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Stem Cell Therapies: Time to Step Back or Forge Ahead?
By Nancy Touchette

Doctors are now trying experimental treatments that were once unimaginable. Bone marrow cells are being used to repair damaged hearts, and similar treatments are on the horizon for people with diabetes and Parkinson’s disease.

Fused bone marrow and liver cells have three X chromosomes (pink) and one Y chromosome (green).

The therapies are based on studies in animals that show that stem cells from bone marrow can become heart cells, brain cells, muscle cells and liver cells. Nerve stem cells can turn into muscle or blood, and muscle cells become bone marrow.

But recent studies in mice suggest that the stem cells can fuse with other cells. In some cases the new cells have too many chromosomes.

Some scientists believe it is time to step back and try to figure out the mechanism by which the cells change their identity before forging ahead with experimental treatments in humans. Others say that as long as a treatment works, understanding how it works doesn’t really matter.

“There is no simple answer,” says Ronald McKay of the U.S. National Institute of Neurological Disease and Stroke in Bethesda, Maryland, who studies embryonic stem cells. “In one way, we have to know mechanisms if we are going to improve things. But in other ways, we don’t know the mechanisms of lots of medicines that work very well. It’s a subtle game.”

The controversy arises from two new studies that demonstrate that bone marrow stem cells become specialized liver cells by fusing with mature liver cells in mice.

“These papers show for the first time that bone marrow cells can fuse with liver cells and then change their characteristics to those of liver cells,” says Naohiro Terada of the University of Florida in Gainesville.

It is not known, however, whether all cells that change their identity do so through cell fusion. In fact, a third study shows that bone marrow cells can become insulin-producing pancreas cells in mice without cell fusion.

“It may be that different tissues work in different ways with different scientists,” says David Russell of the University of Washington in Seattle, who led one of the recent studies.

If stem cells are fusing, that could be good news for gene therapy researchers, who are trying to find effective ways to deliver new genes to cells.

“This could be a safe way to transfer a normal gene,” says Terada. “You could put a gene into an engineered stem cell and take advantage of cell fusion to cure a genetic deficiency.”

Bone marrow cells from male mice form insulin-producing cells (red) in female pancreas. (Arrows point to cells with Y chromosomes.)

One thing is clear, says Mehboob A. Hussain, a stem cell researcher at New York University: whether a blood cell becomes a liver cell or pancreas cell by fusion or some other mechanism, there is a change in the pattern of gene activation throughout the genome.

“Regardless of fusion or not, there is a reprogramming of the properties of the cell,” he says. “It would be of no help if the bone marrow cell went into the liver and continued expressing the genes of the bone marrow. You want a cell to change its identity. Whatever the mechanism, the bone marrow cell is getting reprogrammed by its environment.”

See related GNN articles
»Cultured Eggs Could Defuse Stem Cell Politics
»Bone Marrow Heals the Heart
»Stem Cell Alert: Laws and Players

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Vassilopoulos, G. et al. Transplanted bone marrow regenerates liver by cell fusion. Nature 422, 901-904 (2003).
Wang, X. et al. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 422, 897-901 (2003).
Ianus, A. et al. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J. Clin. Invest. 111, 843-850 (2003).

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