June 22, 2006 For many years, researchers believed that stem cells in the bone marrow spent most of their existence in a slumber-like state, unaware of—and unaffected by—the daily battles fought by the body’s immune system.
Scientists at the Oklahoma Medical Research Foundation have discovered that marrow stem cells—undifferentiated cells that eventually give rise to the blood cells that fight infection—possess receptors that recognize bacteria and viruses. When activated, these receptors kick the stem cells and immature blood cells into action, enlisting them to help fight whatever pathogen is attacking the body.
The findings, which appear in the new issue of the journal Immunity, could have important implications for treating leukemias and autoimmune diseases such as lupus and rheumatoid arthritis.
“We have long known that so-called hematopoietic (blood) stem cells create the blood cells that are the front-line soldiers in the body’s immune system,” said Paul Kincade, Ph.D., the senior author on the paper. “But we did not believe that infectious agents played an active role in the process.”
“What we have now discovered is that these stem cells have a sort of antennae that detect bacteria and viruses,” continued the OMRF researcher. “And when stem cells receive these distress signals, they spring to action, creating cells the body most needs early in life-threatening situations.”
This messaging system normally serves as an effective means of quickly replacing cells that are damaged or killed while keeping us healthy. But investigators suspect that the system also can be detrimental in certain circumstances—for example, in leukemia patients that are vulnerable to infections after receiving bone marrow or cord blood transplants or in autoimmune diseases like lupus, where immunosuppressive treatments often leave the body subject to long-term infection.
“Scientists need to study stem cells and leukemia cells in these diseases to determine if they are using this messaging system,” said Kincade.
Another key, he said, will be to figure out how best to control the receptors in stem cells. “It may be possible to boost immunity when necessary and also shut down inappropriate responses. That could provide a powerful tool to fight cancer, lupus and many other diseases.”
In an accompanying commentary, Garnett Kelsoe, a professor of immunology at Duke University, wrote that Kincade’s discovery “merits widespread attention and will surely be the object of further investigation." The paper, he said, “requires a new appraisal of just how innate immunity and acquired immunity are intertwined."
The research, which was led by Kincade and Yoshinori Nagai, Ph.D., used purified stem cells obtained from the bone marrow of laboratory mice. This type of stem cells, possessed by humans of all ages, are not to be confused with embryonic stem cells, which are found only in early-stage embryos.
Done in collaboration with researchers at the University of Tokyo, Osaka University and Saga University (Japan), the research was supported by grants from the National Institute of Allergy and Infectious Disease.
Kincade heads the Immunobiology and Cancer Research Program at OMRF, where he holds the William H. and Rita Bell Chair in Biomedical Research. A former president of both the American Association of Immunologists and the Federation of American Societies for Experimental Biology, his laboratory focuses on understanding the development and function of cells in the immune system.
Celebrating its 60th birthday in 2006, OMRF (www.omrf.org) is a nonprofit biomedical research institute dedicated to understanding and curing human disease. Its scientists focus on such critical research areas as Alzheimer’s disease, cancer, lupus and cardiovascular disease. It is home to Oklahoma’s only member of the National Academy of Sciences.
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