The race is ON

Sharing information on an international level is crucial for stem cell research to progress

Recent research undertaken at the University of Edinburgh has shown that the protein Mbd3 plays a crucial role in the process through which embryonic stem cells become specialised cells.
In the body, stem cells divide to produce both copies of themselves or other, more specialised cell types. Researchers at Edinburgh University made mouse embryonic stem cells lacking the Mbd3 protein. Unlike non-engineered cells, the Mbd3-lacking cells failed to form different cell types when induced to do so in a dish. Instead they remained in an uncommitted state.  When injected into very early mouse embryos, the Mbd3-lacking cells behaved in a similar way, disrupting the normal development of the embryo.
Mbd3 is a part of a large complex of proteins called the NuRD (Nucleosome Remodelling and Histone Deacetylation) complex. NuRD is known as an epigenetic silencer, as its role in cells is to turn genes off.

StemDB
The results from this research is merely a fraction of information of what is starting to be known as the World Wide Web for bioinformaticians working in stem cell research – the StemDB database. The institute for Stem Cell Research (ISCR), a multidisciplinary research institute focused on the molecular, cellular and developmental biology of stem cells, is building one of the world’s largest stem cell bioinformatics database.
Led by Dr Simon Tomlinson from the University of Edinburgh, this project will establish a stem cell database (StemDB) containing a wide range of information about stem cells - from basic biology to clinical applications.
According to Dr Tomlinson the first release of the database will be in the late summer this year.
The primary objective of the project is to develop a database that can be used to disseminate the EuroStemCell project results to all EuroStemCell labs and ultimately to the wider public. Storage of microarray data follows the MIAME guidelines and they intend to support interchange of data to GEO and also Array Express.
The data stored by the database comes from the EuroStemCell participating
labs together with some data from the public domain.  The database will
allow the downloading of individual data sets as well as supporting common
queries across multiple experiments.
While there are already a number of excellent microarray databases available within the UK, what makes the StemDB database different is the focus of the project on the stem cell research community represented by the members of the EuroStemCell project.
The interpretation of gene expression data from stem cell populations can be quite difficult not least because of the capacity of the cells to differentiate to many different cell types and to adapt to their culture conditions. Ultimately the database, backed up with multiple profiling experiments and custom analysis tools, will be used to make interpretation of stem cell profiling data more robust.

High throughput techniques
The advent of high throughput techniques such as high throughput microarray expression profiling, is creating daily huge amounts of data that needs to be stored, analysed and visualised.
One of the many research areas of the ISCR is involved in combining this data and bioinformatics to gain understanding of key molecular features of stem cell biology. The StemDB database is being created to store stem cell related information such as cell line formation and expression profiling data. This data can then be accessed and analysed to help piece together the pieces of the puzzle that make up the process through which stem cells differentiate.
Also central to this research is refining data integration approaches to query across multiple experiments and different types of data. This involves working across several other projects. For example, discovering new surface markers that define specific stem/progenitor cell populations.
Much of the work being carried out exploits methodologies that allow the cells to be grown as relatively pure cell populations in feeder free (and serum free) conditions. The projects also make use of a range of gene targeting techniques that allow the activity of specific genes to be modulated under precisely controlled conditions.

European collaboration
The potential implications for the availability of this information are gigantic – from tailor-made therapeutic medical treatments to a future big headache for ethicists should possible future screening and modification (or elimination) of genetic conditions in utero be a possibility one day.
The StemDB database while an entity in its own, will link to other stem cell databases through the Eurostem Consortium’s €11.9 million EuroStemCell project. The aim of the latter is to develop an advanced technological platform for new cell-based therapies and create a foundation for translational research. Drawing together 11 academic centres across eight European countries, its key aim is to develop well-characterised cell lines of therapeutic potential derived from stem cells. Unprecendented in the stem cell filed worldwide, the project will enable for the first time a systematic comparison of the properties and therapeutic potential of stem cells of embryonic, foetal and adult origin – whoever said that the European spirit is dead?

