Category Archives: Stem Cells

Newswise DALLAS May 31, 2012 An immune-system receptor plays an unexpected but crucially important role in keeping stem cells from differentiating and in helping blood cancer cells grow, researchers at UT Southwestern Medical Center report today in the journal Nature.

Cancer cells grow rapidly in part because they fail to differentiate into mature cells. Drugs that induce differentiation can be used to treat cancers, said Dr. Chengcheng Alec Zhang, assistant professor in UT Southwesterns departments of physiology and developmental biology. Our research identified a protein receptor on cancer cells that inhibits differentiation, and knowing the identity of this protein should facilitate the development of new drugs to treat cancers.

The family of proteins investigated in the study could help open a new field of biology integrating immunology with stem cell and cancer research, he added.

The receptor we identified turned out to be a protein called a classical immune inhibitory receptor, which is known to maintain stemness of normal adult stem cells and to be important in the development of leukemia, he said.

Stemness refers to the blood stem cells potential to develop into a range of different kinds of cells as needed, for instance to replenish red blood cells lost to bleeding or to produce more white blood cells to fight off infection. Once stem cells differentiate into adult cells, they cannot go back to being stem cells. Current thinking is that the body has a finite number of stem cells and it is best to avoid depleting them, Dr. Zhang explained.

Prior to this study, no high-affinity receptors had been identified for the family of seven proteins called the human angiopoetic-like proteins. These seven proteins are known to be involved in inflammation, supporting the activity of stem cells, breaking down fats in the blood, and growing new blood vessels to nourish tumors. Because the receptor to which these proteins bind had not been identified, the angiopoetic-like proteins were referred to as orphans, he said.

The researchers found that the human immune-inhibitory receptor LILRB2 and a corresponding receptor on the surface of mouse cells bind to several of the angiopoetic-like proteins. Further studies, Dr. Zhang said, showed that two of the seven family members bind particularly well to the LILRB2 receptor and that binding exerts an inhibitory effect on the cell, similar to a cars brakes.

In the case of stem cells, inhibition keeps them in their stem state. They retain their potential to mature into all kinds of blood cells as needed but they dont use up their energy differentiating into mature cells. That inhibition helps stem cells maintain their potential to create new stem cells because in addition to differentiation, self-renewal is the cells other major activity, Dr. Zhang said. He stressed that the inhibition doesnt cause them to create new stem cells but does preserve their potential to do so.

In future research, the scientists hope to find subtle differences between stem cells and leukemia cells that will identify treatments to block the receptors action only in leukemia.

Other UT Southwestern researchers involved in the study from the departments of physiology and developmental biology include postdoctoral researchers Dr. ChangHao Cui, Dr. Xiaoli Chen, Dr. Chaozheng Zhang, Dr. HoangDinh Huynh, and Dr. Xunlei Kang; senior research associates Robert Silvany and Jiyuan Li; and graduate student Xuan Wan. Researchers from the department of immunology include former technician Alberto Puig Cant and Dr. E. Sally Ward, professor of immunology.

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UT Southwestern Researchers Identify Mechanism That Maintains Stem-Cell Readiness, Helps Leukemia Cells Growth

ScienceDaily (May 31, 2012) An immune-system receptor plays an unexpected but crucially important role in keeping stem cells from differentiating and in helping blood cancer cells grow, researchers at UT Southwestern Medical Center report today in the journal Nature.

"Cancer cells grow rapidly in part because they fail to differentiate into mature cells. Drugs that induce differentiation can be used to treat cancers," said Dr. Chengcheng "Alec" Zhang, assistant professor in UT Southwestern's departments of physiology and developmental biology. "Our research identified a protein receptor on cancer cells that inhibits differentiation, and knowing the identity of this protein should facilitate the development of new drugs to treat cancers."

The family of proteins investigated in the study could help open a new field of biology integrating immunology with stem cell and cancer research, he added.

"The receptor we identified turned out to be a protein called a classical immune inhibitory receptor, which is known to maintain stemness of normal adult stem cells and to be important in the development of leukemia," he said.

