Biomedical Engineering Reference
In-Depth Information
irrespective of its spermatogenic activity indicates that the mechanisms responsible
for survival of hamster testis grafts are primarily dependent on developmentally
controlled differentiation events and are not related to the spermatogenic activity of
the seminiferous epithelium. In contrast, suppression of spermatogenesis in adult
mouse testes by treatment with gonadotropin antagonists or experimentally induced
cryptorchidism prior to grafting resulted in improved graft survival and resurgence
of spermatogenesis compared to allografting of adult testis tissue with full
spermatogenesis, indicating that poor graft survival is largely due to the increased
metabolic activity and therefore heightened sensitivity to hypoxic damage in testis
tissue undergoing full spermatogenesis, and is not intrinsic to the adult testis
(Arregui et al. 2008b ). Therefore, species-specific differences as well as different
mechanisms of suppression of spermatogenesis prior to grafting may influence
graft survival and germ cell differentiation after grafting of adult testis tissue.
10.3
Testicular Xenografting Using Testicular
Cell Suspensions
Xenografting of testicular tissue fragments maintains the integrity of the seminifer-
ous epithelium but does not open routes for manipulation of selected cell types. The
strong morphogenetic ability of isolated testis cells to reconstitute cord-like struc-
tures after grafting creates new opportunities to target specific cell types and their
role during testis development and initiation of spermatogenesis. Grafting of isolated
testis cells has only been described recently. This approach has thus far been evalu-
ated using cells from newborn donors in pigs (Honaramooz et al. 2007 ), rodents
(Dufour et al. 2002 ; Gassei et al. 2006, 2008 ; Kita et al. 2007 ) and sheep (Arregui
et al. 2008a ). For this strategy, cells obtained after enzymatic digestion of testicular
tissue are injected subcutaneously in recipient mice as pellets or cultured for several
days embedded in extracellular matrix gel and then injected with the matrix.
Formation of seminiferous cords and tubules from transplanted testicular cell
suspensions was first reported in experiments testing immunoprotection of Sertoli
cells for co-transplanted pancreatic islets cells (Kin et al. 2002 ). Using this
approach, spermatogenesis up to and beyond the level of round spermatids was
obtained in testicular tissue that was reconstituted from crude cell suspensions of
immature pigs, sheep, and embryonic or neonatal rats and mice (Honaramooz et al.
2007 ; Kita et al. 2007 ; Arregui et al. 2008a ). The rodent studies revealed an oppor-
tunity to manipulate the system by adding mouse germ line stem cells carrying a
GFP marker to the cell suspension prior to grafting into mouse hosts. The GFP-
positive spermatids obtained in this system were successfully used for assisted
fertilization (Kita et al. 2007 ). Recently, the ability to form seminiferous tubules
from isolated Sertoli cells after grafting into mouse hosts has also been demonstrated
for bovine Sertoli cells (Zhang et al. 2008 ). A combination of in vitro culture of
Sertoli cells and grafting has demonstrated the importance of neurotrophic tyrosine
receptor kinases controlled aggregation of Sertoli cells for formation of cord-like
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