Bogus research
These latest development in stem cell research have come amidst a period where stem cell research has seen a barrage of criticism both for the scientific and ethical communities.
The most recent scandal, where South Korean scientist Dr Hwang Woo-suk claimed to have created 11 stem cell lines from human embryos, cloned so that the cells exactly matched an individual patient, turned to be fake. To add further insult, it was revealed that the scientists had actually needed far more human eggs to create the cell lines than claimed, and that the human eggs used had been procured through unethical means.
In the UK it is currently illegal to produce embryos solely for stem cell research purposes. Scientist have to obtain their stem cells from adult tissue, donated human eggs (in short supply), or leftover embryos from IVF treatment. Embryonic stem cell research has historically been a highly debatable activity, not least by the scarcity of embryos available.
Therefore, after the excitement surrounding the South Korean claims — a new technique that allows the formation of perfect cell lines from relatively small amounts of human eggs and offering scientists a novel way of creating their cells line — the scientific community turned back to the drawing board.

Cooperation between scientists
However, the failed South Korea love affair may yet have a positive outcome.
At a mayor international conference on stem cell research held at Cambridge University in February 2006, an international collaboration of leading scientists and ethicists have called for reform in the laws restricting stem cell research — much needed bearing in mind that virtually each country worldwide have their own stem cell research laws, thereby hindering research and making international collaboration very difficult.
The international collaboration has formed the Hixton Group, an interdisciplinary consortium on stem cells ethics and law, who have called upon scientists, journals and founding bodies worldwide to set an international ethical standard for research in this area. The recommendations made by the Group include: getting journals to ask researchers to include statements confirming their research conforms to national guidelines; a public website for international researchers to share information about research codes and ethical protocols; and an attempt to reach ethical consensus on new areas of research, including the creation of human-animal chimeras.

UK-led initiatives
On 1 December 2005 the UK Stem Cell Initiative (set up by Chancellor Gordon Brown in his March 2005 Budget) launched its first report and called for more Government founding and better coordination. Sir John Pattison, chair of the UKSCI recommended that the UK should spend at least £350 million over the next decade on stem cell research. The report called for a consortium of pharmaceutical, healthcare and biotechnology companies backed by the Government to develop stem cell technology as a basis for new medical treatments. The report also suggests that the Government to strengthen the infrastructure supporting UK stem cell research via the consolidation of the UK Stem Cell Bank and the establishment of Centres of Excellence and a UK-wide national Stem Cell Cooperative.
The Government is yet to allocate specific funds for the establishment of a Cooperative. However, the Biotechnology and Biological Sciences Research Council (BBSRC) has launched an online consultation on April 2006 on behalf of the UK Research Councils, the Department of Health, the Office of Science and Innovation, and the Department of Trade and Industry. The aim of the consultation is to provide stem cell researchers the opportunity to express their opinions on how they would like to see the UK Stem Cell Cooperative established and run. The consultation is open until the end of May 2006 (www.bbsrc.ac.uk).
Despite the lack of Government movement however, in the last couple of months, and fuelled by the South Korea fiasco, the UK stem cell research community has pulled ranks and has embarked on research more vigorously than ever.
Dr Stephen Minger, from Kings College, London, is planning on using cloned human-animal hybrids to create stem cell lines, thereby bypassing the need for embryos to obtain cells from. However, he has warned that the technique would not be perfected for another 10 years.
A team of researchers at Cambridge University are developing a technique relying on off-the-shelf matches from a bank of stem cell lines from selected donors. One such bank has been in existence in the UK since 2002 at the UK Stem Cell Bank.
Dr Mohammed Taranissi, a fertility expert, is promoting what he calls ‘stem-brid’ technology, which uses the stem cell line itself as a surrogate egg. The race is on.

By Maria Anguita rodriguez