Fertility preservation for female cancer patients by manipulating ovarian stem cells that survive oncotherapy

Abstract

Infertility and premature ovarian failure are unwanted side effects of oncotherapy in females; however, a large number of patients survive cancer due to recent advances in their management. One of the available options to restore fertility in cancer survivors is to transplant ovarian cortical tissue slices at orthotopic sites which has resulted in the birth of 130 babies. Spontaneous pregnancies have also been reported after heterotopic transplantation of cortical tissue slices which can only be explained by the presence of stem cells and paracrine support provided by transplanted ovarian slices to the nonfunctional ovary. The ovary harbors two populations of stem cells, including very small embryonic-like stem cells (VSELs) and slightly bigger ovarian stem cells (OSCs) that divide and undergo clonal expansion to form germ cell nests in adult ovary before undergoing neo-oogenesis and primordial follicle assembly. Being relatively quiescent, VSELs survive oncotherapy and can regenerate the nonfunctional ovary. Stem cells niche gets affected by oncotherapy and transplanting autologous bone marrow mesenchymal stem cells (MSCs, which provide paracrine support) have shown to normalize ovarian function in rodents with the birth of healthy pups. Similarly, transplanting of autologous MSCs in human ovary with premature ovarian failure resulted in the birth of a baby. These advances in the field of OSCs need to be put in proper context before considering making transplantation of ovarian cortical tissue at orthotopic sites as method of standard care. Transplanting autologous MSCs is safe, and efficacy to regenerate nonfunctional ovaries needs to be evaluated in clinical settings.