Intra-ovarian injection of bone marrow-derived c-Kit+ cells for ovarian rejuvenation in menopausal rats

Introduction: Cell-based therapies with certain cell types are touted as novel and hopeful therapeutic intervention in the clinical setting. Here, we aimed to assess the regenerative potential of c-Kit+ cells in the rejuvenation of ovarian tissue and fertility rate in rat model of premature ovarian...

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Main Authors: Sepideh Sheshpari, Mahnaz Shahnazi, Shahin Ahmadian, Mohammad Nouri, Mehran Mesgari Abbasi, Rahim Beheshti, Reza Rahbarghazi, Ali Honaramooz, Mahdi Mahdipour
Format: Article
Language:English
Published: Tabriz University of Medical Sciences 2022-07-01
Series:BioImpacts
Subjects:
Online Access:https://bi.tbzmed.ac.ir/PDF/bi-12-325.pdf
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Summary:Introduction: Cell-based therapies with certain cell types are touted as novel and hopeful therapeutic intervention in the clinical setting. Here, we aimed to assess the regenerative potential of c-Kit+ cells in the rejuvenation of ovarian tissue and fertility rate in rat model of premature ovarian failure (POF). Methods: Rats were treated with 160 mg/kg/BW of 4-vinylcyclohexene dioxide for 15 days. Freshly enriched rat bone marrow-derived c-Kit+ (MACS) and c-Kit- cells (4×105 cells/10 µL) were transplanted into the ovaries of treatment and control animals. Prior to transplantation as well as 2, 4, 6, and 8 weeks post-transplantation, randomly-selected rats were euthanized and ovarian tissues were subjected to pathophysiological examinations and real-time PCR analyses. Results: POF status was confirmed by the presence of pathological features and a decreased number of immature and mature follicles compared with the control group (P<0.05). Histological examination revealed a substantial reduction of atretic follicles in POF rats receiving c-Kit+ cells in comparison with POF rats that did not receive these cells (P<0.05). Compared with the control samples, angiogenesis-related genes, Angpt2 and KDR, showed increased and decreased expressions in POF ovaries, respectively (P<0.05). c-Kit+ cells had potential to restore angiogenesis in the ovarian tissue within normal ranges. Systemic levels of FSH did not significantly change in pre- or post-transplantation time points for any group (P>0.05). Notable reduction of collagen deposition was found in c-Kit-treated rats. Transplantation of c-Kit+ cells also restored the reduced fertility rate (P<0.05). Conclusion: The administration of c-Kit+ cells can modulate angiogenesis and pathological changes, leading to the rejuvenation of ovarian function of a rat model of premature menopause.
ISSN:2228-5660
2228-5652