Researchers use embryonic stem cells to develop functioning immune system blood cells

For the first time, researchers have used embryonic stem cells to develop functioning immune system blood cells -- an important step in eventually using embryonic stem cells as an alternative source of cells for traditional bone marrow transplantations.

The study team was led by a researcher with the University of Iowa and the Veterans Affairs (VA) Iowa City Health Care System.

The study, which was done on animal models, used a previously discovered protein to overcome the fact that new blood cells derived from embryonic stem cells are normally not self-renewing. The finding was published online in December in Blood, the official journal of the American Society of Hematology.

"These results show, for the first time, that functional white blood cells, the key players in the body's immune system, can be successfully derived from embryonic stem cells expressing a protein called HOXB4," said the study's lead author Nicholas Zavazava, M.D., Ph.D., professor of internal medicine and director of transplant research at the UI Roy J. and Lucille A. Carver College of Medicine and a staff physician at the VA Iowa City Health Care System.

"The finding may help leverage an existing advantage that embryonic stem cells have over traditional transplants, which use donated bone marrow, umbilical cord blood or peripheral blood," he added.

Currently, people with severe blood and immune disorders need these traditional transplants for treatment. The antigens on the surface of donated cells must be compatible with those of the patient to prevent rejection. Compatibility is checked using a method called HLA matching. Embryonic stem cells have low levels of these antigens and therefore, unlike bone marrow cells, may be less likely to provoke a defensive reaction by the patient's body. Thus, using embryonic stem cells may allow patients who cannot find suitable HLA-matched donors to receive transplants.

In the study, the scientists induced into embryonic stem cells the protein HOXB4, already known for its ability to greatly enhance cell proliferation. The researchers then coaxed these stem cells to differentiate into hematopoietic cells for transplantation.

The scientists then explored how these cells function within the animal model, showing that these cells rebuilt defunct immune systems in mice. Although the number of T cells (white blood cells involved in immune defense) generated by the new hematopoietic cells was low, the hematopoietic cells also produced B cells and other defensive cells, which help signal T cells to action.

In addition to Zavazava, the study team included Kun-Ming Chan, a visiting researcher at the VA and UI who is a research fellow from Chang Gung University of Medicine in Taoyuan, Taiwan; Sabrina Bonde, UI researcher; and Hannes Klump, a collaborator from Hannover Medical School in Germany.

This study was supported by grants from the National Heart, Lung and Blood Institute, a VA Merit Review and the Roche Organ Transplantation Research Foundation.