Bone Marrow Stromal Cells with the Granulocyte Colony-Stimulating Factor in the Management of Chemotherapy-Induced Ovarian Failure in a Rat Model

Abstract

Background: Bone marrow stromal cells (BMSCs), as a type of mesenchymal stem cells, and the granulocyte colony-stimulating factor (G-CSF), as a type of growth factor, may recover damaged ovaries. The aim of the present study was to investigate the effects of the coadministration of BMSCs and the G-CSF on damaged ovaries after creating a chemotherapy model with cyclophosphamide (CTX) in rats.Methods: The present study was performed in Semnan, Iran, in the late 2016 and the early 2017. BMSCs were cultured and were confirmed using the CD markers of stromal cells. Forty female Wistar rats were randomly divided into 4 groups. The rats were injected intraperitoneally with CTX for 14 days to induce chemotherapy and ovarian destruction. Then, the BMSCs were injected into bilateral ovaries and the G-CSF was injected intraperitoneally, individually and together. Four weeks later, the number of ovarian follicles using H&E staining, the number of apoptotic granulosa cells using the TUNEL assay, the number of produced oocytes from the ovaries, and the levels of serum E2 and FSH using an ELISA reader were assessed. Statistical analysis was done using one-way ANOVA with SPSS, version 16.0.Results: The results showed that the effects of the coadministration of 2×106 BMSCs and 70 µg/kg of the G-CSF were significantly more favorable than those in the control group (P<0.001), the BMSC group (P=0.016), and the G-CSF group (P<0.001) on the recovery of damaged ovaries. Conclusion: The efficacy of the coadministration of BMSCs and the G-CSF in the recovery of ovaries damaged by chemotherapy was high by comparison with the administration of either of them separately.

Keywords

• Mesenchymal stromal cells
• Granulocyte colony-stimulating factor
• Chemotherapy
• Ovary
• Regeneration