New approach to treating type 1 diabetes? Transforming gut cells into insulin factories

ScienceDaily (Mar. 11, 2012) A study by Columbia researchers suggests that cells in the patient's intestine could be coaxed into making insulin, circumventing the need for a stem cell transplant. Until now, stem cell transplants have been seen by many researchers as the ideal way to replace cells lost in type I diabetes and to free patients from insulin injections.

The research -- conducted in mice -- was published 11 March 2012 in the journal Nature Genetics.

Type I diabetes is an autoimmune disease that destroys insulin-producing cells in the pancreas. The pancreas cannot replace these cells, so once they are lost, people with type I diabetes must inject themselves with insulin to control their blood glucose. Blood glucose that is too high or too low can be life threatening, and patients must monitor their glucose several times a day.

A longstanding goal of type I diabetes research is to replace lost cells with new cells that release insulin into the bloodstream as needed. Though researchers can make insulin-producing cells in the laboratory from embryonic stem cells, such cells are not yet appropriate for transplant because they do not release insulin appropriately in response to glucose levels. If these cells were introduced into a patient, insulin would be secreted when not needed, potentially causing fatal hypoglycemia.

The study, conducted by Chutima Talchai, PhD, and Domenico Accili, MD, professor of medicine at Columbia University Medical Center, shows that certain progenitor cells in the intestine of mice have the surprising ability to make insulin-producing cells. Dr. Talchai is a postdoctoral fellow in Dr. Accili's lab.

The gastrointestinal progenitor cells are normally responsible for producing a wide range of cells, including cells that produce serotonin, gastric inhibitory peptide, and other hormones secreted into the GI tract and bloodstream.

Drs. Talchai and Accili found that when they turned off a gene known to play a role in cell fate decisions -- Foxo1 -- the progenitor cells also generated insulin-producing cells. More cells were generated when Foxo1 was turned off early in development, but insulin-producing cells were also generated when the gene was turned off after the mice had reached adulthood. "Our results show that it could be possible to regrow insulin-producing cells in the GI tracts of our pediatric and adult patients," Dr. Accili says.

"Nobody would have predicted this result," Dr. Accili adds. "Many things could have happened after we knocked out Foxo1. In the pancreas, when we knock out Foxo1, nothing happens. So why does something happen in the gut? Why don't we get a cell that produces some other hormone? We don't yet know."

Insulin-producing cells in the gut would be hazardous if they did not release insulin in response to blood glucose levels. But the researchers say that the new intestinal cells have glucose-sensing receptors and do exactly that.

The insulin made by the gut cells also was released into the bloodstream, worked as well as normal insulin, and was made in sufficient quantity to nearly normalize blood glucose levels in otherwise diabetic mice.

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New approach to treating type 1 diabetes? Transforming gut cells into insulin factories

A new approach to treating type I diabetes? Gut cells transformed into insulin factories

Public release date: 11-Mar-2012 [ | E-mail | Share ]

Contact: Karin Eskenazi ket2116@columbia.edu 212-342-0508 Columbia University Medical Center

NEW YORK, NY -- A study by Columbia researchers suggests that cells in the patient's intestine could be coaxed into making insulin, circumventing the need for a stem cell transplant. Until now, stem cell transplants have been seen by many researchers as the ideal way to replace cells lost in type I diabetes and to free patients from insulin injections.

The researchconducted in micewas published 11 March 2012 in the journal Nature Genetics.

Type I diabetes is an autoimmune disease that destroys insulin-producing cells in the pancreas. The pancreas cannot replace these cells, so once they are lost, people with type I diabetes must inject themselves with insulin to control their blood glucose. Blood glucose that is too high or too low can be life threatening, and patients must monitor their glucose several times a day.

A longstanding goal of type I diabetes research is to replace lost cells with new cells that release insulin into the bloodstream as needed. Though researchers can make insulin-producing cells in the laboratory from embryonic stem cells, such cells are not yet appropriate for transplant because they do not release insulin appropriately in response to glucose levels. If these cells were introduced into a patient, insulin would be secreted when not needed, potentially causing fatal hypoglycemia.

