The study, done in immune deficient mice, showed that human stem cells that normally produce blood cells also can form liver-like cells in a damaged liver. The findings are published in the May 15 issue of the journal Blood.
"There is a huge demand for liver transplants but there are never enough organs, and the procedure is not always successful," says study leader Jan A. Nolta, Ph.D., associate professor of medicine. "We're hoping that in the future we can use bone marrow or umbilical cord blood stem cells from matched donors to help treat liver disease and reduce the need for liver transplants."
Nolta and her colleagues isolated highly purified human stem cells from bone marrow and umbilical cord blood and transplanted them into immune-deficient mice. The purified stem cells normally give rise to cells that mature into red blood cells and white blood cells.
A month later, after the human stem cells had established themselves in the animal's bone marrow, the investigators induced liver damage. Some mice also were given human hepatocyte growth factor to increase the number of stem cells that developed, or differentiated, into liver cells (also known as hepatocytes).
A month after inducing the liver damage, the investigators compared the damaged organs to healthy ones from control mice that also had been transplanted with human stem cells. They tested the livers for the presence of human albumin, a protein produced only by liver cells. Any human albumin found in these mice would have to have come from transplanted human stem cells that had developed into liver-like cells.
Nolta and her colleagues found the greatest number of human-albumin-producing cells in the damaged livers of mice that had been treated with human hepatocyte growth factor. In some cases, albumin began showing up as early as five days after treatment. The number of stem cells that had differentiated into liver-like cells was low, however, making up less than 1 percent of all liver cells. Human albumin was not detected in mice with healthy livers.
The investigators believe that the stem cells moved from the bone marrow into the circulating blood, then left the blood to reside in the damaged liver, where they became liver-like cells that produced human albumin.
"These results show that human stem cells from bone marrow and umbilical cord blood are a potential source of liver cells," says Nolta, who also is a member of the Hematopoietic Development and Malignancy Research Program at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.
The study also represents the first successful animal model for studying how stem cells from human bone marrow and umbilical cord blood might be used to treat liver disease.
Nolta and her colleagues now are working to increase the number of human stem cells that differentiate into liver cells in this model by studying the signals that draw the cells into the liver and control their transformation, a feature known as stem-cell plasticity. In addition, they are investigating the use of blood-forming stem cells for the repair of heart and skeletal muscle.
Wang X, Ge S, McNamara G, Hao Q-L, Crooks GM, Nolta JA. Albumin-expressing hepatocyte-like cells develop in the livers of immune-deficient mice that received transplants of highly purified human hematopoietic stem cells. Blood, 101 (10), 4201-4208, May 15, 2003.
Funding from the National Heart, Lung, and Blood Institute and from the National Institute of Diabetes and Digestive and Kidney Diseases supported this research.