Transplanted bone marrow cells reduce liver fibrosis in mice

Transplanted bone marrow cells can reduce carbon tetrachloride-induced liver fibrosis in mice and significantly improve their survival rates, according to a new study published in the December 2004 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience.

Previous reports have shown that bone marrow cells can differentiate into a number of other types of cells, including liver cells, which could help patients with liver cirrhosis and chronic liver failure. To study this possibility, researchers, led by Isao Sakaida, M.D. of Japan's Yamaguchi University, studied the effect of transplanted bone marrow cells on mice with liver fibrosis.

The researchers first caused liver fibrosis in the mice by injecting them with carbon tetrachloride (CCI4) twice a week for four weeks. They then divided the mice into two groups and treated one with green fluorescent protein-positive blood marrow cells. They treated the control group with saline. All mice continued to be treated with carbon tetrachloride. After 1, 2, 3 or 4 weeks, the researchers assessed the extent of liver fibrosis in the mice. To measure survival rates, 15 mice from the experimental group and 15 from the control group were then treated with carbon tetrachloride for an additional 25 weeks.

After five weeks of treatment with carbon tetrachloride, the researchers detected liver fibrosis in the mice. Just one week after blood marrow cell transplantation, they found evidence of those cells in the liver, with more appearing as the weeks passed.

"Surprisingly," the researchers report, "four weeks later, the blood marrow cell-transplanted liver clearly showed reduction of liver fibrosis compared with the liver treated with CCI4 alone at 8 weeks."

Furthermore, the mice that received blood marrow cell transplants along with continuing carbon tetrachloride treatments showed a gradually increased serum albumin level and had significantly improved survival rates compared with mice that only received carbon tetrachloride treatments.

The transplanted blood marrow cells degraded collagen fibers and reduced liver fibrosis, exhibiting strong expression of matrix metalloproteinases (MMPs), especially MMP-9. "The reason for the strong expression of MMP-9 is still unknown," report the authors, but report that it was somehow related to the migration of the blood marrow cells to the inflammatory liver and to those cells' degradation of the liver fibrosis.

"The present study clearly indicates that this subpopulation of blood marrow cells is responsible for the resolution of liver fibrosis induced by CCI4 treatment," the authors conclude, and "introduces a new concept for the treatment of liver fibrosis."