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FROM: Nature Science update Excess DNA prompts stem-cell rethink Transplanted bone-marrow cells may be fusing with, not replacing, damaged tissues. 31 March 2003 HELEN R. PILCHER " Transplanted adult stem cells may repair liver damage by fusing with host cells, rather than by producing new liver cells, two new studies suggest. The stem cells may reprogramme host cells' genetic material. The findings are likely to fuel the debate over how versatile adult stem cells are and how they repair tissues. Adult stem cells' apparent ability to produce myriad cell types has raised hopes that transplants could treat conditions from liver disease to stroke, without recourse to the ethically contentious use of embryonic stem cells. Previous studies have indicated, for instance, that adult bone-marrow stem cells can turn into several cell types, including blood, liver, muscle and pancreas. In light of the new results, there is now "serious concern about whether these [previous] data reflect reality", says Markus Grompe, the cell biologist from Oregon Health and Sciences University in Portland who led one of the studies. "I'm not convinced that these stem cells give rise to anything other than blood," he says. When Grompe and his colleagues injected bone-marrow stem cells into mice with damaged livers, the animals' "shrivelled-up, ugly-looking livers" became normal, he recalls. But closer analysis revealed that the cells of the restored livers contained both donor and recipient genes. Some had double or triple the normal amount of DNA1. David Russell and his team from the University of Washington, Seattle, found similar evidence of fusion when they grafted bone-marrow stem cells into mice with a different metabolic liver disorder2. Rather than making new liver cells, the transplanted stem cells seem to be reprogramming damaged liver cells to function normally once again. But bone-marrow transplants contain more than one stem-cell type, so just which cell is doing the fusing is not clear. "We don't as yet know which are responsible for the contribution to adult tissues now being seen in many labs," says stem-cell biologist Helen Blau of Stanford University in California. To fuse or not to fuse But the jury is still out on how adult bone-marrow stem cells restore damaged organs, as most studies have not been designed to test for fusion. One human study that tested for fusion found no evidence of it3. Eva Mezey from the National Institutes for Health in Bethesda, Maryland, and colleagues studied female leukaemia patients who received male bone-marrow transplants four years ago. They could identify donor cells' progeny by their male chromosomes. Cells from the women's cheeks containing male chromosomes are completely normal, says Mezey. Unlike those in the mouse experiments, they had no extra DNA. "We should all team up for a multi-centre study," argues Simon Tran, who worked with Mezey on the leukaemia study. Most research uses different animal models, patient populations and techniques, making studies difficult to compare. "By pooling our resources, we'll have a better chance to come up with an accurate answer," he adds. References Grompe, M. et al. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature, 422, published online, doi:10.1038/nature01531 (2003). |Article| Vassilopoulos, G., Wang, P. & Russell, D.W. Transplanted bone marrow regenerates liver by cell fusion. Nature, 422, published online, doi:10.1038/nature01539 (2003). |Article| Tran, S. et al. Differentiation of human bone marrow-derived cells into buccal epithelial cells in vivo: an analystical study. Lancet, 361, 1084 - 1088, (2003). |Homepage| ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn