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. Author manuscript; available in PMC: 2017 Jan 13.
Published in final edited form as: Nat Clin Pract Endocrinol Metab. 2006 Feb;2(2):99–108. doi: 10.1038/ncpendmet0098

Figure 4.

Figure 4

Germline stem-cell therapy. Proposed outline for isolation of human spermatogonial stem cells, expansion by proliferation in culture, with possible genetic modification, and transplantation into recipient testes. Spermatogonial stem cells may be cryopreserved at any point between isolation and transplantation. In cancer patients, spermatogonial stem cells could be isolated by testis biopsy before treatment with chemotherapy or radiation, and the stem-cell number increased in culture. After successful treatment, the spermatogonial stem cells would be transplanted to the patient’s testes to restore fertility. This approach is particularly valuable for prepubertal patients because they do not have mature spermatozoa that can be cryopreserved for future use. Before transplantation of spermatogonial stem cells into a recovered patient, contamination by cancer cells must be ruled out. This could be accomplished by a combination of several techniques: first, by enrichment of testis cells and/or cultured cells using antibodies to specific surface antigens for spermatogonial stem cells; second, by culturing spermatogonial stem cells under conditions that will not support cancer cells; and third, by testing an aliquot of the cells in immunodeficient mice to determine if cancer cells are present. Development of an in vitro differentiation system to allow intracytoplasmic spermatid injection to fertilize oocytes would eliminate any problem with contaminating cancer cells. For patients carrying a genetic defect, spermatogonial stem cells could be isolated and cultured in vitro, the defective gene corrected, and the spermatogonial stem cells with the corrected gene transplanted into the testes of the patient. To enhance colonization of corrected spermatogonial stem cells, local irradiation could be used to destroy endogenous spermatogenesis. Although the transplantation of gene-corrected spermatogonial stem cells back to the patient is feasible, the approach is more likely to find use when in vitro differentiation of spermatogonial stem cells to spermatids or spermatozoa can be achieved. SSC, spermatogonial stem cell.