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Macrophages, not stem cells, correct liver disease by fusion

PORTLAND, Ore. -- An Oregon Health & Science University study is defying a long-accepted assertion among many scientists that stem cells repair diseased tissue by transforming into other cell types in a process called plasticity.

The first study from OHSU's new Oregon Stem Cell Center, published in the current issue of the journal Nature Medicine, found that mature macrophages derived from bone marrow stem cells, and not bone marrow stem cells themselves, are what fuse with diseased liver cells, ultimately curing a genetic liver disease.

"The most important discovery is you don't need to transplant stem cells at all," said study co-author Markus Grompe, M.D., professor of molecular and medical genetics, and pediatrics, OHSU School of Medicine, and director of the Oregon Stem Cell Center. "If you transplant only macrophages, you'll get liver cells that correct liver disease in mice."

Holger Willenbring, M.D., postdoctoral fellow of molecular and medical genetics, and the study's lead author, called fusion between macrophages and hepatocytes, the cells in the liver that provide the typical functions of this organ, "a rare physiological, but potentially therapeutically exploitable, phenomenon."

"Macrophages are known to fuse with themselves," Holger said. "Therefore, it is not absolutely surprising that they can fuse with other cells as well, especially, since macrophages physiologically reside in the liver and comprise a substantial fraction of the liver cells.

Usually, they participate in resolving inflammation, taking care of debris and producing factors that help the liver to function. In addition, they provide a link between the bone marrow compartment and highly specified organ cells, and this is new and exciting because of therapeutic implications."

The findings are the latest in a series of discoveries by Grompe's laboratory since 2000, when it first showed blood-forming stem cells derived from bone marrow, calle
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Contact: Jonathan Modie
modiej@ohsu.edu
503-494-8231
Oregon Health & Science University
6-Jul-2004


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