Tabriz University of Medical Sciences BioImpacts 2228-5652 12 4 2022 07 01 Intra-ovarian injection of bone marrow-derived c-Kit+ cells for ovarian rejuvenation in menopausal rats 325 335 10.34172/bi.2021.23499 EN Sepideh Sheshpari https://orcid.org/0000-0001-8590-8111 Mahnaz Shahnazi Shahin Ahmadian Mohammad Nouri Mehran Mesgari Abbasi Rahim Beheshti Reza Rahbarghazi Ali Honaramooz Mahdi Mahdipour https://orcid.org/0000-0002-2729-4593 Journal Article 10.34172/bi.2021.23499 2020 11 07 2021 04 22 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.