Two paths. Cells in mouse-conditioned medium (a) stay undifferentiated; without it they start to differentiate (b).

Getting the Mouse Out

Researchers in Wisconsin have cleared a critical hurdle on the path to treating disease with human embryonic stem (HES) cells. Their newly developed cell culture method eliminates the need for mouse-related components. Scientists call the work a big step toward abolishing contamination and ensuring that the cells will not be rejected when transplanted into a human patient.

The recipe for maintaining HES cells in the lab usually calls for non-human ingredients, including mouse feeder cells or mouse-conditioned growth medium. These components help keep the cells undifferentiated and able to be transformed into almost any bodily tissue. In the past few years, several groups have announced success in growing stem cells in media free of mouse factors. But none of them has sustained the cells over time, says developmental biologist Ren-He Xu of the WiCell Research Institute in Madison, Wisconsin. A group in Singapore has claimed success using human feeder cells, but Xu says human cells comprise an "unknown mixture" of compounds, some of which could be pathogenic.

Xu's team, which includes James Thomson (who first successfully derived HES cells), has now gotten rid of what is regarded as the primary contaminant: the mouse-conditioned medium. The team found that high doses of a synthetic human molecule known as fibroblast growth factor 2 (FGF2) can itself sustain stem cells in an undifferentiated state. FGF2 works by inhibiting the activity of bone morphogenetic protein (BMP), a molecule that promotes stem cell differentiation. That means researchers no longer have to rely on mouse components for this function, says Xu, whose team reports its findings in the March issue of Nature Methods.

The study is "a major step forward," says Ajit Varki, professor of medicine at the University of California, San Diego. He warns, however, that much work lies ahead. His group found that a serum component of the cell medium, which is derived from cows, was "the major source of contamination" for HES cells.

Related sites
WiCell Research Institute
Varki's homepage
Abstract of Nature Methods paper