Buigues A, Marchante M, de Miguel-Gómez L, et al. - Ovarian senescence is a normal age-associated phenomenon, however, diminished ovarian reserves or premature ovarian insufficiency is increasingly affecting younger women. Researchers here examined if various human plasma sources, enriched in stem cell secreted factors, can aid in repairing ovarian damage and promoting follicular development. In addition, they determined the mechanisms behind their regenerative properties. In a first phase, they investigated how human plasma enriched in bone marrow stem cell soluble factors by granulocyte colony stimulating factor (G-CSF) mobilization, umbilical cord blood (UCB) plasma, and their activated forms affect ovarian niche, follicle development and breeding performance in mouse models of chemotherapy-induced ovarian damage (n = 7/group). In addition, they analyzed the proteomic profile of each plasma to determine putative proteins and mechanisms involved in their regenerative properties in ovarian tissue. In a second phase, validation of the most effective plasma treatment was done in human ovarian cortex xenografted in immunodeficient mice (n = 4/group). Infusion of human plasma enriched in bone marrow stem cell soluble factors by G-CSF mobilization or of UCB plasma resulted in induction in variable degrees of microvessel formation and cell proliferation, and decreased apoptosis in ovarian tissue to rescue follicular development and fertility in mouse models of ovarian damage. Outcomes suggest effectiveness of stem cell secreted factors present in both G-CSF mobilized and UCB plasmas as treatment for raising the reproductive outcomes in women with impaired ovarian function due to several causes. The activated G-CSF plasma (G-CSFa), which is already enriched in both stem cell secreted factors and platelet enclosed growth factors, appears to be the most promising therapy because of its most potent restorative effects on ovary together with the autologous source.