My coworkers and I study adult stem cells that live in the bone marrow. Some of these cells give rise to red and white blood cells and are called hematopoietic stem cells (HSCs). Others give rise to bone, cartilage, and fat and are called bone marrow stromal cells (BMSCs). I find the BMSCs especially interesting. Unlike most cells in the body, cells from any donor can be given to any recipient. We have found that when BMSCs are given to mice that have severe, life threatening infections of the blood (i.e., "sepsis"), many more animals survive than untreated, control animals do. The response of the mouse (and human) immune system to sepsis is so strong that it injures organs like the lungs, liver, and kidney. We die of organ failure. The BMSCs "listen" to the response of the immune cells and modulate them so that they no longer make factors that are harmful to the body. Based on our discovery, clinical scientists are planning to treat patients suffering from sepsis with BMSCs. Based on another study of severe asthma that we did, clinicians are planning to treat asthma patients with the cells as well, but BMSCs from different donors differ in their abilities to correct these problems. Therefore, we are looking for ways to predict which BMSCs are likely to be most useful to patients with a variety of health problems. It may seem obvious that if BMSCs are such good listeners, some signals could prove harmful to them. This is true in a disease called mastocytosis. In this disorder, mast cells produce too much histamine. The excess histamine, in turn, makes it hard for BMSCs to build bone efficiently. We hope to learn how to correct this problem. Recently, we have discovered that BMSCs, which are known to live in close proximity to HSCs and "nurse" them, also pass along signals to them that they might otherwise ignore. When we lose a lot of blood, for example, BMSCs detect the problem and stimulate the HSCs to produce new blood cells. Clearly, BMSCs have many jobs. We believe that it is important to learn how they accomplish these so that we can sometimes help them when they need assistance, and exploit them when giving extra BMSCs can correct problems with immune function.

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Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2013
Total Cost
$1,287,554
Indirect Cost
Name
National Institute of Dental & Craniofacial Research
Department
Type
DUNS #
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