Category Archives: Stem Cells

Washington, May 25 : A study led by an Indian origin scientist has discovered a drug that successfully kills cancer stem cells in the human while avoiding the toxic side-effects of conventional cancer treatments.

Unlike chemotherapy and radiation, the drug - thioridazine - appears to have no effect on normal stem cells, according to the scientists at McMaster University.

"The unusual aspect of our finding is the way this human-ready drug actually kills cancer stem cells; by changing them into cells that are non-cancerous," said Mick Bhatia, the principal investigator for the study and scientific director of McMaster's Stem Cell and Cancer Research Institute in the Michael G. DeGroote School of Medicine.

The finding holds the promise of a new strategy and discovery pipeline for the development of anticancer drugs in the treatment of various cancers. The research team has identified another dozen drugs that have good potential for the same response.

To test more than a dozen different compounds, McMaster researchers pioneered a fully automated robotic system to identify several drugs, including thioridazine.

Bhatia's team found thioridazine works through the dopamine receptor on the surface of the cancer cells in both leukemia and breast cancer patients.

This means it may be possible to use it as a biomarker that would allow early detection and treatment of breast cancer and early signs of leukemia progression, he said.

The research team's next step is to investigate the effectiveness of the drug in other types of cancer. In addition, the team will explore several drugs identified along with thioridazine.

The research has been published in the science journal CELL. (ANI)

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New drug destroys human cancer stem cells without affecting healthy ones

By Jenny Hope

PUBLISHED: 18:09 EST, 22 May 2012 | UPDATED: 01:35 EST, 23 May 2012

Scientists claim they can rejuvenate broken hearts using skin cells that have been turned into heart muscle cells.

New research opens up the prospect of reprogramming cells taken from heart failure patients that would not be rejected by their bodies.

It is the first time that stem cells taken from the skin of elderly and diseased patients - who are most likely to need such treatment - have been transformed into heart cells.

New developments: The research opens up the prospect of reprogramming cells taken from heart failure patients that would not be rejected by their bodies

Previously skin cells taken from young and healthy people have been transformed into heart muscle cells.

But researchers from Israel warn that clinical trials could be a decade away, as more work in the laboratory and major investment are needed.

The research is the latest advance in stem cell therapy where the intention is to infused repair cells directly into the scarred heart muscle of patients suffering debilitating symptoms such as breathlessness and fatigue.

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How damaged hearts could be healed by growing stem cells

ScienceDaily (May 22, 2012) Researchers at the Hebrew University of Jerusalem have achieved, for the first time, the generation of neuronal cells from stem cells of Fragile X patients. The discovery paves the way for research that will examine restoration of normal gene expression in Fragile X patients.

Absence of expression of the FMR1 gene is caused by a mutation in the regulatory elements that govern its expression. The abnormal addition of chemical methyl groups to the regulatory elements causes gene silencing in patients, culminating in severe mental retardation.

A potential way to help patients is to find compounds that will clear the abnormal methyl groups from the regulatory elements and reactivate normal gene expression. In their work, the Hebrew University researchers have identified a chemical compound that restored normal gene expression specifically in neuronal cells, the cell type most affected in patients.

The research was conducted in the laboratory of Nissim Benvenisty, the Herbert Cohn Professor of Cancer Research at the Hebrew University, by PhD student Ori Bar-Nur and undergraduate student Inbal Caspi. They demonstrated, for the first time, the generation of brain neuronal cells from patients of Fragile X syndrome in a dish culture. In doing so, they were able to find a substance that restored normal gene expression in patients' cells.

In a previous study conducted in the Benvenisty laboratory, a novel technology was used to induce pluripotent stem cells from skin cells of Fragile X patients. Pluripotent stem cells have the amazing ability to differentiate into any human cell type in a dish culture.

In their latest study (published in the Journal of Molecular Cell Biology), the researchers harnessed this ability to turn the stem cells into neuronal brain cells. After generating the cells, they screened several chemical substances with the aim of finding one that would restore FMR1 normal gene expression. They showed that the substance 5-azaC was able to clear the methyl groups from the regulatory elements of the gene, allowing for the efficient restoration of FMR1 expression in both stem and neuronal brain cells.

