Biomedical Engineering Reference
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in 10 or 1 in 15 (6.6-10%) germ cells in our mouse SSC culture are true SSCs
(Kubota et al.
2004b
). Others have reported that the true concentration of SSCs in
culture can be as low as 0.02% (Kanatsu-Shinohara et al.
2005b
). The remaining
cells within the culture are considered to be daughter cells that are committed to
differentiation.
5.3.2
Implications
The ability to culture the SSC has many important implications for human health,
animal management, and basic stem cell research. Culture of the human SSC would
allow for amplification of SSC numbers prior to transplantation into testes of indi-
viduals that underwent childhood chemotherapy or irradiation. Boys that would
need to undergo either of these procedures are often infertile as adults, but if SSCs
could be isolated from testis biopsies before cytotoxic treatment, they could be
amplified
in vitro
and stored until an appropriate time for SSC transplantation,
thereby restoring fertility. Similar procedures could be utilized for the amplification
of SSCs obtained from valuable livestock or endangered species. Culture of SSCs
from genetically valuable individuals, followed by transplantation or xenotrans-
plantation to inferior or less-endangered recipients could perpetuate genetic mate-
rial indefinitely; thereby conferring a biological immortality to the male. Cultured
SSCs have been demonstrated to be readily used to generate transgenic mice
(Nagano et al.
2000
), rats (Ryu et al.
2007
), and goats (Honaramooz et al.
2008
).
The ability to introduce foreign genes into the SSCs of livestock, followed by trans-
plantation and ultimately the production of transgenic offspring, would allow for
the production of economically valuable compounds that could be secreted in milk
or produced in meat. These techniques might also be utilized for gene therapy to
correct mutations present in an individual's germline. Because many stem cell sys-
tems in the body may share regulatory mechanisms, SSCs could serve as a model
to understand the fate decisions of self-renewal vs. differentiation in other tissues
dependent on stem cells for maintenance. Thus, culture of SSCs could serve as a
valuable tool to identify these mechanisms in other adult stem cell populations.
Finally, culture of SSCs will serve as a foundation for experiments to develop a
system for
in vitro
spermatogenesis. The production of spermatozoa
in vitro
would
revolutionize assisted reproductive techniques and allow for spermatozoa produc-
tion without SSC transplantation.
5.3.3
Short- Versus Long-Term Culture
SSCs can be cultured for various periods of time. The first report of a long-term
SSC culture system (Nagano et al.
1998
) demonstrated that SSCs could be maintained,
but did not actively proliferate, over a 4-month period on STO (SIM mouse embryo-
derived thioguanine and ouabain resistant) mouse embryonic fibroblast feeder layers.
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