:The 2012 World Stem Cell Summit is presented by GPI and is co-organized by the Interdisciplinary Stem Cell Institute (ISCI) at the University of Miami Miller School of Medicine, Diabetes Research Institute, Beckman Research Institute at City of Hope, Karolinska Institute (home of the Nobel Prize in Physiology and Medicine), International Translational Regenerative Medicine Center (ITRC) and the Institute for Integrated Cell-Material Sciences (iCeMS) at Kyoto University. The Summit is the flagship meeting of the world stem cell community. The 2012 Summit will be held at the Palm Beach County Convention Center in West Palm Beach, Florida, December 3-5, 2012. For more information, visit http://www.worldstemcellsummit.com.

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Bernard Siegel to Deliver Keynote Addresses at Midwest Conference on Stem Cell Biology and Therapy and BioFlorida ...

Baby Mice Born from Eggs Made from Stem Cells

Mouse pups from induced pluripotent stem cell-derived eggs; image courtesy of Katsuhiko Hayashi

Stem cells have been coaxed into creating everything from liver cells to beating heart tissue. Recently, these versatile cells were even used to make fertile mouse sperm, suggesting that stem cell technology might eventually be able to play a role in the treatment of human infertility.

Now two types of stem cells have been turned into viable mouse egg cells that were fertilized and eventually yielded healthy baby mice. Details of this achievement were published online October 4 in Science.

Mouse oocytes; image courtesy of Katsuhiko Hayashi

Katsuhiko Hayashi, of Kyoto Universitys School of Medicine, were able to create the eggs with embryonic stem cells as well as with induced pluripotent stem cells (formed from adult cells).

The team started with female embryonic stem cells and then coaxed them genetically to revert to an earlier developmental stage (primordial germ cell-like cells). These cells were blended with gonadal somatic cells, important in the development of sexual differentiation, to create reconstituted ovaries. The researchers then transplanted these cultured assemblages into female mice (in either the actual ovary or the kidney) for safekeeping and to allow the stem cells to mature into oocytes in a natural environment.

Healthy adult mice from litter produced from induced pluripotent stem cell-based oocytes; image courtesy of Katsuhiko Hayashi

To test the eggs fertility, the new oocytes were removed from the mice for an in vitro fertilization with mouse spermand then re-implanted into the female mice. The experimental females went on to bear normally developing and fertile offspring. The procedure was then also performed successfully with induced pluripotent stem cells from adult skin cells with similar results.

Our system serves as a robust foundation to investigate and further reconstitute female germline development in vitro, the researchers noted in their paper, not only in mice, but also in other mammals, including humans.

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Baby Mice Born from Eggs Made from Stem Cells

Todd Akin’s ‘War on Women’ Started Seven Years Ago

Rep. Todd Akin, R-Mo., ignited a firestorm Aug. 19 when he claimed women who are the victims of "legitimate rape" biologically don't carry a baby to term. Voters in Missouri had a heads-up moment seven years ago when Akin made an ultra-conservative speech on the floor of Congress regarding embryonic stem cell research. Three years later, the representative made odd remarks about abortion doctors.

Akin's so-called "war on women" didn't begin in August. It may have started seven years ago.

What exactly did Akin say on the floor of the House of Representatives?

Slate.com found two videos of the representative speaking before his fellows in Congress. In May 2005, Akin slammed embyronic stem cell research. The representative claimed to be telling a story his daughter wrote about how a child is named "5-25-61-B" instead of a human name. Akin further likened a mother's womb to "climate control" for the "unique information that defines a person."

A second video Slate found on C-SPAN was from January 2008. Akin slammed abortion doctors as people who have a "culture of death" along with "all kinds of other law-breaking: not following good sanitary procedure, giving abortions to women who are not actually pregnant, cheating on taxes misuse of anesthetics so that people die or almost die."

What has been the reaction to these videos?

Dan Amira of New York Magazine found a Chicago Tribune story that seems to corroborate Akin's testimony on abortion doctors . Arnold Bickham had his license revoked for 18 months beginning in 1979 for performing abortions on women "not pregnant and sometimes not fully under anesthesia."

