Category Archives: Stem Cell Videos

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

Date: Thursday May. 24, 2012 12:48 PM ET

An old drug once used routinely as a treatment for schizophrenia appears to be able to successfully kill human cancer stem cells while leaving healthy cells intact, Canadian researchers have discovered.

The discovery is an important one since traditional chemotherapy and radiationoften fail toeradicate cancer stem cells, which are cells that can lurk in the body and cause certain kinds ofcancer to return.

But a team of scientists at McMaster University has discovered that the antipsychotic medication thioridazine can destroy cancer stem cells by changing them into cells that are non-cancerous. And unlike chemotherapy and radiation, thioridazine appears to have no effect on normal stem cells, which could mean side effects like hair loss.

The team at McMaster's Stem Cell and Cancer Research Institute made their finding while testing hundreds of compounds using an automated robotic stem cell screening system. Thioridazine was one of abouta dozen already-known compounds that the robotic team found had good potential as cancer treatments.

Mick Bhatia, the principal investigator for the study and scientific director of the Institute, says what makes this drug so exciting is that it has already been approved for use in patients.

"I think it is fascinating because the drug has already been used already -- albeit for another purpose; here it is being repurposed for cancer. The fact that all that workup has been done already allows us to move this into the clinic quickly," he says.

The research is published in the science journal, Cell.

The next step is to test thioridazine in clinical trials on cancer patients. The first study will focus on 30 patients with acute myeloid leukemia, or AML, whose disease has relapsed after chemotherapy.

The team wants to find out if the drug can put their cancer into remission, and prevent it from returning, says co- investigator Terry Sachlos.

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Old drug could have new use as cancer stem cell killer

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?

McMaster researchers have discovered an anti-psychotic drug kills cancer stem cells without the toxic side-effects of other treatments.

Patients taking thioridazine for Parkinsons Disease and schizophrenia have 10 times less instance of cancer after being on the drug for a few years.

Were connecting dots that we werent connecting before, said Dr. Mick Bhatia, principal investigator of the study and scientific director of McMasters Stem Cell and Cancer Research Institute.

Were excited we have something interesting, but were always nervous because we want to make sure it helps people. The impact of this will be determined if we can put some patients in remission and certainly thats my romantic goal.

He expects a small number of Hamilton leukemia patients with no other treatment options will have access to the drug through a clinical trial within a year. Hes also hoping to set up a second trial at another Ontario cancer centre.

Its not everyday you find a drug you can move into the clinic, said Bhatia. The only thing we can hope for is that what weve seen in the laboratory, were hoping will work in a patient.

If it works, it could dramatically change cancer treatment. Thioridazine on its own reduced leukemia stem cells by 50 per cent in 24 hours in mice injected with primary human samples, found the study published Thursday in the science journal CELL.

That was quite surprising, said Bhatia. We have certainly not seen any drug weve ever tested have that kind of potency.

One of the reasons it works so well is that patients can be given much higher doses for longer than conventional cancer treatments because it has no effect on normal stem cells.

Finding smart drugs that only kill cancer stem cells is a major research focus of Bhatia and McMaster.

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McMaster University researchers discover drug that kills cancer stem cells

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?

ScienceDaily (May 24, 2012) Stem cells are essential building blocks for all organisms, from plants to humans. They can divide and renew themselves throughout life, differentiating into the specialized tissues needed during development, as well as cells necessary to repair adult tissue.

Therefore, they can be considered immortal, in that they recreate themselves and regenerate tissues throughout a person's lifetime, but that doesn't mean they don't age. They do, gradually losing their ability to effectively maintain tissues and organs.

Now, researchers at the Salk Institute for Biological Studies have uncovered a series of biological events that implicate the stem cells' surroundings, known as their "niche," as the culprit in loss of stem cells due to aging. Their findings, published May 23rd in Nature, have implications for treatment of age-related diseases and for the effectiveness of regenerative medicine.

"The findings suggest, for example, that putting new or young stem cells into an old environment -- that of an aged patient -- might not lead to the best outcome in tissue regeneration," says the study's senior investigator, Leanne Jones, associate professor in Salk's Laboratory of Genetics.

Stem cells reside within a microenvironment of other cells-the niche-that is known to play a role in stem cell function. For example, after a tissue is injured, the niche signals to stem cells to form new tissue. It is believed that stem cells and their niche send signals to each other to help maintain their potency over a lifetime.

But while the loss of tissue and organ function during aging has been attributed to decreases in stem cell function, it has been unclear how this decline occurs. Jones' lab has been investigating a number of possible scenarios, such as whether the loss of tissue function is due to a decrease in the number of stem cells, to the inability of stem cells to respond to signals from their niche, or to reduced signaling from the niche.

To explore stem cell aging, Jones uses cells found in the testes of the male fruit fly, Drosophila melanogaster, which are remarkably similar to those found in humans.

The researchers show how signals from the niche that act to maintain the vitality of the flies' stem cells are lost over time, leading to a decline in the number of stem cells available to maintain the tissue. They also show that restoring those signals revitalizes the cells.

