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ScienceDaily (Aug. 2, 2012) UCLA stem cell researchers have found for the first time a surprising and unexpected plasticity in the embryonic endothelium, the place where blood stem cells are made in early development.

Scientists found that the lack of one transcription factor, a type of gene that controls cell fate by regulating other genes, allows the precursors that normally generate blood stem and progenitor cells in blood forming tissues to become something very unexpected -- beating cardiomyocytes, or heart muscle cells.

The finding is important because it suggests that the endothelium can serve as a source of heart muscle cells. The finding may provide new understanding of how to make cardiac stem cells for use in regenerative medicine, said study senior author Dr. Hanna Mikkola, an associate professor of molecular, cell and developmental biology in Life Sciences and a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

"It was absolutely unbelievable. These findings went beyond anything that we could have imagined," Mikkola said. "The microenvironment in the embryonic vasculature that normally gives rise to blood cells can generate cardiac cells when only one factor, Scl, is removed, essentially converting a hematopoietic organ into a cardiogenic organ."

The two-year study is published Aug. 3, 2012 in the peer-reviewed journal Cell.

The findings were so surprising, in fact, that Mikkola and her team did not want to believe the results until all subsequent assays proved the finding to be true, said Amelie Montel-Hagen, study co-first author and a post-doctoral fellow.

"To make sure we had not switched the samples between blood forming tissues and the heart we ran the experiments again and repeatedly got the same results," Montel-Hagen said. "It turns out Scl acts as a conductor in the orchestra, telling the other genes in the endothelium who should be playing and who shouldn't be playing."

The team used microarray technology to determine which genes were "playing" in embryonic endothelium to generate blood stem and progenitor cells and found that in the absence of Scl, the genes required for making cardiomyocytes were activated instead, said study co-first author Ben Van Handel, a post-doctoral fellow.

The lone difference was that Scl was missing in the process that resulted in the fate switch between blood and heart.

"Scl has a known role as a master regulator of blood development and when we removed it from the equation, no blood cells were made," Van Handel said. "That the removal of Scl resulted in fully functional cardiomyocytes in blood forming tissues was unprecedented."

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Embryonic blood vessels that make blood stem cells can also make beating heart muscles

Not one, not two, but three brand new studies point to growing evidence that the reason cancer is so stubbornly resistant to treatment is that it has its very own stem cells. These cells may allow the cancer to start growing again. Speaking to a HealthDay reporter, Dr. Max Wicha, director of the University of Michigan Comprehensive Cancer Center, commented on one of the studies, which was published online in the journal Nature."Cancer stem cells are still controversial, but with progress in studies like these, it's less about whether they exist and more about 'what does this mean?'" he said.

One study involved mice with a common and particularly lethal form of brain cancer. Lead researcher Luis Prada of the University of Texas Southwestern Medical Center in Dallas and colleagues genetically engineered mice so they would develop the cancer. After that they created a "transgene" that would only to become active in stem cells in healthy adult brains and they gave the transgene a green fluorescent marker. Finally, they added a virus gene that would self-destruct if treated with a drug called acyclovir. When they put the transgene into the mice with tumors, cells in the tumors were green.

HealthDay quotedPrada as saying, "The next obvious question was: Since the 'transgene' was designed to be active in stem cells, might these be stem cells?" To answer their question, the research team gave acyclovir to the mice. "And when we did that, the tumors stopped growing," Prada said.

"It's interesting that all the studies came to the same conclusion with different types of cancer," Wicha told HealthDay. He added that early clinical studies are already in the works using drugs to target the cancer stem cells.

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Cancer May Have Its Own Stem Cells

SAN DIEGO (CNS) - Researchers at San Diego-based life science organizations have discovered a molecule that converts stem cells into healthy heart cells, possibly setting the stage for therapies that would replace some heart transplants, according to a study published in a scientific journal Friday.