The Slate article notes Akin or his daughter may have read a book entitled "Never Let Me Go ." The novel focuses on children who grow up to be clones designed to be harvested for their organs. The piece, written in 2005, is by Kazuo Ishiguro. Akin's speech denouncing cloning and stem cell research was made the same year "Never Let Me Go" was published.

How do these new revelations change the Missouri Senate race?

Slate published an article Tuesday evening regarding Akin's chances of winning the statewide vote. Despite his comments, voter Dee Eukel supports Akin even though she was the victim of rape. Eukel told the media outlet, "I understand [legitimate rape] because I was a victim. And our local prosecutor told me: We best accept a plea bargain because we can't get a prosecution on rape."

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Todd Akin’s ‘War on Women’ Started Seven Years Ago

Study suggests stem cell transplant survivors at increased risk of developing heart disease

Public release date: 3-Oct-2012 [ | E-mail | Share ]

Contact: Claire Gwayi-Chore cgwayi-chore@hematology.org 202-776-0544 American Society of Hematology

(WASHINGTON, October 3, 2012) New research appearing online today in Blood, the Journal of the American Society of Hematology (ASH), suggests that long-term survivors of hematopoietic cell transplants (HCT) are at an increased risk of developing heart disease risk factors such as high blood pressure, diabetes, and high cholesterol when compared to the general population. These risk factors, combined with exposure to pre-HCT therapy, contribute to a noticeably increased risk of heart disease over time.

HCT, the transplantation of blood-forming stem cells from the bone marrow, circulating blood, or umbilical cord blood, is the primary treatment option for many patients with blood disorders. The healthy transplanted stem cells replace patients' damaged cells that caused their illness. Advances in transplantation strategies have contributed to marked improvements in patient outcomes, resulting in a growing number of long-term transplant survivors, many of whom struggle with one or more chronic, post-transplant health conditions. Previous researchers have speculated that survivors' exposure to potentially heart damaging pre-transplant chemotherapy and radiation or treatment for a life-threatening transplant complication known as graft-versus-host-disease (GVHD) can increase their risk of developing heart disease and its associated risk factors. However, there have been limited data to validate the contribution of pre-conditioning chemotherapy or radiation and GVHD to the eventual development of heart disease in long-term HCT survivors.

"While we know that heart disease is a real concern for long-term HCT survivors, small sample sizes and a lack of long-term follow up in previous studies have only allowed us to look at a small piece of the puzzle of how this chronic condition develops in these patients," said Saro H. Armenian, DO, MPH, the study's first author, Assistant Professor in the Division of Outcomes Research, and Medical Director of the Pediatric Survivorship Clinic in the Childhood Cancer Survivorship Program at City of Hope in Duarte, CA. "Our study sought to better determine the specific factors before and after transplant that can lead to heart disease in a large group of transplant recipients."

In order to more thoroughly evaluate heart disease risk and development in HCT recipients, Dr. Armenian and his team of researchers designed a retrospective study to evaluate factors that may affect a survivor's risk of developing high blood pressure, diabetes, and high cholesterol after HCT. These factors included transplant recipients' exposure to pre-transplant chemotherapy and radiation, conditioning therapy for HCT, their type of HCT transplant, and whether they developed and were treated for GVHD post transplant.

To better determine HCT survivors' incidence of high blood pressure, diabetes, and high cholesterol compared to the general population, researchers analyzed medical records of 1,885 patients who underwent a first-time HCT for a blood cancer at City of Hope between 1995 and 2004 and had survived at least one year. The National Health and Nutrition Examination Survey was used to generate expected heart disease risk factor rates for the general population.

Following their analysis, researchers found a higher prevalence of high blood pressure, diabetes, and high cholesterol in long-term HCT transplant survivors when compared to the general population. HCT conditioning with total body radiation was associated with a 1.5-fold increase in risk of developing diabetes and a 1.4-fold increase in risk of developing high cholesterol, regardless of HCT type, a finding that validates previous reports from long-term childhood and adult HCT survivors. While the mechanism by which total body radiation increases the risk of diabetes and high cholesterol in HCT recipients is not clear, previous studies have shown that abdominal radiation may contribute to known heart disease risk factors such as insulin resistance and an increase in belly fat in conventionally treated cancer patients. This evidence suggests that radiation-induced pancreatic or liver injury may play a role in an HCT transplant survivor's development of heart disease by increasing their risk for heart disease risk factors.

