Promise and limitations of germ cell transplantation in the testis.

In 1994, the first successful stem cell transplantation in the mammalian testis was reported (Brinster and Zimmermann, 1994). In the early studies, a mixture of germ cells from either mouse or rat testes was successfully transplanted by microinjection into a germ cell-depleted recipient mouse testis (Clouthier et al, 1996). Stem cells in this mixture colonized the repopulation of all of the germ cells in the seminiferous epithelium and, ultimately, initiated the process of spermatogenesis. After these initial studies, the Brinster laboratory showed that the mixtures of germ cells could be frozen and successfully transplanted at a later time (Avarbock et al, 1996). After these initial papers were published there was hope that this technology could be applied in a number of areas. One goal advanced in the early publications was to culture germ cells, transfect or genetically manipulate them in some manner, and then transplant to recipient testes. This would be a way to create transgenic sperm that would provide a continuous source of transgenic animals. This technology would also provide for the removal, genetic engineering, and replacement of germ cells in the case of genetic disease. Some envisioned this technology as a way to maintain viable spermatogenesis from an endangered species in a recipient laboratory rodent. Perhaps a rodent could even serve as a temporary receptacle for human spermatogenesis when an individual was required to undergo a treatment or a procedure that normally killed the testicular stem cells. The early studies by the Brinster laboratory were exciting and provocative. However, further progress toward