Category Archives: Stem Cell Videos

Newswise LOS ANGELES (June 19, 2012) Cedars-Sinais Regenerative Medicine Institute has pioneered research on how motor-neuron cell-death occurs in patients with spinal muscular atrophy, offering an important clue in identifying potential medicines to treat this leading genetic cause of death in infants and toddlers.

The study, published in the June 19 online issue of PLoS ONE, extends the institutes work to employ pluripotent stem cells to find a pharmaceutical treatment for spinal muscular atrophy or SMA, a genetic neuromuscular disease characterized by muscle atrophy and weakness.

With this new understanding of how motor neurons die in spinal muscular atrophy patients, we are an important step closer to identifying drugs that may reverse or prevent that process, said Clive Svendsen, PhD, director of the Cedars-Sinai Regenerative Medicine Institute.

Svendsen and his team have investigated this disease for some time now. In 2009, Nature published a study by Svendsen and his colleagues detailing how skin cells taken from a patient with the disorder were used to generate neurons of the same genetic makeup and characteristics of those affected in the disorder; this created a disease-in-a-dish that could serve as a model for discovering new drugs.

As the disease is unique to humans, previous methods to employ this approach had been unreliable in predicting how it occurs in humans. In the research published in PLoS ONE, to the team reproduced this model with skin cells from multiple patients, taking them back in time to a pluripotent stem cell state (iPS cells), and then driving them forward to study the diseased patient-specific motor neurons.

Children born with this disorder have a genetic mutation that doesnt allow their motor neurons to manufacture a critical protein necessary for them to survive. The study found these cells die through apoptosis the same form of cell death that occurs when the body eliminates old, unnecessary as well as unhealthy cells. As motor neuron cell death progresses, children with the disease experience increasing paralysis and eventually death. There is no effective treatment now for this disease. An estimated one in 35 to one in 60 people are carriers and about in 100,000 newborns have the condition.

Now we are taking these motor neurons (from multiple children with the disease and in their pluripotent state) and screening compounds that can rescue these cells and create the protein necessary for them to survive, said Dhruv Sareen, director of Cedars-Sinais Induced Pluripotent Stem Cell Core Facility and a primary author on the study. This study is an important stepping stone to guide us toward the right kinds of compounds that we hope will be effective in the model and then be reproduced in clinical trials.

The study was funded in part by a $1.9 million Tools and Technology grant from the California Institute for Regenerative Medicine aimed at developing new tools and technologies to aid pharmaceutical discoveries for this disease.

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Researchers, with Stem Cells, Advance Understanding of Spinal Muscular Atrophy

Public release date: 20-Jun-2012 [ | E-mail | Share ]

Contact: Rod Dashwood rod.dashwood@oregonstate.edu 541-737-8101 Oregon State University

CORVALLIS, Ore. Researchers at Oregon State University for the first time have traced the actions of a known carcinogen in cooked meat to its complex biological effects on microRNA and cancer stem cells.

The findings are part of a growing awareness of the role of epigenetics in cancer, or the ways in which gene expression and cell behavior can be changed even though DNA sequence information is unaltered.

The scientists also found that consumption of spinach can partially offset the damaging effects of the carcinogen. In tests with laboratory animals, it cut the incidence of colon tumors almost in half, from 58 percent to 32 percent.

The research at OSU's Linus Pauling Institute was recently reported in the journal Molecular Nutrition and Food Research, in work supported by the National Institutes of Health.

"Cancer development is a complex, multi-step process, with damaged cells arising through various means," said Mansi Parasramka, a postdoctoral scholar with LPI. "This study showed that alterations of microRNAs affect cancer stem cell markers in colon cancer formation.

"MicroRNAs are very small factors that do very big things in cells," she said.

Traditionally, cancer was thought to be caused by changes in DNA sequence, or mutations, that allowed for uncontrolled cell growth. That's still true. However, there's also increasing interest in the role played by epigenetics, in which such factors as diet, environmental toxins, and lifestyle affect the expression of genes not just in cancer, but also cardiovascular disease, diabetes, and neurological disorders.

Included in this epigenetic equation is the formation of microRNAs once thought to be "junk DNA" - which researchers were at a loss to understand. It's now known that they influence which areas of DNA get expressed or silenced.

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Study links carcinogens to cancer stem cells -- but spinach can help

Results from a new study suggest low doses of the diabetes drug metformin may effectively destroy pancreatic cancer stem cells, reducing the risk of tumor growth or recurrence.

