Testicular Xenografting - Male Germline Stem Cells Developmental and Regenerative Potential - page 219

structures (Gassei et al. 2008 ). Isolated testis cells from neonatal males transplanted
under the dorsal skin of mice rearrange to generate testis-like structures that exhibit
not only spermatogenic but also endocrine function (Gassei et al. 2006 ; Honaramooz
et al. 2007 ; Kita et al. 2007 ). These studies demonstrate an amazing capability of
isolated postnatal testis cells to recapitulate testis development, rearrange into semi-
niferous cords, and initiate steroidogenesis and spermatogenesis. These approaches
offer fascinating novel scenarios to explore morphogenetic events during testicular
development (Dobrinski 2005 ). Furthermore, since it has been shown that sperm
obtained from testis tissue xenografts could be used for intracytoplasmic sperm
injection to produce embryos and offspring (Honaramooz et al. 2002, 2004, 2007 ;
Schlatt et al. 2003 ) these in vivo strategies represent new approaches for preserving
the germline of valuable males or endangered species (Dobrinski 2005 ).

10.4 Xenografting of Primate Testicular Tissue: Clinical

and Experimental Perspectives

Survival of fetal human testicular tissue as xenograft was described shortly after
nude mice became available as immunodeficient recipients of tissue grafts
(Skakkebaek et al. 1974 ). The grafts survived but no developmental progression of
spermatogenesis was observed in the grafted tissue. Improved grafting methods and
a better understanding of the critical steps came from studies using immature testis
tissue from domestic animals and rodents. These studies revealed a promising
developmental capacity of the grafted tissue. Therefore, xenografting of non-human
primate and human tissue was revisited. A schematic representation of primate
testis grafting with recovery of functional spermatozoa from primate testis grafts is
presented in Fig. 10.1 . The potential to generate sperm from prepubertal testes
(Honaramooz et al. 2004 ) created novel opportunities to explore primate testis
development and offered a clinically relevant strategy for fertility preservation in
boys undergoing oncological therapies. Table 10.2 summarizes the strategies and
outcome of studies that were performed using testicular xenografting with postnatal
monkey or human as tissue donors. From 2002 to 2005 the studies revealed that
xenografted monkey tissue survives as xenografts and has a promising ability to
differentiate in the mouse recipient (Schlatt et al. 2002 ; Honaramooz et al. 2004 ;
Orwig and Schlatt 2005 ). As discussed above, a prominent exception was the mar-
moset (Wistuba et al. 2004 ). Xenografts of immature marmosets show limited
capacity to differentiate. As for other species it was shown that xenografting of
immature testes from monkeys and humans is much superior compared to adult
tissue that undergoes almost complete degeneration after grafting (Arregui et al.
2008b ; Schlatt et al. 2006 ; Geens et al. 2006 ). Xenografting of monkey tissue then
became a strategy for preservation of fertility and to study the effects of hormonal
manipulation or exposure to radiation or gonadotoxins on testicular development.