Category Archives: Stem Cells

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

Public release date: 2-Aug-2012 [ | E-mail | Share ]

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center

STANFORD, Calif. Stem cells are special. Nestled in muscle and skin, organ and bone, they bide their time over years or decades until called to replace damaged or lost tissue. One secret to their longevity is an enzyme called telomerase, which stills the relentless ticking of the molecular clock that limits the life span of other cells.

This cellular fountain of youth prevents the progressive shortening of the tips of our chromosomes that occurs with each cell division. But the presence of telomerase can be a double-edged sword: The same activity that ensures long life for stem cells can also keep a cancer cell dividing long after its aging neighbors have thrown in the towel. Conversely, a malfunction can prevent stem cells from doing their job and lead to devastating diseases.

Now, for the first time, researchers at the Stanford University School of Medicine have identified how telomerase is recruited to chromosome ends and figured out a way to block it.

"If telomerase is unable to maintain the ends of the chromosomes, cells will stop multiplying," said professor of medicine Steven Artandi, MD, PhD. "This would be advantageous in cancer cells, but in normal stem cells it can cause severe dysfunction and lead to diseases such as pulmonary fibrosis, aplastic anemia and a genetic condition called dyskeratosis congenita. We want to understand how telomerase works, and to develop therapies for cancer and these other diseases."

Artandi is the senior author of the research, which will be published Aug. 3 in Cell. He is also a member of the Stanford Cancer Institute. Graduate student Franklin Zhong is the first author of the study.

Telomerase is normally expressed in adult stem cells and immune cells, as well as in cells of the developing embryo. In these cells, the enzyme caps off the ends of newly replicated chromosomes, allowing unfettered cell division. Without telomerase, cells stop dividing or die when the ends called telomeres fall below a minimum length. Unfortunately, the enzyme is also active in nearly all cancer cells.

Earlier research in Artandi's lab identified a protein called TCAB1 that brings the telomerase complex (actually a large clump of many proteins) to a processing area in the cell's nucleus called a Cajal body. But no one knew how the complex was then ferried to the ends of telomeres, and research was stymied by the complex's large size, multiple components and relative scarcity.

"This problem has been really intractable," said Artandi. "The enzyme is extremely hard to study. But we've now found that telomerase is recruited to the telomeres through an interaction with a protein called TPP1 that coats the ends of chromosomes." What's more, the researchers have identified the exact region of TPP1 to which telomerase binds a section called an OB-fold.

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Research shows how protein component that enables cell replication gets ferried to chromosome tips

ScienceDaily (Aug. 2, 2012) Stem cells are special. Nestled in muscle and skin, organ and bone, they bide their time over years or decades until called to replace damaged or lost tissue. One secret to their longevity is an enzyme called telomerase, which stills the relentless ticking of the molecular clock that limits the life span of other cells.

This cellular fountain of youth prevents the progressive shortening of the tips of our chromosomes that occurs with each cell division. But the presence of telomerase can be a double-edged sword: The same activity that ensures long life for stem cells can also keep a cancer cell dividing long after its aging neighbors have thrown in the towel. Conversely, a malfunction can prevent stem cells from doing their job and lead to devastating diseases.

Now, for the first time, researchers at the Stanford University School of Medicine have identified how telomerase is recruited to chromosome ends -- and figured out a way to block it.

"If telomerase is unable to maintain the ends of the chromosomes, cells will stop multiplying," said professor of medicine Steven Artandi, MD, PhD. "This would be advantageous in cancer cells, but in normal stem cells it can cause severe dysfunction and lead to diseases such as pulmonary fibrosis, aplastic anemia and a genetic condition called dyskeratosis congenita. We want to understand how telomerase works, and to develop therapies for cancer and these other diseases."

Artandi is the senior author of the research, published Aug. 3 in Cell. He is also a member of the Stanford Cancer Institute. Graduate student Franklin Zhong is the first author of the study.

Telomerase is normally expressed in adult stem cells and immune cells, as well as in cells of the developing embryo. In these cells, the enzyme caps off the ends of newly replicated chromosomes, allowing unfettered cell division. Without telomerase, cells stop dividing or die when the ends -- called telomeres -- fall below a minimum length. Unfortunately, the enzyme is also active in nearly all cancer cells.

