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Human Mesenchymal Stem Cells Partially Reverse Infertility in Chemotherapy-Induced Ovarian Failure

Reproductive sciences (Thousand Oaks, Calif.), 2018-01, Vol.25 (1), p.51-63 [Peer Reviewed Journal]

The Author(s) 2017 ;The Author(s) 2017 2017 Society for Gynecologic Investigation ;ISSN: 1933-7191 ;EISSN: 1933-7205 ;DOI: 10.1177/1933719117699705 ;PMID: 28460567

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  • Title:
    Human Mesenchymal Stem Cells Partially Reverse Infertility in Chemotherapy-Induced Ovarian Failure
  • Author: Mohamed, Sara A. ; Shalaby, Shahinaz M. ; Abdelaziz, Mohamed ; Brakta, Soumia ; Hill, William D. ; Ismail, Nahed ; Al-Hendy, Ayman
  • Subjects: Animals ; Antineoplastic Agents - adverse effects ; Bone Marrow Cells ; Busulfan - adverse effects ; Cyclophosphamide - adverse effects ; Embryology ; Female ; Humans ; Medicine & Public Health ; Mesenchymal Stem Cell Transplantation ; Mice ; Obstetrics/Perinatology/Midwifery ; Original ; Original Article ; Primary Ovarian Insufficiency - chemically induced ; Primary Ovarian Insufficiency - therapy ; Reproductive Medicine ; Treatment Outcome
  • Is Part Of: Reproductive sciences (Thousand Oaks, Calif.), 2018-01, Vol.25 (1), p.51-63
  • Description: Introduction: Chemotherapy is the most commonly used modality to treat human cancers; however, in many cases it causes irreversible ovarian failure. In this work, we plan to evaluate the restorative function of human bone marrow mesenchymal stem cells (BMSCs) in a chemotherapy-induced ovarian failure mouse model. Methods: Acclimatized 4 to 6 week-old female mice (C57BL/6) were assigned randomly to a vehicle-treated control group (group 1), chemotherapy-treated group followed by vehicle alone (group 2), or chemotherapy-treated group followed by stem cell intraovarian injection (group 3). Outcomes were evaluated using immunohistochemistry (IHC), serum hormonal assays, and estrous cycle monitoring and breeding potential. Results: Post BMSCs administration, group 3 promptly showed detectable vaginal smears with estrogenic changes. Increase in total body weight, ovarian weight, and weight of estrogen-responsive organs (uterus and liver) was observed at 2 weeks and continued to end of the experiment. Hematoxylin and Eosin histological evaluation of the ovaries demonstrated a higher mean follicle count in group 3 than in group 2. Group 3 had lower follicle-stimulating hormone (FSH) levels (P = .03) and higher anti-Müllerian hormone serum (AMH) levels (P = .0005) than group 2. The IHC analysis demonstrated higher expression of AMH, FSH receptor, inhibin A, and inhibin B in growing follicles of group 3 versus group 2. Tracking studies demonstrated that human BMSCs evenly repopulated the growing follicles in treated ovaries. Importantly, breeding data showed significant increases in the pregnancies numbers, 2 pregnancies in group 1 and 12 in group 3 (P = .02). Conclusions: Intraovarian administered BMSCs are able to restore ovarian hormone production and reactivate folliculogenesis in chemotherapy-induced ovarian failure mouse model.
  • Publisher: Los Angeles, CA: SAGE Publications
  • Language: English
  • Identifier: ISSN: 1933-7191
    EISSN: 1933-7205
    DOI: 10.1177/1933719117699705
    PMID: 28460567
  • Source: MEDLINE
    Alma/SFX Local Collection
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