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Is transplantation of a few leukemic cells inside an artificial ovary able to induce leukemia in an experimental model?

  • Fertility Preservation
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the tumor-inducing ability of a few leukemic cells xenotransplanted inside an artificial ovary.

Methods

Ten and 100 BV-173 leukemic cells were embedded in a fibrin matrix along with 50,000 human ovarian stromal cells, and grafted to the peritoneal bursa of 5 and 5 SCID mice respectively. Four mice grafted with 3x106 leukemic cells in fibrin served as positive controls. At 20 weeks post-transplantation, the grafts, liver, spleen, blood and bone marrow were analyzed for the presence of leukemia by anti-CD79α IHC, flow cytometry (FC) and PCR.

Results

All mice grafted with 3x106 cells developed peritoneal masses 4 weeks after xenotransplantation, and systemic disease was confirmed by IHC, PCR and FC. Among mice grafted with 10 or 100 leukemic cells, none showed any sign of leukemia after 20 weeks, and IHC, FC and PCR on the different recovered tissues all proved negative.

Conclusion

This study investigates the tumor-inducing potential of a few leukemic cells grafted inside an artificial ovary. Transplantation of 100 leukemic cells appears to be insufficient to induce leukemia after 20 weeks. These results in an immunodeficient xenografting model are quite reassuring. However, for clinical application, follicle suspensions must be purged of leukemic cells before grafting, as even the slightest risk should be avoided.

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Acknowledgments

The authors thank Mira Hryniuk for reviewing the English language of the manuscript and Olivier Van Kerk and Dolores Gonzalez for their technical assistance. Help from specialized technicians, namely Patricia Leveugle and Anne-Marie Mazzon for flow cytometry experiments and Béatrice Delepaut for PCR, was also greatly appreciated.

This work was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (5/4/150/5 and 7.4518.12F), Fonds Spéciaux de Recherche, Fondation Saint Luc, Foundation Against Cancer, and donations from Mr. Pietro Ferrero, Baron Frère, and Viscount Philippe de Spoelberch.

Author information

Authors and Affiliations

  1. Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium

    Michelle Soares, Karima Sahrari, Christiani A. Amorim & Marie-Madeleine Dolmans

  2. Département de Biologie Clinique, Université Catholique de Louvain et Cliniques universitaires Saint-Luc, Brussels, Belgium

    Pascale Saussoy

  3. Société de Recherche pour l’Infertilité, Brussels, Belgium

    Jacques Donnez

  4. Département de Gynécologie, Cliniques Universitaires Saint-Luc , Av Hippocrate 10, 1200, Brussels, Belgium

    Michelle Soares & Marie-Madeleine Dolmans

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  1. Michelle Soares
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  2. Pascale Saussoy
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  4. Christiani A. Amorim
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  5. Jacques Donnez
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  6. Marie-Madeleine Dolmans
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Corresponding author

Correspondence to Marie-Madeleine Dolmans.

Additional information

Capsule The tumor-inducing ability of a few BV-173 leukemic cells was evaluated in an artificial ovary by xenotransplantation. One hundred BV-173 cells proved insufficient to induce disease in mice after 20 weeks.

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Supplementary Fig 1

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Supplementary Table 1

Flow cytometry results for leukemic cell detection expressed as the percentage of total events showing the BV-173 lineage phenotype. This table presents results obtained using panel 2 (CD44-FITC/CD10-PE/CD45-ECD/CD38-PC5/CD19-PC7), but percentages were similar with panel 1 (CD44-FITC/CD10-PE/CD45-ECD/CD38-PC5/CD19-PC7). Mice grafted with 10 or 100 leukemic cells showed no sign of leukemia in any of the different tissue samples by FC. Conversely, in all mice grafted with 3 million leukemic cells, the BV-173 cell phenotype was identified in peritoneal grafts and at least one other sample, showing the presence of systemic disease after 4 weeks of grafting. Neg = negative, Pos = positive, NP = analysis not possible due to small sample volume. (DOC 43 kb)

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Soares, M., Saussoy, P., Sahrari, K. et al. Is transplantation of a few leukemic cells inside an artificial ovary able to induce leukemia in an experimental model?. J Assist Reprod Genet 32, 597–606 (2015). https://doi.org/10.1007/s10815-015-0438-x

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  • DOI: https://doi.org/10.1007/s10815-015-0438-x

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