Blood stem cell transplantation, widely known as bone marrow transplantation, is a powerful technique that potentially can provide a lifelong cure for a variety of diseases. But the procedure is so toxic that it is currently used to treat only the most critical cases.

Now, researchers at the Stanford University School of Medicine have come up with a way of conducting the therapy that, in mice, dramatically lowers its toxicity. If the method eventually proves safe and effective for humans, it potentially could be used to cure autoimmune diseases like lupus, juvenile diabetes and multiple sclerosis; fix congenital metabolic disorders like “bubble boy” disease; and treat many more kinds of cancer, as well as make organ transplants safer and more successful.

“There is almost no category of disease or organ transplant that is not impacted by this research,” said Irving Weissman, MD, a co-author of the research and professor of pathology and of developmental biology at Stanford. A paper describing the technique was published Aug. 10 in Science Translational Medicine.

The paper’s senior author is Judith Shizuru, MD, PhD, professor of medicine. The lead authors are research associate Akanksha Chhabra, PhD; former graduate student Aaron Ring, MD, PhD, who is now on the faculty at Yale; and Kipp Weiskopf, MD, PhD, a former graduate student who is now a resident at Brigham and Women’s Hospital.

Noxious treatment

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 result in death.

“The chemotherapy and radiation used for transplant damage DNA and can cause both immediate problems and long-term damage to many tissues in the body,” Shizuru said. “Among the many known toxic side effects, these treatments can cause damage to the liver, reproductive organs and brain, potentially causing seizures and impairing neurological development and growth in children.” For these reasons, blood stem cell transplantation is used only when the risks of serious disease outweigh the complications from the transplant.

To avoid these terrible side effects, the Stanford researchers composed a symphony of biological instruments that clear the way for blood stem cell transplantation without the use of chemotherapy or radiotherapy.

Using antibodies

The scientists started with 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 resulted in depletion of blood stem cells in immune-deficient mice. “However, this antibody alone would not be effective in immune-competent recipients, who represent a majority of potential bone marrow transplant recipients,” Chhabra said. The researchers sought to enhance the effectiveness by combining it with antibodies or with biologic agents that block another cell surface protein called CD47. Blocking CD47 liberated macrophages to “eat” target cells covered with c-kit antibody, Chhabra said.