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Mechanistic action of mesenchymal stem cell injection in the treatment of chemically induced ovarian failure in rabbits
Authors:Somia H. Abd-Allah  Sally M. Shalaby  Heba F. Pasha  Amal S. El-Shal  Nermin Raafat  Sheren M. Shabrawy  Hanan A. Awad  Mona G. Amer  Mahmoud A. Gharib  Eman A. El Gendy  Amal A. Raslan  Hassan M. El-Kelawy
Affiliation:1. Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt;2. Histology & Cell Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt;3. Obestetrics and Gynecology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt;4. The Veterinary Clinic, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt;5. Animal Production Department, Institute of Efficient Production, Zagazig University, Zagazig, Egypt;1. Laboratory of Translational Cell Biology, Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA;2. Department of Ob-Gyn-Repro Sci, University of Pittsburgh School of Medicine, Pittsburgh, PA 15108, USA;3. Magee Womens Research Institute, Pittsburgh Development Center, Pittsburgh, PA 15108, USA;1. National Agricultural and Food Centre, Research Institute for Animal Production Nitra, Lu?ianky, Slovak Republic;2. Constantine the Philosopher University, Department of Zoology and Anthropology, 949 74, Nitra, Slovak Republic;3. Czech Centre for Phenogenomics, Division BIOCEV, Institute of Molecular Genetics, Department of Transgenic Models of Diseases, ASCR, 252 50, Vestec, Czech Republic;4. Selye Janos University, Faculty of Education, 945 01, Komárno, Slovak Republic;5. Slovak University of Agriculture, Faculty of Biotechnology and Food Science, 949 76, Nitra, Slovak Republic;6. UTP University of Science and Technology, Faculty of Animal Breeding and Biology, Mazowiecka 28, 85-084, Bydgoszcz, Poland;1. Reproductive Medicine Center of Peking University Shenzhen Hospital, Shenzhen, Guangdong, China;2. Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China;3. Department of Obstetrics and Gynecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;1. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;2. Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA;3. Department of Cell Biology, Center for Research in Contraceptive and Reproductive Health, University of Virginia, Charlottesville, VA 22908, USA;4. Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran;5. Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran;6. Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran
Abstract:BackgroundNo curative treatment is known for primary ovarian failure; however, mesenchymal stem cells (MSCs), through self-renewal and regeneration, push the trial to evaluate their role in the treatment of ovarian failure. The aim of this study was to explore the impact of MSCs on cyclophosphamide (CTX)-induced ovarian failure in rabbits and to clarify the mechanism(s) by which MSCs exert their action.MethodsThirty-five adult female rabbits were injected with CTX to induce ovarian failure. Five rabbits were euthanized after the last injection of CTX for histological examination. The others (30 rabbits) were further subdivided into two groups: group 1 (ovarian failure group, 15 rabbits) received no treatment; group 2 (ovarian failure and MSC recipient group, 15 rabbits) received MSCs isolated from extracted bone marrow of male rabbits.ResultsA decrease of follicle-stimulating hormone and an increase of estrogen and vascular endothelial growth factor (VEGF) levels in the MSC recipient group versus the ovarian failure group were found. Weak caspase-3 expression and +ve proliferating cell nuclear antigen staining after MSC injection were detected. Cytological and histological examinations showed increased follicle numbers with apparent normal structure of ovarian follicles in the MSC recipient group. Moreover, Y chromosome–containing cells from male donors were present within the ovarian tissues in group 2.ConclusionsThe current study suggests that intravenous injection of MSCs into rabbits with chemotherapy-induced ovarian damage improved ovarian function. MSCs accomplish this function by direct differentiation into specific cellular phenotypes and by secretion of VEGF, which influence the regeneration of the ovary.
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