Stemness refers to the blood stem cells' potential to develop into a range of different kinds of cells as needed, for instance to replenish red blood cells lost to bleeding or to produce more white blood cells to fight off infection. Once stem cells differentiate into adult cells, they cannot go back to being stem cells. Current thinking is that the body has a finite number of stem cells and it is best to avoid depleting them, Dr. Zhang explained.

Prior to this study, no high-affinity receptors had been identified for the family of seven proteins called the human angiopoetic-like proteins. These seven proteins are known to be involved in inflammation, supporting the activity of stem cells, breaking down fats in the blood, and growing new blood vessels to nourish tumors. Because the receptor to which these proteins bind had not been identified, the angiopoetic-like proteins were referred to as "orphans," he said.

The researchers found that the human immune-inhibitory receptor LILRB2 and a corresponding receptor on the surface of mouse cells bind to several of the angiopoetic-like proteins. Further studies, Dr. Zhang said, showed that two of the seven family members bind particularly well to the LILRB2 receptor and that binding exerts an inhibitory effect on the cell, similar to a car's brakes.

In the case of stem cells, inhibition keeps them in their stem state. They retain their potential to mature into all kinds of blood cells as needed but they don't use up their energy differentiating into mature cells. That inhibition helps stem cells maintain their potential to create new stem cells because in addition to differentiation, self-renewal is the cells' other major activity, Dr. Zhang said. He stressed that the inhibition doesn't cause them to create new stem cells but does preserve their potential to do so.

In future research, the scientists hope to find subtle differences between stem cells and leukemia cells that will identify treatments to block the receptors' action only in leukemia.

Other UT Southwestern researchers involved in the study from the departments of physiology and developmental biology include postdoctoral researchers Dr. ChangHao Cui, Dr. Xiaoli Chen, Dr. Chaozheng Zhang, Dr. HoangDinh Huynh, and Dr. Xunlei Kang; senior research associates Robert Silvany and Jiyuan Li; and graduate student Xuan Wan. Researchers from the department of immunology include former technician Alberto Puig Cant and Dr. E. Sally Ward, professor of immunology.

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Mechanism that maintains stem cells readiness identified

Public release date: 30-May-2012 [ | E-mail | Share ]

Contact: Dian Land dj.land@hosp.wisc.edu 608-261-1034 University of Wisconsin-Madison

MADISON Breast-cancer researchers at the University of Wisconsin-Madison have found that two related receptors in a robust signaling pathway must work together as a team to maintain normal activity in mammary stem cells.

Mammary stem cells produce various kinds of breast cell types. They may also drive the development and growth of malignant breast tumors.

Published recently in the Journal of Biological Chemistry, the research also suggests that a new signaling pathway may be involved, a development that eventually could take cancer-drug manufacturers in a new direction.

"We wanted to know if we could use this knowledge to inform us about what might be the transition that occurs to start tumor growth and maintain it," says senior author Dr. Caroline Alexander, professor of oncology at the McArdle Laboratory for Cancer Research at the School of Medicine and Public Health.

The paper describes new information about the Wnt signaling pathway. Wnt signaling underlies numerous activities in normal development, but when the system is unregulated, cancer often occurs.

"Wnt signaling is very important for both stem cells and tumor growth. We need to know the details of the signaling process so that we can use the positive aspects of Wnt signaling for regenerative medicine, and eliminate the negative cancer-causing aspects," says Alexander, a member of the UW Carbone Cancer Center (CCC).

Regenerative biologists typically add Wnt proteins together with other agents to guide the differentiation of lung, bone and heart stem cells, she notes.

The UW researchers zeroed in on two related Wnt receptors on the cell surface--LRP5 and LRP6. The receptors normally respond to Wnt ligands that approach cells to initiate a signaling cascade inside.

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Breast stem-cell research: Receptor teamwork is required and a new pathway may be involved

GRAND RAPIDS, MI -- A stem cell treatment investigated for Huntingtons disease holds out hope that scientists will someday be able to reverse damage caused by the degenerative brain disorder.

The technique, which uses reprogrammed skin cells from a Huntingtons patient, successfully restored motor functions in rats, said Dr. Patrik Brundin, a Van Andel Institute researcher who was involved in the study.

Its an interesting step, one weve been hoping for, he said. Its exciting.

