BioWorld International Correspondent

LONDON — Scientists from around the world who are conducting work on embryonic stem (ES) cells can now be certain, when they try to duplicate one another's research findings, that they are using the same kinds of cells in their experiments.

A collaborative research project known as the International Stem Cell Initiative (ISCI) has completed a survey of the kinds of molecules that are found on the surfaces of various ES cell lines, and of which genes the cells express.

Learning how to manipulate ES cells so that they differentiate into various types of mature cells — insulin-producing pancreatic islet cells to treat diabetes, or dopamine-producing neurons to treat Parkinson's disease, for example — will be vital in the future development of new therapies for many different diseases.

Yet very little has been known to date about the characteristics of the ES cell lines that researchers have been working with, which are estimated to number from 200 to more than 300 worldwide.

The latest study, published in Nature Biotechnology, which reports the characteristics of 59 ES cell lines from 17 different laboratories around the world, fills this gap. The title of the paper is: "Characterization of human embryonic stem cell lines by the International Stem Cell Initiative."

Peter Andrews, co-director of the Centre for Stem Cell Research at the University of Sheffield, UK, told BioWorld International: "We found that the expression of key markers by all the ES cell lines was remarkably similar; there was no evidence of substantially different subgroups of cell lines. This is not to say that there are no differences, however, and there is some anecdotal evidence that some lines differentiate differently to others."

The study also identified a clear set of genes and a set of protein markers that are commonly expressed by the cells. When the cells begin to differentiate, so losing their pluripotency, these genes are switched off.

Andrews said: "We can regard this set of data as a good subset of markers for characterizing the cells in future. It means that if someone in Japan has derived some ES cells and is doing some work on them, everyone will know if they are working with similar cells to someone doing similar work in the Czech Republic, for example."

The ISCI also set up a reference collection of hybridomas that produce the antibodies that can be used to detect some of the markers that characterize the ES cell lines. This collection is now held at the UK Stem Cell Bank at the National Institute of Biological Standards and Control in London (see http://www.ukstemcellbank.org.uk/).

Funding for the ISCI came from the International Stem Cell Forum, an organization that brings together leading agencies that fund stem cell research from many different countries. The forum, which aims to promote best practice in the area of stem cell research, provided £426,000 funding for the project.

One intriguing finding reported in Nature Biotechnology is that some genes in the ES cell lines were consistently expressed by only one allele (in other words, these genes showed imprinting). Yet other genes known to be subject to imprinting varied — sometimes both alleles were being expressed, and sometimes only one allele was expressed.

"This suggests that there is a degree of stability of imprinting in these cells but it is gene specific," Andrews said. "We don't know what this means in biological terms, but it will be an important observation to explore as we go forward."

The International Stem Cell Forum has recently agreed further funding of US$2 million for a project that is being called ISCI2. This will focus on the culture media used to grow cell lines, and the genetic variations that can occur over prolonged periods of growth in vitro. The funding will also help to expand the ES cell registry to include new lines.

Colin Blakemore, who chairs the International Stem Cell Forum and is the chief executive of the UK Medical Research Council, said: "The Forum is committed to stimulating collaborations and providing backbone funding to allow these to flourish. The potential of stem cell research is great. We hope stem cell science will lead to the treatment of all manner of illnesses, from diabetes to multiple sclerosis. By creating this registry and making it freely available, the ISCI will not only be a great resource for scientists across the world, but will set the tone for the collaborative spirit in which we hope research will continue to be carried out, for the benefit of the many, not the few."