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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author Sepideh Sheshpari
Mahnaz Shahnazi
Shahin Ahmadian
Mohammad Nouri
Mehran Mesgari Abbasi
Rahim Beheshti
Reza Rahbarghazi
Ali Honaramooz
Mahdi Mahdipour
author_facet Sepideh Sheshpari
Mahnaz Shahnazi
Shahin Ahmadian
Mohammad Nouri
Mehran Mesgari Abbasi
Rahim Beheshti
Reza Rahbarghazi
Ali Honaramooz
Mahdi Mahdipour
author_sort Sepideh Sheshpari
collection DOAJ
description 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.
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spelling doaj.art-906456248b00488c99b03f7e4d4931202022-12-22T01:18:43ZengTabriz University of Medical SciencesBioImpacts2228-56602228-56522022-07-0112432533510.34172/bi.2021.23499bi-23499Intra-ovarian injection of bone marrow-derived c-Kit+ cells for ovarian rejuvenation in menopausal ratsSepideh Sheshpari0Mahnaz Shahnazi1Shahin Ahmadian2Mohammad Nouri3Mehran Mesgari Abbasi4Rahim Beheshti5Reza Rahbarghazi6Ali Honaramooz7Mahdi Mahdipour8Department of Midwifery, Faculty of Nursing and Midwifery, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Midwifery, Faculty of Nursing and Midwifery, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Biology, Faculty of Science, Azerbaijan Shahid Madani University, Tabriz, IranStem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, IranDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Veterinary Science, Islamic Azad University, Shabester Branch, Shabestar, IranStem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, S7N 5B4, CanadaStem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, IranIntroduction: 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.https://bi.tbzmed.ac.ir/PDF/bi-12-325.pdfpremature ovarian failurebone marrow c-kit+ cellsfollicular competenceangiogenesisfertility
spellingShingle Sepideh Sheshpari
Mahnaz Shahnazi
Shahin Ahmadian
Mohammad Nouri
Mehran Mesgari Abbasi
Rahim Beheshti
Reza Rahbarghazi
Ali Honaramooz
Mahdi Mahdipour
Intra-ovarian injection of bone marrow-derived c-Kit+ cells for ovarian rejuvenation in menopausal rats
BioImpacts
premature ovarian failure
bone marrow c-kit+ cells
follicular competence
angiogenesis
fertility
title Intra-ovarian injection of bone marrow-derived c-Kit+ cells for ovarian rejuvenation in menopausal rats
title_full Intra-ovarian injection of bone marrow-derived c-Kit+ cells for ovarian rejuvenation in menopausal rats
title_fullStr Intra-ovarian injection of bone marrow-derived c-Kit+ cells for ovarian rejuvenation in menopausal rats
title_full_unstemmed Intra-ovarian injection of bone marrow-derived c-Kit+ cells for ovarian rejuvenation in menopausal rats
title_short Intra-ovarian injection of bone marrow-derived c-Kit+ cells for ovarian rejuvenation in menopausal rats
title_sort intra ovarian injection of bone marrow derived c kit cells for ovarian rejuvenation in menopausal rats
topic premature ovarian failure
bone marrow c-kit+ cells
follicular competence
angiogenesis
fertility
url https://bi.tbzmed.ac.ir/PDF/bi-12-325.pdf
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