The finding published in the journal Cell Stem Cell could lead to new treatments for heart disease. The study was conducted at Sanford-Burnham Medical Research Institute, the Human BioMolecular Research Institute, and ChemRegen Inc.

The molecule known as ITD-1 is able to generate an unlimited supply of heart cells, which would give scientists more cells to study in their research and give physicians healthy cells to use to treat diseased hearts, according to the study.

Mark Mercola, director of Sanford-Burnham's Muscle Development and Regeneration Program, said heart disease is the leading cause of death in the United States, but doctors can't replace damaged heart muscle.

"The only way to effectively replace lost heart muscle cells -- called cardiomyocytes -- is to transplant the entire heart," said Mercola, the senior author of the study. "Using a drug to create new heart muscle from stem cells would be far more appealing than heart transplantation."

Stem cells were targeted for the study because they can self-replicate and convert to other, specialized types of cells. The challenge for scientists is to discover the signals that direct the stem cells to turn into the types of cells they want.

The researchers said ITD-1 works by preventing a protein from sending signals to cells that regulate various functions, allowing them to re-create themselves into heart cells.

According to Sanford-Burnham, Mercola has been looking for ways to convert stem cells into heart cells for 15 years.

"This particular molecule could be useful to enhance stem cell differentiation in a damaged heart," said Erik Willems, another author of the study. "At some point, it could become the basis for a new therapeutic drug for cardiovascular disease -- one that would likely limit scar spreading in heart failure and promote new muscle formation."

According to Sanford-Burnham, Mercola, Willems, and John Cashman of the Human BioMolecular Research Institute are now working with San Diego biotech company ChemRegen Inc. to develop ITD-1 into a drug that one day might be used to treat patients.

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SD researchers find stem cells can repair damaged heart tissue

Scientists have found evidence that cancerous tumors might originate as stem cells - undifferentiated master cells which can grow into any tissue in the body. Investigators say if this proves true, it could provide a new way to prevent or cure cancer.

Stem cells are primitive structures in the human body that normally transform themselves into healthy, specialized tissue, everything from blood and bone cells to heart and liver cells. Now there is evidence that stem cells can also develop into cancer cells that multiply into life-threatening tumors.

The conventional theory of cancer formation is that it begins with the division of a single mutated cell. The new study challenges this theory with evidence that mutated, cancerous cells may develop directly from stem cells.

Luis Parada, head of developmental biology at the University of Texas Southwestern Medical Center in Dallas, and his colleagues studied an aggressive, lethal form of human brain cancer called glioblastoma multiforme in genetically bred mice. The cancer is usually fatal within a year of diagnosis. Researchers used chemotherapy on the rodents that temporarily halted the growth of their tumors. But when investigators stopped the drug, the cancer came back. Parada says a molecular analysis showed the tumors recurred because a small number of stem cells clustered within the brain tissue began dividing, producing new tumor cells.

But when a group of mice with glioblastoma were given both chemotherapy and a drug that destroyed the stem cells in their brain tissue, their cancer was cured.

Parada says the findings could radically change the way cancer is treated.

Then its no longer valid to evaluate the volume of a tumor and say whether therapy is working or not. What will be important is to know is how that therapy is affecting the cancer stem cells within the tumor, Parada said.

Two other independent studies published this week provide additional evidence that stem cells may be the starting point for cancerous tumors. One team of researchers from Universite Libre de Bruxelles in Brussels, Belgium, and the Wellcome Trust Cancer Research Institute in Britain looked at the role of the master cells in the development of squamous cell carcinoma, a form of skin cancer.

Another group of investigators at the University Medical Center in Utrecht, the Netherlands, engineered a multi-colored model of an intestinal tumor known as an adenoma so they could trace the progression of stem cells to an early-stage tumor. Researchers tagged the master cells with a red color and watched as they produced a protein that stimulated the growth of pre-cancerous blue cells.

