Blood stem cell transplants represent an opportunity to “restart” a biological process gone awry and are used to treat cancers such as leukemia and lymphoma, as well as various blood diseases. Transplants, however, can be risky and fraught with complications, relegating the procedure to a last-resort option in life-threatening situations. Recipients must first undergo preconditioning treatments involving chemotherapy and/or radiation to suppress their immune system and destroy their own blood stem cells before donor cells can be safely transplanted into their bone marrow. The side effects of chemotherapy and radiation can be challenging enough while underway, and patients may also experience damaging late effects, such as cardiac and vascular problems, lung and liver disease, and infertility, long after treatment has ended. But without myeloablation, patients run the risk of transplant rejection or developing graft-versus-host disease, a complication in which the transplanted cells attack their new host. Developing effective but safer preconditioning treatments could improve transplant patient outcomes and allow treatment of diseases and conditions where the risks are currently considered greater than the rewards.

A group of researchers at the Stanford University School of Medicine have recently developed a preconditioning treatment in mice that allowed them to successfully transplant hematopoietic stem cells (HSCs) without toxic drugs or radiation (Sci. Transl. Med. 8, 351ra105; 2016). Their strategy relied on the mouse's own immune system, combining two biological agents to effectively deplete host HSCs. The first agent, the mouse antibody ACK2, is capable of reducing HSCs in mice with already compromised immune systems. The second, known as CV1mb, blocks the CD47 transmembrane protein found on HSCs; without this protein, the immune system no longer recognizes the cells and will begin to destroy them. In isolation, neither agent worked effectively in mice with normally functioning immune systems. But used together, the treatment resulted in almost complete depletion of HSCs and a mouse ready to receive a donor transplant. Successful engraftment of transplanted HSCs in the ACK2/CV1mb-treated mice equaled or exceeded that of mice treated with different preconditioning doses of radiation. If the technique can be translated into humans, doctors could perform the procedure without the side effects of chemotherapy and radiation, allowing treatment of less dire cases and potentially expanding the use of blood stem cell transplants into new territories.