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Cellular alchemy
By Bijal P. Trivedi

A "lack of commitment" is not a particularly admirable trait in humans, but this feature is exactly what gives stem cells their potential and promise.

A Y chromosome (yellow arrowhead) indicates that this liver cell is derived from a bone marrow stem cell.

Stem cells have very little preprogramming and are not committed to becoming a specific type of cell, giving them the capacity to generate any type of tissue. A report in the July issue of Hepatology shows that bone marrow stem cells, which are known primarily for their role in generating the entire repertoire of blood cells, can also produce liver cells.

There has been a surge of experiments in rats and mice showing that stem cells from one organ can give rise to cells of another; bone marrow stem cells can produce brain or skeletal muscle cells and vice versa, neural stem cells give rise to muscle and liver, and bone marrow can produce lung tissue. "But ours is the first study to show this sort of stem cell plasticity in humans," says Neil Theise, a liver pathologist at New York University School of Medicine.

The study involved two experiments. The first focussed on two female leukemia patients who received bone marrow transplants from male donors. As all cells from females contain two X chromosomes, any liver cell with a Y chromosome could only have come from the donor bone marrow. Theise's team took tissue samples of the liver after four and a half months and treated them with two dyes: a green fluorescent dye that only binds to the Y chromosome, and a red dye that only binds to the X. When Theise examined the liver samples he found that between 5 and 10 percent of liver cells contained a "brightly glowing green Y chromosome."

In a second experiment, four men received liver transplants from female donors. These transplanted liver cells have two X chromosomes in each cell. When Theise and his colleagues examined the livers, almost 40 percent of the cells contained a glowing Y chromosome, indicating that the liver had been infiltrated with cells derived from the patients' own bone marrow.

"This work suggests that there could be many pathways of liver regeneration," says Theise. The most immediate clinical implications could involve the treatment of some liver diseases with bone marrow transplants, says Theise. Further down the road there is also the possibility of making personalized artificial livers using the patient's own bone marrow stem cells, which are easier to work with than liver stem cells.

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Theise, N.D. et al. Liver from bone marrow in humans. Hepatology 32, 11-16 (July 2000).

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