Earlier research in Artandi's lab identified a protein called TCAB1 that brings the telomerase complex (actually a large clump of many proteins) to a processing area in the cell's nucleus called a Cajal body. But no one knew how the complex was then ferried to the ends of telomeres, and research was stymied by the complex's large size, multiple components and relative scarcity.

"This problem has been really intractable," said Artandi. "The enzyme is extremely hard to study. But we've now found that telomerase is recruited to the telomeres through an interaction with a protein called TPP1 that coats the ends of chromosomes." What's more, the researchers have identified the exact region of TPP1 to which telomerase binds -- a section called an OB-fold.

"When we mutated this site in TPP1," said Artandi, "we blocked the interaction between the two proteins and prevented telomerase from going to the telomeres. And when we interfered with this interaction in human cancer cells, the telomeres began to shorten." The researchers are now assessing whether the life span of the cancer cells, and their ability to divide unchecked, will also be affected by the treatment.

To confirm their finding, Artandi and his colleagues used cells from patients with pulmonary fibrosis -- a debilitating scarring or thickening of lung tissue associated with telomerase mutations. The disease had been troubling to researchers and clinicians, however, because the patients' mutated telomerase seemed to be fully active when tested in the laboratory. Zhong and Artandi found that the disease-associated mutations occurred in the portion of telomerase that interacted with TPP1, and interfered with their binding. As a result the enzyme, although active, couldn't get to where it was needed.

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How protein component that enables cell replication gets ferried to chromosome tips

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

Featured Article Academic Journal Main Category: Cancer / Oncology Also Included In: Stem Cell Research;Biology / Biochemistry Article Date: 02 Aug 2012 - 2:00 PDT

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Papers on all three studies appeared online on Wednesday, two in Nature and one in Science.

In all three studies, the teams used genetic cell-marking techniques to track cell lineage and show that a restricted cell population appears to be the source of new tumor cells, in much the same way as stem cells are the "master builders" of new healthy cells.

GBM is a type of brain cancer that is currently considered incurable. It is a fast-growing tumor with a median survival of about 15 months. Although initially it responds to chemotherapy, the cancer nearly always comes back.

In their study, Parada and colleagues used genetically engineered mice bred to develop GBM and found that the resting tumor cells act more like stem cells.

They used a genetic marker that labels healthy adult neural stem cells, but not their more specialized descendants, to see if it would do the same for cancer stem cells in GBM. When they did so, they found all the tumors contained at least a few labelled cells, which they presumed to be stem cells.

The tumors also contained unlabelled cells, which could be killed with standard chemotherapy, but then the tumors came back soon afterwards. When they tested them again, they found the tumors contained unlabelled cells that came from labelled predecessors.

When they applied chemotherapy with a technique that suppressed the labelled cells, the researchers found the tumors shrank back to what Parada described to Nature NEWS as "residual vestiges" that bore no resemblance to GBM.

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Cancer Stem Cells May Drive Tumor Growth

ScienceDaily (July 30, 2012) In the first human study of its kind, researchers found that using stem cells to re-grow craniofacial tissues -- mainly bone -- proved quicker, more effective and less invasive than traditional bone regeneration treatments.

Researchers from the University of Michigan School of Dentistry and the Michigan Center for Oral Health Research partnered with Ann Arbor-based Aastrom Biosciences Inc. in the clinical trial, which involved 24 patients who required jawbone reconstruction after tooth removal.

Patients either received experimental tissue repair cells or traditional guided bone regeneration therapy. The tissue repair cells, called ixmyelocel-T, are under development at Aastrom, which is a U-M spinout company.

"In patients with jawbone deficiencies who also have missing teeth, it is very difficult to replace the missing teeth so that they look and function naturally," said Darnell Kaigler, principal investigator and assistant professor at the U-M School of Dentistry. "This technology and approach could potentially be used to restore areas of bone loss so that missing teeth can be replaced with dental implants."

William Giannobile, director of the Michigan Center for Oral Health Research and chair of the U-M Department of Periodontics and Oral Medicine, is co-principal investigator on the project.

The treatment is best suited for large defects such as those resulting from trauma, diseases or birth defects, Kaigler said. These defects are very complex because they involve several different tissue types -- bone, skin, gum tissue -- and are very challenging to treat.

The main advantage to the stem cell therapy is that it uses the patient's own cells to regenerate tissues, rather than introducing human-made, foreign materials, Kaigler said.

