Category Archives: Stem Cells

June 27, 2013 A chemical code scrawled on histones -- the protein husks that coat DNA in every animal or plant cell -- determines which genes in that cell are turned on and which are turned off. Now, Stanford University School of Medicine researchers have taken a new step in the deciphering of that histone code.

In a study published June 27 in Cell Reports, a team led by Thomas Rando, MD, PhD, professor of neurology and neurological sciences and chief of the Veterans Affairs Palo Alto Health Care System's neurology service, has identified characteristic differences in "histone signatures" between stem cells from the muscles of young mice and old mice. The team also distinguished histone-signature differences between quiescent and active stem cells in the muscles of young mice.

"We've been trying to understand both how the different states a cell finds itself in can be defined by the markings on the histones surrounding its DNA, and to find an objective way to define the 'age' of a cell," said Rando, who is also director of Stanford's Glenn Laboratories for the Biology of Aging and deputy director of the Stanford Center on Longevity.

While all cells in a person's body share virtually the same genes, these cells can be as different from one another as a nerve cell is from a fat cell. This is because only a fraction of a cell's genes are actually "turned on" -- actively involved in the production of one or another protein. A muscle cell produces the proteins it uses to be a muscle cell, a liver cell produces those it needs in order to be a liver cell and so forth. Rando's team thinks the same kinds of on/off differences may distinguish old stem cells from young stem cells.

In human cells, the DNA in which genes are found doesn't float loose inside the cell nucleus but is, rather, packaged inside protein "husks" called histones. Chemical marks on the histones, which sheathe our chromosomal DNA in each cell's nucleus, act as "stop" and "go" traffic signals. These signals tell the complex molecular machinery that translates genes' instructions into newly produced proteins which genes to read and which ones to skip.

In 2005, Rando and his colleagues published a study in Nature showing that stem cells in several tissues of older mice, including muscle, seemed to act younger after continued exposure to younger mice's blood. Their capacity to divide, differentiate and repopulate tissues, which typically declines with an organism's advancing age, resembled those of their stem-cell counterparts in younger animals.

This naturally led to curiosity about exactly what is happening inside a cell to rejuvenate it, said Rando. One likely place to look for an answer was histones, to see if changes in the patterns of the chemical marks on them might reveal any secrets, at the cellular level, of the aging process we all experience -- and, perhaps, whether there might be anything we can do about it. Rando and his colleagues also wanted to learn more about what kinds of difference in these patterns accompany a cell's transition from one level of activity to another.

To do that, Rando and his team looked at satellite cells, an important class of stem cells that serve as a reserve army of potential new muscle tissue. Under normal circumstances, these rather rare stem cells sit quietly adjacent to muscle fibers. But some signal provided by muscular injury or degeneration prompts satellite cells to start dividing and then to integrate themselves into damaged fibers, repairing the muscle tissue. The investigators profiled the histone markings of mice that are as old, in mouse years, as young human adults, as well as mice whose human counterparts would be 70 to 80 years old.

The researchers harvested satellite cells from both healthy and injured muscle tissue of young mice and from healthy tissue of old mice; extracted these cells' DNA with the histone coatings intact; and used tagged antibodies targeting the different kinds of marks to find which spots on those histones were flagged with either "stop" or "go" signals.

"Satellite cells can sit around for practically a lifetime in a quiescent state, not doing much of anything. But they're ready to transform to an activated state as soon as they get word that the tissue needs repair," Rando said. "So, you might think that satellite cells would be already programmed in a way that commits them solely to the 'mature muscle cell' state." The researchers expected that in these quiescent stem cells, the genes specific for other tissues like skin and brain would be marked by "stop" signals.

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Scientists discern signatures of old versus young stem cells

Javascript is currently disabled in your web browser. For full site functionality, it is necessary to enable Javascript. In order to enable it, please see these instructions. 3 hours ago by David Tenenbaum Su-Chun Zhang (left) talks with postdoctoral student Lin Yao as she prepares stem-cell cultures in the Zhangs research lab at the Waismam Center. Credit: Jeff Miller

Many scientists use animals to model human diseases. Mice can be obese or display symptoms of Parkinson's disease. Rats get Alzheimer's and diabetes.

