Stem cell transfusions may someday replace the need for transplants in patients who suffer from liver failure caused by hepatitis B, according to a new study coming out of Beijing. . The results are published in the October issue of STEM CELLS Translational Medicine. Worldwide more than 500,000 people die each year from this condition.

Durham, NC (PRWEB) October 11, 2012

In China, hepatitis B virus (HBV) infection accounts for the highest proportion of liver failure cases. While liver transplantation is considered the standard treatment, it has several drawbacks including a limited number of donors, long waiting lists, high cost and multiple complications. Our study shows that mesenchymal stem cell (MSCs) transfusions might be a good, safe alternative, said Fu-Sheng Wang, Ph.D., M.D., the studys lead author and director of the Research Center for Biological Therapy (RCBT) in Beijing.

Wang along with RCBT colleague, Drs. Ming Shi and Zheng Zhang of the Research Center for Biological Therapy, The Institute of Translational Hepatology led the group of physician-scientists from the centers and Beijing 302 Hospital who conducted the study.

MSC transfusions had already been shown to improve liver function in patients with end-stage liver diseases. This time, the researchers wanted to gauge the safety and initial efficacy of treating acute-on-chronic liver failure (ACLF) with MSCs. The American Association for the Study of Liver Diseases and the European Association for the Study of the Liver define ACLF as an acute deterioration of pre-existing chronic liver disease usually related to a precipitating event and associated with increased mortality at three months due to multisystem organ failure. The short-term mortality rate for this condition is more than 50 percent.

MSCs have self-renewing abilities and the potential to differentiate into various types of cells. More importantly, they can interact with immune cells and cause the immune system to adjust to the desired level.

Of the 43 patients in this pilot study each of whom had liver failure resulting from chronic HBV infection 24 were treated with MSCs taken from donated umbilical cords and 19 were treated with saline as the control group. All received conventional therapy as well. The liver function, adverse events and survival rates were then evaluated during the 48-week or 72-week follow-up period.

Along with increased survival rates, the patients liver function improved and platelet count increased. No significant side effects were observed throughout the treatment and follow-up period.

While the results are preliminary and this pilot study includes a small number of patients, MSC transfusions appear to be safe and may serve as a novel therapeutic approach for HBV-associated ACLF patients, Dr. Shi said.

The study also highlights several key issues that will need to be considered in the design of future clinical studies, such as the optimal type of stem cells that will be infused, the minimum effective number of the cells and the best route of administration, Dr. Wang added.

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Early Results Show Promise for Stem Cells in Treating Chronic Liver Failure

Four young boys with a rare, fatal brain condition have made it through a dangerous ordeal. Scientists have safely transplanted human neural stem cells into their brains.

Twelve months after the surgeries, the boys have more myelin a fatty insulating protein that coats nerve fibers and speeds up electric signals between neurons and show improved brain function, a new study in Science Translational Medicine reports. The preliminary trial paves the way for future research into potential stem cell treatments for the disorder, which overlaps with more common diseases such as Parkinson's disease and multiple sclerosis.

"This is very exciting," says Douglas Fields, a neuroscientist at the National Institutes of Health in Bethesda, Md., who was not involved in the work. "From these early studies one sees the promise of cell transplant therapy in overcoming disease and relieving suffering."

Without myelin, electrical impulses traveling along nerve fibers in the brain can't travel from neuron to neuron says Nalin Gupta, lead author of the study and a neurosurgeon at the University of California, San Francisco (UCSF). Signals in the brain become scattered and disorganized, he says, comparing them to a pile of lumber.

"You wouldn't expect lumber to assemble itself into a house," he notes, yet neurons in a newborn baby's brain perform a similar feat with the help of myelin-producing cells called oligodendrocytes. Most infants are born with very little myelin and develop it over time. In children with early-onset Pelizaeus-Merzbacher disease, he says, a genetic mutation prevents oligodendrocytes from producing myelin, causing electrical signals to die out before they reach their destinations. This results in serious developmental setbacks, such as the inability to talk, walk or breathe independently, and ultimately causes premature death.

Although researchers have long dreamed of implanting human neural stem cells to generate healthy oligodendrocytes and replace myelin, it has taken years of research in animals to develop a stem cell that can do the job, says Stephen Huhn, vice president of Newark, Calif.-based StemCells Inc., the biotechnology company that created the cells used in the study and that funded the research. However, he says, a separate study by researchers at Oregon Health and Science University, in Portland, found that the StemCells Inc. cells specialized into oligodendrocytes 60 percent to 70 percent of the time in mice, producing myelin and improved survival rates in myelin-deficient animals. So the team was able to test the cells' safety and efficacy in the boys.

