Published on November 20, 2005 at 5:25 PM
"It will be quite valuable to bring this to the rat because it would enable us to generate knockout rats to do genetic studies," said Dr. Kent Hamra, assistant professor of pharmacology at UT Southwestern and lead author of the PNAS study. "It is a larger animal, it's often better for toxicology and physiology studies, and its behavior is more in tune with that of humans in many cases. It's also important to be able to produce pluripotent rat cells, because we would then have another animal model to test stem cell-based therapies, such as correcting diabetes."
One of the next steps is to determine whether human male germ-line stem cells can also be immortalized in culture. Although genetic modification of human sperm is not one of their goals, the researchers say it may be possible someday to correct genetic defects in humans - cystic fibrosis, for example - by identifying and eliminating in culture a man's sperm stem cells that carry the gene.
Dr. Garbers said that a renewable source of cultured sperm stem cells, rat or human, also could be used to test for male-directed contraceptives, and a company is already interested in this possibility.
One of the breakthroughs in this study was developing a new type of medium to grow the cells in, and another was the use of a genetically manipulated "tag" that specifically labeled germ cells with a green fluorescent protein, making the germ cells easier to identify when mixed with other cell types.
"The rat testes contain other cells types in addition to stem cells," Dr. Hamra said. "If these other cells are included in the culture, they produce chemicals that block the ability of the stem cells to remain stem cells. We're still trying to figure out why. But the key is to start with a sample that is 100 percent pure germ cells, which we achieved using the fluorescent marker and other purification methods that are different from those used by other research groups."
Other UT Southwestern researchers involved with the work were Dr. Robert Hammer, professor of biochemistry and in the Green Center, and research technicians Karen Chapman, Derek Nguyen and Ashley Williams-Stephens.