"Stem cell behavior is similar between flies and humans, so our findings have major implications for breakthroughs in using tissue stem cells to treat age-related tissue decline or regeneration after an injury," says one of the paper's first authors, Hila Toledano, a former Salk investigator who is now at the University of Haifa in Israel.

The Salk researchers discovered that as the stem cell niche ages, the cells produce a microRNA (a molecule that plays a negative role in the production of proteins from RNA) known as let-7. This microRNA is known to exist in a number of species, including humans, and helps time events that occur during development.

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Method to delay aging of stem cells developed

Public release date: 24-May-2012 [ | E-mail | Share ]

Contact: Lisa Lyons elyons@cell.com 617-386-2121 Cell Press

An anti-psychotic drug used to treat schizophrenia appears to get rid of cancer stem cells by helping them differentiate into less threatening cell types. The discovery reported in the Cell Press journal Cell on May 24th comes after researchers screened hundreds of compounds in search of those that would selectively inhibit human cancer stem cells, and it may lead rather swiftly to a clinical trial.

"You have to find something that's truly selective for cancer stem cells," said Mickie Bhatia, lead author of the study from McMaster University. "We've been working for some time and it's hard to find that exact formula."

The survival of cancer patients is largely unchanged from 30 years ago, and many suspect that greater success will come by addressing the rare and chemotherapy-resistant cancer stem cells.

Unlike normal stem cells, cancer stem cells resist differentiating into stable, non-dividing cell types. Bhatia's team exploited this difference to simultaneously screen compounds for their activity against human cancer stem cells versus normal human stem cells.

By testing hundreds of compounds, they identified nearly 20 potential cancer stem cell specific drugs. The one that appeared most promising is an antipsychotic drug, thioridazine, which is known to work against schizophrenia by targeting dopamine receptors in the brain. The drug doesn't appear to kill cancer stem cells, but rather encourages them to differentiate, thus exhausting the pool of self-renewing cells.

The researchers showed that thioridazine kills leukemia stem cells without affecting normal blood stem cells. Comparing the proteins in leukemia versus normal blood cells helped to explain this specificity. The leukemia cells, but not normal blood stem cells, express a dopamine receptor on their surfaces. Dopamine receptors also appear on some breast cancer stem cells, they found.

"This gives us some explanation," Bhatia said. It also suggests that dopamine receptors might serve as a biomarker for rare, tumor-initiating cells.

In light of the findings, Bhatia's team is already planning for a clinical trial of the FDA-approved thioridazine in combination with standard anti-cancer drugs for adult acute myeloid leukemia.

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Anti-psychotic drug pushes cancer stem cells over the edge

Salk scientists say their findings may lead to strategies to treat age-related diseases and improve regenerative medicine

Newswise LA JOLLA, CA----Stem cells are essential building blocks for all organisms, from plants to humans. They can divide and renew themselves throughout life, differentiating into the specialized tissues needed during development, as well as cells necessary to repair adult tissue.

Therefore, they can be considered immortal, in that they recreate themselves and regenerate tissues throughout a person's lifetime, but that doesn't mean they don't age. They do, gradually losing their ability to effectively maintain tissues and organs.

Now, researchers at the Salk Institute for Biological Studies have uncovered a series of biological events that implicate the stem cells' surroundings, known as their "niche," as the culprit in loss of stem cells due to aging. Their findings, published May 23rd in Nature, have implications for treatment of age-related diseases and for the effectiveness of regenerative medicine.

"The findings suggest, for example, that putting new or young stem cells into an old environment----that of an aged patient----might not lead to the best outcome in tissue regeneration," says the study's senior investigator, Leanne Jones, associate professor in Salk's Laboratory of Genetics.

Stem cells reside within a microenvironment of other cells-the niche-that is known to play a role in stem cell function. For example, after a tissue is injured, the niche signals to stem cells to form new tissue. It is believed that stem cells and their niche send signals to each other to help maintain their potency over a lifetime.

But while the loss of tissue and organ function during aging has been attributed to decreases in stem cell function, it has been unclear how this decline occurs. Jones' lab has been investigating a number of possible scenarios, such as whether the loss of tissue function is due to a decrease in the number of stem cells, to the inability of stem cells to respond to signals from their niche, or to reduced signaling from the niche.

To explore stem cell aging, Jones uses cells found in the testes of the male fruit fly, Drosophila melanogaster, which are remarkably similar to those found in humans.

The researchers show how signals from the niche that act to maintain the vitality of the flies' stem cells are lost over time, leading to a decline in the number of stem cells available to maintain the tissue. They also show that restoring those signals revitalizes the cells.

"Stem cell behavior is similar between flies and humans, so our findings have major implications for breakthroughs in using tissue stem cells to treat age-related tissue decline or regeneration after an injury," says one of the paper's first authors, Hila Toledano, a former Salk investigator who is now at the University of Haifa in Israel.

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Researchers Find a Way to Delay Aging of Stem Cells

Thirty Percent of Patients Show Improved Functioning after Stem Cell Therapy

Philadelphia, Pa. (May 17, 2012) One of the first long-term studies of stem cell treatment for spinal cord injury shows significant functional and other improvements in three out of ten patients, reports a study in the May issue of Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

The results support the safety of mesenchymal stem cells (MSCs) derived from the patient's own bone marrow, showing "continuous and gradual motor improvement" in at least some patients with disability caused by spinal cord injury. The lead author of the new study was Dr. Sang Ryong Jeon of University of Ulsan College of Medicine, Seoul, South Korea.

