Is transplantation of a few leukemic cells inside an artificial ovary able to induce leukemia in an experimental model?
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To evaluate the tumor-inducing ability of a few leukemic cells xenotransplanted inside an artificial ovary.
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.
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.
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.
KeywordsArtificial ovary Leukemia Ovarian tissue cryopreservation Ovarian follicles Malignant cell purging Minimal disseminated disease Follicle isolation
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.
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