The findings will be published in the Sept. 3 issue of Stem Cells.
"Wounds may not heal the way we thought they did," says Dr. Richard Ikeda, a biochemist at the National Institute of General Medical Sciences, one of the National Institutes of Health, which supported the work. "This study shows that bone marrow stem cells, in addition to cells from the surrounding tissue, may actually contribute to the healing process. If this is the case, it could lead to completely new ways of treating serious wounds."
When a body is wounded, the body immediately tries to form a clot in order to stop the bleeding. The seal is formed with the help of cells that circulate in your blood all the time and are on the spot immediately. The body also has an inflammatory response: signals direct white blood cells to the area of the wound. The white blood cells arrive to fight off foreign bacteria and infection. This inflammatory response is responsible for the red area around a wound. The inflammatory response goes away within a few days to a week, assuming there is no continued infection.
"Scientists have long assumed that once the inflammatory response concludes, the white blood cells mostly either then die or go into circulation in the bloodstream. We did not know, until now, that the bone marrow-derived cells go on to become a significant part of the new skin," said Dr. Frank Isik, professor of surgery at the University of Washington. "We've known that bone marrow cells are involved in wound healing and inflammation - now we have data that shows bone marrow cells are involved in normal skin maintenance, in maintaining the matrix environment and integrity of the skin."
Bone marrow has been studied for a number of purposes in recent years because it is rich in stem cells - cells that can go on to become many different kinds of cells. In order to conduct this research, Isik and colleagues obtained a strain of mice whose bodies glow green under fluorescent light. The researchers removed bone marrow from the mice and then performed a stem cell transplant into a genetically identical strain of normal mice, whose cells do not glow green. Afterward, only the bone marrow of the transplanted mice glowed green inside the bodies of the mice, allowing researchers to track the bone marrow cells throughout the body. Researchers found green cells throughout the body, but observed that the highest concentration of bone marrow cells was in normal skin.
That was a surprise. People have known for awhile that there are a few white blood cells in the skin - that's how people come down with contact dermatitis. Contact dermatitis happens when someone develops an inflammatory reaction to a substance that touches his or her skin. However, the white blood cells involved in contact dermatitis express a certain protein, CD45. The new cells identified in the transplanted mice did not produce that protein, and do not seem to be implicated in contact dermatitis. Researchers found that even after six weeks, long after the infection-fighting role seems to be over, the bone marrow-derived cells cluster within the healing area of a wound.
The researchers ran these skin cells through a flow cytometer to separate them into green and non-green fractions and found only the green cells in the skin produced collagen type III, which is one of the two most abundant collagens in skin. The native skin cells produced only collagen type I. Researchers do not know why bone marrow would produce collagen III, which is typically found in connective tissues such as skin.
"What we have here is a new cell population that was not previously recognized," Isik said. "The bone marrow cells help form the matrix of the skin. Collagen is what gives your skin its tough nature. It's expandable, and it's tough. You cannot break your skin without a sharp object. The reason is because of the collagen content, a scaffolding that is very strong."
Isik is involved in follow-up studies to determine exactly what role the cells of bone marrow origin have within the skin. One question is whether diseases such as diabetes, which leads to poor wound healing, affect the function of bone marrow cells in the skin and wounds. Researchers hope that someday, scientists might use new mechanisms to promote wound healing, and troubleshoot chronic wounds.