Next, researchers assessed the role of transplant type on long-term HCT survivors' risk of developing key heart disease risk factors. After reviewing the data, researchers observed that those who had received transplanted stem cells from a donor (allogeneic HCT) were at a significantly higher risk of developing high blood pressure, diabetes, or high cholesterol after transplant than those who had received blood-forming stem cells from their own body (autologous HCT). Over the 10-year study period, 45.3 percent of allogeneic HCT recipients developed high blood pressure, 20.9 percent developed diabetes, and 50.5 percent developed high cholesterol; whereas only 32 percent, 15.9 percent, and 43.3 percent of autologous HCT recipients developed these same conditions, respectively. Transplant recipients who had undergone an allogeneic HCT and who had experienced GVHD had the highest risk of developing heart disease risk factors, researchers concluded; 54.7 percent of this group developed high blood pressure, 25.8 percent developed diabetes, and 52.8 percent developed high cholesterol.

Not only did more allogeneic than autologous HCT recipients develop these heart disease risk factors over this time period, but they also developed them more quickly. Allogeneic HCT recipients developed high blood pressure and high cholesterol both at a median time to onset of 2.5 months, compared with autologous HCT recipients who developed the same conditions at 3.7 years and 1.6 years, respectively. Allogeneic HCT recipients also developed diabetes more than two years earlier than autologous recipients (1.2 year median time to onset for allogeneic HCT recipients vs. 3.3 years for autologous transplant recipients).

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Study suggests stem cell transplant survivors at increased risk of developing heart disease

CU Cancer Center opens phase i clinical trial of anti-cancer stem cell agent OMP-54F28

Public release date: 3-Oct-2012 [ | E-mail | Share ]

Contact: Garth Sundem garth.sundem@ucdenver.edu University of Colorado Denver

The University of Colorado Cancer Center, together with other participating academic medical centers, recently opened a phase I human clinical trial of the drug OMP-54F28 in patients with advanced solid tumor cancers. OMP-54F28, a candidate investigational drug discovered by OncoMed Pharmaceuticals, targets cancer stem cells (CSCs), also known as tumor-initiating cells, which many researchers believe are at the root of tumor occurrence and growth. These CSCs are notoriously resistant to existing chemotherapies and so may survive current treatments to repopulate a tumor, leading to relapse and metastasis.

"It's a terrific opportunity to put a drug targeting cancer stem cells in the clinic, especially a drug with as much promise in preclinical studies as this one," says Antonio Jimeno, MD, PhD, investigator at the CU Cancer Center, director of the university's Cancer Stem Cell-Directed Clinical Trials Program, and principal investigator of the clinical trial at the CU Cancer Center site. "It is a privilege to work with such a science-focused partner, whose vision totally aligns with ours: bringing to the clinic cutting-edge drugs and ideas that are supported by robust scientific data. In the context of the collaboration between the Gates Center for Stem Cell Biology and the CU Cancer Center this will be the second clinical trial we will be offering to our patients with the specific intent to target the CSCs in their tumors."

Specifically, OMP-54F28 is an antagonist of the Wnt pathway, a key CSC signaling pathway that regulates the fate of these cells. The Wnt pathway has been intensively studied and is now known to be inappropriately activated in many major tumor types, including colon, breast, liver, lung and pancreatic cancers, and is thought to be critical for the function of CSCs. Because of this extensive preclinical validation, the Wnt pathway has been a major focus of anti-cancer drug discovery efforts. OMP-54F28 and a sister compound also developed by OncoMed, OMP-18R5, are believed to be two of the first therapeutic agents targeting this key pathway to enter clinical testing. Both OMP-54F28 and OMP-18R5 are part of OncoMed's Wnt pathway strategic alliance with Bayer Pharma AG.