The substance 5-azaC has been known for many years to clear methyl groups from regulatory elements of genes, and is also an already established drug for other diseases. However, this is the first time that it has been shown to successfully clear the methylation in neurons or stem cells of Fragile X patients.

In addition, the researchers were able to show that gene expression is maintained even after 5-azaC withdrawal, so there is no need to administer it continuously. This raises hopes for the use of the compound as a potential drug for the benefit of Fragile X patients.

According to Bar-Nur, "There is still a substantial gap between the restoration of gene expression in cultured patients' cells and restoring it in patients; however, the finding that it is possible to restore gene expression in neuronal cells paves the way for further study of its restoration in patients." He concludes: "New technologies developed in recent years in the stem cell field allow us to conduct research that was not possible until recently."

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Stem cell research paves way for progress on dealing with Fragile X

ATLANTA and ROYAL OAK, Mich., May 22, 2012 /PRNewswire/ -- Findings from a multi-center trial led by researchers at Beaumont Hospital in Royal Oak, Mich. may give urologists another minimally invasive treatment option for women with stress urinary incontinence. The study showed that treating a woman with her own muscle-derived stem cells was both safe and effective. Unlike surgical treatments, this procedure takes place in a physician's office.

According to the National Institutes of Health, millions of women experience urinary incontinence, a medical condition that causes involuntary loss of urine. There are several types of incontinence. This study focused on women with stress urinary incontinence, the most common type, affecting women of all ages. It causes leakage of urine when sneezing, coughing, lifting, laughing or physical exertion.

The study's principal investigator, Kenneth Peters, M.D., medical director, Women's Urology Center, Beaumont Health System; and professor and chairman of Urology, Oakland University William Beaumont School of Medicine presented the results at the American Urological Association's Annual Meeting on May 22 in Atlanta.

Along with Beaumont, Royal Oak; Vanderbilt University Medical Center in Nashville, Tenn.; and Sunnybrook Health Sciences Centre in Toronto, Canada served as study sites.

The three sites enrolled 64 participants. Cells were taken from a biopsy of the patient's thigh muscle, which was then sent to a laboratory where stem cells were isolated from the muscle. The isolated cells were cultured to grow more of the patient's stem cells. After six to eight weeks, the stem cells were available for treatment. The cells were injected into the sphincter. Four different doses were studied over one year: 10 million cells; 50 million cells; 100 million cells; and 200 million cells.

"This was an incredibly safe method of treatment. There were no significant side effects," explains Dr. Peters. "Also noteworthy, is the majority of patients treated had a significant improvement in their urinary leakage and up to 60 percent of the women became dry, leading to an improved quality of life. Because of the positive results, our research team is considering a larger phase III trial."

The women who participated in the study were age 18 and older with symptoms of stress urinary incontinence. They failed prior treatment for their condition and showed no improvement in their symptoms over the previous six months.

"It's a very practical study that applies stem cell technology, specifically muscle-derived cells. We're treating patients with their own tissue - their own building blocks," adds Dr. Peters. "And we're moving from a surgical to an office-based treatment."

The study was funded by Cook MyoSite Inc. in Pittsburgh, a Cook Group company.

Available Topic Expert(s): For information on the listed expert(s), click appropriate link. Kenneth Peters, M.D. https://profnet.prnewswire.com/Subscriber/ExpertProfile.aspx?ei=48407

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Beaumont Researchers: Patient's Stem Cells Show Promise In Treating Female Stress Urinary Incontinence

A growth factor isolated from human stem cells shows promising results in a mouse model of multiple sclerosis.

Human mesenchymal stem cells (hMSCs) have become a popular potential therapy for numerous autoimmune and neurological disorders. But while these bone marrow-derived stem cells have been studied in great detail in the dish, scientists know little about how they modulate the immune system and promote tissue repair in living organisms.

