Translating Spermatogonial Stem Cell Transplantation to the Clinic - Male Germline Stem Cells Developmental and Regenerative Potential - page 243

to detect different alleles of the MHC Class I antigens that vary between unrelated
individuals, a strategy developed to identify peripheral blood chimerism (³1%) fol-
lowing hematopoietic stem cell transplantation (Kean et al. 2007 ). To date there have
been no reports of primate-to-primate SSC transplantation that provided definitive
identification of donor-derived spermatogenesis.

11.4 Clinical Implications and Considerations

for SSC Transplantation

As discussed at the beginning of this chapter, there is potential for utilizing SSCs
to preserve the fertility of patients who will undergo sterilizing therapies for the
treatment of a disease or condition. For this purpose, patient testicular tissue
containing SSCs would need to be obtained prior to therapy, processed appropri-
ately, and cryopreserved for future use. Considerations for clinical application of
SSC transplant technologies include: (1) when and how to obtain patient testicular
tissue, (2) how much tissue is required for future use, (3) appropriate techniques for
tissue processing and cryopreservation, and (4) risks of malignant cell contamina-
tion in cancer patient testicular tissue.

11.4.1 Patient Testis Accrual

Obtaining testicular tissue from patients for preserving testicular cells must occur
prior to potentially gonadotoxic therapies. In most cases, testicular tissue would
be recovered from patients using a subcapsular, “open” biopsy approach with
care taken to access the parenchyma through an avascular region of the tunica
albuginea (e.g., towards the middle of the medial, lateral, or anterior surface of
the testis) to minimize bleeding and potential scarring/fibrosis to the remaining
tissue. The amount of testicular tissue recovered by biopsy should meet the
expected need for producing a cell suspension useful for eventual SSC transplan-
tation without any additional manipulations. The biopsy surgery, though, should
balance the amount of tissue removed with the goal of leaving the remaining tis-
sue potentially functional.
For patients who will receive chemotherapy or radiation for treatment of their
primary disease, the patients' surgeon(s) would need to determine hemostasis after
surgery and provide clearance for initiation of therapy, thus introducing the possibility
of delaying their primary therapy. In most cases, treatments would begin in a time-
frame dictated by clinical management of their primary disease or condition, typically
within one week. In some cases, chemotherapy or radiation treatments have been
initiated as soon as one day following testicular biopsy surgery (Bahadur et al. 2000 ).
Besides the inherent risks of surgery, the potential costs to patients is another concern