July 05, 2004
Bone Marrow Stem Cells Confirmed To Convert To Liver Cells

Diane Krause and colleagues at Yale report that bone marrow stem cells can differentiate into epithelial cells. (which are found in skin and on the surface of inner body cavities)

New Haven, Conn. -- Epithelial cells derived from bone marrow cells can be a result of differentiation, not fusion, according to a study published in Science by Yale researchers who arrived at some of the earliest findings on non-blood cells derived from bone marrow.

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.

This result is important because it restores some of the luster of adult stem cells that was lost when it was found that in at least some cases adult stem cells were providing benefits by fusing with existing cells. In 2003 some researchers reported that bone marrow hematopoietic stem cells were repairing livers by fusing with existing liver cells rather than by differentiation into liver cells.

The phenomenon of cell fusion between adult stem cells and other cell types has been demonstrated with heart, brain, and liver cells.

In a study that calls into question the plasticity of adult stem cells, Howard Hughes Medical Institute (HHMI) researchers and colleagues at the University of California, San Francisco, have demonstrated that adult bone marrow cells can fuse with brain, heart and liver cells in the body.

The phenomenon of fusion would give the appearance that bone marrow stem cells are altering themselves to become mature cells in other tissues, when in fact they are not, according to one of the study's senior authors, HHMI investigator Sean J. Morrison at the University of Michigan.

Note that the fusion does appear to provide benefits. If, say, you have a fatal liver disease and you can get better by having adult stem cells fuse instead of having the stem cells convert into liver cells are you going to turn down the treatment? Of course not. But the ability of adult stem cells to convert into various fully differentiated (specialized for particular functions) cells opens up the door for many more potential medical uses such as growth of replacement organs and replacement of lost cells such as happens with Parkinson's Disease and heart disease.

Krause's group is not the only team to recently report success at getting bone marrow stem cells to take on specialized liver cell functions without fusing with existing liver cells. A month ago a team at Johns Hopkins also reported success in using bone marrow stem cells to convert into liver cells without fusing with existing liver cells.

Bone marrow stem cells, when exposed to damaged liver tissue, can quickly convert into healthy liver cells and help repair the damaged organ, according to new research from the Johns Hopkins Kimmel Cancer Center.


There has been debate among the scientific community over whether these cells also can differentiate into other tissue types such as the liver, says Saul J. Sharkis, Ph.D., senior author of the study and a professor of oncology at the Johns Hopkins Kimmel Cancer Center. Some studies suggest that the bone marrow cells fuse with other types of cells, taking on those cells' properties. But in this study, the researchers found, through highly thorough analysis with a microscope and other tests, that the cells did not fuse, suggesting that "microenvironmental" cues from existing liver cells caused them to convert.

I've never viewed the obstacles to making adult stem cells more plastic (i.e. capable of changing into more cell types) as insurmountable. It is possible that it will be quicker to use embryonic stem cells for some purposes. But eventually techniques will be developed to allow adult stem cells to be converted into all cell types. As more adult stem cell sources are found in the body and as better techniques for growing them are discovered the range of potential target cell types that adult stem cells will be able to make will steadily increase.

My point here is not to argue for or against embryonic stem cell research. My point is that even a complete ban on human embryonic stem cell research will only delay the developmetn of cell therapies and organ growth methods. Granted, such a delay would result in human deaths that would otherwise would be avoided. But legal obstacles can be literally programmed around once our knowledge of genetic programming advances far enough and we have the ability to change the epigenetic programming of cells to whatever state we desire.

Share |      Randall Parker, 2004 July 05 02:01 PM  Biotech Organ Replacement

Satish Khurana said at November 19, 2004 11:40 AM:

Instead of a comment i want to put a question. If the trans-differentiation potential of the hematopoietic stem cells is true then isn't it possible that during the development of liver the HSCs from fetal liver differentiate to produce functional liver cells.

Arri Adajar said at September 29, 2008 4:27 AM:

I just want to ask questions instead of giving comments. What are the processes an adult stem cell undergoes to be a liver cell? Is the adult stem cells from bone marrow have the same mechanism of development to be a liver cell to those from umbilical cord? If not, what are the differences?

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