Public Health News Daily

Uterine Stem Cells Used to Treat Diabetes
ScienceDaily (Sep. 15, 2011) — Controlling diabetes may someday involve mining stem cells from the lining of the uterus, Yale School of Medicine researchers report in a new study published in the journal Molecular Therapy. The team treated diabetes in mice by converting cells from the uterine lining into insulin-producing cells.

The endometrium or uterine lining, is a source of adult stem cells. These cells generate uterine tissue each month as part of the menstrual cycle. Like other stem cells, however, they can divide to form other kinds of cells.
The Yale team's findings suggest that endometrial stem cells could be used to develop insulin-producing islet cells, which are found in the pancreas. These islet cells could then be used to advance the study of islet cell transplantation to treat people with diabetes.
Led by Yale Professor Hugh S. Taylor, M.D., the researchers bathed endometrial stem cells in cultures containing special nutrients and growth factors. Responding to these substances, the endometrial stem cells adopted the characteristics of beta cells in the pancreas that produce insulin. Over the course of a three-week incubation process, the endometrial stem cells took on the shape of beta cells and began to make proteins typically made by beta cells. Some of these cells also produced insulin.
After a meal, the body breaks food down into components like the sugar glucose, which then circulates in the blood. In response, beta cells release insulin, which allows the body's cells to take in the circulating glucose. In this study, Taylor and his team exposed the mature stem cells to glucose and found that, like typical beta cells, the cultured cells responded by producing insulin. The team then injected diabetic mice with the mature, insulin-making stem cells. The mice had few working beta cells and very high levels of blood glucose.
Mice that did not receive the stem cell therapy continued having high blood sugar levels, developed cataracts and were lethargic. In contrast, mice that received the cell therapy were active and did not develop cataracts, but the animals' blood sugar levels remained higher than normal.
Taylor said that the next step in the research will be to verify how long this treatment remains effective. "We will also investigate how changing the nutrient bath or increasing the dose of injected cells could make this treatment more effective," he said. "Endometrial stem cells might prove most useful for Type 1 diabetes, in which the immune system destroys the body's own insulin-producing cells. As a result, insulin is not available to control blood glucose levels."
Other Yale authors on the study included Xavier Santamaria, Elfi E. Massasa, Yuzhe Feng, and Erin Wolff.
The study was funded by the National Institutes of Health's Eunice Kennedy Shriver National Institute of Child Health and Human Development

Journal Reference:
1. Xavier Santamaria, Efi E Massasa, Yuzhe Feng, Erin Wolff, Hugh S Taylor. Derivation of Insulin Producing Cells From Human Endometrial Stromal Stem Cells and Use in the Treatment of Murine Diabetes. Molecular Therapy, 2011; DOI: 10.1038/mt.2011.173

Science Daily (Sep. 16, 2011) — Young adults whose mothers experienced psychological trauma during their pregnancies show signs of accelerated aging, a UC Irvine-led study found.
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The researchers discovered that this prenatal exposure to stress affected the development of chromosome regions that control cell aging processes. The study results, which appear online this week in the Proceedings of the National Academy of Sciences, point to the importance of maternal health and well-being during pregnancy.
"Our previous research on prenatal stress exposure has shown its effects on long-term metabolic, immune, endocrine and cognitive function," said the paper's lead author, Dr. Pathik D. Wadhwa, UCI professor of psychiatry & human behavior, obstetrics & gynecology, pediatrics, and epidemiology. "But this is the first to show the impact of prenatal stress on cell aging in humans, and it sheds light on an important biological pathway underlying the developmental origins of adult disease risk."
Study participants were healthy 25-year-old women and men born to mothers who had, during pregnancy, experienced psychosocial stress in the form of major, traumatic life events, such as the death or sudden severe illness of an immediate family member. Blood tests revealed that subjects' white blood cells had aged an average of three and a half more years -- five among women -- than those of individuals whose mothers had uneventful pregnancies.
This hastened aging was evidenced by the shortened length of telomeres, repetitive stretches of DNA-protein complexes that cap and protect the ends of chromosomes. Telomeres maintain chromosomal stability and control the processes that underlie cellular aging by functioning as a "clock" that regulates how many times a cell can divide. The shorter the telomere strands, the faster the cell ages.
The telomere maintenance system plays an important role in human disease and longevity, and scientists now know that telomere length is correlated to the risk of disease and premature mortality in humans. Truncated telomeres -- such as those found in the white blood cells of study participants -- can, for example, be a precursor to diabetes, cancer and coronary heart disease.
"These results indicate that stress exposure in intrauterine life is a significant predictor of adult telomere length -- even after accounting for other established prenatal and postnatal influences on telomere length," said Sonja Entringer, UCI assistant professor of pediatrics and first author on the paper.
A rapidly emerging body of human and animal research indicates that intrauterine conditions play an important role not only in all aspects of fetal development and health across gestation and birth, but also in a wide range of physical and mental health outcomes over an individual's entire lifespan.
Elizabeth H. Blackburn, Elissa S. Epel and Jue Lin of UC San Francisco and German researchers Robert Kumsta, Dirk H. Hellhammer and Stefan Wust contributed to the study, which was supported by the National Institutes of Health and the Barney & Barbro Fund

