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Helping Stem Cells Find Their Niche

Researchers have reversed infertility in male mice using transplants of specialized cells involved in sperm formation, offering hope that a leading cause of male infertility may someday be reversible. Between 70 and 90% of cases of male infertility arise from defects in spermatogenesis.

Sertoli cells, which compose the epithelial surface of the seminiferous tubules, nourish and support the germ cells, promoting their maturation into functional spermatozoa. Sertoli cells also provide what is known as a “niche” for the testicular stem cells that produce the germ cells, helping to maintain the stem cells in the undifferentiated state that is essential to their function.

Now, Ralph Brinster's group at the University of Pennsylvania (Philadelphia, PA) has announced the successful reestablishment of a niche, by means of the transplantation of functional murine Sertoli cells into infertile mice (Biol. Repr., November 2002). Steel/Steeld mice produce defective Sertoli cells that are incapable of supporting spermatogenesis. When these mice were injected with dissociated testicular tissue from wild-type perinatal mice, between 30 and 40% of the recipients exhibited enhanced tubule development and restored spermatogenesis.

Before this procedure can become a viable option for male infertility treatment, it will be necessary to overcome a number of obstacles. Mature Sertoli cells no longer divide and cannot be expanded in culture, making it difficult to procure sufficient donor material. Furthermore, spermatogenesis in “restored” tubules is relatively inefficient, and further refinement will be necessary to maximize production of viable spermatozoa. Nonetheless, the amounts produced might be sufficient for intracytoplasmic sperm injection, a technique that, according to Brinster, is “very effective for achieving fertilization of human eggs when few spermatozoa are available.”

Although the potential implications for infertility therapy are fairly obvious, Brinster sees greater possibilities in niche transplantation and its impact on the field of stem and germ cell research. He tells Lab Animal, “The ability to freeze stem cells allows long-term storage of any germline. In this context, transplantation and studies on the cells that support the process are enormously valuable.”

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Helping Stem Cells Find Their Niche. Lab Anim 32, 12 (2003).

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