Biomedical Engineering Reference
In-Depth Information
an avenue to future fertility for young cancer survivors. Additional studies are
needed to determine the optimal conditions to achieve complete spermatogenesis
in xenografts of immature human testicular tissue (see Chap. 10).
In order to solidify the foundation for clinical translation of fertility-preserving
therapies such as SSC transplantation and xenografting, we must gain additional
fundamental insights into the biology of SSCs in the primate testis, including
human. Thus, this chapter begins with an introduction of the current understanding
of primate SSC biology. The majority of this chapter is devoted to describing
approaches for isolating primate SSCs, nonhuman primate models for SSC
transplantation, methods for introducing donor SSCs into primate testes, and evalu-
ation of transplant outcomes. We will also discuss some of the clinical implications
and considerations for responsible translation of SSC transplantation to the fertility
clinic, including safety, efficacy, and ethics.
11.2
Primate Spermatogonial Stem Cells
SSCs are undifferentiated germ cells that occupy a niche in testicular seminiferous
tubules (see Chap. 8) and balance self-renewing and differentiating divisions to
maintain spermatogenesis throughout adult life. Several experimental approaches
are used to distinguish rodent SSCs from other germ cells and testicular somatic
cells, including their functional capacity to establish and maintain spermatogenesis
in a transplantation assay (see Chap. 5), expression of a variety of specific molecular
markers (see Chap. 7), and their clonal arrangement on the basement membrane of
seminiferous tubules (A
single
and some A
paired
; see Chap. 4).
In contrast, relatively little is known about primate SSCs, including humans, but
recent advances are expanding our understanding of the primate germline stem cell
system [reviewed by (Hermann et al.
2010
)]. Primate testes contain two distinct
types of undifferentiated (Type-A) spermatogonia classified morphologically as
A
dark
and A
pale
, based on differences in nuclear architecture and staining intensity
with hematoxylin (Clermont and Leblond
1959
; Clermont
1972
; Clermont and
Antar
1973
; Cavicchia and Dym
1978
). A
dark
and A
pale
are both found on the base-
ment membrane of primate seminiferous tubules, but there is limited data describing
their molecular characteristics or clonal arrangement (Clermont and Leblond
1959
;
Fig. 11.1 (
continued
)
patients, a SSC transplant could potentially restore fertility. For this purpose,
vials of cryopreserved testis cell suspension would be thawed and introduced into the seminiferous
tubules of the patient's testis by ultrasound-guided rete testis injection. (
g
) Any transplanted SSCs
that find a niche in the patient's seminiferous tubules could engraft and regenerate spermatogenesis.
In the ideal scenario, this could lead to the production of sperm from the transplanted testis, allowing
the patient to father his own genetic children, possibly through normal coitus. Alternatively, trans-
planted SSCs could produce small foci of donor spermatogenesis from which functional sperm could
be retrieved by TESE for use in assisted reproduction by ICSI. Artwork produced by Molly Feuer
Search WWH ::
Custom Search