The technique also will be tested in treatments for Parkinsons disease, said Brundin, who came to VAI from Sweden in October to lead the institutes Parkinsons research.

Scientists from Sweden, South Korea and the U.S. collaborated on the study, which was published online Monday in the journal Stem Cells.

Brundin said researchers took stem cells derived from the skin of a patient with Huntingtons disease and converted them to brain cells or nerve cells in culture dishes in the lab. The cells were transplanted into the brains of rats that had an experimental form of Huntingtons, and the rats motor functions improved.

The unique features of the (stem cell approach) means that the transplanted cells will be genetically identical to the patient, Jihwan Song, an associate professor at CHA University in Seoul and co-author of the study, said in a statement released by VAI. Therefore, no medications that dampen the immune system to prevent graft rejection will be needed.

Brundin estimated the research might lead to treatments for humans in five to 10 years, although he acknowledged a timeframe is difficult to predict. Researchers are eager to find a new treatment for Huntingtons because there is nothing really powerful to offer currently, he said.

Huntingtons is a genetic disorder affecting one in every 10,000 Americans that slowly diminishes a persons ability to walk, talk and reason. A child of a parent who has Huntingtons has a 50 percent chance of inheriting the gene that causes it.

Medications can relieve some symptoms in some cases, but there are no treatments available that can slow the disease, according to the Huntingtons Disease Society of America.

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First treatment for Huntington's disease shows promise in rats, Van Andel Institute scientist says

Be cautious with stem cells

EDITOR

The secret of restoring health lies in replacing decrepit cells ravaged by disease with stem cells. This advance in stem cell research follows and is closely linked to the simultaneous announcement by former US President Bill Clinton and British Prime Minister John Major in 2000 that scientists had unravelled the human genome by more than 90 percent. The breakthrough of the Human Genome Project was hailed in superlative terms as advancement in the treatment of cancer and hereditary diseases. Clinton described it as the first survey of the entire human genome and "the most wondrous map ever produced by humankind". A couple of years earlier, physician-geneticist Francis Collins, that leading light noted for his discoveries of disease genes, had described the advance in breaking the human genetic code as something that would be judged by history as "more significant than even splitting the atom or going to the moon".

However, the same sage had warned: "We have a small lantern in the form of a gene, but the lantern doesn't penetrate more than a couple of hundred feet. We don't know whether we're going to encounter chasms, rock walls or mountain ranges along the way." It is this warning that we want to draw attention to. In doing so, we recall that Dolly, the cloned sheep that was eventually euthanised after being diagnosed with progressive lung disease in 2003, was the culmination of embryonic stem cell research that pitted moral scruples against science in yet another of their cyclical rancorous confrontations. In the end, governments ordered a stop to what they feared could degenerate into man playing God. It is important to note that the theatre of this apparent antipathy between metaphysics and science was the citadel of the latter in Western Europe and North America, and not some windswept desert country on a plateau in southern Africa. We feel compelled to issue this warning because countries defined by widespread ignorance have often provided the ideal environment for rogue scientists to conduct their nefarious experiments in pursuit of wicked goals. We say this because while the Ministry of Agriculture (MoA) has perhaps the highest concentration of educated Batswana, they simply looked the other way as controversy around genetically modified foods raged everywhere else in the world.

Our country being a net exporter of food, it was incumbent upon MoA to at least mount a deliberate awareness campaign and insist on adequate labelling of food. But where food production remains an elusive goal, it must be too much to expect MoA to understand that the end aim of food and pharmaceutical multinationals is depletion of botanical resources in the so-called Third Word and dependence on the West. Hence we receive news that enabling legislation for a stem cell facility is to be passed in July with a sense of trepidation.

Today's thought"The world is a dangerous place, not because of those who do evil, but because of those who look on and do nothing."

- Albert Einstein

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Be cautious with stem cells

LONDON, May 30,2012 /PRNewswire/ --Stem cell research is very dynamic with research trends, focus, and approaches evolving extremely rapidly. The tool market has to quickly adapt to these challenges and develop innovative tools that address and accelerate research accomplishments.

