Clinical-use stem cells made in Singapore
Lines designed for safe use in humans make their debut.
Four 'safe' embryonic stem-cell lines, which have been made from scratch specifically for clinical use, make their debut this week. Singapore-based biotech company ESI will announce on 27 July the existence of these lines, plus four more in the pipeline, and have said they will make them available to researchers worldwide by the end of this year.
The announcement comes just as the United States is locked in debate about the need for new human embryonic stem (ES) cell lines to do research. A bill that would allow US federal funds to be used for such work passed the House and then the Senate, but was predictably vetoed by President George Bush last week (see ' A long week in stem cell politics').
Against the backdrop of that debate, academic and biotech groups have been gearing up to generate clinical-grade lines to speed the cells' entry into medicinal use once therapeutic value has been demonstrated. Early embryonic lines, including those currently licensed for use with US federal monies, were developed using animal products, and some researchers have been worried that they might have negative effects (see ' Human stem cells trigger immune attack').
"Most people don't think the existing human ES cell lines are good enough for clinical use," says Peter Andrews of the University of Sheffield, UK, which this year built its own facility for deriving human stem-cell lines.
Regulatory agencies have not yet said what standards cell lines would need to meet to be used in humans. But there is a general 'Good Manufacturing Practice (GMP)', which describes how pharmaceutical products should be manufactured under carefully controlled laboratory conditions to minimize contamination, along with meticulous documentation of the methods and reagents used. ESI used these standards to make their lines, which are also free of non-human cells; other groups are planning to do the same.
Two versions of the cell lines will be available. Research-grade cells will be available to academic researchers for "a modest administrative fee", says Alan Colman, ESI's chief executive, and will be distributed through the ASTAR Singapore Stem Cell Consortium, the government agency that coordinates stem-cell research in Singapore.
Clinical-grade cells will come at a bigger cost. ESI will maintain control of these lines, so any groups wanting to use them will need to negotiate a fee and royalty agreement with the company in order to obtain the cells and the crucial documentation needed for regulatory approval.
The company's objective, says Colman, is to get as many researchers as possible interested in working on the research lines, and thereby maximize demand for the clinical-grade siblings.
There is a growing need for facilities that can derive and bank GMP-grade human ES cell lines, say researchers. Groups around the world, including in the United Kingdom, Japan and the United States, are building facilities for deriving this kind of high-quality human ES lines. Some in vitro fertilization (IVF) clinics also happen to be adopting the same protocols, so the blastocyst embryos themselves will be created under these conditions.
Others say that another option is to bring the older lines up to clinical standards, rather than starting from scratch. The stem-cell company Geron, based in Menlo Park, California, claims to have derived clinical-grade lines using well-characterized cells already registered for use with federal funds: H1 and H9, which were initially grown on mouse 'feeder' cells.
To purify their cell lines, Geron cultivated the cells free of animal feeder cells for several years. The cells "have passed every single test that the regulatory agencies mandate for human use", says Tom Okarma, Geron's president and chief executive. The company will apply for the US Food and Drug Administration (FDA) approval to start clinical trials in 2007, using glial cells differentiated from their embryonic stem-cell lines to treat spinal-injury patients.
ESI also argues that their lines adhere to FDA guidelines for other cell cultures. But for the meantime, both groups will have to battle the fact that the definition of 'safe' for ES cells remains unclear. "The regulatory agencies haven't defined it," admits Andrews, who is also the head of the International Stem Cell Consortium. "But that's the nature of the beast. They say 'tell us what you've got and we'll tell you whether it is OK'."
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