The study, conducted by Chutima Talchai, PhD, and Domenico Accili, MD, professor of medicine at Columbia University Medical Center, shows that certain progenitor cells in the intestine of mice have the surprising ability to make insulin-producing cells. Dr. Talchai is a postdoctoral fellow in Dr. Accili's lab.

The gastrointestinal progenitor cells are normally responsible for producing a wide range of cells, including cells that produce serotonin, gastric inhibitory peptide, and other hormones secreted into the GI tract and bloodstream.

Drs. Talchai and Accili found that when they turned off a gene known to play a role in cell fate decisionsFoxo1the progenitor cells also generated insulin-producing cells. More cells were generated when Foxo1 was turned off early in development, but insulin-producing cells were also generated when the gene was turned off after the mice had reached adulthood.

"Our results show that it could be possible to regrow insulin-producing cells in the GI tracts of our pediatric and adult patients," Dr. Accili says.

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A new approach to treating type I diabetes? Gut cells transformed into insulin factories

Osiris Therapeutics Reports Fourth Quarter and Full Year 2011 Financial Results

COLUMBIA, Md.--(BUSINESS WIRE)--

Osiris Therapeutics, Inc. (NASDAQ: OSIR - News), the leading stem cell company focused on developing and commercializing products to treat medical conditions in inflammatory, cardiovascular, orthopedic, and wound healing markets, announced today its results for the fourth quarter and full year ended December 31, 2011.

Recent and Full Year Highlights

We are very pleased with the commercial performance of our two Biosurgery products, Grafix and Ovation, said C. Randal Mills, Ph.D., President and Chief Executive Officer of Osiris. As interest in stem cell products for surgical applications intensifies, Osiris remains uniquely positioned as the clear leader in this space. Additionally, with Prochymal being used around the world to treat patients with life-threatening GvHD through our Expanded Access program, our Therapeutic and Biosurgery units are carrying out our mission of bringing Smart Medicine, to patients, Right Now.

Fourth Quarter Financial Results

Net income for the fourth quarter of 2011 increased to $5.0 million, compared to $4.4 million for the fourth quarter of 2010. Revenues were $11.0 million in the fourth quarter of 2011, consisting primarily of the amortization of license fees from our collaboration agreements. Our fourth quarter Biosurgery product revenues were $0.8 million. Revenues during the fourth quarter of 2010 were $10.8 million. As of December 31, 2011, Osiris had $48.0 million of cash, receivables, and short-term investments.

Research and development expenses for the fourth quarter of 2011 were $4.2 million, compared to $5.0 million incurred in the fourth quarter of 2010. General and administrative expenses were $1.5 million for the fourth quarter of 2011 compared to $1.8 million for the same period of the prior year. Net cash used in operations for the quarter was $4.6 million.

Full Year 2011 Financial Highlights

Net income was $14.9 million for the fiscal year ended December 31, 2011 compared to $13.1 million in fiscal 2010. Revenues of $42.4 million were recognized in 2011, including $40.0 million from the Genzyme collaboration agreement, $1.0 million from the research, development and commercialization agreement with the JDRF and $1.3 million of revenues from our Biosurgery products. Revenues in 2010 were $43.2 million, which included $40.0 million from the Genzyme collaboration agreement, $0.5 million from the U.S. Department of Defense contract, $1.2 million from the JDRF agreement and a $1.0 million milestone earned on our license agreement with JCR Pharmaceuticals.

R&D expenses for the 2011 fiscal year were $19.2 million compared to $23.5 million in the prior year. G&A expenses in fiscal 2011 were $7.9 million, which include $2.4 million of non-cash share based payments. G&A expenses in fiscal 2010 were $6.5 million, including $0.7 million of share-based payments.

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Osiris Therapeutics Reports Fourth Quarter and Full Year 2011 Financial Results

Eastday-Student who twice backed out of cell donation divides opinion

A SHANGHAI student who registered as a stem cell donor but then twice backed out of donating at the last moment has found herself at the center of public debate.

The would-be recipient, a leukemia patient in neighboring Jiangsu Province, had already received medication to stop blood-forming functions in preparation for the transplant when the intended donor pulled out.