In multiple preclinical models, OMP-54F28 has shown its effectiveness in reducing CSC populations, leading to associated anti-tumor activity, either as a single agent or when combined with chemotherapy.

The Phase I clinical trial of OMP-54F28 is an open-label dose escalation study in patients with advanced solid tumors for which there is no remaining standard curative therapy. These patients are assessed for safety, immunogenicity, pharmacokinetics, biomarkers, and initial signals of efficacy. The trial is being conducted at Pinnacle Oncology Hematology in Scottsdale, Arizona, the University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, and the CU Cancer Center under the direction of Principal Investigators Dr. Michael S. Gordon, Dr. David Smith and Dr. Antonio Jimeno, respectively.

"We all hope and expect this drug to live up to its preclinical potential," Jimeno says. "And if it does, we will have a powerful new therapy, exploiting a novel pathway to target this most dangerous subpopulation of cancer cells."

###

About OncoMed Pharmaceuticals

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CU Cancer Center opens phase i clinical trial of anti-cancer stem cell agent OMP-54F28

Sigma® Life Science Launches Novel, Affordable Pluripotent Stem Cell Culture Medium

ST. LOUIS, Oct. 3, 2012 /PRNewswire/ --Sigma-Aldrich Corporation (SIAL) announced today that Sigma Life Science, its innovative biological products and services research business, has launched Stemline Pluripotent Culture Medium, a novel human pluripotent stem cell culture medium that provides a consistent environment for the long-term maintenance and growth of healthy pluripotent stem cells. The new medium performs equivalently to the industry's leading medium and provides academic and pharmaceutical stem cell research labs with a substantially lower cost alternative to higher priced media. Additional information and sample requests of the Stemline Pluripotent Culture Medium are available at http://www.sigma.com/stemlinepsc.

"The exorbitant cost of media for pluripotent stem cells is a universal complaint from the stem cell research community. Our Stemline Pluripotent Culture Medium performs equivalently to the leading medium for maintaining pluripotency and optimal growth rates, and is produced more efficiently than traditional media, resulting in lower costs. For example, a typical academic lab that consumes three 500 mL bottles of media per week could save at least $12,000 annually using our new Stemline medium. A high-throughput pharmaceutical development team that consumes 20 liters of media weekly could save more than $160,000 annually," said John Listello, Market Segment Manager for Regenerative Medicine at Sigma Life Science.

Culturing pluripotent stem cells can be challenging as many media's undefined, heterogenous mixtures can cause inconsistent growth rates and undesired spontaneous differentiation. The Stemline Pluripotent Stem Cell Culture Medium is serum-free, composed of fully-defined components and has 80% less basic fibroblast growth factor than the leading pluripotent stem cell culture medium. This provides a consistent environment for long-term maintenance of optimal growth rates, viability and pluripotency. Rigorous characterization of the Stemline Pluripotent Stem Cell Culture Medium has demonstrated that cultured pluripotent stem cells display all established pluripotency markers and maintain proper karyotype and the ability to differentiate into each of the three germ layers. The feeder-independent medium also enables culturing with synthetic matricies, thereby eliminating a source of variability that would prohibit later clinical applications.

"Academic and pharmaceutical groups performing toxicology screens, disease-specific stem cell research or studies of the basic mechanisms behind pluripotency and differentiation depend upon a steady supply of consistent, high-performance cell culture medium. This novel Stemline medium extends Sigma's existing position as one of the largest global providers of cell culture media," said Listello.

Existing Stemline stem cell culture media include specialized formulations for expansion of six human adult stem cell and progenitor cell types: hematopoietic, neural, dendritic, mesenchymal, T-cells, and keratinocytes. These six Stemline media are produced under good manufacturing practices (GMP) and have Device Master File certificates from the U.S. Food and Drug Administration.

Sigma Life Science's comprehensive stem cell product portfolio includes custom iPS cell CompoZr ZFN-mediated genetic engineering, Stemgent Reprogramming Lentiviruses, the MISSION shRNA Library with the latest content release from The RNAi Consortium, 3D matrices, growth factors, small molecules, other cell culture media and the industry's most validated antibodies. Sigma Life Science acquired a worldwide license to Kyoto University's iPS cell patent portfolio in February, 2012.

