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A new technology for the treatment of premature ovarian insufficiency: Cell sheet

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Abstract

Premature ovarian insufficiency (POI) is defined as the development of hypergonadotropic hypogonadism before the age of 40 with definitive treatment being absent. In the current study, we aim to compare the efficacy of the cell sheet method with an intravenous (IV) application of adipose-derived mesenchymal stem cells (AdMSCs) to the POI with an animal model. In the current prospective study, 6-to-8-week-old Sprague Dawley rats were generated four groups: (i) a control group in which only PBS was administered; (ii) an only-POI group generated by cyclophosphamide; (iii) a POI group treated by way of IV AdMSCs; and (iv) a POI group treated by way of the cell sheet method. Twenty-eight days after an oophorectomy was performed, intracardiac blood was taken. Follicle count, immunohistochemical examination for GDF9, BMP15, and TUNEL were conducted, gene expressions of GDF9 and BMP15 were examined, and E2 was measured in the serum samples. With hematoxylin-eosin, in the third group, multi oocytes follicles were the most remarkable finding. In the fourth group, most of the follicles presented normal morphology. GDF9 involvement was similar between the first and fourth groups. BMP-15 immunoreactivity, in contrast to fourth group, was weak in all stages in the second and third groups. The current attempt represents a pioneer study in the literature in which a cell sheet method is used for the first time in a POI model. These results suggest that the cell sheet method may be a feasible and efficient method for the stem cell treatment of models with POI and could be a new treatment approach in POI.

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Data availability

The data that supports the findings of this study are available on requests.

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Acknowledgements

The authors wish to thank the TSRM and TAJEV societies for their support.

Funding

The study was awarded the “Best Research” award at the TSRM 2018 Congress and was also awarded the “Best Abstract” award at the TAJEV 2022 Congress. The study was funded by award money.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Gazi University Faculty of Medicine, Ankara, 06100, Turkey

    Pinar Calis

  2. Department of Histology and Embryology, Gazi University Faculty of Medicine, Ankara, Turkey

    Pinar Calis, Gokcenur Arik, Cemile Merve Seymen & Gulnur Take Kaplanoglu

  3. Department of Biomedical Engineering, Izmir Bakircay University, Izmir, Turkey

    Gokce Kaynak Bayrak

  4. Department of Bioengineering, Hacettepe University, Ankara, Turkey

    Ozge Ekin Akdere

  5. Department of Biochemistry, Gazi University Faculty of Medicine, Ankara, Turkey

    Canan Yilmaz

  6. Department of Medical Biology and Genetics, Gazi University Faculty of Medicine, Ankara, Turkey

    Atiye Seda Yar Saglam

  7. Department of Chemical Engineering, Hacettepe University, Ankara, Turkey

    Menemşe Gümüşderelioğlu

Authors
  1. Pinar Calis
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  2. Gokcenur Arik
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  3. Cemile Merve Seymen
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  4. Gokce Kaynak Bayrak
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  5. Ozge Ekin Akdere
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  6. Canan Yilmaz
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  8. Menemşe Gümüşderelioğlu
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  9. Gulnur Take Kaplanoglu
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Correspondence to Pinar Calis.

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Ethics approval

All procedures involving animals followed the European Community Council Directive of 24 November 1986, and ethical approval was granted by the Gazi University Ethical Committee on Animal Research (Approval No: 21/12/2018-E.168939).

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Calis, P., Arik, G., Seymen, C.M. et al. A new technology for the treatment of premature ovarian insufficiency: Cell sheet. Cell Tissue Res 395, 117–131 (2024). https://doi.org/10.1007/s00441-023-03848-5

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