It was said that the would-be donor, who has not been named, had faced pressure from her family not to go ahead with the procedure.

The incident has stirred up discussion online, with some web users accusing the student of putting the patient's life in danger through her actions.

Some argued that donors should be legally prevented from backing out once the intended recipient has been given preparatory medication.

However, local medical officials said that donations should be based on freewill and that a donor must be allowed to change his or her mind.

The 23-year-old leukemia patient, Jiang Jing, is being treated in a hospital in Suzhou. As an emergency solution, a partial match was found yesterday using a sample from the Shanghai Stem Cell Blood Bank and cells from Jiang's mother. The success rate is likely to be around 60 percent, local doctors told Shanghai Daily.

Jiang was diagnosed with leukemia last April and a full match was found with the Shanghai college student who had registered as a donor with the Red Cross in the city.

The transplant had been scheduled for Tuesday and the patient had been receiving medication since late last month to stop her body forming blood cells.

But last Thursday, the donor said she did not want to proceed.

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Eastday-Student who twice backed out of cell donation divides opinion

Nimer named new director for University of Miami’s cancer center

Medical breakthroughs discovered in the laboratory can take a long time to be put into practice in the examination room, often because there is little communication between research scientists and clinical physicians.

Dr. Stephen D. Nimer, a renowned researcher and physician named Wednesday as director of the University of Miamis Sylvester Cancer Center, is vowing to bring equal emphasis to leading-edge scientific research and quality patient care. His goal: to make Miami a worldwide destination for cancer treatment.

I am going to devote my energies toward bringing the center to the next level, said Nimer, 57, who has pioneered novel therapies for cancer and advocated for more compassionate care of patients. I want to build on the greatness that exists here.

Nimers appointment comes nearly 18 months after the Sylvester Centers board launched a global search for a new director to succeed Dr. W. Jarrard Goodwin, who stepped down after 14 years at the helm to become chief medical officer for the center.

Joan Scheiner, board chair of the Sylvester Center, said Nimer is the perfect candidate to lead the 20-year-old center into the next stage.

Hes going to help us build the kind of cancer center we deserve, said Scheiner, who beat metastatic soft tissue sarcoma with the help of Sylvester Center doctors in the late 1990s. It validates our past and ensures a future with no limits.

A key member of one of the nations leading cancer centers Memorial Sloan-Kettering in New York Nimer is considered one of the worlds premier leukemia and stem cell transplant researchers and physicians.

During nearly two decades at Sloan-Kettering, Nimer established an inpatient program for patients with blood disorders, and a blood stem cell transplant program for adults with malignant blood diseases, focusing primarily on patients with non-Hodgkin and Hodgkin lymphoma, or multiple myeloma, a cancer of the plasma cells in the bone marrow.

Among Nimers notable achievements in the laboratory: developing a bone marrow transplant treatment using stem cells to eliminate cancer cells from the blood and coaxing tumor-reducing proteins out of stem cells, then using those proteins to help enhance the effects of chemotherapy and radiotherapy for cancer patients.

A prolific researcher who has authored more than 200 scientific publications in numerous medical journals, Nimer also has made important discoveries in the field of pre-cancerous oncogenes, which can mutate and trigger cancer.

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Nimer named new director for University of Miami’s cancer center

Tonsils make t-cells, too, Ohio State study shows

Public release date: 5-Mar-2012 [ | E-mail | Share ]

Contact: Darrell E. Ward Darrell.Ward@osumc.edu 614-293-3737 Ohio State University Medical Center

COLUMBUS, Ohio A new study provides evidence that a critical type of immune cell can develop in human tonsils. The cells, called T lymphocytes, or T cells, have been thought to develop only in the thymus, an organ of the immune system that sits on the heart.

The study, led by researchers at the Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James), could improve the understanding of T-cell cancers and autoimmune diseases, and how stem-cell transplantation is done.

The study identified T cells at five distinct stages of development in the tonsil. These stages, identified using molecular signposts on the cells, were very similar to the stages of T-cell development in the thymus, although some differences were found as well.

The study also discovered that the cells develop in a particular region of the tonsil, in areas near the fibrous scaffold of the tonsil.

The findings are published in the Journal of Clinical Investigation.

