Oxygen is Toxic...

U-M scientist says oxygen is toxic to stem cells. Too much O2 turns muscle cells into fat

ANN ARBOR, Mich. oxygen may be good for you, but it's not so great for your stem cells -- according to a new study by scientists at the University of Michigan Medical School. Too much oxygen can kill stem cells, slow growth and even trigger an alternate developmental pathway that converts pre-muscle stem cells into fat cells.

The U-M study, published in the November 2001 issue of the Journal of Cellular Physiology, shows that gene expression patterns change significantly when stem cells are exposed to varying amounts of oxygen, and that these changes alter the basic biologic function of stem cells. In addition to its scientific importance, the U-M study could have important clinical implications for treatment of obesity and diabetes.

"The more primitive the stem cell, the more sensitive it is to oxygen," says Marie Csete, M.D., Ph.D., an assistant professor of cell and developmental biology and an associate professor of anesthesiology in the U-M Medical School, who directed the study.

"We found that skeletal muscle satellite cells grew faster, lived longer and developed into muscle cells more consistently when cultured with the amount of oxygen found in their natural environment." In their natural environment in the body, stem cells never are exposed to the amount of oxygen they encounter in the typical biomedical laboratory.

Csete and colleagues compared growth rates and developmental patterns of stem cell lines and skeletal muscle satellite cells grown in a laboratory atmosphere of 20 percent oxygen to cells grown with the 2 percent to 6 percent oxygen levels found inside the body. Csete grows stem cell cultures in a custom-designed facility, which she can adjust to create an atmosphere with specific amounts of oxygen and other gases.

"The big surprise was that satellite cells isolated from muscle fiber

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