Metformin has previously shown promise in reducing breast cancer risk, after researchers found women who took the drug were 25 percent less likely to develop breast cancer during their lifetimes than women who did not.

This study, conducted in mice, is the first to suggest metformin may actually target the root of certain cancers the tumor-initiating stem cells.

We didnt have any clue regarding the effects of metformin on pancreatic stem cancer cells, study researcher Dr. Christopher Heeschen, professor for experimental medicine at the Spanish National Cancer Research Centre in Madrid, Spain, told FoxNews.com. Its been implied in past studies of pancreatic cancer that patients who use metformin show better outcomes, but there have been no randomized trials yet.

When metformin was combined with a standard chemotherapy to treat pancreatic cancer, the drugs were able to eradicate both cancer stem cells and the differentiated cells that made up the tumor.

Novel strategies for treating pancreatic cancer have to be multi-modal, Heeschen explained. Right now, metformin is used as a second phase treatment, but I could also envision it as a first phase treatment but it has to be in combination with chemotherapy. I dont think the drug alone could wipe out the primary tumor, which is crucial.

In the study, it appeared that metformin merely arrested cancer cell growth in existing tumors, rather than destroying them.

Metformin targets the root of cancer, which has more of an effect on preventing cancer relapse, Heeschen said.

According to Heeschen, researchers are not yet certain as to why metformin appears to have cancer stem cell-killing properties, but from a pragmatic point of view, you see this striking response with a well-established drug thats safe I think its reasonable to move forward with clinical trials, he said.

One clinical trial is already in the recruitment phase, and Heeschen predicted results of the trial would be available by the end of the year.

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Diabetes drug may kill cancer stem cells, study says

Mesenchymal Stem Cells (hMSCs) cultured on a Polyacrylamide gel for 7 days: Cells stained in blue are ALP positive which is a marker for osteogenic differentiation, while the cells that contain red oil droplets underwent adipogenic differentiation. Credit: Bojun Li and Prof. Viola Vogel / ETH Zurich

(Phys.org) -- Researchers were positive: a substrates softness influences the behaviour of stem cells in culture. Now other researchers have made a new discovery: the number of anchoring points to which the cells can adhere is pivotal.

How stem cells differentiate is evidently not so much a question of the stiffness of the substrate upon which they thrive, as the cells mechanical anchoring on the substrate surface. This is shown in a study recently published in Nature Materials by researchers from various European universities, including ETH Zurich.

Since 2006 the research community has been convinced that stem cells can feel the softness of materials they grow upon. Scientists mainly drew this conclusion from correlations between the softness of the substrate and the cells behavior.

The new research project, to which ETH-Zurich professor Viola Vogel and her doctoral student Bojun Li made a key contribution, has come to another conclusion. It reveals that the properties of the network structure of polymers are instrumental in regulating the anchoring of the collagen proteins to which the cells ultimately adhere. And these anchors influence the differentiation of stem cells.

Good protein adhesion makes surface seem stiff

In a series of experiments, which Britta Trappmann from Cambridge University partly conducted at ETH Zurich, the cells were applied to two different polymers of the same softness. However, the polymers differed in terms of their surface structure, which regulates the number of firmly anchored collagen proteins.

If the researchers reduced the number of well-anchored proteins on a hard surface, the cells behaved in the same way as on a soft base. If the anchors were close together, the stem cells differentiated into bone cells. If the anchors were further apart, they became fat cells. The simple correlation that a materials stiffness or elasticity can govern the differentiation of stem cells is therefore not universally valid, says Vogel.

Paradigm shift in cultivation of stem cells

With their experiment, the researchers shake a paradigm. In a study conducted in 2006, scientists revealed a connection between polymer stiffness and the degree of cell differentiation. However, the researchers varied the stiffness of the polymer by varying its network structure.

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Anchoring points determine fate of stem cells

By Jason Napodano, CFA

Neuralstem, Inc. (NYSE MKT: CUR ) has developed a technology that allows large-scale expansion of human neural stem cells ("hNSC") from all areas of the developing human brain and spinal cord. The company owns of has exclusive license to 25 patients and 29 patent applications pending worldwide in the field of regenerative medicine and cell therapy. Management is currently focusing the company's efforts on replacing damaged, malfunctioning, or dead neural cells with fully functional ones that may be useful in treating many central nervous system diseases and neurodegenerative disorders.

Neuralstem's lead development program is for Amyotrophic Lateral Sclerosis ("ALS"), also known as Lou Gehrig 's disease, named after the famous New York Yankee first baseman who was diagnosed with the disease in 1939, and passed in 1941 at the age of only 37.