But animal models are seldom perfect, and so scientists are looking at a relatively new type of stem cell, called the induced pluripotent stem cell (iPS cell), that can be grown into specialized cells that become useful models for human disease.

IPS cells are usually produced by reprogramming a skin sample into a primitive form that is able to develop into all of the specialized cells in the body. In the laboratories at the Waisman Center at UW-Madison, scientists are growing iPS cells into models of disorders caused by defective nerve cells. The technology depends on work pioneered over the past decade or so by Su-Chun Zhang, a neuroscientist who leads the iPS Core at Waisman, which also produces cells for other investigators on campus.

The multidisciplinary Waisman Center, now in its 40th year, combines treatment with clinical and basic research to address many of the most complex and disabling disorders of development.

"Animals are small and incredibly helpful," says Zhang, a professor of neuroscience and neurology, "but if we take the neurological disorders that the Waisman Center focuses on, including Parkinson's, Huntington's, retinal degeneration, ALS, spinal muscular dystrophy, Down syndrome and autism, animal models often do not precisely mimic what we see in patients."

Zhang was the first in the world to overcome the primary challenge for using embryonic stem cells, and now iPS cells, to model neurological disease: mastering the subtle chemical cues that force a stem cell to develop into neurons, which carry nerve signals. "Now, we can not only direct iPS cells to become neurons, but also into very defined types of neurons that are involved in the diseases that most interest us," he says.

In his own research, Zhang focuses on ALS (Lou Gehrig's disease) and other fatal diseases that destroy the neurons that control movement. "IPS cells can create motor neurons that grow in a Petri dish and tell you, 'I am sick.' We see the same characteristic blobs and tangles in the long fiber of the nerve cells. Something is blocking traffic so the sub-units inside the cell cannot pass through these long fibers. This is exactly what we see in patients."

Using iPS-derived cells, Zhang is attempting to find drugs that ease the traffic. "We can take the traffic jam and use it as a readouta signalin a dish, and screen as many as 1,000 compounds and approved drugs at a time, to see if we can find something that can open this traffic jam."

Drug screening, in fact, is only one goal of the focus on iPS cells as neurological disease models at Waisman:

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Scientists model human disease in stem cells

Researchers believe killing stem cells is key to improving cancer treatment

Newswise ANN ARBOR, Mich. A major reason that breast cancer returns after treatment and spreads to other parts of the body is that current chemotherapy and radiation treatments do not kill the cancer stem cells.

That premise provides the basis for a clinical trial open at the University of Michigan Comprehensive Cancer Center and two other sites testing a drug that has been found in laboratory studies to attack cancer stem cells. The drug, reparixin, will be used in combination with standard chemotherapy.

This is one of only a few trials testing stem cell directed therapies in combination with chemotherapy in breast cancer. Combining chemotherapy with stem cell therapy has the potential to lengthen remissions for women with advanced breast cancer, says principal investigator Anne Schott, M.D., associate professor of internal medicine at the University of Michigan.

Cancer stem cells are the small number of cells within a tumor that fuel its growth and spread.

The phase Ib study will test reparixin, which is taken orally, along with the chemotherapy drug paclitaxel in women with HER2-negative metastatic breast cancer. The study is primarily intended to test how patients tolerate this drug combination, but researchers will also look at how reparixin appears to be impacting markers for cancer stem cells and signs of inflammation. The study will also look at how effective this treatment combination is at controlling the cancer and impacting survival.

The clinical trial stems from laboratory research at U-M that identified a receptor called CXCR1 on the cancer stem cells that triggers growth of stem cells in response to inflammation and tissue damage. Adding reparixin to chemotherapy in laboratory studies specifically targeted and killed breast cancer stem cells by blocking CXCR1.

Mice treated with reparixin or the combination of reparixin and chemotherapy had dramatically fewer cancer stem cells than those treated with chemotherapy alone. In addition, reparixin-treated mice developed significantly fewer metastases than mice treated with chemotherapy alone.

