Immuno-Isolating capsule for delivery of cell-based therapy for restoration of ovarian endocrine function in an animal model

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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. Our results in an ovariectomized adult mouse model have demonstrated that transplantation of an ovarian allograft encapsulated in an immunoisolating hydrogel-based capsule restores normal physiological endocrine ovarian function without eliciting immune rejection. Yet, rodents present limitations for clinical translation to humans, such as 1) the small size of a prepubertal female limits intervention before puberty and onset of puberty is regulated differently in primates than in rodents; 2) the small size and multiovulatory character of the mouse ovaries have a limited translational potential; and 3) the differences in immune response limit the reach of our findings. To overcome these challenges and increase the translational potential, we propose to extend preclinical testing of our therapy into non-human primates (NHPs). We will test the efficacy of encapsulated ovarian allograft to initiate physiological puberty in adolescent NHPs, we will study the longevity of graft function as well as the dynamics of the recipient’s immune response to initial and repeat implantations and evaluate the quality of oocytes grown in capsules for fertility restoration. If successful, this approach will offer a clinically relevant and unexplored tool to restore ovarian endocrine function in young women with POI. We have demonstrated in an ovariectomized adult mouse model that implantation of an ovarian allograft encapsulated in an immunoisolating hydrogel-based capsule restores normal physiological endocrine ovarian function without eliciting immune rejection. Yet, rodents present limitations for clinical translation to humans, such as the small size of a prepubertal female, which limits intervention before puberty and the differences in allo-immune response between rodents and humans. The proposed research To overcome these challenges and increase the translational potential, we propose to extend preclinical testing of our therapy into non-human primates (NHPs). We will test the efficacy of encapsulated ovarian allograft to initiate physiological puberty in adolescent NHPs, we will study the longevity of graft function as well as the dynamics of the recipient’s immune response to initial and repeat implantations and evaluate the quality of oocytes grown in capsules for fertility restoration. If successful, this approach will offer a clinically relevant and unexplored tool to restore ovarian endocrine function in young women with POI.