The results were promising. At six and 12 weeks following the experimental cell therapy treatment, patients in the study received dental implants. Patients who received tissue repair cells had greater bone density and quicker bone repair than those who received traditional guided bone regeneration therapy.

In addition, the experimental group needed less secondary bone grafting when getting their implants.

The cells used for the therapy were originally extracted from bone marrow taken from the patient's hip. The bone marrow was processed using Aastrom's proprietary system, which allows many different cells to grow, including stem cells. These stem cells were then placed in different areas of the mouth and jaw.

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Stem cell therapy could offer new hope for defects and injuries to head, mouth

ScienceDaily (July 30, 2012) Stem cells can actually replace dead heart tissue after a heart attack very early in life -- but those same cells lose that regenerative ability in adults, according to researchers at Cornell University and the University of Bonn.

The study, using mice as subjects, found that undifferentiated precursor cells grow new heart cells in a two-day-old mouse, but not in adult mice, settling a decades-old controversy about whether stem cells can play a role in the recovery of the adult mammalian heart following infarction -- where heart tissue dies due to artery blockage.

"While the existence of these cells in adults is controversial, if one did have fully capable stem cells in adults, why are there no new heart cells after an infarct? Whether this is due to a lack of stem cells or to something special about the infarct that inhibits stem cells from forming new heart cells is the question we addressed, taking advantage of the fact that the newborn mouse has these cells," said Michael Kotlikoff, dean of Cornell's College of Veterinary Medicine and senior author of the paper. The paper will appear Aug. 29 in the Proceedings of the National Academy of Sciences.

Kotlikoff and his fellow researchers found that two-day-old mice grew new heart cells and almost completely recovered from infarction, proving that the injury did not inhibit stem cells from growing new heart cells. The same procedure was carried out on adult mice and no new heart cells formed, confirming that adults do not have the requisite stem cells to create new heart cells, called myocytes, though new blood vessel cells were created.

The stem cells found in the adult heart "have lost the ability to become heart cells, and are only capable of forming new vessels," Kotlikoff said. Single stem cells differentiate into all tissues at the start of life, but over time these cells become "developmentally restricted" or specialized to form only certain tissues.

Sophie Jesty, Michele Steffey, and Frank Lee are the paper's lead authors and the work is part of a long-term collaboration with Professor Bernd Fleischmann's team at the University of Bonn.

The study was funded by the National Institutes of Health, New York State Stem Cell Science and the European Union Seventh Framework Programme.

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Stem cells repair hearts early in life, but not in adults

A US federal court rules that procedures in which a patients own stem cells are extracted, manipulated, and reinjected should be regulated by the FDA.

By Bob Grant | July 30, 2012

Leonardini | stock.xchng

After years of legal wrangling, the US District Court in Washington, DC, last week upheld the Food and Drug Administrations power to regulate adult stem cell treatments in which the cells are more than minimally manipulated before being injected back into the patient. The court ruled that the FDA was operating within its legal mandate when it filed suit against Colorado-based stem cell treatment clinic Regenerative Sciences in 2010 to stop them from extracting, processing, and then reinjecting patients own bone marrow stem cells to treat bone and joint disorders.

The FDA argued that the treatment fell under its purview and was subject to approval like any new drug because the extracted cells were significantly modified using reagents that cross state lines. Regenerative Sciences disagreed, characterizing the treatment as a simple medical procedure, which dont require FDA approval. The court sided with the FDA, making similar stem cell clinics popping up in the United States take notice. University of Minnesota bioethicist Leigh Turner told Nature that the ruling was spot on. It is much too simplistic to think that stem cells are removed from the body and then returned to the body without a manufacturing process that includes risk of transmission of communicable diseases, he said. Maintaining the FDAs role as watchdog and regulatory authority is imperative.

But Chris Centeno, Regenerative Sciences medical director told Nature that the clinic plans to continue offering patients 3 of its 4 stem cell treatments, in which cells are only processed for 2 days before reinjection. He added that the company will continue to treat patients using the process now prohibited by the FDA in a clinic located in the Cayman Islands and that Regenerative Sciences plans to appeal the courts ruling.

By Edyta Zielinska

The National Institutes of Health will fund 17 projects developing lab-on-a-chip applications to improve drug screening.

By Cristina Luiggi

After treating terminally ill patients with an unauthorized experimental probiotic procedure, two California doctors can no longer participate in human research.

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Stem Cell Treatment = Drug