Led by Gupta, the researchers drilled four small holes in each child's skull and then used a fine needle to insert millions of stem cells into white matter deep in their frontal lobes. The scientists administered a drug that suppressed the boys' immune systems for nine months to keep them from rejecting the cells and checked their progress with magnetic resonance imaging and a variety of psychological and motor tests. After a year, each of the boys showed brain changes consistent with increased myelination and no serious side effects such as tumors, says David Rowitch, one of the neuroscientists on the UCSF team. In addition, three of the four boys showed "modest" improvements in their development. For example, the 5-year-old the oldest child in the study had begun for the first time to feed himself and walk with minimal assistance.

Although these signs are encouraging, Gupta and Rowitch say, a cure for Pelizaeus-Merzbacher disease is not near. Animal studies strongly support the idea that the stem cells are producing myelin-making oligodendrocytes in the boys, but it's possible that the myelination didn't result from the transplant but from a bout of normal growth. Rowitch adds that although such behavioral improvements are unusual for the disease, they could be a fluke. Huhn acknowledges that the study is small and has no control, but he's is still excited.

"We are for the first time seeing a biological effect of a neural stem cells transplantation into the brain [in humans]." The most important thing, he says, is that the transplants appear safe. This gives the researchers a green light to pursue larger, controlled studies, he says.

It "isn't the flashiest thing," but demonstrating that it's feasible to transplant these stem cells into children's brains without negative consequences at least so far is "extremely hopeful," says Timothy Kennedy, a neuroscientist at McGill University in Montreal.

Link:
Stem cells safe for rare brain disorder

10/11/2012 10:05 JAPAN Nobel Prize for Yamanaka, scientific research and ethics must go hand in hand by Pino Cazzaniga Research on iPS (induced pluripotent stem cells) can produce stem cells from adult cells, for use in regenerative medicine. Shinya Yamanakas discovery reveals that research on embryonic stem cells is unnecessary, saving the lives of many embryos. The Japanese researcher has searched for new ways driven by ethical question.

Tokyo (AsiaNews) - Shinya Yamanaka, fresh from the Nobel Prize for medicine, states that science and ethics must go hand in hand. Interviewed by the Mainichi Shimbun after the award, he said: "I would like to invite ethical experts as teachers at my laboratory and work to guide iPS [induced pluripotent stem] cell research from that direction as well. The work of a scientific researcher is just one part of the equation. "

Yamanaka, 50, found that adult cells can be transformed into cells in their infancy, stem cells (iPS), which are, so to speak, the raw material for the reconstruction of tissue irreparably damaged by disease. For regenerative medicine the implications of Yamanaka's discovery are obvious. Adult skin cells can for example be reprogrammed and transformed into any other cell that is desired: from the skin to the brain, from the skin to the heart, from the skin to elements that produce insulin.

"Their discovery - says the statement of the jury that awarded him the Nobel Prize on October 8 - has revolutionized our understanding of how cells and organisms develop. Through the programming of human cells, scientists have created new opportunities for the study of diseases and development of methods for the diagnosis and therapy ".

These "opportunities" are not only "scientific", but also "ethical". Much of the scientific research and global investment is in fact launched to design and produce stem cells from embryos, arriving at the point of manipulating and destroying them, facing scientists with enormous ethical problems.

" Ethics are really difficult - Yamanaka explainsto Mainichi - In the United States I began work on mouse experiments, and when I returned to Japan I learned that human embryonic stem cells had been created. I was happy that they would contribute to medical science, but I faced an ethical issue. I started iPS cell research as a way to do good things as a researcher, and I wanted to do what I could to expand the merits of embryonic stem cells. If we make sperm or eggs from iPS cells, however, it leads to the creation of new life, so the work I did on iPS cells led to an ethical problem. If we don't prepare debates for ethical problems in advance, technology will proceed ahead faster than we think.. "

The "ethical question" Yamanaka pushed to find a way to "not keep destroying embryos for our research."

Speaking with his co-workers at the University of Kyoto, immediately after receiving the award, Yamanaka showed dedication and modesty.

"Now - he said - I strongly feel a sense of gratitude and responsibility" gratitude for family and friends who have supported him in a demanding journey of discovery that lasted decades; responsibility for a discovery that gives hope to millions of patients. Now iPS cells can grow into any tissue of the human body allowing regeneration of parts so far irretrievably lost due to illness.

