A Source of Men's Stem Cells

Stem cells from human testes could be used for personalized medicine.

Adult stem cells that behave much like embryonic ones have been isolated from human testes, raising hopes for a new source of versatile stem cells without genetic manipulation or the destruction of embryos. If the new stem cells can be used therapeutically, a simple testicular biopsy could provide the starting material for personalized regenerative medicine.

Testicular transformation: Stem cells from adult human testes normally produce only sperm, but when cultured in the lab with special growth factors, they begin to resemble embryonic stem cells and can differentiate into many adult cell types. Credit: Thomas Skutella

The new stem cells, known as human adult germline stem cells (GSCs), were grown by researchers in Germany and the U.K. by adding special growth factors to spermatogonial cells extracted from testes. Spermatogonial cells are stem cells in the adult testis that normally generate only one type of differentiated cell (sperm). But with the right growth factors, these spermatogonial cells can change to become pluripotent. They begin to produce proteins normally made by embryonic stem cells and acquire the ability to differentiate into many different cell types.

In a paper published today in Nature, Thomas Skutella of the University of Tübingen, in Germany, and his colleagues raise the possibility that adult GSCs could overcome many of the hurdles still facing alternative approaches.

Unlike embryonic stem cells, which require the destruction of human embryos and pose immunological challenges because a patient's body will reject foreign cells, adult GSCs do not require embryos and should be tolerated by patients because they are made from their own cells. Adult GSCs should also be more versatile than other types of adult stem cells, which typically can only give rise to one or a few types of differentiated cells.

Furthermore, in contrast with induced pluripotent stem cells (iPS), which are made by engineering embryonic stem-cell genes into normal adult cells with the help of retroviruses, the adult GSCs do not require significant manipulations and therefore avoid the associated cancer risks.

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Skutella says that his results are similar to those from recent experiments performed on mice, but that it was much trickier to isolate the right kind of cells in humans. "You can use the power of genetics to make transgenic mice with green spermatogonia to easily isolate these cells," he says. "But for regenerative medicine, it's essential to use the human system. We obviously cannot make transgenic humans, so we had to go back to the roots of cell biology, and try a mixture of things to isolate the stem cells."

Using 22 testis-tissue samples from men ages 17 to 81, the researchers isolated spermatogonial stem cells with the help of magnetic beads that physically pulled the right cells out of the cell mix. These beads were coated with an antibody that recognizes a surface molecule that is enriched on germline cells. The researchers followed this with two more rounds of purification: one that used culture-dish coatings that preferentially stick to germline cells, and a second one that used coatings that stick to somatic (nongermline) cells.