"We've known for a long time that a functional thymus is necessary to develop a complete repertoire of T-cells, but whether a T-cell factory existed outside the thymus has been controversial," says principal investigator Dr. Michael A. Caligiuri, director of Ohio State's Comprehensive Cancer Center and CEO of the James Cancer Hospital and Solove Research Institute.

"I believe our study answers that question. It is the first report to describe a comprehensive, stepwise model for T-cell development outside the thymus."

It also raises a number of questions. Caligiuri notes that it's still unclear whether T-cells that develop in the tonsil also mature there or whether they leave the tonsil to mature elsewhere.

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Tonsils make t-cells, too, Ohio State study shows

Tonsils make T-cells, too

ScienceDaily (Mar. 5, 2012) A new study provides evidence that a critical type of immune cell can develop in human tonsils. The cells, called T lymphocytes, or T cells, have been thought to develop only in the thymus, an organ of the immune system that sits on the heart.

The study, led by researchers at the Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James), could improve the understanding of T-cell cancers and autoimmune diseases, and how stem-cell transplantation is done.

The study identified T cells at five distinct stages of development in the tonsil. These stages, identified using molecular signposts on the cells, were very similar to the stages of T-cell development in the thymus, although some differences were found as well.

The study also discovered that the cells develop in a particular region of the tonsil, in areas near the fibrous scaffold of the tonsil.

The findings are published in the Journal of Clinical Investigation.

"We've known for a long time that a functional thymus is necessary to develop a complete repertoire of T-cells, but whether a T-cell factory existed outside the thymus has been controversial," says principal investigator Dr. Michael A. Caligiuri, director of Ohio State's Comprehensive Cancer Center and CEO of the James Cancer Hospital and Solove Research Institute.

"I believe our study answers that question. It is the first report to describe a comprehensive, stepwise model for T-cell development outside the thymus."

It also raises a number of questions. Caligiuri notes that it's still unclear whether T-cells that develop in the tonsil also mature there or whether they leave the tonsil to mature elsewhere.

"The complete implications of this phenomenon for human health and disease are not entirely known," adds first-author Susan McClory, a graduate fellow in Caligiuri's laboratory. "It could be important in the development of T-cell cancers and autoimmune diseases, or it might suggest a location for T-cell development when thymus function is poor. We hope to do additional studies to explore these possibilities," she says.

Caligiuri, McClory and their colleagues conducted the study using tonsil tissue obtained from children undergoing routine tonsillectomy at Nationwide Children's Hospital in Columbus, and thymic tissue obtained from children undergoing thoracic surgery.

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Tonsils make T-cells, too

Planarian genes that control stem cell biology identified

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

Contact: Nicole Giese Rura rura@wi.mit.edu 617-258-6851 Whitehead Institute for Biomedical Research

FINDINGS: Devising a novel method to identify potential genetic regulators in planarian stem cells, Whitehead Institute scientists have determined which of those genes affect the two main functions of stem cells. Three of the genes are particularly intriguing because they code for proteins similar to those known to regulate mammalian embryonic stem cells. Such genetic similarity makes planarians an even more attractive model for studying stem cell biology in vivo.

RELEVANCE: Stem cells may hold the promise to regrow damaged, diseased, or missing tissues in humans, such as insulin-producing cells for diabetics and nerve cells for patients with spinal cord injuries. With its renowned powers of regeneration and more than half of its genes having human homologs, the planarian seems like a logical choice for studying stem cell behavior. Yet, until now, scientists have been unable to efficiently identify the genes that regulate the planarian stem cell system.

CAMBRIDGE, Mass. 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 cellsinsights 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.

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Planarian genes that control stem cell biology identified

Why This Top Supplement Stacks Up

(PRWEB) February 29, 2012

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"It is now acknowledged worldwide that adult stem cells are the bodys primary system of renewal and restoration. However, with age, the release rate of one's own adult stem cells from the bone marrow decreases significantly, leaving us more prone to aging, illness and disease. Therefore, it is extremely important one's own adult stems continue to be activated throughout each individual's life time, no matter what their age.