The study is sponsored by Domp S.p.A. For more information about this trial, Phase Ib pilot study to evaluate reparixin in combination with chemotherapy with weekly paclitaxel in patients with HER-2 negative metastatic breast cancer (MBC), call the U-M Cancer AnswerLine at 800-865-1125.

Breast cancer statistics: 234,580 Americans will be diagnosed with breast cancer this year and 40,030 will die from the disease, according to the American Cancer Society

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Breast Cancer Clinical Trial Looks at Targeting Cancer Stem Cells

Lower layer of skin cells lie 'sleeping' and are used to repair damaged skin Model predicts these stem cells lose the ability to regenerate as we age Scientists claim preventing this process could be key to everlasting youth

By Daily Mail Reporter

PUBLISHED: 07:45 EST, 27 June 2013 | UPDATED: 07:52 EST, 27 June 2013

The secret to the fountain of youth lies in awakening sleeping' stem cells in the skin, according to new research.

A computer model found that as we grow older, we lose the ability to trigger these master cells to kick into action and regenerate damaged skin.

British and U.S. scientists say the breakthrough may open the door to the development of better beauty treatments to zap wrinkles for good.

Fountain of youth: Scientists say targeting inactive skin-stem cells may be the answer to overcoming signs of ageing

In the longest study of its kind, they carried out a complex virtual simulation to test the three most popular hypotheses of how our skin regenerates over three years.

Engineer Dr Xinshan Li said: 'The theory which seems to fit best says skin has a population of "sleeping" stem cells, which sit in the lowest layer of the skin but do not constantly divide to make new cells.

'However, these sleeping cells can be called into action if the skin is damaged, or if the numbers of other types of more mature skin cells decrease, ensuring the skin can be constantly regenerated under all conditions.'

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The secret to eternal youth? Awakening 'sleeping' stem cells in the skin, say scientists

Public release date: 27-Jun-2013 [ | E-mail | Share ]

Contact: Bruce Goldman goldmanb@stanford.edu 650-725-2106 Stanford University Medical Center

STANFORD, Calif. A chemical code scrawled on histones the protein husks that coat DNA in every animal or plant cell determines which genes in that cell are turned on and which are turned off. Now, Stanford University School of Medicine researchers have taken a new step in the deciphering of that histone code.

In a study to be published June 27 in Cell Reports, a team led by Thomas Rando, MD, PhD, professor of neurology and neurological sciences and chief of the Veterans Affairs Palo Alto Health Care System's neurology service, has identified characteristic differences in "histone signatures" between stem cells from the muscles of young mice and old mice. The team also distinguished histone-signature differences between quiescent and active stem cells in the muscles of young mice.

"We've been trying to understand both how the different states a cell finds itself in can be defined by the markings on the histones surrounding its DNA, and to find an objective way to define the 'age' of a cell," said Rando, who is also director of Stanford's Glenn Laboratories for the Biology of Aging and deputy director of the Stanford Center on Longevity.

While all cells in a person's body share virtually the same genes, these cells can be as different from one another as a nerve cell is from a fat cell. This is because only a fraction of a cell's genes are actually "turned on" actively involved in the production of one or another protein. A muscle cell produces the proteins it uses to be a muscle cell, a liver cell produces those it needs in order to be a liver cell and so forth. Rando's team thinks the same kinds of on/off differences may distinguish old stem cells from young stem cells.

In human cells, the DNA in which genes are found doesn't float loose inside the cell nucleus but is, rather, packaged inside protein "husks" called histones. Chemical marks on the histones, which sheathe our chromosomal DNA in each cell's nucleus, act as "stop" and "go" traffic signals. These signals tell the complex molecular machinery that translates genes' instructions into newly produced proteins which genes to read and which ones to skip.

In 2005, Rando and his colleagues published a study in Nature showing that stem cells in several tissues of older mice, including muscle, seemed to act younger after continued exposure to younger mice's blood. Their capacity to divide, differentiate and repopulate tissues, which typically declines with an organism's advancing age, resembled those of their stem-cell counterparts in younger animals.

