Clinical applications and limitations of current ovarian stem cell research: a review

  • Karla J Hutt
  • David F Albertini
Open Access


The publication of a report in Nature in 2004 by the Tilly group suggesting that mouse ovaries are capable of generating oocytes de novo post-natally, has sparked interest in a problem long thought to have been resolved from classical studies in a variety of mammalian species. Within a nearly two year time period, laboratories around the world have taken up the challenge to dogma raised by this initial report, either to test this concept in an experimental basic science setting or give direction to clinical applications that could result, were the original premises of this work in the mouse valid for extrapolation to humans. This review provides a status report for this promising area of research, (1) to summarize recent findings in the literature with respect to the validity of the original hypothesis proffered by the Tilly group, and, (2) to gauge the potential utility of ovarian stem cells as a treatment for certain forms of human infertility.



We thank members of the Albertini lab for their encouragement and support and the funding provided from the Hall Family Foundation.


  1. 1.
    Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL: Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature. 2004, 428: 145-150. 10.1038/nature02316.CrossRefPubMedGoogle Scholar
  2. 2.
    Johnson J, Bagley J, Skaznik-Wikiel M, Lee HJ, Adams GB, Niikura Y, Tschudy KS, Tilly JC, Cortes ML, Forkert R, Spitzer T, Iacomini J, Scadden DT, Tilly JL: Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell. 2005, 122: 303-315. 10.1016/j.cell.2005.06.031.CrossRefPubMedGoogle Scholar
  3. 3.
    Kerr JB, Duckett R, Myers M, Britt KL, Mladenovska T, Findlay JK: Quantification of healthy follicles in the neonatal and adult mouse ovary: evidence for maintenance of primordial follicle supply. Reproduction. 2006, 132: 97-111. 10.1530/rep.1.01128.CrossRefGoogle Scholar
  4. 4.
    Byskov AG, Faddy MJ, Lemmen JG, Andersen CY: Eggs forever?. Differentiation. 2005, 73: 438-446. 10.1111/j.1432-0436.2005.00045.x.CrossRefPubMedGoogle Scholar
  5. 5.
    Bristol-Gould SK, Kreeger PK, Selkirk CG, Kilen SM, Mayo KE, Shea LD, Woodruff TK: Fate of the initial follicle pool: Empirical and mathematical evidence supporting its sufficiency for adult fertility. Developmental Biology. 2006, doi: 10.1016/j.ydbio.2006.06.023Google Scholar
  6. 6.
    Peters H: The development of the mouse ovary from birth to maturity. Acta Endocrinol (Copenh). 1969, 62: 98-116.Google Scholar
  7. 7.
    Eggan K, Jurga S, Gosden R, Min IM, Wagers AJ: Ovulated oocytes in adult mice derive from non-circulating germ cells. Nature. 2006, 441: 1109-1114. 10.1038/nature04929.CrossRefPubMedGoogle Scholar
  8. 8.
    Telfer EE: Germline stem cells in the postnatal mammalian ovary: a phenomenon of prosimian primates and mice?. Reprod Biol Endocrinol. 2004, 2: 24-10.1186/1477-7827-2-24.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Telfer EE, Gosden RG, Byskov AG, Spears N, Albertini D, Andersen CY, Anderson R, Braw-Tal R, Clarke H, Gougeon A, McLaughlin E, McLaren A, McNatty K, Schatten G, Silber S, Tsafriri A: On regenerating the ovary and generating controversy. Cell. 2005, 122: 821-822. 10.1016/j.cell.2005.09.004.CrossRefPubMedGoogle Scholar
  10. 10.
    Sanders JE, Buckner CD, Amos D, Levy W, Appelbaum FR, Doney K, Storb R, Sullivan KM, Witherspoon RP, Thomas ED: Ovarian function following marrow transplantation for aplastic anemia or leukemia. J Clin Oncol. 1988, 6: 813-818.CrossRefGoogle Scholar
  11. 11.
    Sanders JE, Hawley J, Levy W, Gooley T, Buckner CD, Deeg HJ, Doney K, Storb R, Sullivan K, Witherspoon R, Appelbaum FR: Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation. Blood. 1996, 87: 3045-3052.PubMedGoogle Scholar
  12. 12.
    Hershlag A, Schuster MW: Return of fertility after autologous stem cell transplantation. Fertil Steril. 2002, 77: 419-421. 10.1016/S0015-0282(01)02987-9.CrossRefPubMedGoogle Scholar
  13. 13.
    Oktay K: Spontaneous conceptions and live birth after heterotopic ovarian transplantation: is there a germline stem cell connection?. Hum Reprod. 2006, 21: 1345-1348. 10.1093/humrep/del007.CrossRefPubMedGoogle Scholar
  14. 14.
    Oktay K, Oktem O: Sustained endocrine function and spontaneous pregancies after subcutaneous transplantation of cryopreserved ovarian tissue in stem cell transplant recipients. Fertil Steril. 2005, 84 (Supl 1): S68-10.1016/j.fertnstert.2005.07.162.CrossRefGoogle Scholar

Copyright information

© Hutt and Albertini; licensee BioMed Central Ltd. 2006

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Authors and Affiliations

  1. 1.Center for Reproductive Sciences, Department of Molecular and Integrative SciencesUniversity of Kansas Medical CenterKansas CityUSA
  2. 2.Marine Biological LaboratoryWoods HoleUSA

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