Media Coverage : European Science Foundation

Media Coverage

Third EuroSTELLS Workshop, 10-12 January 2008

Article 1 (released 14 January 2008)

Minister predicts role for stem cell biologists in re-shaped pharmaceutical industry

Stem cell research should have a bright future and could play an important role in tomorrow’s pharmaceutical industry, Spain’s Minister for Health told an international conference of stem cell biologists on January 11.

Professor Bernat Soria, himself a distinguished cell biologist, was speaking at the EuroSTELLS conference in Barcelona organised by the European Science Foundation. EuroSTELLS is an ESF EUROCORES programme, managed by the European Medical Research Councils that aims to develop a ‘toolbox’ for the fundamental study of stem cells – the ‘blank’ cells that have the potential to become programmed to form a wide range of different types of cell and which could one day be used to repair damaged tissues and organs in human patients.

Fundamental research into stem cells could eventually play an important role in a ‘new look’ pharmaceutical industry, Professor Soria said. “The pharmaceutical industry is confronting big changes. Big pharma is facing complete re-shaping in the sense that traditionally it has come from chemistry. We are now moving into a pharmaceutical industry more based upon biotechnology, with academic researchers and university spin-out companies playing a greater and more influential role.”

In this environment, stem cell biologists could play a more prevalent part in the discovery of new therapies, Professor Soria said. But he urged caution. “While I do not wish to be a pessimist, we are still a long way from producing cells that behave like adult cells,” he said.

Nevertheless, the outlook was potentially rosy. “There are new niches in which biotechnology and biological scientists can play a certain role,” Professor Soria predicted. “I anticipate that you will have a nice future. And I hope you will have a splendid future.”

EuroSTELLS is the European Collaborative Research (EUROCORES) programme on “Development of a Stem Cell Tool Box” run by the European Medical Research Councils (MED (formerly EMRC)) Unit in the European Science Foundation. ESF provides scientific coordination and support for the networking activities of funded scientists through the EC FP6 Programme, under contract no. ERAS-CT-2003-980409. Research funding is provided by the participating national organisations.

Article 2 (released 18 January 2008)

Stem cell research aims to tackle Parkinson’s disease

Scientists in Sweden are developing new ways to grow brain cells in the laboratory that could one day be used to treat patients with Parkinson’s disease, an international conference of biologists organised by the European Science Foundation (ESF) was told.

Professor Ernest Arenas of the Karolinska Institute in Stockholm presented his research to the EuroSTELLS “Stem Cell Niches” conference in Barcelona on January 11. Stem cell therapy hold the promise of treating disease by growing new tissues and organs from stem cells – ‘blank’ cells that have the potential to develop into fully mature or ‘differentiated’ cells. The EuroSTELLS is an ESF EUROCORES programme, managed by the European Medical Research Councils (MED (formerly EMRC)), that aims to develop a stem cell ‘toolbox’ by generating fundamental knowledge on stem cell biology.

Parkinson’s disease affects around three in a hundred of people aged over 65. The condition can cause muscles to become rigid and limbs to tremble uncontrollably. Parkinson’s disease results from the loss of a particular type of brain cell called dopaminergic (DA) neurons in the part of the brain called the substantia nigra.

Among the various approaches that are currently being discussed from an ethical perspective, is the possible approach of taking stem cells, growing them into new brain cells and transplanting these into the patient. “The idea is to start with stem cells and induce them to become neurons,” said Professor Arenas, whose research is carried out as part of a EuroSTELLS collaboration. “These could then be transplanted into the brain of the patient. Also, such cells could be ideal for developing and testing new drugs to treat brain disease.”

However, to create such cells that function efficiently and safely is a major challenge. Early efforts at growing DA neurons from embryonic stem cells produced cells which, when transplanted into animal models, had a tendency to form tumours or clumps, or die without an obvious reason.

Professor Arenas’s team studied the development of DA neurons in animals to determine the important biological molecules in the brain that were necessary for the cells to grow and function efficiently. The scientists identified one particular molecule that seemed to be key, a protein called Wnt5a. They showed that when this molecule, together with a second protein called noggin, was included in cultures of stem cells, far more DA neurons were produced than when these ingredients were not present.

The team then carried out a series of molecular, chemical and electrophysiological tests on the newly grown neurons to check their proficiency, which was shown to be good.

Crucially the team also moved away from embryonic stem cells – which can be induced to grow into a wide variety of different cells. Instead they used neural stem cells – which are programmed to develop only into nerve cells.

When the researchers transplanted the cells into laboratory animals whose substantia nigra region of the brain was damaged, the results were promising. “We reversed almost completely the behavioural abnormalities, and neurons differentiated, survived and re-innervated the relevant part of the brain better” Professor Arenas said. “Furthermore we do not see the kind of proliferation of the cells that has occurred in the past and we get very little clustering when the cells are treated with Wnt5a. The cells are safer than embryonic stem cells and more efficient than fetal tissue.”

