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A safer way for bone marrow transplants

Aug 10, 2016

A team of researchers led by Judith Shizuru, an investigator at the Ludwig Center at Stanford, has devised a method for conducting bone marrow transplants that, in mice, dramatically lowers the toxicity of the procedure. If it proves safe and effective for humans, the approach could be used to cure autoimmune diseases like lupus, juvenile diabetes and multiple sclerosis, and to treat many kinds of cancer.

To successfully transplant blood stem cells, a patient’s own population of blood stem cells must be killed. Currently, this is done using chemotherapy or radiotherapy, treatments that are toxic enough to damage a variety of organs and even cause death.

The method developed by the Ludwig Stanford team relies on an antibody against a cell surface protein called c-kit, which is a primary marker of blood stem cells. Attaching the antibody to c-kit results in the depletion of blood stem cells in immune-deficient mice. The researchers also used antibodies or biologic agents to block another cell surface protein called CD47, liberating macrophages to “eat” and so deplete target cells covered with c-kit antibody. This cleared the way for blood stem cells transplanted from a donor to take up residence in the bone marrow and generate an entirely new blood and immune system.

Comparing blood stem cell transplants to planting a new field of crops, Shizuru noted that the researchers not only found a safer way to clear the field for planting, but “we also used safer techniques to seed the new blood-generating cells.” Currently, bone marrow transplants involve a mix of cells that includes blood stem cells as well as various immune cells from the donor, which can attack the tissue of the transplant recipient, causing graft-versus-host disease. In their new approach, the team purified the donor tissue so that it contained only blood stem cells and not the other immune cells that cause graft-versus-host disease.

The success of these techniques in mice raises hopes that similar techniques will succeed in human patients. “If and when this is accomplished, it will be a whole new era in disease treatment and regenerative medicine,” said Irv Weissman, who is a co-author on the paper and director of the Ludwig Center at Stanford.

The full version of this news release is available here.