Biomedical Engineering Reference
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the niche is a remarkable phenomenon. The mechanisms involved presumably are
mediated by the expression of specific molecules on the surface of the SSC and the
interaction of these molecules with Sertoli cells within the seminiferous epithelium.
The efficiency of SSC homing to the niche has been estimated to be approximately
5-10% in adult mice (Shinohara et al.
2001
; Ogawa et al.
2003
). Past experiments
have suggested several possible modifiers of SSC homing. For example, coloniza-
tion of donor cells in pup compared to adult testes is 9- to 10-fold greater, and each
colony in the pup testis is approximately four times longer (Shinohara et al.
2001
).
Also, rat donor SSCs form two to three times longer colonies than mouse SSCs in
nude mouse recipients (Orwig et al.
2002
). Thus, both the microenvironment
(niche) as well as the donor cells are likely to influence homing. It is possible that
the presence of endogenous SSCs and the treatments used to remove these cells for
successful donor SSC colonization could influence donor SSC homing. It is very
difficult to study these effects; however, some experiments do give indirect insight
into the effects of these treatments on SSC homing. The presence of endogenous
SSCs and spermatogenesis in the seminiferous tubules decreases the colonization
ability of donor SSCs, and the W mouse pup, which is devoid of endogenous sper-
matogenesis, has been regarded as the best recipient for mouse SSC transplantation
(Brinster et al.
2003
). Lack of colonization in testes with endogenous SSCs is pos-
sibly due to occupation of available niches by the endogenous SSCs and the pres-
ence of differentiating germ cells in the seminiferous epithelium, however, an effect
of the resident SSC on the ability of a donor SSC to home to the niche cannot be
ruled out. Studying the effects of SSC ablation techniques on homing and coloniza-
tion would be very difficult due to the necessity to remove endogenous spermato-
genesis for efficient colonization and quantification. However, examination of these
techniques (chemotoxic drugs and irradiation) using naturally sterile recipients
would allow for the evaluation of any direct effects of SSC ablation treatment on
homing.
A recent publication describes experiments designed to identify molecules that
may be important for homing of the SSC to the niche (Kanatsu-Shinohara et al.
2008b
). The role of the b1-integrin surface antigen was examined, probably
because it has been shown to be present on SSCs and is known to bind to laminin,
a common cell matrix/basement membrane molecule found in the seminiferous
epithelium (Shinohara et al.
1999
). In this work b1-integrin was experimentally
knocked-out of a cultured SSC population using a cre-lox system. The removal of
the gene from SSCs also resulted in the expression of the lacZ gene, thereby providing
a colorimetric marker for donor SSCs. Following transplantation, the authors
demonstrated that at 3 months, there were fewer colonies in the animals trans-
planted with b1-integrin knockout cells than in control cells, and indicated that
b1-integrin was important for binding of the SSC in the niche. In addition, defects
in spermatogenesis within the knockout colonies were found. Therefore, b1-integrin
appears to be important for both maintenance of the SSC within the niche and germ
cell differentiation. As previously suggested, b1-integrin, in conjunction with
a6-integrin, is a likely essential binding molecule for SSCs, and this binding is
important in maintaining the SSC within the niche as well as for maintenance of
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