Bone marrow-derived mesenchymal stem cells (MSC) have been used to treat various diseases because of their self-renewal capacity and multipotency [17, 18].  For example, stems cells have been successful in tissue repair after spinal, renal and myocardial injury [19, 20].  The potential benefit of stem cell therapy after acute tissue damage appears to be related to tissue integration and differentiation to replace damaged cells, angiogenesis and anti-apoptosis. Adult MSC have not been equivocally proven to differentiate into follicles, however several rodent studies have been conducted to assess the role of MSC as an ovarian protection agent from chemotherapy.  Kilic et al showed preservation of primordial and primary follicles in in vivo rat MSC studies, suggesting that MSC may preferentially migrate to the injured follicular cells and repair the ovarian tissue by decreased programmed cell death[21].  Similarly, Fu et al demonstrated an increase in follicle number as well as a normalization of FSH and Estradiol levels after several weeks in rodents treated with MSC after cyclophosphamide therapy [22].  They also illustrated in-vitro production of angiogenic and anti-apoptotic cytokines vascular endothelial growth factor (VEGF), insulin like growth factor (IGF-1) and hepatocyte growth factor (HGF) from MSC.  Effects of therapy on progeny were not assessed in either study. Abd-Allah et al further demonstrated MSC protection of ovarian follicles in rabbit studies and were able to show in vivo cytokine production [23].  Despite the potential promise of MSC as an ovarian protection agent, studies of MSC injected intravenously in rodent models have shown MSC-mediated resistance to chemotherapeutics, specifically cisplatin [24].  Therefore route, dose, and efficacy of MSC as an ovarian protective agent in primates and humans are warranted.

 

 

References