ALS Background

ALS is a rapidly progressive neurodegenerative disease characterized by weakness, muscle atrophy and twitching, spasticity, dysarthria (difficulty speaking), dysphagia (difficulty swallowing), and respiratory compromise. The disease is almost always fatal, typically due to respiratory compromise or pneumonia, in two to four years. Initial symptoms of ALS include weakness and/or stiffness followed by muscle atrophy in the arms and legs. This is followed by slurred speech or difficulty swallowing, and loss of tongue mobility. Approximately a third of ALS patients also experience pseudobulbar affect (uncontrollable emotions). As the disease progresses, worsening dysphagia and respiratory failure leads to death. A small percentage of patients may also experience cognitive affects such as frontotemporal dementia and anxiety.

The vast majority (~95%) of cases are idiopathic, although there is a known hereditary factor that leads to familial ALS associated with a defect on the 21st chromosome that accounts for approximately 1.5% of all cases. There are also suspected environmental causative factors, including exposure to a dietary neurotoxin called BMAA and cyanobacteria, and use of pesticides. However, in all cases, the defining factor of ALS is rapid and progressive death of upper and lower motor neurons in the motor cortex of the brain, brain stem, and spinal cord. Prior to their destruction, motor neurons develop proteinaceous inclusions in their cell bodies and axons. This may be partly due to defects in protein degradation.

Treatment for ALS is limited, and as of today only riluzole, marketed by Sanofi-Aventis as Rilutek, has been found to improve survival to a modest extent (several months). Riluzole preferentially blocks TTX-sensitive sodium channels, which are associated with damaged neurons. This reduces influx of calcium ions and indirectly prevents stimulation of glutamate receptors. Together with direct glutamate receptor blockade, the effect of the neurotransmitter glutamate on motor neurons is greatly reduced. Riluzole does not reverse the damage already done to motor neurons, and people taking it must be monitored for liver damaged (about 10% incidence).

The remaining treatments for ALS are designed to relieve symptoms and improve quality of life. This supportive care includes a multidisciplinary approach that may include medications to reduce fatigue, control spasticity, reduce excess saliva and phlegm, limit sleep disturbances, reduce depression, and limit constipation. As noted above, median survival is two to four years. In the U.S., approximately 30,000 persons are currently living with ALS.

Neuralstem's Approach For ALS

Neuralstem is seeking to treat the symptoms of ALS via transplantation of its hNSCs directly into the gray matter of the patient's spinal cord. In ALS, motor neurons die, leading to paralysis. In preclinical animal work, Neuralstem cells both made synaptic contact with the host motor neurons and expressed neurotrophic growth factors, which are protective of cells.

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Neuralstem Pioneering Efforts In ALS - Analyst Blog

Bangalore: A recent study led by an Indian American researcher Bikul Das, at the Stanford University School of Medicine proved that in times of stress certain human embryonic stem cells produce molecules that benefit themselves along with the helping the nearby cells to survive. Altruism has been reported among bacterial populations and among humans and other animals, like monkeys and elephants, said Stanford postdoctoral scholar Bikul Das, MBBS, PhD. But in mammalian cells at the cellular level the idea of altruism has never been described before.

Das has recently published a research paper documenting altruistic behavior by human embryonic stem cells, in a prominent international magazine 'Stem Cells'.

"Altruism in cells can mean it will be possible to treat cancer without chemotherapy. In future, altruistic stem cells may be cultured and injected into cancerous tissue for treatment, said Dr Chandan J Das, assistant professor in the radio-diagnosis department at AIIMS, Delhi, about the study.

Dr Purna Kurkure, senior paediatric oncologist at Tata Memorial Hospital says "this research will have a bearing on not just cancer research but in the overall understanding of the repair and regeneration mechanism of the human body. Altruism has been observed in bacteria, which is why bacteria are great survivors. So far, we haven't been able to beat cancer because there is a lack of complete understanding about it. Chemotherapy only targets the end cells, not the root. This research is, therefore, a major leap in the battle against cancer'', reports Times of India.

Das has been congratulated by UK scientist Dr Peter W Andrews, one of the two gurus of embryonic stem cell research, for his findings.

