Human Amniotic Membrane-derived Mesenchymal Stem Cells Are Effective In Improving Ovarian Function

Objectives:Fetal mesenchymal stem cells is potential therapeutic material for many intractable diseases, such as premature ovarian failure (POF). The potential of human amniotic mesenchymal stem cells (hAMSCs) to improve ovarian function was explored in mice models with the age-related ovarian dysfunction or X-irradiation induced sterilization.Methods:Female C57B6mice aged32weeks were used as the model of physiologic ovarian dysfunction. Female C57B6mice aged8weeks treated with4Gy X-irradiation were used as the sterilization model. hAMSCs is successfully developed in our institute. hAMSCs is injected into mice via tale vein. Ovaries were excised after1month of transplantation,. Ovarian functions were evaluated by monitoring ovulation, estrous cycle, serum gonadal hormone and categorized follicles. Cell tracking, microarray analysis on cytokines, and transmission electron microscope were used to assess the repairmen the roles of hAMSCs.Results:Compared to young mice, the aged mice had a higher level of FSH and lower levels of estrogen and AMH. The number of follicles in young mice was less than the aged mice. Mice irradiated by X-ray exhibited not only ovarian failure but also whole-body premature aging. The hAMSCs injection significantly increased the number of oocyte and the formation rate of fertilization and blastocyst in physiologic aging mice. Some immature primary follicles like structure and reduced degree of ovarian stromal fibrosis presented in sterilized mice. Serum levels of estrogen in all hAMSCs-treated groups were higher than those in control. However, cell tracking analysis revealed that hAMSCs did not directly differentiate into follicle component. Microarray analysis indicated that hAMSCs secreted kinds of growth factors, immunomodulatory factors, and chemokines.Conclusion:The increased hormones and hAMSCs-secreted factors may be benefit to the follicle development and resisting fibrosis in ovarian dysfunction. This work would pave the way of hAMSCs transplantation in ovarian dysfunction to clinical therapies and researches.