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Testes May Prove Fertile Source of Stem Cells

Tracking down powerful adult stem cells in mouse testes may benefit humans, too
mouse



© ISTOCKPHOTO.COM/ANDREI TCHERNOV
Researchers say they have found a way to pluck out a potent type of stem cell from the testes of adult mice and transform it into other kinds of tissue, including heart muscle and blood vessels.

The result—the second such finding in the past year—suggests that similar cells from human testicles might have similar powers, paving the way to creating replacement tissue for men who have suffered damage from heart attacks or other injuries and avoiding some of the controversy surrounding embryonic stem cells (ESC).

Three separate groups reported in June that they had reprogrammed adult mouse skin cells into a form nearly indistinguishable from ESCs. But researchers still have to figure out how to prevent those cells from causing cancer.

Women already have a source of custom stem cells (in principle) in the form of parthenogenetic embryos grown without sperm.

To give men their fair shake, Shahin Rafii, professor of genetic medicine at Weill Cornell Medical College in New York City, along with Memorial Sloan-Kettering Cancer Center medical oncologist Marco Seandel and their colleagues homed in on a specific group of mouse spermatogonial progenitors—stemlike cells that give rise to cellular sperm factories called spermatogonia.

Normally, adult stem cells can only morph into the type of tissue in which they reside, such as blood, brain or muscle. Rafii says, however, that cells giving rise to sperm—and, therefore, embryos—should have the same developmental potential as sperm do. He notes that testicular and ovarian cancers often produce teratomas, noninvasive tumors made up of tissues from all three embryonic layers.

The group first extracted and purified progenitor cells bearing a protein molecule called GPR125. When transplanted back into the mouse testis, they produced spermatogonia as expected.

The team then cultured the cells for several months in a bath of growth-promoting proteins, trying to get the cells to reverse course and become more like stem cells. When they injected the tissue into growing mouse embryos, the cells formed teratomas like ESCs do, and mingled with the blood vessels of the mice, the group reports in this week in Nature.

Other groups reprogrammed mouse skin cells by inserting four embryonic genes, some of which are oncogenes (genes that promote cancer). "To me the therapeutic potential of this is much more tremendous than to reprogram a skin cell with four oncogenes," Rafii says. "We reprogram without genetic tweaking."

The challenge, he says, will be figuring out how to force the transition from progenitors to stem cells, which spontaneously occurred in about one third of testicular cell lines.

Scientists in Germany last year reported that they could transform adult mouse spermatogonial progenitors into cells genetically resembling ESCs by using a different growth medium for just a few weeks. Without a marker, however, "they have no clue where their cells came from," Rafii says.

Better markers would be valuable for purifying and studying cells, says molecular geneticist Takashi Shinohara of Kyoto University in Japan, who led a group that in 2004 discovered cells similar to ESCs from newborn mouse testes. But he is skeptical about the newer studies, which are yet to be confirmed by other labs.

Others are more upbeat, but agree more research is needed. "The studies seem carefully done to me," says stem cell biologist Sean Morrison of the University of Michigan Medical School, who has not studied the new paper. "I suspect a lot of people are watching to see if the results will fully hold up or whether it will turn out to be only partially true."

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