Project Summary Premature ovarian insufficiency (POI) is a common complication of anticancer treatments, such as chemotherapy and bone marrow transplantation, due to treatment toxicity. In female cancer survivors POI causes sterility, and loss of the ovarian endocrine function, which in turn results in premature osteopenia, muscle wasting, and accelerated cardiovascular disease. These long- lasting effects are significant, particularly for young girls reaching puberty. The long-term goal of our research is to develop a means to restore ovarian endocrine function in young women with POI by utilizing allogeneic transplantation of ovarian tissue. We designed an immuno-isolating capsule based on well-characterized biomaterials and tuned to the unique physiology of ovarian tissue. Our approach proved to be successful in mice using donor tissue from rodents, yet the significant differences in ratio between stroma and follicles in human ovarian tissue, size that human follicles reach at maturity and the balance between dormant and activated follicles between rodents and humans require further investigation using human ovarian tissue. If successful, this approach will offer a clinically relevant and unexplored tool to restore ovarian endocrine function in young women with POI.