Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 May 21;12(6):1139.
doi: 10.3390/biomedicines12061139.

Ovarian Stem Cells for Women's Infertility: State of the Art

Krzysztof Grettka  1   2 , Katarzyna Idzik  1   2 , Katarzyna Lewandowska  1   2 , Ksena Świętek  1   2 , Simone Palini  1   2   3 , Franco Silvestris  1   2   4
Affiliations
Review

Ovarian Stem Cells for Women's Infertility: State of the Art

Krzysztof Grettka et al. Biomedicines. .

Abstract

Today, women's infertility is considered a social disease in females, occurring not only as an effect of POF (premature ovarian failure) but also as CTRI (cancer treatment-related infertility) in oncologic patients. Several procedures for FP (fertility preservation) are currently adopted to prevent this condition, mostly based on utilization of retrieved eggs from the patients with subsequent IVF (in vitro fertilization) or cryopreservation. However, great interest has recently been devoted to OSCs (ovarian stem cells), whose isolation from female ovaries, followed by their in vitro culture, led to their maturation to OLCs (oocyte-like cells), namely, neo-oocytes comparable to viable eggs suitable for IVF. Translation of these data to FP clinical application creates new hope in the treatment of infertility. Thus, in line with the significant progress in using stem cells in the regenerative medicine field, neo-oogenesis via OSCs, which is currently unapplicable in fertility preservation procedures, will provide novel possibilities for young and adult females in motherhood programs in the future.

Keywords: cancer treatment-related infertility (CTRI); infertility; oocyte-like cells (OLCs); ovarian stem cells (OSCs); premature ovarian failure (POF); stem cells.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest. Authors Krzysztof Grettka, Katarzyna Idzik, Katarzyna Lewandowska, Ksena Świętek, Simone Palini, Franco Silvestris were employed by the company Fertilita sp. z o.o., Ruda Śląska, Poland; Globiana sp. z o.o., Katowice, Poland. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The Fertilita sp. z o.o. and Globiana sp. z o.o. had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Structural anatomy of a woman’s ovary with emphasis on the location of ovarian stem cells which are normally residents within the cortex, as depicted in the schematic drawing (left) and detected in the histologic specimen (right).
Figure 2
Figure 2
After immunoadsorption of OSC populations, their purity is evaluated with flow cytometry analysis measuring their enrichment in both Ddx4+ and Fragile+ subsets as specific OSC markers. Representative analyses from two patients are shown. Both cases depict the major content of isolated OSC fractions as the number of recruited cells and fluorescence intensity, with Ddx4+cells included at a higher magnitude with respect to the Fragile+ ones, thus suggesting that immunoselection was highly efficient in isolating the full OSC population.
Figure 3
Figure 3
Sequential steps for isolation and culture of ovarian stem cells (OSCs) expressing the Ddx4 molecule. The ovarian cortex fragment is primarily lysed to obtain a cell suspension, which is then incubated with anti-Ddx4 antibodies conjugated to magnetic beads and further immunoadsorbed to discharge other cells. Thus, isolated OSCs are cultivated on a feeder layer including mesenchymal cells from the patient. After three weeks of culture with specific growth factors, they differentiate to large oocyte-like cells, namely, mature oocytes suitable for ICSI (intracytoplasmic sperm injection).
Figure 4
Figure 4
Representative microscope images of morphologic changes of OSCs in cultures, leading to generation of oocyte-like cells (OLCs) with extrusion of polar bodies after three weeks, thus entering the MII phase with the final shape of the mature oocyte.
See this image and copyright information in PMC

References

    1. Hanson B., Johnstone E., Dorais J., Silver B., Peterson C.M., Hotaling J. Female infertility, infertility-associated diagnoses, and comorbidities: A review. J. Assist. Reprod. Genet. 2017;34:167. doi: 10.1007/s10815-016-0836-8. - DOI - PMC - PubMed
    1. Dolmans M.M., Luyckx V., Donnez J., Andersen C.Y., Greve T. Risk of transferring malignant cells with transplanted frozen-thawed ovarian tissue. Fertil. Steril. 2013;99:1514. doi: 10.1016/j.fertnstert.2013.03.027. - DOI - PubMed
    1. Martin J.J., Woods D.C., Tilly J.L. Implications and Current Limitations of Oogenesis from Female Germline or Oogonial Stem Cells in Adult Mammalian Ovaries. Cells. 2019;8:93. doi: 10.3390/cells8020093. - DOI - PMC - PubMed
    1. White Y.A., Woods D.C., Takai Y., Ishihara O., Seki H., Tilly J.L. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat. Med. 2012;18:413–421. doi: 10.1038/nm.2669. - DOI - PMC - PubMed
    1. Johnson J., Canning J., Kaneko T., Pru J.K., Tilly J.L. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature. 2004;428:145. doi: 10.1038/nature02316. - DOI - PubMed

LinkOut - more resources