Negative results provide reality check for stem-cell therapies.
Fresh concerns have been raised over the usefulness of adult stem cells after a spate of papers throwing doubt on their regenerative abilities.
Reports claiming that stem cells from adults are capable of repairing every tissue in the have raised hopes that these cells could prove a panacea for conditions from Parkinson's to heart disease.
But the recent rash of studies dispute these claims. Stem-cell biologist Irving Weissman of Stanford University in California has now dealt a blow to the suggested repair properties of blood stem cells.
All stem-cell experiments need to be repeated before clinicians pursue potential therapies, Weissman says. Some trials are already underway. "I worry that non-experts just accept and practise it," he says. "We do not have solid science for that."
Experiments from researchers outside the stem-cell establishment are under particular scrutiny. Scientific journals may also be at fault, says stem-cell biologist Tariq Enver of the Institute of Cancer Research in London, UK. In their eagerness to publish the hottest papers, "perhaps people weren't as rigorous as they ought to have been", he says.
Scientists agree that some cells are 'multipotent' - capable of making many other tissue types. What they are squabbling over is whether these cells exist naturally in the adult body, or whether they are artefacts of lab treatments. This is crucial if the right cells are to be selected for stem-cell therapies.
“Transdifferentiation may be vastly overblown Stuart Orkin , Harvard Medical School”
Last year, for example, a celebrated paper by Diane Krause of Yale University and co-workers reported that a single stem cell from bone marrow that normally makes only blood had transdifferentiated - switched to making liver, lung and skin1.
Weissman and his team dispute those results. Using slightly different methods they isolated a single mouse blood stem cell, injected it into mice and tracked its progeny with a green fluorescent protein. They found that, apart from blood, it made only eight cells of any other tissue in three mice2.
"It's very difficult to compare one [experiment] with another," comments Stuart Orkin, who studies blood stem cells at Harvard Medical School in Boston. But "transdifferentiation may be vastly overblown", he agrees.
The slew of negative results do not spell the end for stem-cell therapies - they merely provide a reality check.
Other cells in the bone marrow or elsewhere may be genuinely multipotent; one of these cells could explain Krause's results, she herself admits. But some suspect that these stem-cell types may be very rare, making them harder to extract and use in treatments.
Alternatively, cells may be converted into multipotent ones in the lab. Some think that this phenomenon explains findings earlier this year from Catherine Verfaillie at the University of Minnesota, Minneapolis3. She cultured her adult stem cells for weeks before showing that they are multipotent when transplanted into mice. Cultured cells may, however, have a greater risk of forming cancers or otherwise behaving oddly.
Many in the field now want more rigorous experimental standards for all stem-cell experiments. "We need to step back and do definitive experiments rather than flashy ones," says Orkin.
Krause, D. S. et al. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell, 105, 369 - 377, (2001).
Wagers, A.J. et al. Little evidence for developmental plasticity of adult hematopoietic stem cells. Sciencexpress, 10.1126/science.1074807, (2002).
Verfaille, C.M. et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 417, published online 20 June; doi:10.1038/nature00870, (2002).
Harvard Medical School