Study Identifies Mechanism That Makes Ordinary Stem Cells Create Tumours

Epigenetic effects on cell signalling leads healthy stem cells to create benign fibromas in the jaw

Thursday, 07 November 2013

This is Professor Songtao Shi of the Ostrow

School of Dentistry at the University of Southern

California. Credit: John Skalicky. 

A new study from the Ostrow School of Dentistry at the USC published in Cell Stem Cell illustrates how changes in cell signalling can cause ordinary stem cells in the jaw to start forming benign but potentially harmful tumours.

Principal investigator Songtao Shi, professor at the Ostrow School of Dentistry Center for Craniofacial Molecular Biology, says ossifying fibromas, the tumours focused on in the study, are benign but can grow aggressively and cause progressive enlargement of the jaw.

"The only treatment option for ossifying fibromas is surgical, which leads to major loss of vital tissues and challenging post-surgical reconstruction," Shi says.

"Quality of life is largely compromised. Thus, there is an urgent need to understand the underlying mechanism by which stem cells may contribute to the pathophysiology of oro-facial benign tumours and to develop target-specific treatment."

Shi and his collaborators uncovered a cellular signalling pathway that converts healthy mesenchymal stem cells in the jaw into ossifying fibroma mesenchymal stem cells (OFMSC), lessening their ability to make healthy bone tissue and greatly increasing the rate at which they multiply. The tumour stem cells display increased signalling activity with TGF-beta (TGF-b), a signalling protein already shown to be heavily tied to other craniofacial malformations.

Epigenetic up-regulation – switching existing but inactive genes "on" – of the TGF-b cell signalling loop appears to increase the formation of ossifying fibroma tumours. Conversely, suppressing TGF-b signalling seems to quell the tumour's proliferation rate, Shi says.

While there is still much more investigation needed, Shi says hopes that the findings have shed light on a way to stop the harmful growth of the tumours before risky surgery is needed.

"With an increased understanding of the mechanism of OFMSC, we can induce them to turn into normal jawbone MSC," he says.

"But before we can put this into clinical use, more translational research is needed."

Source: University of Southern California 

Contact: Beth Newcomb

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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at

http://cellnews-blog.blogspot.com/

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Human Stem Cell Research in Europe

New Report Calls for Sustained Public Endorsement and Funding for Human Stem Cell Research

Wednesday, 06 November 2013

A strategic report from the European Science Foundation examines the key scientific questions for human stem cell research in the context of the rapidly emerging field of regenerative medicine. In parallel to the potential new treatments for incurable diseases resulting from stem cell research, heated ethical and legal debates have arisen across the world. This report presents a comparative view of the legislative framework on human stem cell research across Europe and provides a selection of success stories in frontier research and clinical trials that underpin the advances achieved in Europe to date.

In recent years, international research on regenerative medicine and stem cells has yielded some promising results and even greater expectations in society. In this medical field, human embryonic stem cells could be applied in a variety of ways, for example to identify new compounds for drug development, or as cell-based therapies. The potential to use human stem cells to repair or replace tissue or organ functions lost through age, disease, damage or birth defects may raise ethical issues that must be considered integrally with any research. Europe is currently witnessing developments and debates that will impact regulation and public funding of stem cell research and innovation for years to come.

The report observes that Europe plays a leading role in regenerative medicine research, with most countries featuring legislative frameworks that are globally favourable to human stem cell research. The 30 countries' position on human stem cell research was grouped into five broad categories; very permissive, permissive with restrictions, restrictive by default, very restrictive and unlegislated. The report found that 63% of the countries fell into the first two categories.

"Europe has a valuable track record in the area of stem cell research. The report highlights the need to continue to fund this research so that its full potential can be realised." said Professor Stig Slørdahl, Dean of the Faculty of Medicine at Norwegian University of Science and Technology, who chaired the report.

The authors recommend that sustained public endorsement and funding need to continue in order for further research to be carried out and public-private partnerships to develop, bringing safe and innovative therapies to the market, with a potential benefit to millions of patients worldwide.

Dr Vanessa Campo-Ruiz, ESF Science Officer to the Chief Executive and lead author of the report commented:

"We hope this report may help to inform future policy and funding decisions across Europe and thus contribute to ensure this continent's scientific leadership, social welfare and economic growth."

About The European Science Foundation

The European Science Foundation coordinates collaboration in research, networking, and funding of international research programmes, as well as carrying out strategic and science policy activities at a European level. Its members are 67 national research funding and performing organisations, learned societies and academies in 29 countries.

Source: European Science Foundation 

Contact: Emma Knott

Reference:

Human Stem Cell Research and Regenerative Medicine: Focus on European policy and scientific contributions

(available online, pdf)

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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at

http://cellnews-blog.blogspot.com/

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Riboswitches in Action

Scientists at SISSA investigate a mechanism that switches genes on and off 

Monday, 04 November 2013

Riboswitch RNA. 

Riboswitches are RNA segments that switch genes on and off, either during DNA transcription or during protein translation, but little is known about the precise workings of this process. A study at SISSA uncovers some of the basic steps in this complex mechanism and paves the way for future research.

A cell is a complex environment in which substances (metabolites) must maintain a correct state of equilibrium, which may vary depending on specific needs. Cells can maintain the proper concentrations of metabolites by regulating gene protein encoding through specific “switches”, called riboswitches, which are able to block or activate protein synthesis. The precise mechanism by which these short strands of RNA carry out this function is still poorly understood. However, a study conducted by SISSA scientists Giovanni Bussi, Francesco Colizzi and Francesco De Palma and published in the journal RNA, now provides some important insights. 

A riboswitch is contained in a strand of messenger RNA, an RNA fragment that acts as a sort of template that “prints” the proteins that are needed for cell metabolism. However, unlike the rest of the messenger RNA unit, riboswitches don’t actually encode any portion of the protein (i.e., they form part of what geneticists call non-coding RNA) but they serve to activate or deactivate the protein printing process and are located, in bacteria, in a stretch preceding the coding sequence. Scientists know that this switching action is made possible by a change in shape, which occurs when a part of the riboswitch (the aptamer) binds to a molecule in the cell environment which acts as a signal. Bussi and colleagues used computer simulations to reproduce the dynamics of the process and understand how binding to the metabolite brings about the change in shape.

More specifically, Bussi and colleagues simulated the riboswitch that uses an adenine molecule as a signal, to regulate the gene expressing a protein involved in the metabolism of adenine itself. Their findings clarify how adenine stabilizes the active form of the riboswitch (the one triggering protein synthesis) to the detriment of the inactive conformation.

“We used molecular dynamics as a kind of ‘virtual microscope’ with which we observed the workings of the process”, explained Bussi.

“It’s very important to understand these regulatory mechanisms since they are present in many bacteria – as well as in multicellular organisms – and may be useful for developing new antibiotics in the future.”

The computer-based simulations carried out in the study relied on PLUMED software, the latest release of which was presented in another recent paper published by Bussi in Computer Physics Communications. PLUMED is a software program devised to create and analyse simulations.

“This more advanced version of the program was developed as a team of five young researchers from international institutions”.

It’s no coincidence that the researchers involved in this work are all young: the research project was in part funded by a special grant provided for young, non-permanent research fellows at SISSA and awarded to Bussi in 2011.

The research was carried out within the framework of a European Research Council (ERC)-funded project coordinated by  Bussi.

Source: Sissa Medialab

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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at

http://cellnews-blog.blogspot.com/

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