Reconstituting mammalian spermatogenesis using stem cells.

W hile stock markets and economies are smoldering all over the world, stem cell science is on fire. The promise of curing many untreatable forms of human male infertility is now one small step closer based on a recent paper in Cell. In this work, scientists from Kyoto University in Japan created mature, fertile sperm from embryonic and induced pluripotent stem cells by grabbing the primitive germ cells called primordial germ cells just as they were being made from their pluripotent precursors in vitro and transplanting them back into genetically sterile mice. As background, stem cells possess the unique ability to either propagate by selfrenewal or to differentiate to mature tissues under the influence of appropriate molecular cues. This remarkable dual behavior has focused the research spotlight on using stems for regenerative medicine. There are now several classes of stem cells, all varying in degrees of pluripotency. Among these, embryonic stem cells represent the prototypical pluripotent stem cells. Another, more recent stem cell is derived from the reprogramming of somatic cells to pluripotent stem cells (iPSCs) and is based on a set of landmark studies conducted by Yamanaka and others that showed that just four factors (Oct4, Sox2, Klf4 and c-Myc) normally produced in the embryo are sufficient to reprogram differentiated, non-embryonic cells into pluripotent cells. In addition, during development, a small population of embryonic stem cells are allocated to the germ line (primordial germ cells), while the remaining cells give rise to the three germ layers. It is this particular stem cell type that has now captured the research limelight. Over the past 2 years, germ line stem cell research has seen spectacular advance which suggests that these particular stem cells are quite plastic and manipulatable for potential cell-based therapy. Some of these advances include: