May 16, 2003
Bone Marrow Stem Cells Shown To Migrate To Damaged Livers

Human adult bone marrow stem cells transplanted into immune-deficient mice migrated to the livers of the mice and showed signs of differentiating into functional liver cells.

"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.

Cell therapies will become incredibly useful very quickly once scientists develop better ways to control how stem cells migrate and turn into target tissue cell types (the process of cellular differentiation). Gene therapies will be developed that have the effect of ordering stem cells to become particular types or go to particular organs. Also, additional growth factors will be identified and worked into therapeutic regimes performed on stem cells to instruct them to multiply and become desired cell types.

We are coming ever closer to the era when repair and replacement of the most diseased and damaged tissue will become routine and easy to do. It is difficult to say when that era will arrive in full force. However, there are enough early stage successes being reported that it seems unlikely that we will have to wait longer than 20 years before it becomes common to basically order large numbers of stem cells to go hither or thither to meet some urgent need.

Fifty years from now youth will find it hard to believe that people used to die because of organ failure. The techniques used for the production of human replacement parts will become so well understood and cheap to employ that the idea of dying for lack of a healthy liver or kidney will seem as absurd as dying of scarlet fever seems today in industrialized countries (where most people no longer even know what scarlet fever is).

The future will be marked by the end of long-believed inevitabilities. The biggest shock to come will happen when people realize that aging is going to cease to be inevitable. There are already hundreds of millions of people alive who will live to see that day.

Share |      Randall Parker, 2003 May 16 01:45 AM  Biotech Organ Replacement

Satish Khurana said at November 15, 2004 7:44 AM:

I agree that transdiferentiation of hematopoietic stem cells into liver cells will be very useful. It is quite interesting to think about liver and the blood systems together. Both systems are quite different from each other even then the strong relationship between the ontogeny of the two systems lead us to think in a different way about the two. I think that there can be a similar type of transition of cells from blood lineage to hepatic lineage. If it is true then many of the concepts of liver development will be under question.

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