For more information and to request pricing, visit http://www.sigma.com/stemlinepsc.

Cautionary Statement: The foregoing release contains forward-looking statements that can be identified by terminology such as "could," "could expect," "can be," "predictive" or similar expressions, or by expressed or implied discussions regarding potential future revenues from products derived there from. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that pluripotent stem cells, pluripotent stem cell media, or related custom services will assist the Company to achieve any particular levels of revenue in the future. In particular, management's expectations regarding products associated with pluripotent stem cells, pluripotent stem cell media, or related custom services could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; the Company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; the impact that the foregoing factors could have on the values attributed to the Company's assets and liabilities as recorded in its consolidated balance sheet, and other risks and factors referred to in Sigma-Aldrich's current Form 10-K on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Sigma-Aldrich is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Sigma Life Science: Sigma Life Science is a Sigma-Aldrich business that represents the Company's leadership in innovative biological products and services for the global life science market and offers an array of biologically-rich products and reagents that researchers use in scientific investigation. Product areas include biomolecules, genomics and functional genomics, cells and cell-based assays, transgenics, protein assays, stem cell research, epigenetics and custom services/oligonucleotides. Sigma Life Science also provides an extensive range critical bioessentials like biochemicals, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, amino acids and their derivatives, and cell culture media.

About Sigma-Aldrich: Sigma-Aldrich is a leading Life Science and High Technology company whose biochemical, organic chemical products, kits and services are used in scientific research, including genomic and proteomic research, biotechnology, pharmaceutical development, the diagnosis of disease and as key components in pharmaceutical, diagnostics and high technology manufacturing. Sigma-Aldrich customers include more than 1.3 million scientists and technologists in life science companies, university and government institutions, hospitals and industry. The Company operates in 38 countries and has nearly 9,100 employees whose objective is to provide excellent service worldwide. Sigma-Aldrich is committed to accelerating customer success through innovation and leadership in Life Science and High Technology. For more information about Sigma-Aldrich, please visit its website at http://www.sigma-aldrich.com.

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Sigma® Life Science Launches Novel, Affordable Pluripotent Stem Cell Culture Medium

Stem cell transplant survivors at increased risk of developing heart disease, study suggests

ScienceDaily (Oct. 3, 2012) New research appearing online October 3 in Blood, the Journal of the American Society of Hematology (ASH), suggests that long-term survivors of hematopoietic cell transplants (HCT) are at an increased risk of developing heart disease risk factors such as high blood pressure, diabetes, and high cholesterol when compared to the general population. These risk factors, combined with exposure to pre-HCT therapy, contribute to a noticeably increased risk of heart disease over time.

HCT, the transplantation of blood-forming stem cells from the bone marrow, circulating blood, or umbilical cord blood, is the primary treatment option for many patients with blood disorders. The healthy transplanted stem cells replace patients' damaged cells that caused their illness. Advances in transplantation strategies have contributed to marked improvements in patient outcomes, resulting in a growing number of long-term transplant survivors, many of whom struggle with one or more chronic, post-transplant health conditions. Previous researchers have speculated that survivors' exposure to potentially heart damaging pre-transplant chemotherapy and radiation or treatment for a life-threatening transplant complication known as graft-versus-host-disease (GVHD) can increase their risk of developing heart disease and its associated risk factors. However, there have been limited data to validate the contribution of pre-conditioning chemotherapy or radiation and GVHD to the eventual development of heart disease in long-term HCT survivors.

"While we know that heart disease is a real concern for long-term HCT survivors, small sample sizes and a lack of long-term follow up in previous studies have only allowed us to look at a small piece of the puzzle of how this chronic condition develops in these patients," said Saro H. Armenian, DO, MPH, the study's first author, Assistant Professor in the Division of Outcomes Research, and Medical Director of the Pediatric Survivorship Clinic in the Childhood Cancer Survivorship Program at City of Hope in Duarte, CA. "Our study sought to better determine the specific factors before and after transplant that can lead to heart disease in a large group of transplant recipients."

