By adding leukemia inhibitory factor (LIF)–a molecule that is normally used to keep embryonic stem cells from differentiating–the team managed to transform the resulting spermatogonial stem cells into stem cells that much more closely resembled embryonic stem cells and can form a similar variety of cell types.
Skutella thinks that germ stem cells are fundamentally more amenable to reprogramming than cells that do not participate in the germline (the production of sperm or eggs). In support of this, a similar transformation into pluripotent cells had previously been observed with primordial germ cells–cells in the embryo that later go on to form sperm and egg precursors. But obtaining these germ cells requires destroying the embryo, while the testicular adult cells do not face this issue. “The DNA of germ cells is more open to manipulations, so they have advantages compared to other adult stem cells,” says Skutella.
Fari Izadyar, director of scientific development for the germline stem-cell program at biotech company PrimeGen, says that his team has also had promising results with getting human testicular tissue to differentiate into cardiac, brain, bone, and cartilage cells, although the company has not yet published the data. “It has been difficult to produce consistent results without a steady supply of normal human testicular tissue,” he says.
While the starting material is easy to obtain with small testicular biopsies, Skutella admits that his method of producing stable pluripotent germ stem-cell lines takes several months, and that this would need to be sped up if the cells are to be used therapeutically. “We are currently looking to improve our enrichment procedure by finding more-specific cell surface molecules which can be used to isolate the cells more quickly in the future,” he says.
Another open question is whether and how women might be able to benefit from the discovery. Skutella argues that at the very least, male germ stem cells could be used to treat women in much the same way that bone marrow is used in cancer therapy: by finding a closely related male donor and treating the patient with immunosuppressants, to prevent the body from rejecting the cells.
But others are hopeful that similarly versatile stem cells can be obtained from the female reproductive tract. Antonin Bukovsky of the University of Knoxville, in Tennessee, has previously found stem cells on the surface of the ovary and managed to differentiate them into neuronal cells. “I think these cells might hold very similar potential to the testicular ones, and they would be just as easy to obtain,” he says. “You would only have to brush the surface of the ovary, and we already know they still exist in women of advanced age.”