Much of the power of self-repair in the liver comes, of course, from the liver’s own cells, but a substantial portion is derived from a previously unsuspected source outside the liver, according to a paper published in Hepatology.

That novel source of liver cells is bone marrow, the producer of multipotent stem cells, which can develop into many different kinds of cells throughout the body. In the human adult, bone marrow stem cells have long been known for their unusual ability to give rise to both white and red blood cells, but their potential also to become nerve or muscle or epithelial cells has only been discovered in the last several years. Investigators including Yale’s Diane Krause, M.D., found that stem cells that travel through the bloodstream to the liver can develop into both hepatocytes and bile-duct cells, which are responsible for normal liver function.

The Hepatology paper describes the analysis of tissue samples from transplants in male patients who had received livers (but no bone marrow) from females, and in female patients who had received bone marrow (but not their livers) from males. That is, both groups of transplant patients had bone marrow from one sex (male) and livers from the other (female).

In each case, some of the new cells that developed in the liver contained a Y chromosome, indicating their male origin. The researchers reason that in the male transplant recipients, these new cells could only have come from the males’ own bone marrow, and in the females, the new cells must have come from the (male) donated bone marrow.

“This is an exciting finding, and it is incredibly surprising, because the bone marrow has never been considered as a source of liver cells,” says senior author Krause, an assistant professor of laboratory medicine. Not only does the finding open up new possibilities for treating many kinds of liver disease, it also indicates that fully functional stem cells with a remarkable plasticity can be found within adult bone marrow.