In order to more thoroughly evaluate heart disease risk and development in HCT recipients, Dr. Armenian and his team of researchers designed a retrospective study to evaluate factors that may affect a survivor's risk of developing high blood pressure, diabetes, and high cholesterol after HCT. These factors included transplant recipients' exposure to pre-transplant chemotherapy and radiation, conditioning therapy for HCT, their type of HCT transplant, and whether they developed and were treated for GVHD post transplant.

To better determine HCT survivors' incidence of high blood pressure, diabetes, and high cholesterol compared to the general population, researchers analyzed medical records of 1,885 patients who underwent a first-time HCT for a blood cancer at City of Hope between 1995 and 2004 and had survived at least one year. The National Health and Nutrition Examination Survey was used to generate expected heart disease risk factor rates for the general population.

Following their analysis, researchers found a higher prevalence of high blood pressure, diabetes, and high cholesterol in long-term HCT transplant survivors when compared to the general population. HCT conditioning with total body radiation was associated with a 1.5-fold increase in risk of developing diabetes and a 1.4-fold increase in risk of developing high cholesterol, regardless of HCT type, a finding that validates previous reports from long-term childhood and adult HCT survivors. While the mechanism by which total body radiation increases the risk of diabetes and high cholesterol in HCT recipients is not clear, previous studies have shown that abdominal radiation may contribute to known heart disease risk factors such as insulin resistance and an increase in belly fat in conventionally treated cancer patients. This evidence suggests that radiation-induced pancreatic or liver injury may play a role in an HCT transplant survivor's development of heart disease by increasing their risk for heart disease risk factors.

Next, researchers assessed the role of transplant type on long-term HCT survivors' risk of developing key heart disease risk factors. After reviewing the data, researchers observed that those who had received transplanted stem cells from a donor (allogeneic HCT) were at a significantly higher risk of developing high blood pressure, diabetes, or high cholesterol after transplant than those who had received blood-forming stem cells from their own body (autologous HCT). Over the 10-year study period, 45.3 percent of allogeneic HCT recipients developed high blood pressure, 20.9 percent developed diabetes, and 50.5 percent developed high cholesterol; whereas only 32 percent, 15.9 percent, and 43.3 percent of autologous HCT recipients developed these same conditions, respectively. Transplant recipients who had undergone an allogeneic HCT and who had experienced GVHD had the highest risk of developing heart disease risk factors, researchers concluded; 54.7 percent of this group developed high blood pressure, 25.8 percent developed diabetes, and 52.8 percent developed high cholesterol.

Not only did more allogeneic than autologous HCT recipients develop these heart disease risk factors over this time period, but they also developed them more quickly. Allogeneic HCT recipients developed high blood pressure and high cholesterol both at a median time to onset of 2.5 months, compared with autologous HCT recipients who developed the same conditions at 3.7 years and 1.6 years, respectively. Allogeneic HCT recipients also developed diabetes more than two years earlier than autologous recipients (1.2 year median time to onset for allogeneic HCT recipients vs. 3.3 years for autologous transplant recipients).

In addition to evaluating incidence rates of key heart disease risk factors in this large group of long-term HCT survivors, investigators also assessed their impact on survivors' subsequent development of heart disease. A total of 115 patients went on to develop heart disease at a median rate of four years after HCT. At 10 years post HCT, the cumulative incidence of post-HCT heart disease in all survivors was approximately 7.8 percent, with the rate exceeding 11 percent in the survivors with multiple heart disease risk factors. In those survivors with multiple heart disease risk factors and past exposure to cardiotoxic chemotherapy or radiation, the incidence rose to approximately 18 percent, demonstrating that certain pre-transplant therapeutic exposures compound HCT recipients' risk of developing heart disease.

"Our findings show that the process of receiving a stem cell transplant alone increases a recipient's risk of developing heart disease; however, the type of transplant and whether the recipient was treated for GVHD can also increase that survivor's heart disease risk as well," said Dr. Armenian. "The results of this study demonstrate the importance of intervention strategies that can help mitigate these modifiable heart disease risk factors in transplant recipients before and after transplant, and we hope they can serve as a basis for creating a predictive model to identify those patients at highest risk of developing heart disease."