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Indian American Doctor Makes Breakthrough in Cancer Research

As of now, management is planning to conduct the pivotal program on its own, mostly likely seeking funding through grants with the ALS Association and U.S. National Institutes of Health. However, management is also in discussion with potential pharmaceutical partners on the pivotal program. ALS is a highly attractive area for Big Pharma. Depending on the strength of the phase 1 / 2 data, Neuralstem may be able to strike a commercialization partnership in 2014 to help defer the costs of the planned pivotal trial. We expect that any deal with a larger pharmaceutical company would include a substantial upfront payment that Neuralstem would then use to fund expansion of the development platform into new indications, such as spinal cord injury (IND filed) or stroke.

Market Opportunity

In February 2011, the U.S. FDA granted Neuralstem an Orphan Drug designation for its human spinal cord stem cells (HSSC) for the treatment of ALS. As noted above, there are approximately 30,000 patients in the U.S. living with ALS. We estimate that approximately half of these patients are characterized with an FVC > 60% and may be eligible for treatment with Neuralstems hNSCs. Given the Orphan Drug designation, the limited patient population, and the lack of any meaningful treatment options, we think Neuralstem or its commercialization partner could price this therapy at upwards of $100,000. Therefore, the peak market opportunity for Neuralstem is $1.5 billion.

That being said, drug development in ALS has been a graveyard for pharmaceutical companies. One would assume, based on numerous past clinical failures, that Neuralstems chances in ALS are slim. Small molecules including gabapentin, topiramate, celecoxib, tamoxifen, indinavir, minocycline, and xaliproden, many of which are approved for other indications and have posted annual sales over a billion dollars, have all failed human clinical programs for ALS. Even Vitamin E and Creatine have been tested, to little avail, in ALS. Failed mechanisms of action included calcium channel blockers, glutamate regulators, neuroprotectants, immunosuppressants, GABA receptors, anti-inflammatory agents, and antioxidants.

However, there is one thing in common we see in all of the above failures. They are one molecule targeting one mechanism of action or one pathway. ALS is a high complex and largely uncharacterized disease. Neuralstems approach uses human spinal stem cells that, once injected, can provide multiple mechanisms of action on multiple pathways to affect the disease. Plus, Neuralstems approach is highly targeted, with the cells injected directly into the lumbar or cervical spine. Following grafting, the hypothesis is that the cells rebuild circuitry with the patient motor neurons and protect existing neurons from further degradation. Its clearly a unique approach, and one we believe has a better chance of success than many of the previous failed theories enacted over the past decade.

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CUR - Neuralstem Pioneering Efforts In ALS

By Jason Napodano, CFA

Neuralstem, Inc. (NYSE MKT:CUR) has developed a technology that allows large-scale expansion of human neural stem cells ("hNSC") from all areas of the developing human brain and spinal cord. The company owns of has exclusive license to 25 patients and 29 patent applications pending worldwide in the field of regenerative medicine and cell therapy. Management is currently focusing the company's efforts on replacing damaged, malfunctioning, or dead neural cells with fully functional ones that may be useful in treating many central nervous system diseases and neurodegenerative disorders.

Neuralstems lead development program is for Amyotrophic Lateral Sclerosis ("ALS"), also known as Lou Gehrigs disease, named after the famous New York Yankee first baseman who was diagnosed with the disease in 1939, and passed in 1941 at the age of only 37.

ALS Background

ALS is a rapidly progressive neurodegenerative disease characterized by weakness, muscle atrophy and twitching, spasticity, dysarthria (difficulty speaking), dysphagia (difficulty swallowing), and respiratory compromise. The disease is almost always fatal, typically due to respiratory compromise or pneumonia, in two to four years. Initial symptoms of ALS include weakness and/or stiffness followed by muscle atrophy in the arms and legs. This is followed by slurred speech or difficulty swallowing, and loss of tongue mobility. Approximately a third of ALS patients also experience pseudobulbar affect (uncontrollable emotions). As the disease progresses, worsening dysphagia and respiratory failure leads to death. A small percentage of patients may also experience cognitive affects such as frontotemporal dementia and anxiety.

The vast majority (~95%) of cases are idiopathic, although there is a known hereditary factor that leads to familial ALS associated with a defect on the 21st chromosome that accounts for approximately 1.5% of all cases. There are also suspected environmental causative factors, including exposure to a dietary neurotoxin called BMAA and cyanobacteria, and use of pesticides. However, in all cases, the defining factor of ALS is rapid and progressive death of upper and lower motor neurons in the motor cortex of the brain, brain stem, and spinal cord. Prior to their destruction, motor neurons develop proteinaceous inclusions in their cell bodies and axons. This may be partly due to defects in protein degradation.

