Researchers, writing in the Proceedings of the National Academy of Sciences, say they a step closer to coaxing sperm stem cells to behave like embryonic stem cells, which are capable of growing into many other types of cells in the body. 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.
The UT Southwestern Medical Center researchers have devised methods to keep male rat germ-line stem cells (sperm precursor cells) from differentiating into sperm proper. The researchers say they have developed a new type of medium to grow the cells in, along with 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 ability to manipulate male germ-line stem cells and get them to grow and self-renew is a major step,” said Dr. David Garbers, of 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.”
Normally, 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.
With a renewable source of rat sperm stem cells, the researchers are now working to genetically manipulate those cells for all sorts of purposes. In one strand of investigation, 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,” 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. “It will be quite valuable to bring this to the rat because it would enable us to generate knockout rats to do genetic studies. 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,” said co-researcher Dr. Kent Hamra.
Another important step is to see whether human male germ-line stem cells can also be coaxed into behaving like embryonic stem cells. Dr. Garbers said that a renewable source of cultured sperm stem cells, rat or human, could also be used to develop new types of male contraceptives.