An alternative to bone-marrow donation

Researchers have developed a method to reconstitute bone marrow and blood cells from embryonic stem (ES) cells. As reported in The Journal of Experimental Medicine, this method was effective even in genetically mismatched mice. If the same is true in humans, this would remove the need to find genetically matched human bone-marrow donors for patients with leukemia, immune deficiencies and autoimmune diseases.

ES cells are cells derived from embryos that have the potential to grow into many different cell types. Richard Burt and colleagues identified the most effective mix of growth factors to induce mouse ES cell lines to develop into bone-marrow and blood precursor cells in culture. They also devised a method to select the best cells from these cultures. Injection of the selected cells into the bone marrow of mice that had been depleted of their own bone-marrow cells resulted in restoration of blood cells, including cells of the immune system, which are normally produced in the bone marrow.

Despite the genetic mismatch between donor and recipient, the injected cells were not rejected. This is consistent with previous evidence that ES cells are somehow less susceptible than adult cells to being identified as foreign by the immune system. The basis of this difference is not understood.

There was also no evidence that the immune cells derived from ES cells were attacking the recipient. The equivalent process after bone marrow transplantation is an often fatal complication known as graft-versus-host disease. The immune response to foreign antigens was, however, normal, indicating that recipients would be able to fight off infection efficiently.

Although the use of ES cell lines is controversial, it has many potential advantages over the use of cells from donor bone marrow or blood. The latter cells are highly variable, cannot be cultured in the lab and often cause graft-versus-host disease. Human ES cell lines can be cultured indefinitely, providing a renewable and well-defined source that is free from bacterial contamination.

Contact: Dr Richard Burt, Northwestern University, Chicago, 312-908-0059, rburt@nwu.edu