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Testicular germline stem cells

Nature Reviews Urology volume 7, pages 94–100 (2010)Cite this article

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Abstract

Stem cells have the ability to both differentiate into other mature cell types and maintain an undifferentiated state by self-renewal. These unique properties form the basis for stem cell use in organ replacement and tissue regeneration in clinical medicine. Currently, embryonic stem cells are the best-studied stem cell type. However alternative stem cells such as induced pluripotent stem cells and other adult stem cells are also being actively investigated for their potential for cell-based therapy. Among adult stem cells, emerging research has focused on evaluating the pluripotency potential of testis stem cells. To date, stem cells with embryonic-like potential have been created from adult testis germ cells. These cells could provide patient-specific, non-embryo-derived stem cells for men in the future.

Key Points

  • A need exists for pluripotent stem cells other than human embryonic cells for cell-based therapy owing to difficulties surrounding procurement, tissue rejection and tumorigenesis with these cells

  • Adult stem cells might provide an alternative source of multipotent stem cells with less rejection and decreased malignant potential than embryonic stem cells

  • Testicular stem cells with multipotent and even pluripotent potential have been isolated in mouse models and, more recently, in humans

  • To achieve the goal of cell-based therapy using any type of stem cell, issues of reliability and safety, in addition to efficiency and expandability, must be overcome

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Figure 1: Protocols for generating human pluripotent stem cells.
Figure 2: Germ cell types in human spermatogenesis.
Figure 3: Protocols for generating pluripotent stem cells from adult human testis.

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References

  1. Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676 (2006).

    Article  CAS  Google Scholar 

  2. Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 (2007).

    Article  CAS  Google Scholar 

  3. Yu, J. et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917–1920 (2007).

    Article  CAS  Google Scholar 

  4. Park, I. H. et al. Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451, 141–146 (2008).

    CAS  Google Scholar 

  5. Zhou, H. et al. Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4, 381–384 (2009).

    Article  CAS  Google Scholar 

  6. Kim, D. et al. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4, 472–476 (2009).

    Article  CAS  Google Scholar 

  7. Greely, H. T. Moving human embryonic stem cells from legislature to lab: remaining legal and ethical questions. PLoS Med. 3, e143 (2006).

    Article  Google Scholar 

  8. Scott, C. T. & Reijo Pera, R. A. The road to pluripotence: the research response to the embryonic stem cell debate. Hum. Mol. Genet. 17, R3–R9 (2008).

    Article  CAS  Google Scholar 

  9. Hyun, I., Hochedlinger, K., Jaenisch, R. & Yamanaka, S. New advances in iPS cell research do not obviate the need for human embryonic stem cells. Cell Stem Cell 1, 367–368 (2007).

    Article  CAS  Google Scholar 

  10. Amann, R. P. & Howards, S. S. Daily spermatozoal production and epididymal spermatozoal reserves of the human male. J. Urol. 124, 211–215 (1980).

    Article  CAS  Google Scholar 

  11. Clermont, Y. The cycle of the seminiferous epithelium in man. Am. J. Anat. 112, 35–51 (1963).

    Article  CAS  Google Scholar 

  12. Heller, C. H. & Clermont, Y. Kinetics of the germinal epithelium in man. Recent Prog. Horm. Res. 20, 545–575 (1964).

    CAS  PubMed  Google Scholar 

  13. Witschi, E. Migration of the germ cells of human embryos from the yolk sac to the primitive gonadal fold. Carnegie Institute Wash. Contrib. Embryol. 209, 67–80 (1948).

    Google Scholar 

  14. Gondos, B. & Hobel, C. J. Ultrastructure of germ cell development in the human fetal testis. Z. Zellforsch. Mikrosk. Anat. 119, 1–20 (1971).

    Article  CAS  Google Scholar 

  15. Ezeh, U. I., Turek, P. J., Reijo, R. A. & Clark, A. T. Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinoma. Cancer 104, 2255–2265 (2005).

    Article  CAS  Google Scholar 

  16. Andrews, P. W. Teratocarcinomas and human embryology: pluripotent human EC cell lines. Review article. APMIS 106, 158–168 (1998).

    Article  CAS  Google Scholar 

  17. Shamblott, M. J. et al. Derivation of pluirpotent stem cells from cultured human primordial germ cells. Proc. Natl Acad. Sci. USA 95, 13726–13731 (1998).

    Article  CAS  Google Scholar 

  18. Oatley, J. M. & Brinster, R. L. Regulation of spermatogonial stem cell self-renewal in mammals. Annu. Rev. Cell Dev. Biol. 24, 263–286 (2008).

    Article  CAS  Google Scholar 

  19. Dym, M. Spermatogonial stem cells of the testis. Proc. Natl Acad. Sci. USA 91, 11287–11289 (1994).

    Article  CAS  Google Scholar 

  20. Yoshinaga, K. et al. Role of c-kit in mouse spermatogenesis: identification of spermatogonia as a specific site of c-kit expression and function. Development 113, 689–699 (1991).