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Stem cell transplant survivors at increased risk of developing heart disease, study suggests

Provocative Biotech Exposition Reveals Significant Advancements in Stem Cell Research, Immunotherapy, Targeted …

STAMFORD, CT--(Marketwire - Oct 3, 2012) - Noble Financial Capital Markets (Noble) announced today that it has released a full high definition video catalog of its Life Sciences Exposition, BIOX, an investor exposition that was held at the University of Connecticut in Stamford, CT on September 24-25, 2012. In addition to the participation of more than two dozen biotechnology companies, the event featured world renowned key opinion leaders Dr. Mark Noble (University of Rochester), R. Phil Greenberg (Fred Hutchinson Cancer Research Center), Dr. Jeffrey Infante (Sarah Cannon Research Institute), and Dr. Charles Vacanti (Harvard Medical School).

Opening remarks were provided by Dr. Sharon White, Director of the UCONN Stamford campus and Richard Blumenthal, United States Senator for Connecticut. "Washington is dysfunctional and broken," Blumenthal said. "The good news is that scientific advancements and research offer a real opportunity to reach across the aisle; this is an area that should inspire bipartisan cooperation."

Overwhelmingly, the message coming from the Exposition was one of encouragement that we are making great strides in the effective treatment of catastrophic disease, in particular cancers. Determining genetic differences in tumors, which has posed challenges for biomarkers, has improved significantly with advancements in molecular biology. Novel and approved targeted agents is the next rationale step in matching tumor types with appropriate therapies; a developmental step that large pharmaceutical companies have already taken.

Dr. Noble, who led a panel moderated by Noble Financial Senior Analyst, Nathan Cali and consisting of executives from Cytomedix, Cytori, MediStem, Mesoblast and NeoStem, expressed optimism that stem cell therapy will continue to grow exponentially. "Stem cells are a natural cascade offering the potential to treat significant unmet medical needs," he said."The path to better cancer treatment comes from a clearer understanding of cancer stem cell biology."

Rahul Jasuja, Noble Financial's Managing Director of Biotechnology Research moderated the panel which focused on immunotherapy and vaccines. Executives from Argos, Galena, Inovio, NewLink and Prima Biomed joined Dr. Phil Greenberg (referred to as Dr. T-Cell) to debate the challenges and advancements in the understanding of how the immune system is suppressed by cancer cells. While a consensus was not reached in terms of specific methods to harness the immune system, all agreed that the next generation of immunotherapy approaches will aim to "realign" the immune system to destroy cancer.

Jules Msing, Chairman of Noble's Scientific Advisory Board and the former head of Global Drug Licensing for Johnson & Johnson addressed attendees at the opening session and again on day two of the Exposition. "The hope is great that all of the technologies and innovations that will be discussed here today will have a huge impact on healthcare around the world," he said. "This, however, is reliant on the underlying assumption that society's acceptance of healthcare innovation and our willingness to invest in it will continue into the future," he added. Msings' presentation to life science corporate executives centered on the question of why some biotech companies can attract the attention of large pharma while others cannot and why many licensing executives in large pharma are unable to convince their R&D groups or executive committees to make substantial investments in these companies. Mr. Msing negotiated deals with various companies such as Vertex Pharmaceuticals, Genentech, OSI Pharmaceuticals, Bristol Meyers Squibb, CTI Inc., Regeneron, Alkermes, Enzon Pharmaceuticals, GTx Inc, Alliance Pharmaceuticals, Allos Therapeutics, Somatogen, Morphotek, Edison Pharmaceuticals, etc.

Based upon the success of this event, Noble Financial has begun planning its second Life Sciences Exposition for the fall of 2013. Noble's Ninth Annual large-format investor conference that will feature 150 public companies is scheduled for January 22-23, 2013 at the Hard Rock Hotel in Fort Lauderdale.

Complete HDVideo webcast catalog available at: http://www.nobleresearch.com/BioExposition.htm

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Provocative Biotech Exposition Reveals Significant Advancements in Stem Cell Research, Immunotherapy, Targeted ...