Biomedical Engineering Reference
In-Depth Information
using 1.4 M DMSO as cryoprotectant, a comparison of various strategies revealed
that juvenile testicular tissue can be maintained on ice for 24 h prior to xenografting
without diminishing the developmental potential of the tissue fragment. Simplifying
the preservation procedures and creating options for safe shipping of testicular tis-
sue provides clinically relevant strategies to centralize these procedures and to
generate testis tissue banks from patient tissue.
The use of testis tissue xenografting as an experimental strategy was illustrated
when the gonadotoxic effects of busulfan were demonstrated in subcutaneous mon-
key xenografts (Jahnukainen et al. 2006a ). Combining grafting for exploration of
long-term effects and organ culture to describe the immediate cellular injury, a dose-
dependent gonadotoxic effect incurred by radiation was shown (Jahnukainen et al.
2007b ). Stimulation of grafted infant primate testis tissue with exogenous gonado-
tropins supported Sertoli cell maturation, thereby terminating the unresponsive
phase of the germinal epithelium, and allowed complete spermatogenesis in testis
tissue from infant rhesus monkeys (Rathi et al. 2008 ). The use of testis tissue xeno-
grafting requires a smaller number of monkeys to perform valid comparative studies.
While differences in pharmacokinetics between primates and rodents have to be
considered, groups of mice carrying xenografts from few juvenile donors can be
exposed to different regimens rather than exposing large groups of monkey to differ-
ent gonadotoxic treatments. Analysis of the grafted tissue then reveals valid param-
eters to determine developmental failures of the testis and spermatogenic damage.
Further studies are needed to optimize the many variables that affect the success
of grafting in non-human primates and humans. Two reports in marmosets have
described the outcome of autologous grafting (Wistuba et al. 2006 ; Luetjens et al.
2008 ). While it appeared that ectopic placement of grafts was associated with a
developmental block at the meiotic stage of spermatogenesis (Wistuba et al. 2006 ),
a more promising development of grafts up to the level of spermatids was observed
when the scrotum was used as an orthotopic grafting site (Luetjens et al. 2008 ).
Other studies revealed that additional supplementation of human gonadotropins to
mouse recipients promoted graft development and function (Rathi et al. 2008 ).
Other studies have focused on xenografting of fetal and immature human testicular
tissue (Goossens et al. 2008 ; Wyns et al. 2007, 2008 ; Yu et al. 2006 ). These studies
showed good survival of testicular tissue and maintenance of integrity of the tubular
architecture. As yet only very limited initiation of spermatogenesis in human tissue
has been achieved but survival of human spermatogonia has been determined.
Grafting of adult human tissue, in contrast, revealed a very poor survival and develop-
ment of xenografts (see Table 10.2 ). So far the human xenografts have always been
placed ectopically, which may have a negative influence on grafting outcome.
Further improvement of xenografting strategies will prepare the ground for using
the amazing regenerative potential of immature primate testicular tissue. This will
create exciting clinically applicable strategies for fertility preservation. The future
development of xenografting as a clinical tool will focus on safety aspects associated
with any xenotransplantation approach and improving the efficiency to generate
sperm. The perspective of novel strategies to generate sperm from spermatogonial
stem cells or immature testicular tissue should stimulate more widely applied
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