Treatment for ALS is limited, and as of today only riluzole, marketed by Sanofi-Aventis as Rilutek, has been found to improve survival to a modest extent (several months). Riluzole preferentially blocks TTX-sensitive sodium channels, which are associated with damaged neurons. This reduces influx of calcium ions and indirectly prevents stimulation of glutamate receptors. Together with direct glutamate receptor blockade, the effect of the neurotransmitter glutamate on motor neurons is greatly reduced. Riluzole does not reverse the damage already done to motor neurons, and people taking it must be monitored for liver damaged (about 10% incidence).

The remaining treatments for ALS are designed to relieve symptoms and improve quality of life. This supportive care includes a multidisciplinary approach that may include medications to reduce fatigue, control spasticity, reduce excess saliva and phlegm, limit sleep disturbances, reduce depression, and limit constipation. As noted above, median survival is two to four years. In the U.S., approximately 30,000 persons are currently living with ALS.

Neuralstems Approach For ALS

Neuralstem is seeking to treat the symptoms of ALS via transplantation of its hNSCs directly into the gray matter of the patients spinal cord. In ALS, motor neurons die, leading to paralysis. In preclinical animal work, Neuralstem cells both made synaptic contact with the host motor neurons and expressed neurotrophic growth factors, which are protective of cells.

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Neuralstem Pioneering Efforts In ALS

French scientists revive stem cells of dead people

A group from the Pasteur Institute was able to reactivate muscle stem cells from deceased persons after 17 days, which functioned normally after transplant...

by Fabrice Chretien

French scientists were able to revive stem cells of muscle and bone marrow from persons who were already dead for 17 days, reports the journal Nature Communications in a paper released on Wednesday (13th) in France.

A team of researchers from the Pasteur Institute demonstrated that it is possible to reactivate the muscle stem cells from human cadavers and transplant them to make new ones born in perfect condition.

The scientists found that these cells did not die with the person. That's because they reduced their activity to a minimum and, after discarding the mitochondria (small bodies that help with breathing), were in a state of hibernation.

Thus, cells could survive even in an environment so hostile, without oxygen and in the middle of an acid bath, as well as in the case of a muscle injury, "sleeping and waiting out the storm," as Professor Fabrice Chrtien affirmed to the newspaper Libration.

"This reserve of stem cells could serve to make bone marrow transplants used to treat leukemia and blood diseases, among other conditions. They could also address the lack of donors," said Chretien, who led the study alongside researcher, Shahragim Tajbakhsh.

Despite the advances that have also been successfully tested in rats, the experiment showed an increase of one type of substance called ROS, which, in turn, has an incompatibility with the cells and genome, Professor Jean-Marc Lemaitre pointed out to the paper, Le Figaro. Due to this fact, the study still needs to determine whether these new cells, even in perfect condition, can hide still undetected malformations.

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French scientists revive stem cells of dead people

Public release date: 18-Jun-2012 [ | E-mail | Share ]

Contact: Shantell M. Kirkendoll smkirk@umich.edu 734-764-2220 University of Michigan Health System

A cutting-edge method developed at the University of Michigan Center for Arrhythmia Research successfully uses stem cells to create heart cells capable of mimicking the heart's crucial squeezing action.

The cells displayed activity similar to most people's resting heart rate. At 60 beats per minute, the rhythmic electrical impulse transmission of the engineered cells in the U-M study is 10 times faster than in most other reported stem cell studies.

An image of the electrically stimulated cardiac cells is displayed on the cover of the current issue of Circulation Research, a publication of the American Heart Association.

For those suffering from common, but deadly, heart diseases, stem cell biology represents a new medical frontier.

The U-M team of researchers is using stem cells in hopes of helping the 2.5 million people with an arrhythmia, an irregularity in the heart's electrical impulses that can impair the heart's ability to pump blood.

"To date, the majority of studies using induced pluripotent stem cell-derived cardiac muscle cells have focused on single cell functional analysis," says senior author Todd J. Herron, Ph.D., an assistant research professor in the Departments of Internal Medicine and Molecular & Integrative Physiology at the U-M.

"For potential stem cell-based cardiac regeneration therapies for heart disease, however, it is critical to develop multi-cellular tissue like constructs that beat as a single unit," says Herron.

Their objective, working with researchers at the University of Oxford, Imperial College and University of Wisconsin, included developing a bioengineering approach, using stem cells generated from skin biopsies, which can be used to create large numbers of cardiac muscle cells that can transmit uniform electrical impulses and function as a unit.

Link:
New method generates cardiac muscle patches from stem cells