Researcher Hugo Snippert, who created the adenoma model, says there can be many genetic mutations in cells that dont cause cancer. He says its only when the stem cells are mutated that cancer develops.

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Study Identifies Stem Cells as Cancer Source

SAN DIEGO (CNS) - Researchers at San Diego-based life science organizations have discovered a molecule that converts stem cells into healthy heart cells, possibly setting the stage for therapies that would replace some heart transplants, according to a study published in a scientific journal Friday.

The finding published in the journal Cell Stem Cell could lead to new treatments for heart disease. The study was conducted at Sanford-Burnham Medical Research Institute, the Human BioMolecular Research Institute, and ChemRegen Inc.

The molecule known as ITD-1 is able to generate an unlimited supply of heart cells, which would give scientists more cells to study in their research and give physicians healthy cells to use to treat diseased hearts, according to the study.

Mark Mercola, director of Sanford-Burnham's Muscle Development and Regeneration Program, said heart disease is the leading cause of death in the United States, but doctors can't replace damaged heart muscle.

"The only way to effectively replace lost heart muscle cells - called cardiomyocytes - is to transplant the entire heart," said Mercola, the senior author of the study. "Using a drug to create new heart muscle from stem cells would be far more appealing than heart transplantation."

Stem cells were targeted for the study because they can self-replicate and convert to other, specialized types of cells. The challenge for scientists is to discover the signals that direct the stem cells to turn into the types of cells they want.

The researchers said ITD-1 works by preventing a protein from sending signals to cells that regulate various functions, allowing them to re-create themselves into heart cells. According to Sanford-Burnham, Mercola has been looking for ways to convert stem cells into heart cells for 15 years.

"This particular molecule could be useful to enhance stem cell differentiation in a damaged heart," said Erik Willems, another author of the study. "At some point, it could become the basis for a new therapeutic drug for cardiovascular disease - one that would likely limit scar spreading in heart failure and promote new muscle formation."

According to Sanford-Burnham, Mercola, Willems, and John Cashman of the Human BioMolecular Research Institute are now working with San Diego biotech company ChemRegen Inc. to develop ITD-1 into a drug that one day might be used to treat patients.

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Stem cell research by local science organizations could lead to new treatments for heart disease

Multicolored intestine tissue in genetically modified mice allow scientists to track which cells give rise to tumors. Image: A. G. Schepers et al., Science (2012)

By Gretchen Vogel, ScienceNOW

All too often, cancer that seems to have been wiped out by treatment comes back. Some scientists have blamed so-called cancer stem cells, a subset of cancer cells that might be able to remain dormant, evading chemotherapy or radiation treatments, only to form new tumors months or years later. The idea has been controversial, but three papers published today report evidence that in certain brain, skin, and intestinal tumors, cancer stem cells are the source of tumor growth.

The cancer stem cell model differs from the traditional idea that tumor growth is equal opportunitythat is, any and all cancerous cells can divide and cause the tumor to grow and spread. The stem cell model says that tumor growth is more hierarchical, mainly driven by a subset of cells that can make new copies of themselves and give rise to the other cell types the tumor contains. Some of the first evidence for cancer stem cells came from studies of leukemia in the 1990s, which showed that only a small subset of the cancerous blood cells could propagate the disease in mice. But it has been harder to test whether cancer stem cells fuel the growth of tumors in other tissues.

In the new studies, three independent groups used genetic cell-marking techniques to trace the proliferation of certain cells within growing tumors. The method gives researchers a glimpse of what happens in the real life of a tumor, says Cdric Blanpain, a stem cell researcher at the Universit Libre de Bruxelles in Belgium. He and his colleagues report online in Nature that in mouse papilloma tumors, a precursor to skin cancer, most of the tumor growth came from a few cells, which in some ways resembled the stem cells that maintain healthy skin.

