Led by Diane Krause, associate professor of Laboratory Medicine and Pathology at Yale School of Medicine, the investigators transplanted marrow-derived cells from male mice into female mice. They followed the fate of the marrow-derived cells (male) by detecting the Y chromosome. If resulting epithelial cells were formed by cell-to-cell fusion, they should express green fluorescent protein (GFP) and not beta-galactosidase.
"Our results show that under normal circumstances, the green fluorescent protein was not expressed, which means that no fusion has occurred and that the marrow derived cells can become non-blood cells without fusing," said Krause, attending physician in Laboratory Medicine at Yale-New Haven Hospital.
Krause said they did find that when the tissues were damaged, there were some cells that expressed GFP and therefore were derived from donor cells fusing with recipient cells.
Several years ago Krause's laboratory published a study showing that bone marrow stem cells can differentiate into liver, lung, kidney, skin, muscle and other cells. Later studies published by other researchers postulated that the bone marrow derived cells had actually fused with epithelial cells.
Krause said the ramifications of these latest findings are still unclear. "The absence of fusion in this model does not necessarily imply that trans-differentiation, a change in phenotype of one mature cell type to that of another mature cell type, has occurred," she said. "In fact, we carefully refrain from using that terminology in this report to avoid making assumptions about the mechanism of the phenotypic change."
She said it may be that an as-yet-unidentified, multipotent epithelial precursor exists in the bone marrow or that a separate population of marrow precursors exhibit a gene expression pattern that can be reprogrammed to express markers of other cell types.
Co-authors include Robert Harris, Erica Herzog, Emanuela Bruscia, Joanna Grove, and John Van Arnam.
Citation: Science, Vol. 305, pp 90-93 (July 2, 2004)
Journal
Science