Evidence of Improved Function after MSC Treatment for Spinal Cord Injury The researchers performed MSC transplantation in ten patients with permanent motor (movement) deficits or paralysis (paraplegia or quadriplegia) after spinal cord injury. Mesenchymal stem cells are a type of "multipotent" cell that can be cultured from adult bone marrow and induced to develop into many different types of cells.

The cultured MSCs were injected directly into the injured spinal cord and the surrounding (intradural) space. Additional cells were injected after another four and eight weeks. The results were assessed by measuring improvement in the patients' ability to move their arms and hands and to perform key activities of daily living. Imaging scans and tests of muscle activity were performed as well.

During the first six months after MSC transplantation, six of the ten patients showed improvement in motor power of the arms and hands. Of these, three patients had gradual improvement in the ability to perform daily activitiesfor example, preparing meals and typing on a keyboard.

These three patients also showed significant changes on MRI scans of the spinal cord, including evidence of healing around the injured area of the spine. They also had improvement in electrophysiologic studies of muscle electrical activity.

No Long-Term Safety Problems of MSC Transplant None of the ten patients had any permanent complications related to MSC transplantation. This helps to alleviate concerns that MSC injection could lead to later problems like the development of tumors or calcifications.

Previous studies have shown promising results with MSC transplantation in animals and humans with spinal cord injury. Mesenchymal cells have some important potential advantages for stem cell therapy, as they are a relatively easily accessible source of the patient's own cells. The ten patients treated by Dr. Jeon and colleagues represent the first attempt at direct spinal injection of MSCs for the treatment of spinal cord injury in humans.

Following up on a previous study reporting initial improvement in six patients, the new paper describes continued improvementincluding meaningful gains in the ability to perform everyday functional tasksin three patients. Dr. Jeon and colleagues note that all three patients with progressive improvement had some "residual neurological function." They write, "Therefore, MSC treatment is more likely to enhance the remaining neurological function rather than rengeneration." They call for further studies to understand the mechanism of improvement after MSC treatment and to clarify which patients with spinal cord injury are most likely to benefit.

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Stem Cells for Spinal Cord Injury: Some Patients Have Long-Term Improvement

Figure 1: Neuroblasts localize polarity complexes (green) on the epithelial side (top) and divide perpendicular to the epithelium in a normal Drosophila embryo (scale bar, 10 m). Credit: 1 2012 Elsevier Inc.

Animals consist of many distinct cell types, all of which originate during development from a single cell: the fertilized egg. To generate this vast cellular diversity, the egg and its descendants must divide unevenly to produce new cells with different fates. Nowhere is this process more important than in the central nervous system, where the asymmetric division of neural stem cells called neuroblasts contributes to the profusion of neurons and glial cells.

Several proteins assemble into so-called polarity complexes that localize at one end of the neuroblast to help guide this unbalanced division (Fig. 1). But the mechanism that controls the orientation of these complexes has remained elusive. Now, a team of RIKEN biologists has discovered the master regulator that directs how these proteins are laid down in the neuroblasts of developing fruit fly, or Drosophila, embryos.

Fumio Matsuzaki and his colleagues at the RIKEN Center for Developmental Biology, Kobe, screened various mutant Drosophila embryos for defects in neuroblast polarity. They uncovered an important player in this process: a gene called trapped in endoderm 1 (Tre1), which encodes a transmembrane receptor protein. In a series of experiments with fly strains in which they deleted the Tre gene, the researchers showed that this receptor is necessary to orient the polarity of the protein complexes in a perpendicular direction relative to the neighboring epithelial cell layer.

Further dissections of proteinprotein interactions revealed that Tre1 recruits and orthogonally orients a critical polarity complex, known as Par, through a cascade of apically localized protein intermediaries. First, Tre1 activates a subunit of an important signal transducing molecule to recruit the protein Pins, which regulates spindle orientation. Another protein, called Inscuteable, then acts as a molecular link between Pins and Par to ensure that every component is in the proper location.

The Par-complex is known to regulate the formation of cell polarity in various cell types including stem cells and neurons, explains team member and co-author Shigeki Yoshiura. So this process might be involved in the orientation of the polarity of various cell types during development.

With Tre1 emerging at the top of the hierarchy controlling the orientation of polarity complexes in the neuroblast, Matsuzaki and colleagues are turning their attention to finding its regulator. We still do not know which molecule or molecules act as the extrinsic signal from epithelial cells, Yoshiura says. The RIKEN team is also investigating whether this mechanism is conserved through evolution and is applicable to mammalian neural stem cells.

More information: Yoshiura, S., et al. Tre1 GPCR signaling orients stem cell divisions in the Drosophila central nervous system. Developmental Cell 22, 7991 (2012).

Provided by RIKEN

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Central nervous system stem cells shed light on mechanism that controls asymmetrical division