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Stem Cells Cure Rare Liver Disease in Mice

Fusion of stem and liver cells was mechanism of repair

MONDAY, March 31, 2003 (HealthDayNews) -- Three years ago, researchers reported that transplantation of bone marrow stem cells cured a rare genetic liver disease in mice.

Now, they've figured out how that happens -- and the results surprised them.

In a new study, researchers report the mechanism of repair was fusion -- the offspring of the stem cells from donor mice delivered genetic material to the liver cells of the sick mice, producing a new generation of healthy cells.

Previously, many researchers believed that repair occurred because of a process called transdifferentiation, in which the stem cells were transformed into liver cells. In fusion, the new cells have genetic elements of both.

"The essence here is that bone marrow-derived liver cells can cure genetic liver disease in mice," says Dr. Holger Willenbring, co-author of the study and a post-doctoral researcher at the Oregon Health and Science University in Portland.

"But the way this works wasn't clear," Willenbring says. "People tended to believe the transplanted stem cells changed its characteristics and became a liver cell. This study shows this is not the mechanism underlying it. Fusion is the mechanism."

The study is one of two papers about stem cells and fusion that appear in the March 30 online issue of Nature.

The second study also found evidence of fusion after bone-marrow derived stem cells were implanted into mice that had the same rare liver disease. The hybrid cells, while maintaining genetic elements of both, functioned like liver cells.

There are two types of stem cells often discussed in science. The first are stem cells from embryos. In an embryo, stem cells are highly "plastic," meaning they give rise to all of the organs of the body, from liver to heart to skin to lungs.

Adults also have stem cells, but they give rise to only the type of tissue they reside in. Bone marrow stem cells, for example, make new blood.

Recently, research in animal models suggested that adult bone marrow stem cells also might have the capacity to develop into other tissues, including liver, kidney or muscle.

"The capacity of stem cells found in adult bone marrow to transdifferentiate raises hope that these cells could be used for a cure for organ failure due to inherited or acquired diseases," Willenbring says.

In the current study, Willenbring and his colleagues transplanted bone marrow stem cells from healthy female mice into male mice suffering from a genetic liver disease. The sex difference and other genetic markings helped researchers keep track of where the stem cells and their offspring ended up.

They were also able to determine if the resulting healthy liver cells were not the product of transdifferentiation, but of fusion between the donor bone marrow cells and the host liver cells.

"It kind of ruins the mystery and the beauty of an adult stem cell being able to become a liver cell," Willenbring says. "The whole concept of adult bone marrow stem cells and transdifferentiation has to be revisited."

Scientists are a long way from using fusion as a treatment for human disease. But a better understanding of the basic science behind stem cells could help scientists develop new lines of research that ultimately could lead to therapy, Willenbring says.

More information

Read this primer on stem cells from the National Institutes of Health. The National Cancer Institute has more on bone marrow and stem cell transplantation.

SOURCES: Holger Willenbring, M.D., post-doctoral researcher, Oregon Health and Science University, Portland; March 30, 2003, online issue, Nature
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