In the PNAS study, Wong and her colleagues transplanted bone marrow cells from female mice into a male mouse model of intestinal cancer. The donor-derived cells were readily detected in the intestinal tumors of the male mice.
To show that the transplanted donor cells fused with the tumor cells, the scientists detected proteins or markers from both the female donor and male recipient cells in tumors. The only way both donor and recipient markers could be present in a single cell, or colocalized, would be if the two cells fused.
One test to prove cell fusion involved looking for the presence of Y chromosomes, or male-characteristic DNA, within the female donor cells marked with a green fluorescent protein. About 60 percent of the epithelial cells were positive for both donor and recipient cell markers. A second test confirmed colocalization using a confocal microscope, which can scan a single cell layer of intestinal cells for the presence of both the green fluorescent protein, indicating female donor cells, and an enzyme from the male recipient cells
Wong said, "Our paper is unique because it's the first example that cell fusion occurs in the epithelial compartment of a tumor."
Other OHSU studies in recent years are giving weight to the fusion theory. A series of discoveries since 2000 by study co-author Markus Grompe, M.D., professor of molecular and medical genetics, and pediatrics, OHSU School of Medicine, and director of OHSU's Oregon Stem Cell Center, showed that blood-forming stem cells derived from bone marrow, called hematopoietic stem cells, cure liver disease in mice through cell fusion rather than transdifferentiation of the transplanted stem cells.
Wong acknowledges fusion is still a new concept. But it's gaining popularity as a way of explaining the molecular mechanisms that may be at work in regene
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Contact: Jonathan Modie
modiej@ohsu.edu
503-494-8231
Oregon Health & Science University
9-May-2006