The liver is resilient. Surgeons removing a tumor, for example, can cut out as much as two-thirds of the liver, and the organ will rapidly grow back to its original size. A sugar-laden protein called stem cell factor (SCF) drives this remarkable regeneration, according to a new study.
The protein has long been known to trigger the proliferation and maturation of bone marrow cells that produce white and red blood cells. Yet there have been an increasing number of hints that SCF influences a wider range of tissues. Several research teams have recently documented the presence of SCF or the activity of its gene in the liver, for example.
Lisa Colletti of the University of Michigan Medical School in Ann Arbor and her colleagues now report that there is a surprisingly large supply of SCF in the livers of mice. The investigators also demonstrated that the removal of 70 percent of a mouse’s liver, a surgical procedure known as a partial hepatectomy, produces a dramatic drop in the concentration of SCF in the remaining organ along with a rise in SCF in the mouse’s blood. The team hypothesized that after the liver operation, SCF, which typically sits inactive on the surface of liver cells, is released in a soluble form that stimulates the growth of the remaining cells.
The researchers then showed that the absence of SCF activity impairs liver regeneration. After a partial hepatectomy, the livers of mice given antibodies that block the protein and of mice genetically engineered to lack SCF grew back more slowly than mouse livers typically do. Injecting the mutant mice with SCF, however, enabled the liver to regenerate at the normal pace, Colletti’s team reports in the November Journal of Clinical Investigation.
“Stem cell factor is a key player” in liver regeneration, says Neil D. Theise of Beth Israel Medical Center in New York. He suggests that physicians may soon test whether SCF can speed the recovery of people who have undergone partial hepatectomies.
The protein may also protect people from acute liver failure, notes Theise, pointing to another recent study. Independently of Colletti’s group, a research team at the University of Michigan Medical School, along with colleagues at the University of Edinburgh, examined whether SCF could defend mice from liver damage caused by an overdose of acetaminophen, which is best known as the active ingredient in Tylenol.
In the February Laboratory Investigations, the scientists reported that mice administered SCF at the same time as acetaminophen suffered less liver damage than did rodents given acetaminophen alone.
University of Michigan’s Nicholas W. Lukacs, a coauthor of the acetaminophen report, cautions that simply injecting SCF into a person with liver problems may activate immune cells that can cause a severe allergic reaction. Targeting delivery of SCF to only the liver could avoid that problem, he suggests. Or, he adds, scientists might use SCF to prod the growth of liver cells in test tubes and then transplant those cells into a patient.
Further studies of the roles of SCF within the liver may also reveal why the celebrated cancer drug imatinib, better known as Gleevec, sometimes causes damage to that organ. SCF seems to work by binding to a protein called c-kit. Gleevec inhibits the function of that protein and therefore may interfere with SCF’s protection of the liver, Lukacs notes.
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