Originally posted here:
10/11/2012 10:05 JAPAN Nobel Prize for Yamanaka, scientific research and ethics must go hand in hand

ScienceDaily (Oct. 11, 2012) The generation of functional thyroid tissue from stem cells could allow the treatment of patients, which suffer from thyroid hormone deficiency due to defective function, or abnormal development of the thyroid gland. The team of Sabine Costagliola at the IRIBHM (Universit Libre de Bruxelles) recently developed a protocol that allowed for the first time the efficient generation of functional thyroid tissue from stem cells in mice and published the results of their studies in the scientific journal Nature.

Thyroid hormones are a class of iodide-containing molecules that play a critical role in the regulation of various body function including growth, metabolism and heart function and that are crucial for normal brain development. The thyroid gland, an endocrine organ that has been specialized in trapping iodide, is the only organ where these hormones are produced. It is, however, of note that one out of 3000 human newborns is born with congenital hypothyroidism, a condition characterized by insufficient production of thyroid hormones. In the absence of a medical treatment with thyroid hormones -- initiated during the first days after birth -- the child will be affected by an irreversible mental retardation. Moreover, a life-long hormonal treatment is necessary in order to maintain proper regulation of growth and general metabolism.

By employing a protocol in which two important genes can be transiently induced in undifferentiated stem cells, the researchers at IRIBHM were able to efficiently push the differentiation of stem cells into thyrocytes, the primary cell type responsible for thyroid hormone production in the thyroid gland.

A first exciting finding of these studies was the development of functional thyroid tissue already within the culture dishes. As a next step, the team of Sabine Costagliola transplanted the stem-cell-derived thyrocytes into mice lacking a functional thyroid gland. Four weeks after transplantation, the researchers observed that transplanted mice had re-established normal levels of thyroid hormones in their blood and were rescued from the symptoms associated with thyroid hormone deficiency. These findings have several important implications. First, the cell system employed by the IRIBHM group provides a vital tool to better characterize the molecular processes associated with embryonic thyroid development. Second, the results of the transplantation studies open new avenues for the treatment of thyroid hormone deficiency but also for the replacement of thyroid tissue in patients suffering from thyroid cancer.

The researchers are currently developing a similar protocol based on human stem cells and explore ways to generate functional human thyroid tissue by reprogramming pluripotent stem cells (iPS) derived from skin cells.

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The above story is reprinted from materials provided by Universit Libre de Bruxelles, via AlphaGalileo.

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Link:
Generation of functional thyroid tissue from stem cells

ScienceDaily (Oct. 11, 2012) In recent years investigators have discovered that breast tumors are influenced by more than just the cancer cells within them. A variety of noncancerous cells, which in many cases constitute the majority of the tumor mass, form what is known as the "tumor microenvironment." This sea of noncancerous cells and the products they deposit appear to play key roles in tumor pathogenesis.

Among the key accomplices in the tumor microenvironment are mesenchymal stem cells (MSCs), a group of adult progenitor cells which have been shown to help breast cancers maneuver and spread to other parts of the body.

Now, new research sheds further light on how this is happening. Led by investigators at Beth Israel Deaconess Medical Center (BIDMC), the findings demonstrate that the lysyl oxidase (LOX) gene is spurred to production in cancer cells as a result of their contact with MSCs, and once produced, can help ensure the spread of otherwise weakly metastatic cancer cells from primary tumors to the lung and bones. Described on-line in the Proceedings of the National Academy of Sciences (PNAS), this discovery not only provides key insights into the basic biology of tumor formation, but also offers a potential new direction in the pursuit of therapies for the treatment of bone metastasis.

"We don't have a lot of therapies that can target breast cancer once it has metastasized, particularly once cancer cells have lodged in the bone," says senior author Antoine Karnoub, PhD, an investigator in the Department of Pathology at BIDMC and Assistant Professor of Pathology at Harvard Medical School. "When breast cancer cells reach the skeleton, one way in which they cause damage is by breaking down bone tissue, which results in the bone's rich matrix releasing numerous factors. These factors, in turn, feed the cancer cells, setting in motion a vicious cycle that leaves patients susceptible to fractures, pain, and further metastasis."

MSCs are non-hematopoietic progenitor cells predominantly produced in the bone marrow that generate bone, cartilage, fat, and fibrous connective tissue. They additionally support immune cell development and are recruited to inflammatory sites throughout the body to help shut down immune responses and regenerate damaged tissues, as might occur during wound healing. Several years ago, as a postdoctoral researcher at the Whitehead Institute of the Massachusetts Institute of Technology, Karnoub began exploring the idea that MSCs were migrating to tumors after mistaking the cancer sites for inflammatory lesions in need of healing.

"We discovered that once MSCs had reached the tumor sites, they were actually helping in cancer metastasis, causing primary cancer cells to spread to other sites in the body," he explains. In this new paper, Karnoub wanted to find out, in greater molecular detail, how breast cancer cells respond to the influences of MSCs in order to better understand how cancer cells cross-talk with recruited cells in the microenvironment.

