Global Advanced Research Journal of Medicine and Medical Sciences (GARJMMS) ISSN: 2315-5159
June 2017 Vol. 6(6), pp. 116-130
Copyright © 2017 Global Advanced Research Journals

 

Full Length Research Paper 

Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Restore Cisplatin Induced Ovarian Damage by Promoting Stem Cell Survival, Meiotic, and Apoptotic Markers

Ayat A Sayed1, Sahar EM EL-Deek1*, Mona A EL-Baz1, Dina Sabry2, Aliaa Al-Rageaey3, Aishaa Mansey4, Fatma Y Meligy5 and Khaled Abdelaziz6.

1Departments of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt
2Departments of Medical Biochemistryand Molecular Biology, Faculty of Medicine, Cairo University, Egypt
3Oral and Dental Medicine, General Histology, Future University, Egypt
4General Histology, Banha University, Egypt
5Departments of Histology, Faculty of Medicine, Assiut University, Assiut,
6Departments of Obstetrics and Gynaecology, Faculty of Medicine, Cairo University, Egypt

*Corresponding Author Email: aaasahar123@yahoo.com, Sahareldeek_123@yahoo.com; Tel: 020/01004419975; Fax: +2-08823337878

Accepted 21 June, 2017

Abstract

Exosomes released by bone marrow mesenchymal stem cell (BMSCs) provide a novel source and a great potential donor cell for regenerative medicine. The current study was set to explore the restorative potential of BMSCs derived exosomes in a rat model of premature ovarian failure (POF) and its underlying mechanisms. Exosomes were prepared and infused to the cisplatin induced POF rats. The ovaries were subjected for histological and immune-histochemical evaluation of survivin and Oct4. RNA extraction and quantitative real time PCR were carried out for evaluation of Stra8, Oct4, Lin28, and Nanos3 gene expression. Serum estradiol (E2) and follicular stimulating hormone (FSH) were monitored. The POF group showed reduced number of follicles, excessive fibrosis, follicular atresia, low serum E2 and high FSH levels compared to controls. BMSCs derived exosomes infusion improved ovarian architecture with normal hormonal profile. There was down and up-regulation of Oct4 and Lin28, markers of stemness and germ cell survival, Stra8 and Nanos3, molecules that judge the cellular fate towards meiosis and oocyte formation in POF, and exosomes treated ovaries respectively. This study demonstrate for the first time that exosomes infusion showed structural and functional reparative properties,possibly through delivering its carriage of protein, molecular content and RNA bioactive molecules to the host ovarian niche inducing neo-oogenesis/folliculogenesis. This provides an effective and novel method for treatment of POF.

Keywords: Ovarian failure, Exosomes, Oct4, Lin28, Nanos3, Stra8, Survivin.

List of Abbreviation

POF, Premature ovarian failure; E2, stradiol; FSH, Follicular stimulating hormones; MSCs, Mesenchymal stem cells; BMSCs, Bone marrow derived mesenchymal stem cells; Stra 8, Stimulated by retinoic acid gene 8; Oct4, Octmar-binding transcription factor; FACS, Flocytometry

 

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