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Technology Insight: in vitro culture of spermatogonial stem cells and their potential therapeutic uses

Nature Clinical Practice Endocrinology & Metabolism volume 2, pages 99–108 (2006)Cite this article

Abstract

Male germline stem cells—spermatogonial stem cells (SSCs)—self-renew and produce large numbers of differentiating germ cells that become spermatozoa throughout postnatal life and transmit genetic information to the next generation. SSCs are the only germline stem cells in adults, because all female germline stem cells cease proliferation before birth. In this article, we first summarize development of SSCs, and then the relation of SSCs to somatic stem cells in tissues and pluripotent stem cells in vitro, such as embryonic stem cells. Next, we describe a transplantation technique in which donor testis cells from a fertile male can be transplanted to the testes of an infertile male where they re-establish spermatogenesis and restore fertility. The transplantation technique has been used to study the biology of SSCs, which made possible the identification of external factors that support in vitro self-renewal and proliferation of mouse and rat SSCs. Since SSCs of all mammalian species examined, including human, can replicate in mouse seminiferous tubules following transplantation, the growth factors required for SSC self-renewal are probably conserved among mammalian species. Culture techniques should therefore soon be available for human SSCs. In the final section, we discuss current and potential approaches for using the transplantation technique and in vitro culture of SSCs in human medicine. Because assisted reproductive techniques to fertilize oocytes with round or elongated spermatids are available, clinical use of cultured human SSCs will be greatly facilitated by development of techniques for in vitro differentiation of SSCs to mature germ cells.

Key Points

  • Spermatogonial stem cells are the only cells in postnatal mammals that undergo self-renewal and transmit genes to subsequent generations

  • In vitro growth-factor requirements for mouse spermatogonial stem cells have been identified using defined culture conditions

  • Because extrinsic factors for self-renewal of spermatogonial stem cells appear to be conserved among many mammalian species, including humans, in vitro culture techniques for human spermatogonial stem cell will probably be developed in the near future

  • Spermatogonial stem-cell transplantation could be used to restore fertility in men following chemotherapy or radiation treatment

  • Development of techniques for the in vitro differentiation of spermatogonial stem cells to functional spermatozoa is a crucial step for the treatment of infertility or germline gene therapy

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Figure 1: Lineage development of somatic and germline stem cells in vivo and pluripotent stem cells in vitro
Figure 2: Procedure for testis-cell transplantation as developed in the mouse
Figure 3: In vitro proliferation of mouse spermatogonial stem cells
Figure 4: Germline stem-cell therapy

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Acknowledgements

We thank Jon Oatley for helpful comments on the manuscript and James Hayden for assistance in developing the figures. Financial support for the research was from the National Institute of Child Health and Human Development Grant 044445; and the Robert J Kleberg Jr, and Helen C Kleberg Foundation.

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  1. H Kubota is a Research Assistant Professor of Cell Biology, and RL Brinster is the Richard King Mellon Professor of Reproductive Physiology

Authors and Affiliations

  1. the Department of Animal Biology at the School of Veterinary Medicine, University of Pennsylvania, Philadelphia, USA

    Hiroshi Kubota & Ralph L Brinster

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Correspondence to Ralph L Brinster.

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Kubota, H., Brinster, R. Technology Insight: in vitro culture of spermatogonial stem cells and their potential therapeutic uses. Nat Rev Endocrinol 2, 99–108 (2006). https://doi.org/10.1038/ncpendmet0098

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