In a second paper, also published online today in Nature, developmental biologist Luis Parada and his colleagues at the University of Texas Southwestern Medical Center (UTSMC) in Dallas show that in mice that develop glioma, a form of brain cancer, tumor growth seems to come from a small subset of cells in the tumor. They find that the cells can remain dormant during chemotherapy that kills off most of the cancer and can give rise to new tumors once the drug treatment stops.

And in the third paper, published online today in Science, developmental biologists and stem cell researchers Hugo Snippert, Arnout Schepers, Hans Clevers, and their colleagues at the Hubrecht Institute in Utrecht, the Netherlands, used mice with multicolored intestines to look at the kinds of cells that form intestinal adenomas, a precursor to intestinal cancer. The rodents, which the scientists have nicknamed confetti mice, carry genetic markers that can label intestinal cells blue, green, red, or yellow depending on which cell they originate from. The team reports that the adenomas grow from cells that express a gene called Lgr5+, which is also active in normal intestinal stem cells. The tumor is really like a caricature of normal tissue, Snippert says.

Such cell-tracing techniques are the right approach to test the cancer stem cell model, says Sean Morrison, who studies stem cells and cancer at UTSMC and who was not involved in any of the studies. There is now enough evidence to be fairly sure that the model explains at least some types of cancer, he says. Morrison cautions, however, that the studies on papilloma and adenoma looked at precancerous tumors. Indeed, when Blanpain and his colleagues examined mice with squamous cell carcinoma, a malignant outgrowth of the papilloma, they found that most of the cells were actively dividing, not just a small subset of stem-cell-like cells.

Understanding which cancers might grow fromor simply harborcancer stem cells is key to more effective treatments, the researchers say. That is no easy task, however. Morrison notes that tumor growth differs even among patients with the same type of cancer. Still, says Parada, having three examples in which tumors seem to harbor cancer stem cells suggests there will be more. I hope it will bolster and stimulate the community to figure out how to better study the cancer stem cell model, he says. Lets bring this level of scrutiny to all solid tumors.

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Cancer Stem Cells Can Fuel Tumor Growth

(AP) Why does cancer come back after a tumor has been seemingly eradicated? Three new studies from American, Belgian, British and Dutch researchers may have an answer.

Study: Stem cells boost brain tumor treatments

The studies bolster a long-debated idea that tumors contain their own pool of stem cells that can multiply and keep fueling the cancer, seeding regrowth. If that's true, scientists will need to find a way to kill those cells, apart from how they target and attack the rest of the tumor.

Stem cells in healthy tissues are known for their ability to produce any kind of cell. The new research deals with a different kind, cancer stem cells. Some researchers, but not all, believe they lurk as a persisting feature in tumors.

Over the past decade, studies have found evidence for them in tumors like breast and colon cancers. But this research has largely depended on transplanting human cancer cells into mice that don't have immune systems, an artificial environment that raises questions about the relevance of the results.

Now, three studies reported online Wednesday in the journals Nature and Science present evidence for cancer stem cells within the original tumors. Again, the research relies on mice. That and other factors mean the new findings still won't convince everyone that cancer stem cells are key to finding more powerful treatments.

But researcher Luis Parada, of the University of Texas Southwestern Medical Center in Dallas, believes his team is onto something. He says that for the type of brain tumor his team studied, "we've identified the true enemy."

If his finding applies to other cancers, he said, then even if chemotherapy drastically shrinks a tumor but doesn't affect its supply of cancer stem cells, "very little progress has actually been made."

The three studies used labeling techniques to trace the ancestry of cells within mouse tumors.

Collectively, they give "very strong support" to the cancer stem cell theory, said Jeffrey M. Rosen, a professor of molecular and cellular biology at Baylor College of Medicine in Houston. He did not participate in the work but supports the theory, which he said is widely accepted.

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Stem cells in tumors may fuel cancer regrowth, new studies suggest

SAN DIEGO - Researchers at a pair of San Diego-based life scienceorganizations announced Thursday the discovery of a molecule that converts stemcells into healthy heart cells, ending a 15-year hunt.

