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Generation of pluripotent stem cells from adult human testis

Nature volume 456, pages 344–349 (2008)Cite this article

A Retraction to this article was published on 30 July 2014

A Corrigendum to this article was published on 20 August 2009

This article has been updated

Abstract

Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of these cells revealed many similarities to human embryonic stem cells, and the germline stem cells produced teratomas after transplantation into immunodeficient mice. The human adult germline stem cells differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of human embryonic stem cells. We conclude that the generation of human adult germline stem cells from testicular biopsies may provide simple and non-controversial access to individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells.

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Figure 1: Selection of spermatogonial cells from adult human testis.
Figure 2: Generation of human adult GSCs from spermatogonial cells.
Figure 3: Characterization of the human adult GSCs in comparison to normal testis tissue.
Figure 4: Molecular profiling and epigenetics of human adult GSCs.
Figure 5: Human adult GSC-derived human teratoma formation after injection into an immunodeficient mouse.

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Acknowledgements

We thank S. Singer, U. Mau-Holzmann and O. Rieß for karyotyping the human adult GSCs obtained from the patients’ biopsies; M. Schenk for providing support with ELISA; D. Blaurock for proofreading the manuscript; K. Kohler for discussion and encouragement; and P. Bauer for conducting the microsatellite analysis. Financial support for this research was provided by the Department of Urology, Institute of Anatomy and ZRM (University Clinic Tübingen).

Author Contributions S.C. conducted all the major experiments and wrote the manuscript; M.R. and Jö.H. were responsible for the clinical logistics, organization of the human testis biopsies and writing the ethical proposal; L.J. supervised the experimental procedures conducted in Tübingen; M.R., M.M. and Jü.H. provided mRNA and cDNA from human ES cells (H1), determined the doubling time of H1 cells and were involved in the differentiation experiments for comparing H1 with human adult GSCs; T.W. conducted part of the PCR experiments; W.A. was responsible for the real-time PCR experiments, M.B. was responsible for microarray profiling, H.-J.B. was co-responsible for FACS analysis; U.M. and H.-J.W. conducted the electron microscopy study; A.M. performed confocal microscopy; S.M. provided human ES cells; K.-D.S. and A.S. supported and advised the clinical cooperation; and T.S. initiated and supervised the entire project, conducted parts of the experiments and wrote the manuscript. A.S. and T.S. are co-senior authors.

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Authors and Affiliations

  1. Department of Experimental Embryology,, Institute of Anatomy,

    Sabine Conrad, Tina Wiesner, Lothar Just & Thomas Skutella

  2. Department of Cellular Neurobiology, Institute of Anatomy, Österbergstraße 3, 72074 Tübingen, Germany,

    Ulrich Mattheus, Andreas Mack & Hans-Joachim Wagner

  3. Department of Urology, University Clinic Tübingen, Hoppe-Seyler-Straße 3, Tübingen 72076, Germany,

    Markus Renninger, Jörg Hennenlotter, Karl-Dietrich Sievert & Arnulf Stenzl

  4. Institute of Anthropology and Human Genetics, Microarray Facility, University Clinic, Calwerstraße 7, 72076 Tübingen, Germany ,

    Michael Bonin

  5. ZMF Research Laboratories, University Clinic Tübingen, Waldhörnlestraße 22, 72072 Tübingen, Germany ,

    Wilhelm Aicher

  6. Center for Regenerative Biology and Medicine (ZRM), Paul-Ehrlich-Straße 15, 72076 Tübingen, Germany ,

    Wilhelm Aicher & Thomas Skutella

  7. Department of Internal Medicine II, University Clinic Tübingen, Otfried-Müller-Straße 10, 72076 Tübingen, Germany,

    Hans-Jörg Bühring

  8. Stem Cell Biology Laboratory, Wolfson Centre for Age-Related Diseases, King's College London, King's College, London SE1 1UL, UK

    Stephen Minger

  9. Institute of Neurophysiology, University of Cologne, Robert-Koch-Straße 39, 50931 Cologne, Germany ,

    Matthias Matzkies, Michael Reppel & Jürgen Hescheler

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  1. Sabine Conrad
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Corresponding author

Correspondence to Thomas Skutella.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-9 with Legends and Supplementary Tables 1-5. This file was revised on 23 October 2008 to incorporate a correction to Supplementary Figure 1 (the diagram next to the right mouse icon should read ‘teratoma fomation’ and not ‘no teratoma fomation’ as previously shown). (PDF 9498 kb)

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Conrad, S., Renninger, M., Hennenlotter, J. et al. Generation of pluripotent stem cells from adult human testis. Nature 456, 344–349 (2008). https://doi.org/10.1038/nature07404

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