His scientific team first embarked on a straightforward experiment. "We took two dishes of cells, cancer cells and MSCs, and mixed them together," explains Karnoub. After three days, they removed the cancer cells and studied them to see how they had changed.

"We found that the lysyl oxidase [LOX] gene was highly upregulated in the cancer cells," he says. "It turns out that when a cancer cell comes in contact with an MSC, it flips on this LOX gene, turning it up by a factor of about 100. So our next question was, 'What happens to the cancer cells when they encounter this boost of LOX that they themselves have produced?'"

The answer, as revealed in subsequent experiments, was that LOX was setting in motion a cell program called epithelial-to-mesenchymal transition (EMT). During EMT, cancer cells that usually clump together undergo a transformation into cells that exhibit decreased adhesion to their neighbors and go their own way. As a result, these cancerous cells are able to migrate, significantly enhancing their ability to metastasize.

"When we put these cells back into mice, they not only formed tumors that metastasized to the lung, but also to the bone," says Karnoub. "This makes you wonder whether the cancer cells in primary tumors have become so acclimated to interacting with bone-derived MSCs that they can now grow more easily in the bone once they leave the tumor."

Original post:
Clues to cancer metastasis: Discovery points to potential therapies for bone metastasis

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

Contact: Bonnie Prescott bprescot@bidmc.harvard.edu 617-667-7306 Beth Israel Deaconess Medical Center

BOSTON In recent years investigators have discovered that breast tumors are influenced by more than just the cancer cells within them. A variety of noncancerous cells, which in many cases constitute the majority of the tumor mass, form what is known as the "tumor microenvironment." This sea of noncancerous cells and the products they deposit appear to play key roles in tumor pathogenesis.

Among the key accomplices in the tumor microenvironment are mesenchymal stem cells (MSCs), a group of adult progenitor cells which have been shown to help breast cancers maneuver and spread to other parts of the body.

Now, new research sheds further light on how this is happening. Led by investigators at Beth Israel Deaconess Medical Center (BIDMC), the findings demonstrate that the lysyl oxidase (LOX) gene is spurred to production in cancer cells as a result of their contact with MSCs, and once produced, can help ensure the spread of otherwise weakly metastatic cancer cells from primary tumors to the lung and bones. Described on-line in the Proceedings of the National Academy of Sciences (PNAS), this discovery not only provides key insights into the basic biology of tumor formation, but also offers a potential new direction in the pursuit of therapies for the treatment of bone metastasis.

"We don't have a lot of therapies that can target breast cancer once it has metastasized, particularly once cancer cells have lodged in the bone," says senior author Antoine Karnoub, PhD, an investigator in the Department of Pathology at BIDMC and Assistant Professor of Pathology at Harvard Medical School. "When breast cancer cells reach the skeleton, one way in which they cause damage is by breaking down bone tissue, which results in the bone's rich matrix releasing numerous factors. These factors, in turn, feed the cancer cells, setting in motion a vicious cycle that leaves patients susceptible to fractures, pain, and further metastasis."

MSCs are non-hematopoietic progenitor cells predominantly produced in the bone marrow that generate bone, cartilage, fat, and fibrous connective tissue. They additionally support immune cell development and are recruited to inflammatory sites throughout the body to help shut down immune responses and regenerate damaged tissues, as might occur during wound healing. Several years ago, as a postdoctoral researcher at the Whitehead Institute of the Massachusetts Institute of Technology, Karnoub began exploring the idea that MSCs were migrating to tumors after mistaking the cancer sites for inflammatory lesions in need of healing.

"We discovered that once MSCs had reached the tumor sites, they were actually helping in cancer metastasis, causing primary cancer cells to spread to other sites in the body," he explains. In this new paper, Karnoub wanted to find out, in greater molecular detail, how breast cancer cells respond to the influences of MSCs in order to better understand how cancer cells cross-talk with recruited cells in the microenvironment.

His scientific team first embarked on a straightforward experiment. "We took two dishes of cells, cancer cells and MSCs, and mixed them together," explains Karnoub. After three days, they removed the cancer cells and studied them to see how they had changed.

"We found that the lysyl oxidase [LOX] gene was highly upregulated in the cancer cells," he says. "It turns out that when a cancer cell comes in contact with an MSC, it flips on this LOX gene, turning it up by a factor of about 100. So our next question was, 'What happens to the cancer cells when they encounter this boost of LOX that they themselves have produced?'"

Link:
Discovery reveals important clues to cancer metastasis