Testis looms large in the hunt for flexible stem cells among adult tissues. But although mouse and some human studies indicate that such cells exist in testis, isolating the cells reliably has been difficult1. Working in mice, researchers have now identified a novel cell surface marker that can help harvest these cells, as well as a technique that helps them grow2. The cultured cells, termed multipotent adult spermatogonial-derived stem cells (MASCs), display some qualities of embryonic stem cells, most notably a consistent ability to form teratomas. This work, if it can be applied to humans, may uncover a new source of potent, patient-specific stem cells, at least for men.

Led by Shahin Rafii of Cornell University, the researchers found a marker in adult testis, GPR125, when working with a series of knockout mice. Further work showed that the marker was expressed on spermatogonial stem cells but not mature germ-line cells or non-germ-line stromal cells. The researchers found that these cells did not grow well when cultured on top of mouse embryonic fibroblasts but thrived when grown near a cell type normally nearby in the testes.

After about 3 months in culture these cells shifted spontaneously; their colonies resembled those of embryonic stem cells, and they began producing pluripotency markers including Oct4 (also known as POU5F1), Nanog and Sox2. The cells, now termed MASCs, always formed teratomas when injected into immune-deficient mice; when mixed with mouse embryos, the MASCs sometimes contributed to a variety of tissues in chimeras. Additionally, MASCs were able to differentiate into blood vessels both in vitro and in vivo.

Other work has focused on cells from neonatal animals3, and a previous study on adult testis tissue used a different marker, which some scientists believe is also expressed on nonspermatagonial cells4. Rafii believes that his research shows conclusively that adult spermatogonial stem cells can become multipotent cells. In fact, he writes, multipotency could potentially be driven by several distinct sets of signals, including some not typically associated with stem cells.

Whether or not that is the case, multipotent stem cells from testis can now be readily obtained and manipulated. Although therapeutic applications may not be around the corner, a plentiful source of stem cells is certain to allow additional experiments in reprogramming and regeneration.