Adult stem cells are behind practically every success of stem cell treatment and therapies thus far, not embryonic stem cells. Our own adult stem cells are the future of our good health. They are the only known source for rebuilding the body and renewing health by restoring lost or degraded cells.

The key ingredients in the Stem Cell Worx Intraoral Spray are scientifically proven to activate our adult stem cells, strengthen our immune system and provide optimal support for the bodys own repair and renewal system. Having healthy stem cells and a strong immune system are the very essence of life and good health.

Adult stem cells, once in the blood stream, have the ability to seek out areas within the body where they are needed the most. They then migrate to those areas and start the repair and renewal process.

Ask Stem Cell Worx CEO and Co-Founder, Tony Sampson why and he explains, Our formulation is made from the highest grade of natural ingredients in the world and our delivery system of these nutrients is direct and unique compared to main stream applications like tablets and capsules. Spray this dietary supplement under the tongue, hold then swallow.

"It is scientifically proven and referenced that a sublingual delivery method enables 95% of all nutrients to be absorbed directly into the blood stream through the sub-mucosal membrane (that sits directly under the tongue) compared to just 10% - 20% absorption that tablets and capsules provide. "Most people dont know this and many Health Professionals and Health Companies dont want to acknowledge it," states Tony Sampson, Stem Cell Worx CEO and Co-Founder.

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Why This Top Supplement Stacks Up

Study Could Result In Egg Cell Production For Fertility Treatments

February 27, 2012

Researchers from Massachusetts General Hospital (MGH) have for the first time isolated stem cells that are capable of producing what appear to be normal egg cells or oocytes from the ovaries of reproductive age women.

According to BBC News Health and Science Reporter James Gallagher, the research demonstrates that it could be possible to someday create a virtually unlimited supply of human eggs to assist with fertility treatments and help women hoping to have a child.

Gallagher also said that the MGH researchers have shown that it is possible to find stem cells that spontaneously produce new eggs in laboratory conditions, and that additional research involving mice showed that these oocytes could be fertilized.

The AFP said that the discovery, which is detailed in the March issue of the journal Nature Medicine, suggests that women do not have a limited stock of eggs, and instead replaces it with the theory that the supply of these reproductive cells is “continuously replenished from precursor cells in the ovary.”

An MGH press release said that the study, which was spearheaded by Dr. Jonathan Tilly, director of the hospital’s Vincent Center for Reproductive Biology, is a follow up to earlier research, published eight years ago, which suggested that female mammals continued producing egg cells into adulthood.

“The 2004 report from Tilly’s team challenged the fundamental belief, held since the 1950s, that female mammals are born with a finite supply of eggs that is depleted throughout life and exhausted at menopause,” the MGH press release said.

“That paper and a 2005 follow-up published in Cell showing that bone marrow or blood cell transplants could restore oocyte production in adult female mice after fertility-destroying chemotherapy were controversial; but in the intervening years, several studies from the MGH-Vincent group and other researchers around the world have supported Tilly’s work and conclusions,” it added.

Tilly and his colleagues told Gallagher that they were able to find and isolate these egg-producing stem cells by searching for the protein DDX4, which is only found on the surface of this specific type of stem cell.

“When grown in the lab, the stem cells ‘spontaneously generated’ immature eggs – or oocytes, which looked and acted like oocytes in the body,” the BBC News reporter said. “The cells were ‘matured’ when surrounded by living human ovarian tissue, which had been grafted inside mice.”

“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,” Tilly added. “The discovery of oocyte precursor cells in adult human ovaries, coupled with the fact that these cells share the same characteristic features of their mouse counterparts that produce fully functional eggs, opens the door for development of unprecedented technologies to overcome infertility in women and perhaps even delay the timing of ovarian failure.”

In addition to Tilly, co-author Dr. Yasushi Takai, formerly a research fellow at MGH and currently a faculty member at Saitama Medical University in Japan; Dr. Yvonne White and Dr. Dori Woods of the MGH Vincent Center for Reproductive Biology; and Dr. Osamu Ishihara and Hiroyuki Seki of Saitama Medical University.

—

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Source: RedOrbit Staff & Wire Reports

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Study Could Result In Egg Cell Production For Fertility Treatments