Now, one research team has uncovered a molecular mechanism by which hMSCs promote recovery in a mouse model of multiple sclerosis (MS).

According to research, published online Sunday (May 20) in Nature Neuroscience, a growth factor produced by hMSCs fights MS in two ways: blocking a destructive autoimmune response and repairing neuronal damage. The finding could help advance ongoing clinical trials testing hMSCs as a therapy for MS.

The researchers have identified a unique factor that has surprisingly potent activity mediating neuron repair, said Jacques Galipeau, a cell therapy researcher at Emory University in Atlanta, Georgia, who was not involved in the research. The magnitude of the effect on a mouse model of MS is a big deal.

MS is an autoimmune disease in which the immune system attacks myelin sheaths that surround and protect nerve cells. The attack leaves nerves exposed and unable to send signals to the brain and back, resulting in the loss of motor skills, coordination, vision, and cognitive abilities. There is no cure for MS, and most current therapies work to simply suppress the immune system, preventing further neuronal damage. None have demonstrated an ability to also repair damaged myelin and promote recovery.

In 2009, Robert Miller and colleagues at Case Western Reserve University in Cleveland, Ohio, demonstrated that hMSCs dramatically reversed the symptoms of multiple sclerosis in a mouse model of the disorder. The animals got better, recalled Miller. The team hypothesized that the stem cells suppress the immune response and promote remyelination.

But Miller wanted to know exactly what the cells were doing. To find out, his team isolated the medium on which the hMSCs were grown to determine if the cells or something they secreted was responsible for the observed recovery. The medium alone was enough to induce recovery in mice, pointing to the latter.

To find out exactly which molecule or molecules in the medium were responsible, the researchers separated the proteins in the fluid based on the molecular weight and injected each isolate into mice exhibiting symptoms of MS. The mid-weight solution, of proteins with masses between 50 and 100 kilodaltons (kDa), caused recovery. That eliminated a huge number of potential candidates, said Miller.

The researchers then narrowed the field again with a literature search for a molecule that fit their criteria: secreted by hMSCs, 50-100 kDa in size, and involved in tissue repair. They identified hepatocyte growth factor (HGF), a cytokine made by mesenchymal cells that has been shown to promote tissue regeneration and cell survival in numerous experiments. Sure enough, HGF alone was enough to promote recovery in the MS mouse models, and blocking the receptor for HGF in those mice blocked recovery. The team also demonstrated that HGF suppresses immune responses in vivo and accelerates remyelination of neurons in vitro. Finally, they saw that HGF causes remyelination in rats with a lesion on their spinal cord.

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Could Stem Cells Cure MS?

People who suffer from heart failure could someday be able to use their own skin stem cells to regenerate their damaged heart tissue, according to a new Israeli study.

Researchers took stem cells from the skin of two patients with heart failure and genetically programmed them to become new heart muscle cells. They then transplanted the new cells into healthy rats and found that the cells integrated with cardiac tissue that already existed.

The study, published in European Heart Journal, marks the first time ever that scientists could use skin cells from people with heart failure and transform damaged heart tissue this way.

The newly generated cells turned out to be similar to embryonic stem cells, which can potentially be programmed to grow into any type of cell.

"What is new and exciting about our research is that we have shown that it's possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young the equivalent to the stage of his heart cells when he was just born," Dr. Lior Gepstein, lead researcher and a senior clinical electrophysiologist at Rambam Medical Center in Haifa, Israel, said in a news release.

The findings open up the possibility, the authors wrote, that people can use their own skin cells to repair their damaged hearts, which could prevent the problems associated with using embryonic stem cells.

"This approach has a number of attractive features," said Dr. Tom Povsic, an interventional cardiologist at Duke University Medical Center. "We can get the cells that you start with from the patient himself or herself. It avoids the ethical dilemma associated with embryonic stem cells and it removes the possibility of rejection of foreign stem cells by the immune system." Povsic was not involved with the Israeli study.

Another advantage of using skin cells is that other types of cells taken from patients themselves, such as bone marrow cells, could potentially lead to the development of unhealthy tissue.

