Bone marrow derived mesenchymal stem cell restore ovarian activity in cases of premature ovarian failure

Introduction: Approximately 1-5% of women worldwide experience cessation of their menstrual cycle prior to age 40, a condition known as POF.The incidence of POF has increased in recent years. As yet, POF cannot be reversed and though some treatments are currently available, improved treatment strategies are urgently required. Regenerative medicine research suggests that stem cells could be used to treat various human diseases, due to their selfrenewal capacity and multiplex differentiation potential. Mesenchymal stem cells (MSCs) are ideal candidates for this purpose. Aim of Work: The purpose of this study is to assess whether bone marrow stem cells (BMSCs) could enter into ovarian niche and differentiate in to oocytes in a mouse model of ovarian failure. Secondly, to explore the therapeutic potency of autologous bone marrow MSC transplantation for primary and chemotherapy-induced ovarian damage and restoration of ovarian function in a pilot human clinical trial. Study Plan: I. Animal study: 18 adult female rats were subjected to cyclophosphamide injection until induction of ovarian failure. 9 mice were injected by 2x106 MSC/Kg . Hormonal and histologic evaluation was done for evidence of regeneration. II. Pilot human trial: 20 cases of premature ovarian failure were enrolled. Autologous bone marrow derived MSC were injected in to the ovaries laparoscopically. Followup was done by measuring serum FSH& follicle counting by ultrasound. Results and Conclusions: All mice of the stem cell treatment group showed positive ovulation with more than 4 ova/low power field. Human subjects showed nomalization of FSH and E2 with sonographic evidence of ovulation in 5 out of 20 patients. These patients were referred to IVF centers.