A detour in the quest for oogonial stem cells: methods matter (Oct 2015)

A detour in the quest for oogonial stem cells: methods matter
Nature Medicine 21, 1126–1127 (2015) doi:10.1038/nm.3969, Published online 07 October 2015
David F Albertini1, Norbert Gleicher2
Author(s) affiliation:
1University of Kansas Medical Center, Kansas City, Kansas, USA, and the Center for Human Reproduction, New York, New York, USA.
2Center for Human Reproduction, New York, New York, USA, and the Rockefeller University, New York, New York, USA.


Short description:
In a recent issue of Nature Medicine, Albertini and Gleicher in the News and Views section commented on two reported studies from independent laboratories in the same issue of the journal which both were unable to replicate a previously published antibody-based method to isolate oogonial stem cells from ovaries of adult humans, nonhuman primates and mice.
The original manuscript, published in Nature Medicine in 2012 (White et al;18:413-21) reported the successful isolation of putative germline or oogonial stem cells (OSCs) from dissociated mouse ovarian tissue by immunoselection with an antibody specific to the germline transcription factor DEAD-box polypetide 4 (DDX4). That study and a follow up study from the same laboratory (Woods and Tilly, 2013;8:966-88) also reported identification and characterization of these cells in mouse as well as human ovaries, and sorting of OSCs using a polyclonal antibody specific for DD4. These findings, of course, boosted support for existence of OSCs.
Two publications in the same issue of Nature Medicine now questioned the reproducibility of this anti-DDX4-based OSC isolation process (Hernandez et al., 201:1114-6 and Zhang et al., 21:1116-8) and, with it, the existence of and/or ability to isolate OSCs, with potential to regenerate oocytes. Both of these laboratories were unable to duplicate isolation of OSCs, using antibodies to DDX4. Doubts existed even before publication of these two papers because DDX4 is known to be located intracellularly (I.e. cytoplasmic) in germ cells. Surface-bound antibodies should, therefore, not be able to react with it. The studies, however, also called into question the specificity of the antibody since markers for ovarian somatic cells were detected in DDX4-positive cells isolated with this technique from mice and humans.
In yet a third contribution to the same issue of Nature Medicine, White and Tilly were given the opportunity to respond to the criticism (2015;21:1118-21) but were unable to dispel these major concerns. Albertini and Gleicher, in summarizing all three publications, pointed out that “much caution should be exercised (as of this moment) before adopting any OSC technology for the treatment of human infertility,” and stressed “the futility of using what, at best, can be defined as seriously limited approaches."
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Abstract taken from PubMed

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