Journal Reference:
S. Entringer, E. S. Epel, R. Kumsta, J. Lin, D. H. Hellhammer, E. H. Blackburn, S. Wust, P. D. Wadhwa. Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood. Proceedings of the National Academy of Sciences, 2011; 108 (33): E513 DOI: 10.1073/pnas.1107759108

Goal is to find new treatment that takes months, not years, and cures multiple forms of tuberculosis

Announcement made at World TB Day briefing featuring senior US Gov’t Officials
WASHINGTON, DC (19 March 2012) – In an ambitious effort to stem the dangerous tide of tuberculosis (TB) and deadly drug-resistant TB around the world, TB Alliance today announced that it has launched a first-of-its-kind Phase II clinical trial to test a novel drug combination – in both patients who have TB, and those who have multidrug-resistant TB (MDR-TB).

TB is a leading global killer. Each year, 1.4 million people die from the disease, while nearly 9 million more contract it. The current treatment is old and inadequate, and the disease is becoming increasingly resistant to available drugs. Today, 650,000 patients around the world suffer from MDR-TB, and that number is expected to continue to rise. Most MDR-TB patients are unable to access adequate treatment due to the complexity and high cost of treatment. Among the small numbers of people who do receive treatment, 1 in 3 will still not be cured.

“There is new momentum and new hope in TB research – as shown by this and several other novel regimen trials that will soon be launched,” said Mel Spigelman, MD, President and CEO, the TB Alliance. “This novel TB drug regimen has the potential to unlock a new and more efficient approach to tackling TB. In essence, it’s a step toward erasing the distinction between TB and MDR-TB—and in the process, dramatically shortening, simplifying, and improving treatment.”

Currently, someone with ordinary TB must take a course of drugs daily for six months, while those with MDR-TB must take a daily injection for the first six months and a dozen or more pills each day for 18 months or more. Around the world, many patients fail to complete treatment because they can no longer tolerate the difficult side effects of the medications or can’t adhere to the long treatment, leading to drug resistance, be it MDR-TB, or even extensively drug-resistant TB (XDR-TB).

The novel regimen being tested could shorten the length of required treatment to as little as four months in both patients with TB and some forms of drug-resistant TB. For those drug-resistant patients, this completely oral regimen could reduce treatment time by more than 80%, increase the efficacy of treatment, and cost just a fraction of today’s MDR-TB treatment.

“The current TB treatment takes too long—and all around the world, patients needlessly suffer because today’s treatment is completely inadequate,” says Francis George Apina, a TB/HIV advocate working with Network of Men Living with HIV/AIDS in Kenya. “I applaud the TB Alliance for their work to advance new TB regimens and help patients with TB, MDR-TB, and HIV/TB get back to work, and restore their health and their lives, faster.”

This trial builds on the TB Alliance’s two-week New Combination 1 trial, or NC-001, initiated in 2010, which was the first study to test novel TB drugs in combination. The newly launched Phase II trial, New Combination 2 (NC-002), advances the regimen of new TB drug candidates PA-824 and moxifloxacin in combination with pyrazinamide, an existing antibiotic commonly used in TB treatment. NC-002 treats patients for two months and will take place at 8 sites in South Africa, Tanzania, and Brazil, and will advance global capacity for TB trials along with the new innovative approach to TB drug development.

Today, the crude classifications of TB, MDR-TB, and XDR-TB describe patients’ broad drug-resistance profiles, but within each designation exist many different resistance patterns. Because of the frequent unavailability of accurate resistance testing, many health care providers can’t or don’t identify the correct form of the disease, leading to improper treatment. One way to overcome this challenge is the development of completely novel regimens. Completely novel regimens, with little or no pre-existing resistance, would be effective against all forms of TB, and therefore eliminate the need to classify or treat TB in these categories—dramatically simplifying and enabling global scale-up of treatment.

Because the regimen being tested in NC-002 is projected to be effective against both TB and several forms of MDR-TB, NC002 represents an important stepping stone toward the ultimate goal of removing the barrier between treatment of TB and drug-resistant TB. With appropriate use of drug-sensitivity testing, NC-002 offers a new paradigm in TB treatment (but one used widely in the broader field of antibiotic research) - treating patients with the drugs to which they are sensitive, rather than based on what they are resistant to.



About the Global Alliance for TB Drug Development (TB Alliance):

TB Alliance is a not-for-profit organization dedicated to finding faster-acting and affordable drug regimens to fight tuberculosis. Through innovative science and with partners around the globe, we aim to ensure equitable access to faster, better TB cures that will advance global health and prosperity. The TB Alliance operates with funding from the Bill & Melinda Gates Foundation, Irish Aid, the United Kingdom Department for International Development, the United States Agency for International Development, and the United States Food and Drug Administration. For more information, please visit tballiance.org