    CAS  PubMed  Google Scholar 

  21. He, Z., Kokkinaki, M., Jiang, J., Dobrinski, I. & Dym, M. Isolation, characterization, and culture of human spermatogonia. Biol. Reprod. doi:10.1095/biolreprod.109.078550

  22. Kristensen, D. M. et al. Presumed pluripotency markers UTF-1 and REX-1 are expressed in human adult testes and germ cell neoplasms. Hum. Reprod. 23, 775–782 (2008).

    Article  CAS  Google Scholar 

  23. Clermont, Y. Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiol. Rev. 52, 198–236 (1972).

    Article  CAS  Google Scholar 

  24. Ewing, L. L., Davis, J. C. & Zirkin, B. R. Regulation of testicular function: a spatial and temporal view. Int. Rev. Physiol. 22, 41–115 (1980).

    CAS  PubMed  Google Scholar 

  25. Kanatsu-Shinohara, M. et al. Generation of pluripotent stem cells from neonatal mouse testis. Cell 119, 1001–1012 (2004).

    Article  CAS  Google Scholar 

  26. Kanatsu-Shinohara, M. et al. Long-term proliferation in culture and germline transmission of mouse male germline stem cells. Biol. Reprod. 69, 612–616 (2003).

    Article  CAS  Google Scholar 

  27. Guan, K. et al. Pluripotency of spermatogonial stem cells from adult mouse testis. Nature 440, 1199–1203 (2006).

    Article  CAS  Google Scholar 

  28. Ko, K. et al. Induction of pluripotency in adult unipotent germline stem cells. Cell Stem Cell 5, 87–96 (2009).

    Article  CAS  Google Scholar 

  29. Conrad, S. et al. Generation of pluripotent stem cells from adult human testis. Nature 456, 344–349 (2008).

    Article  CAS  Google Scholar 

  30. Kossack, N. et al. Isolation and characterization of pluripotent human spermatogonial stem cell-derived cells. Stem Cells 27, 138–149 (2009).

    Article  CAS  Google Scholar 

  31. Golestaneh, N. et al. Pluripotent stem cells derived from adult human testes. Stem Cells Dev. 18, 1115–1126 (2009).

    Article  Google Scholar 

  32. Mizrak, S. C. et al. Embryonic stem cell-like cells derived from adult human testis. Hum. Reprod. doi: 10.1093/humrep/dep354

  33. Krizhanovsky, V. & Lowe, S. W. Stem cells: the promises and perils of p53. Nature 460, 1085–1086 (2009).

    Article  CAS  Google Scholar 

  34. Kee, K., Angeles, V. T., Flores, M., Nguyen, H. N. & Reijo Pera, R. A. Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation. Nature 462, 222–225 (2009).

    Article  CAS  Google Scholar 

  35. Johnson, J., Canning, J., Kaneko, T., Pru, J. K. & Tilly, J. L. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 428, 145–150 (2004).

    Article  CAS  Google Scholar 

  36. Johnson, J. et al. Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell 122, 303–315 (2005).

    Article  CAS  Google Scholar 

  37. Telfer, E. E. et al. On regenerating the ovary and generating controversy. Cell 122, 821–822 (2005).

    Article  CAS  Google Scholar 

  38. Eggan, K., Jurga, S., Gosden, R., Min, I. M. & Wagers, A. J. Ovulated oocytes in adult mice derive from non-circulating germ cells. Nature 441, 1109–1114 (2006).

    Article  CAS  Google Scholar 

  39. Thomson, J. et al. Embryonic stem cell lines derived from human blastocysts. Science 282, 1145–1147 (1998).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Center for Human Embryonic Stem Cell Research and Education, Institute for Stem Cell Biology & Regenerative Medicine, Stanford University School of Medicine, Stanford University, Palo Alto, 94305, CA, USA

    Kehkooi Kee & Renee A. Reijo Pera

  2. The Turek Clinic, 55 Francisco Street, Suite 300, San Francisco, 94133, CA, USA

    Paul J. Turek

Authors
  1. Kehkooi Kee
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  2. Renee A. Reijo Pera
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  3. Paul J. Turek
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Correspondence to Paul J. Turek.

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Competing interests

P. J. Turek and R. A. Reijo Pera declare that they hold, or have applied for, patents related to testicular germline stem cells, on behalf of The Turek Clinic, San Francisco and Stanford University, CA, USA. K. Kee declares no competing interests.

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Kee, K., Reijo Pera, R. & Turek, P. Testicular germline stem cells. Nat Rev Urol 7, 94–100 (2010). https://doi.org/10.1038/nrurol.2009.263

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