Verification of this approach with human cells is ongoing and if the study is successful, it may lead to a clinical trial. Experts in the field have recently identified this approach as the next step in cell replacement therapy for Parkinson’s disease and the hope is that this may, ultimately, lead to cells suitable for transplant into human patients.

Article 3 (released 13 February 2008)

Stem cells give clues to understanding cancer; make breakthrough in childhood leukaemia

Scientists in Switzerland are uncovering new clues about how cancer cells grow – and how they can be killed – by studying stem cells, ‘blank’ cells that have the potential to develop into fully mature or ‘differentiated’ cells and other scientists in UK have made a breakthrough in understanding the cause of the most common form of childhood cancer, acute lymphoblastic leukaemia (ALL). The research should lead to less aggressive treatment for the disease and could result in the development of new and more effective drugs, an international conference on stem cell biology was told last month.

The conference, organised by the European Science Foundation’s EuroSTELLS programme and held in Barcelona on January 10-13, heard that stem cells and cancer cells share many similar features. For example the cellular machinery that sends signals between stem cells to tell them when and how to develop is in many cases similar to the signalling mechanisms that operate between cancer cells.

On one hand, Professor Ariel Ruiz i Altaba of the University of Geneva in Switzerland is studying key proteins in stem cells and cancer stem cells – cancer cells that are later responsible for tumour growth, the recurrence of tumours and the spread of the cancer to other parts of the body . Four such proteins, called Sonic Hedgehog (Shh) and Gli-1, Gli-2 and Gli-3 act through a biochemical pathway to send important signals between cells. “We have shown that interfering with Shh signalling decreases the size of tumours, which is proof of principle that the tumours require the pathway,” Professor Ruiz i Altaba told the conference participants.

Professor Ruiz i Altaba’s team has been experimenting with samples of brain and other tumours from patients, treating tumour cells and their cancer stem cells – the cells that continuously replenish the growing cancer – in the laboratory with chemicals that inhibit the activity of the Shh pathway and lead to the inhibition of Gli-1. “We take tumour samples and grow them in a variety of ways,” said Professor Ruiz i Altaba. “When we treat them with inhibitors that block the Shh-Gli pathway, they all respond, demonstrating that every tumour we have tested requires this signalling pathway.”

Professor Ruiz i Altaba added, “Hedgehog signalling appears to be involved in many kinds of stem cells and many kinds of cancers. Specifically, Gli-1 seems to be important for the proliferation of tumour cells and especially for the proliferation and perpetuation of cancer stem cells. We think the Gli code, the sum of all Gli activities, is locked in a ‘hyperactivating’ state in cancer, and if we can revert it to a repressive state, this could provide a possible therapeutic approach.”

Meanwhile Dr Manel Esteller of the Spanish National Cancer Research Centre (CNIO) in Madrid has been investigating the way that genes in cancer cells and stem cells are modified by a process called methylation .

In a cell not all of the genes are active. Some are rendered ‘silent’ by the attachment of chemical entities called methyl groups. This is one of the mechanisms by which a cell can switch genes on and off. It has become clear that the pattern of DNA methylation is one key difference between a cell that has become specialised – that is differentiated – and one that remains undifferentiated.

“We have studied plant DNA and have seen that in undifferentiated tissue one particular region of the DNA is always unmethylated,” Dr Esteller told the meeting. “In differentiated tissue this same region is methylated. If we take the undifferentiated cell and add the methylated gene we get differentiation.”

A similar system appears to operate in human cells. And in some cancer cells there are particular patterns of DNA methylation. “We have seen that in some leukaemias there is a gene involved in differentiation that is methylated,” Dr Esteller said. “In cultured cells we see that if we put the unmethylated gene back into the cell, we stop the growth of the cells in culture, and also in mouse models. This gene is acting as a tumour suppressor.”

The hope is that further investigation of factors such as DNA methylation could lead to potential new treatments for cancer.

On the other hand, Professor Tariq Enver of the Weatherall Institute for Molecular Medicine at the University of Oxford presented findings of his research on acute lymphoblastic leukaemia (ALL), which has now been published in the journal Science .

Professor Enver, who is a EuroSTELLS collaborator and his co-workers, demonstrated for the first time the existence of cancer stem cells in ALL. The researchers compared the blood of three-year-old identical twins, one of whom has the disease while the other is healthy.

The researchers found that both twins had genetically abnormal blood cells – ‘pre-leukaemic’ stem cells that reside in the bone marrow. It appears that these cells can either lay dormant or can somehow be triggered to develop into full-blown leukaemia stem cells.

The researchers showed that these cells arise from an abnormal fusion of two genes during the mother’s pregnancy. Professor Enver said, “This research means that we can now test whether the treatment of acute lymphoblastic leukaemia in children can be correlated with either the disappearance or persistence of the leukaemia stem cell. Our next goal is to target both the pre-leukaemic stem cell and the cancer stem cell itself with new or existing drugs to cure leukaemia while avoiding the debilitating and often harmful side effects of current treatments.”

Last Updated March 2008