This naturally led to curiosity about exactly what is happening inside a cell to rejuvenate it, said Rando. One likely place to look for an answer was histones, to see if changes in the patterns of the chemical marks on them might reveal any secrets, at the cellular level, of the aging process we all experience and, perhaps, whether there might be anything we can do about it. Rando and his colleagues also wanted to learn more about what kinds of difference in these patterns accompany a cell's transition from one level of activity to another.

To do that, Rando and his team looked at satellite cells, an important class of stem cells that serve as a reserve army of potential new muscle tissue. Under normal circumstances, these rather rare stem cells sit quietly adjacent to muscle fibers. But some signal provided by muscular injury or degeneration prompts satellite cells to start dividing and then to integrate themselves into damaged fibers, repairing the muscle tissue. The investigators profiled the histone markings of mice that are as old, in mouse years, as young human adults, as well as mice whose human counterparts would be 70 to 80 years old.

Continued here:
Stanford scientists discern signatures of old versus young stem cells

June 24, 2013 A promising new treatment for breast cancer being developed at Virginia Commonwealth University Massey Cancer Center and the VCU Institute of Molecular Medicine (VIMM) has been shown in cell culture and in animal models to selectively kill cancer stem cells at the original tumor site and in distant metastases with no toxic effects on healthy cells, including normal stem cells. Cancer stem cells are critical to a cancer's ability to recur following conventional chemotherapies and radiation therapy because they can quickly multiply and establish new tumors that are often therapy resistant.

The study, published in the International Journal of Cancer, focuses on a gene originally cloned in the laboratory of primary investigator Paul B. Fisher, M.Ph., Ph.D. The gene, melanoma differentiation associated gene-7 (mda-7), also known as interleukin (IL)-24, has been shown to directly impact two forms of cell suicide known as apoptosis and toxic autophagy, regulate the development of new blood vessels and also play a role in promoting cancer cell destruction by the immune system. In the present study, the researchers used a recombinant adenovirus vector, an engineered virus with modified genetic material, known as Ad.mda-7 to deliver the mda-7/IL-24 gene with its encoded protein directly to the tumor.

"Therapy with the mda-7/IL-24 gene has been shown to be safe in a phase I clinical trial involving patients with advanced cancers, and prior studies in my laboratory and with collaborators have shown that the gene could also be effective against breast, prostate, lung, colorectal, ovarian, pancreatic and brain cancers," says Fisher, Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics program at VCU Massey, chairman of VCU School of Medicine's Department of Human and Molecular Genetics and director of the VCU Institute of Molecular Medicine. "Our study demonstrates that this therapy may someday be an effective way to eradicate both early and advanced stage breast cancer, and could even be used to reduce the risk of cancer recurrence."

The researchers found that infection of human breast cancer cells with the adenovirus decreased the proliferation of breast cancer stem cells without affecting normal breast stem cells. It was also shown to induce a stress response in the cells that led to apoptosis by disrupting Wnt/B-catenin signaling, a process cells rely upon to transmit signals that initiate biological functions critical to survival. In mouse models, the therapy profoundly inhibited the growth of tumors generated from breast cancer stem cells and also killed cancer cells in distant, uninjected tumors.

Since discovering the mda-7/IL-24 gene, Fisher and his team have worked to develop better ways to deliver it to cancer cells, including two cancer "terminator" viruses known as Ad.5-CTV and Ad.5/3-CTV. Cancer terminator viruses are unique because they are designed to replicate only within cancer cells while delivering immune-modulating and toxic genes such as MDA-7/IL-24. Coupled with a novel stealth delivery technique known as ultrasound-targeted microbubble destruction (UTMD), researchers can now systemically deliver viruses and therapeutic genes and proteins directly to tumors and their surrounding tissue (microenvironment) at both primary and metastatic tumor sites. UTMD uses microscopic, gas-filled bubbles that can be paired with viral therapies, therapeutic genes and proteins, and imaging agents and can then be released in a site and target-specific manner via ultrasound. Fisher and his colleagues are pioneering this approach and have already reported success in experiments utilizing UTMD technology and mda-7/IL-24 gene therapy in prostate and colorectal cancer models.