"If a patient is already sick with heart disease, one of the reasons it may develop is that stem cells weren't able to repair the heart the way they should," Povsic added. Skin cells, he explained, are generally healthy.

"It is very exciting and very interesting, but we are far away from taking this to patients," said Dr. Marrick Kukin, director of the Heart Failure Program at St. Luke's-Roosevelt Hospital who was also not involved in the Israeli study.

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Can Stem Cells Repair Heart Tissue?

Public release date: 23-May-2012 [ | E-mail | Share ]

Contact: Kate McAlpine kmca@umich.edu 734-763-4386 University of Michigan

ANN ARBOR, Mich.University of Michigan researchers have proven that a special surface, free of biological contaminants, allows adult-derived stem cells to thrive and transform into multiple cell types. Their success brings stem cell therapies another step closer.

To prove the cells' regenerative powers, bone cells grown on this surface were then transplanted into holes in the skulls of mice, producing four times as much new bone growth as in the mice without the extra bone cells.

An embryo's cells really can be anything they want to be when they grow up: organs, nerves, skin, bone, any type of human cell. Adult-derived "induced" stem cells can do this and better. Because the source cells can come from the patient, they are perfectly compatible for medical treatments.

In order to make them, Paul Krebsbach, professor of biological and materials sciences at the U-M School of Dentistry, said, "We turn back the clock, in a way. We're taking a specialized adult cell and genetically reprogramming it, so it behaves like a more primitive cell."

Specifically, they turn human skin cells into stem cells. Less than five years after the discovery of this method, researchers still don't know precisely how it works, but the process involves adding proteins that can turn genes on and off to the adult cells.

Before stem cells can be used to make repairs in the body, they must be grown and directed into becoming the desired cell type. Researchers typically use surfaces of animal cells and proteins for stem cell habitats, but these gels are expensive to make, and batches vary depending on the individual animal.

"You don't really know what's in there," said Joerg Lahann associate professor of chemical engineering and biomedical engineering.

For example, he said that human cells are often grown over mouse cells, but they can go a little native, beginning to produce some mouse proteins that may invite an attack by a patient's immune system.

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Stem-cell-growing surface enables bone repair

May 23, 2012 12:00pm

Replacing dead or dysfunctional nerve cells with new, healthy ones derived from stem cells eases chronic pain in mice, a new study found.

Researchers from the University of California, San Francisco coaxed mouse embryonic stem cells into becoming mature nerve cells that could bridge gaps in the circuitry that triggers neuropathic pain.

One of the major causes of neuropathic pain is the loss of inhibitory control at the level of the spinal cord because of nerve loss or dysfunction, said study author Allan Basbaum, chairman of UCSFs department of anatomy. The idea was to replace or repopulate the spinal cord cells that provide that inhibition.

The same stem cells, destined to become inhibitory neurons that dampen the signals that cause pain, were previously shown to improve symptoms in a mouse model of epilepsy, Basbaum said. The question was whether we could take the exact same cells and put them in the spinal cord.

Before injecting the cells into the spinal cords of mice with neuropathic pain, the researchers labeled them with a fluorescent tracer to track the connections they made.

We were able to show how these cells integrate beautifully, Basbaum said, describingthe waythe transplanted cells looked and behaved like the mouses own.

Not only did the cells set up shop in the spinal cord, sending and receiving signals through a complex network of neurons, they also eased the neuropathic pain.

In four weeks, the animals condition completely disappeared, Basbaum said, adding that transplanted control cells that lacked the inhibitory properties of the stem-cell-derived neurons failed to ease the pain.

The clinical significance is that we think were actually modifying the disease, not just treating the symptoms, Basbaum said, adding that drugs currently used to ease neuropathic pain fail to treat the underlying problem. Instead of taking a drug to suppress the pain, were trying to normalize the circuit that was damaged by the disease or the injury. The cells repopulate, they integrate, and basically they treat the disease.

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Stem Cells Curb Chronic Pain in Mice