The finding, published in Friday's issue of the journal Cell Stem Cell,could lead to new treatments for heart disease. The study was performed atSanford-Burnham Medical Research Institute, the Human BioMolecular ResearchInstitute, and ChemRegen Inc.

The molecule known as ITD-1 is able to generate an unlimited supply ofheart cells, which would give scientists more heart cells to study in theirresearch, and give physicians healthy cells to use to treat diseased hearts,according to the study.

Mark Mercola, director of Sanford-Burnham's Muscle Development andRegeneration Program, said heart disease is the leading cause of death in theU.S., but doctors can't replace damaged heart muscle.

"The only way to effectively replace lost heart muscle cells -- calledcardiomyocytes -- is to transplant the entire heart," said Mercola, the seniorauthor of the study. "Using a drug to create new heart muscle from stem cellswould be far more appealing than heart transplantation."

Stem cells were targeted for the study because they can self-replicateand convert to other, specialized types of cells. The challenge for scientistsis to discover the signals that direct the stem cells to turn into the types ofcells they want.

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15 Year Stem Cell Study Yields Healthy Heart Cells

Researchers have discovered a molecule that converts stem cells into heart cells, which could be used to replace diseased or damaged tissue in patients suffering from heart disease.

Researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham), the Human BioMolecular Research Institute, and ChemRegen, Inc. have been searching for molecules that convert stem cells to heart cells for about eight yearsand now they've found one.

In the new study, the researchers have described how they sifted through a large collection of drug-like chemicals and uncovered ITD-1, a molecule that can be used to generate unlimited numbers of new heart cells from stem cells.

"Heart disease is the leading cause of death in this country. Because we can't replace lost cardiac muscle, the condition irreversibly leads to a decline in heart function and ultimately death. The only way to effectively replace lost heart muscle cellscalled cardiomyocytesis to transplant the entire heart," Mark Mercola, senior author of the study, said.

"Using a drug to create new heart muscle from stem cells would be far more appealing than heart transplantation," he said.

Stem cells are important because they do two unique things self-renew, producing more stem cells and differentiate, becoming other, more specialized cell types.

To obtain a large number of a certain cell type, such as heart cells, the hard part is figuring out the signals that direct them to become the desired cell type.

Mercola's group has been hunting for heart-inducing signals for 15 yearsin embryos and in stem cells.

To find a synthetic molecule that might one day lead to a drug therapy to regenerate the heart, they joined forces with a team of medicinal chemists at the Human BioMolecular Research Institute led by John Cashman, Ph.D.

With funding from the California Institute for Regenerative Medicine, they used sophisticated robotic technology to methodically test a large collection of drug-like chemicals, looking for that needle in a haystack that, when added to stem cells, results in cardiomyocytes.

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How to mend a broken heart

1 August 2012 Last updated at 13:00 ET By Pallab Ghosh Science correspondent, BBC News

Researchers have discovered the cells in tumours that seem to be responsible for the regrowth of tumours.

Three separate studies on mice appear to have confirmed the view that the growth of tumours is driven by so-called cancer stem cells.

The researchers claim to have resolved one of the biggest controversies in cancer research and say their work marks a "paradigm shift" in the field.

The studies have been published in the journals, Nature and Science.

Doctors often successfully reduce the size of tumours through various therapies, but often patients suffer a relapse and the tumour regrows.

Some researchers believe that this happens because therapies fail to eradicate a small proportion of cells that drive tumour growth known as cancer stem cells. They believe that these are the cells that should be targeted to eliminate the tumour forever.

Evidence for the existence of cancer stem cells has been weak. But now three separate groups of researchers working independently have found direct evidence of cancer stem cells driving tumour growth in brain, gut and skin cancers.

The suggestion is that the same may be true of all cancers which produce solid tumours.

We have shown for the first time there is such a thing as a cancer stem cell and that tumours are maintained by them

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Stem cells drive tumour growth