"We are hopeful that this targeted gene therapy could be safely combined with conventional chemotherapies to significantly improve outcomes for patients with breast cancer and potentially a variety of other cancers," says Fisher. "When paired with promising new delivery techniques such as UTMD, physicians may one day be able to better target site-specific cancers and also monitor the effectiveness of these types of therapies in real time."

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Targeted viral therapy destroys breast cancer stem cells in preclinical experiments

ALBANY, New York, June 25, 2013 /PRNewswire/ --

According to a new market report published by Transparency Market Research (http://www.transparencymarketresearch.com) "Stem Cells Market (Adult, Human Embryonic , Induced Pluripotent, Rat-Neural, Umbilical Cord, Cell Production, Cell Acquisition, Expansion, Sub-Culture)-Global Industry Analysis, Size, Share, Growth, Trends and Forecast,2012-2018," the market for stem cells was valued at USD 26.23 billion in 2011 and is expected to reach an estimated value of USD 119.51 billion in 2018, growing at a CAGR of 24.2% from 2012 to 2018.

Browse the full report athttp://www.transparencymarketresearch.com/stem-cells-market.html

The market growth is majorly attributed to therapeutic research activities led by government support worldwide owing to the growing number of patients with chronic diseases across the globe. In addition, rising awareness of regenerative treatment options and growing importance of stem cell banking services are also fostering the growth of the market. Apart from these, development of medical tourism hubs in developing nations such as India and China and in turn migration of patients from developed nations such as the U.S., and Europe for quality treatment at significantly lower prices will also serve the market as a driver especially for the Asian stem cells market.

Stem cells market will be driven by rising proportion of patients with neurological and other chronic conditions and rising disposable incomes of patients induced by economic growth of Asian regions in the next five years In addition, increasing dependence on stem cells for drug discovery and screening will boost the growth of the market in future. Increased outsourcing of contract research and clinical trials to developing Asian regions will further encourage growth of the stem cells market.

Adult stem cells held majority share of the overall stem cells market in 2011 at over 80%. This is due to less laborious procedure of harvesting, and less probability of contamination during expansion and sub-culture of adult stem cells. However, fewer post-transplant complications and lesser risk of graft vs. host reaction from the recently introduced induced pluripotent stem cells will lead to its rapid inclusion in research activities and help the global induced pluripotent stem cells market to grow at a relatively faster CAGR during the forecast period.

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Stem Cells Market is Expected to Reach USD 119.51 Billion Globally in 2018: Transparency Market Research

Philippine Daily Inquirer

Stem cells are the foundation of every organ, tissue and cell in the human body that do not yet have a specific physiological function but have the potential to develop into many different cell types.

They are also distinguished from other cells by their ability to self-

renew. Stem cells divide and give rise to more stem cells. When a stem cell divides, each new cell has the potential to either remain as a stem cell or become another type of cell with a more specialized function, such as a muscle cell, red blood cell or brain cell.

According to the National Institutes of Healths Center for Regenerative Medicine, scientists primarily work with two kinds of stem cellsembryonic stem cells and nonembryonic somatic or adult stem cells.

Embryonic stem cells are obtained from the inner cell mass of a blastocyst, the ball of cells formed when the fertilized egg or zygote divides and forms two cells (then again to form four and so on). It can divide almost indefinitely and can give rise to every cell type in the body.

Adult stem cells, on the other hand, are found in differentiated tissues and organs throughout the body and contribute to the maintenance and repair of organs.

Stem cells offer the possibility of replacement cells to treat a wide variety of diseases and disabilities, including diabetes, neurological disease, cardiovascular disease, blood disease and many other conditions.

According to the Harvard Stem Cell Institute (HSCI), embryonic stem cells have not yet been used to treat diseases in humans, but progress has been made in the introduction of the first clinical trial using embryonic stem cells in the area of treating spinal cord injury.

Adult stem cell-based therapies have been used to treat diseases in humans for over 40 years in the form of bone marrow transplants, according to HSCI. These are used to treat leukemia, lymphoma and inherited blood disorders.

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In the Know: Stem cells