Researchers at the Joslin Diabetes Center have identified a gene that is responsible for the division and movement of marrow-derived, blood-forming stem cells, a finding that could have major implications for the future of bone marrow and blood cell transplantation.
Every year, some 45,000 patients undergo bone marrow or peripheral blood progenitor cell transplantation for the treatment of a variety of diseases, including leukemia, lymphoma, and immunodeficiency. Blood cell transplantation may also one day help people with diabetes better tolerate islet cell transplants without the need for prolonged use of powerful immunosuppressive drugs. In addition, transplantation of blood-forming stem cells, also called hematopoietic stem cells, may prove useful in halting the autoimmune process that causes type 1 diabetes.
The success of bone marrow and blood cell transplants depends on the ability of intravenously infused hematopoietic stem cells, which normally reside predominantly in the bone marrow, to accurately and efficiently migrate from the blood to the marrow of the transplant recipient and, once there, to repopulate their pool of mature blood cells.
In studying mice that lack the transcription factor early growth response gene (EGR-1), a team led by Amy Wagers, Ph.D., found that hematopoietic stem cells in the marrow of these animals divided about twice as often as stem cells in mice with the gene. Mice lacking EGR-1 also had higher numbers of such stem cells circulating in their blood.
The paper, published in the April issue of Cell Stem Cell, is the first to identify EGR-1 as a regulator of hematopoietic stem cell migration and proliferation. The transcription factor has already been identified as a tumor suppressor.
“The transcription factor EGR-1 is important in both of these processes,” said Wagers, Principal Investigator in the Joslin Section on Developmental and Stem Cell Biology, principal faculty member at the Harvard Stem Cell Institute and Assistant Professor of Pathology at Harvard Medical School. “This factor gives us a handle on the discovery of new pathways that regulate the movement of stem cells.”