New analysis from Frost & Sullivan (http://www.drugdiscovery.frost.com), Strategic Analysis of the European Stem Cell Research Tools Market, finds that the market earned revenues of $148.4 million in 2011 and estimates this to reach $322.0 million in 2017. The segments covered include: bio-imaging and microscopy, cell biology tools, immunochemical, molecular biology tools, and protein biochemistry tools.

"Firms with the capacity to supply tools for stem cell research will increase as the science matures," notes Frost & Sullivan Senior Research Analyst Divyaa Ravishankar. "Soon demand and supply will achieve a degree of equilibrium."

Already, a sizeable stem cell research products market has emerged. Another positive sign for the market has been enhanced industry- academic collaboration.

A key step forward has been the stem cell regulations in a few countries allowing the use of certain cell lines. In some countries such as France, for instance, stem cell regulations are being renewed for the procurement and use of stem cells.

"Such trends indicate the potential for a regulatory climate that would be far less restrictive than the current scenario," adds Divyaa Ravishankar. "This, together with the prospect of diverse applications within the healthcare arena, is bolstering the future of the market."

However, the lack of venture capitalists (VC) poses a grave challenge. VC funding is driven by investment concerns, with companies bidding to double their money every few years in order to return revenue to the fund's investors. As a high risk venture, stem cell technology does not exactly present an attractive investment proposition.

"While these are financial concerns, from the technological standpoint, the challenge remains to understand the basic biology behind stem cells," remarks Divyaa Ravishankar. "There is an urgent need to design and develop specific technology platforms that enhance the production, genetic stability and integration of transplanted cells."

If you are interested in more information on this study, please send an e-mail with your contact details to Janique Morvan, Corporate Communications, at janique.morvan@frost.com.

Strategic Analysis of the European Stem Cell Research Tools Market is part of the Clinical Diagnostics Growth Partnership Services programme, which also includes research in the following markets: European PCR Reagent Market for Research and Clinical Diagnostics and European Next Generation Sequencing Market. All research included in subscriptions provide detailed market opportunities and industry trends that have been evaluated following extensive interviews with market participants.

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Rapidly Evolving Stem Cells Market Opens Up Doors for Related Research Tools, Says Frost & Sullivan

This finding can help researchers model diseases in the lab, and allow these diseases to be studied

Researchers from the University of Wisconsin-Madison have found a way to turn both embryonic and induced pluripotent stem cells into cardiomyocytes.

Sean Palecek, study leader and professor of chemical and biological engineering at the University of Wisconsin-Madison, along with Timothy Kamp, professor of cardiology at UW School of Medicine and Public Health, and Xiaojun Lian, a UW graduate student, have developed a technique for abundant cardiomyocyte production, which will allow scientists to better understand and treat diseases.

Cardiomyocytes are important cells that make up the beating heart. These cells are extremely difficult to obtain, especially in large quantities, because they only survive for a short period of time when retrieved from the human heart.

But now, the UW researchers have found an inexpensive method for developing an abundance of cardiomyocytes in the laboratory. This finding can help researchers model diseases in the lab, and allow these diseases to be studied. Researchers will also be able to tests drugs that could help fight these diseases, such as heart disease.

"Many forms of heart disease are due to the loss or death of functioning cardiomyocytes, so strategies to replace heart cells in the diseased heart continue to be of interest, said Kamp. "For example, in a large heart attack up to 1 billion cardiomyocytes die. The heart has a limited ability to repair itself, so being able to supply large numbers of potentially patient-matched cardiomyocytes could help."

The UW research team found that changing a signaling pathway called Wnt can help guide stem cell differentiation to cardiomyocytes. They just turned the Wnt pathway on and off at different times using two small molecule chemicals.

"Our protocol is more efficient and robust," said Palecek. "We have been able to reliably generate greater than 80 percent cardiomyocytes in the final population while other methods produce about 30 percent cardiomyocytes with high batch-to-batch variability.

"The biggest advantage of our method is that it uses small molecule chemicals to regulate biological signals. It is completely defined, and therefore more reproducible. And the small molecules are much less expensive than protein growth factors."

This study was published in the journal Proceedings of the National Academy of Sciences.

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New Method Turns Embryonic/Induced Pluripotent Stem Cells into Cardiac Muscle Cells