New experiments that prevented rat sperm stem cells from changing permanently into sperm have brought researchers one step closer to coaxing such cells to behave like embryonic stem cells, capable of growing into many other types of cells in the body.
Researchers at the Cecil H. and Ida Green Center for Reproductive Biology Sciences at UT Southwestern Medical Center devised methods to keep male rat germ-line stem cells - sperm precursor cells - from differentiating, or changing, into sperm proper.
The researchers also froze the sperm stem cells, thawed them, and transplanted them back into rat testes, where they developed into normal sperm.
Dr. David Garbers, professor of pharmacology, director of the Green Center and senior author of a study appearing in an upcoming issue of the Proceedings of the National Academy of Sciences, said the new work has many potential applications, including a possible alternative to embryonic stem cells, the development of new male contraceptives and new animal models to test stem cell-based therapies. Germ-line cells are those such as egg and sperm and their precursors whose genetic material can be passed to offspring.
"The ability to manipulate male germ-line stem cells and get them to grow and self-renew is a major step," said Dr. Garbers, a Howard Hughes Medical Institute investigator at UT Southwestern.
"We're only one step removed from another major step, the Holy Grail for us certainly, which is pushing these cells back a level to a state that is pluripotent-like, similar to embryonic stem cells. That's what we're focused on now."
Pluripotent cells have the potential to change into many other types of cells in the body, such as liver cells and brain cells. Their potential use in humans to treat diseases like diabetes and Parkinson's is controversial because currently the only source of such cells for research is human embryos or mouse cells. Recently another research team published results showing that mouse male germ stem cells could be made to exhibit pluripotent characteristics, but those findings have yet to be repeated.
Ordinarily, when germ stem cells divide into two cells, one "daughter" cell differentiates to become a sperm while the other remains a stem cell. Until recently, researchers had been unable to keep such germ-line stem cells from differentiating for extended periods of time. In contrast, embryonic stem cells from mice and humans have been kept from differentiating indefinitely.
A research team in Pennsylvania recently reported similar results with rat sperm to those of the UT Southwestern work; however the UT Southwestern team used substantially different techniques for sorting, growing and maintaining their stem cells in culture.
Armed with a long-lived, renewable source of rat sperm stem cells, researchers at UT Southwestern are now working to genetically manipulate those cells. For example, the scientists want to delete specific genes from the sperm stem cells and transplant the cells back into male rats, with the goal of producing "knockout," or genetically altered, animals to study health and behavioral effects related to those missing genes. Knockout mice are often used in research, but they are produced using a different method than the new sperm-cell approach.