Oogonial Stem Cell Characterization in POI and NHP

卵巢早衰/原发性卵巢功能不全是由于特发性原因或化疗或放疗后发生的，导致妇女不能生育自己的基因后代。目前，由于缺乏恢复卵巢功能的药物或手术治疗，来自年轻女性的捐献卵子是这些女性的唯一选择。最近，出现了几项新的干细胞进展，可以用于未来治疗卵巢早衰妇女的策略。 直到最近，人们还认为女性卵巢生殖系干细胞(又名卵巢干细胞、卵原干细胞、OSCs、卵前体细胞或EggPC)并不存在。然而，这些细胞现在已经在小鼠和人类模型中使用磁珠和带有胚系标记Ddx4(又名小鼠Vasa同源物)抗体的FACS分离出来，通过有丝分裂扩增进行体外培养，并移植到小鼠和人类异种移植模型中。成年OSCs在移植回供体卵巢后能够进入减数分裂，在那里它们在小鼠身上产生后代，提高了治疗潜力的可能性。 该项目的目标是将干细胞研究的技术进步转化为帮助患有生殖障碍的妇女的方法。LAB的总体目标是将这些生殖干细胞突破迅速转化为临床试验。然而，啮齿类动物和灵长类动物在生殖生理学上存在显著差异(例如月经周期和血孔胎盘)，这使得在非人灵长类动物(NHP)中进行概念验证研究以确定这种方法在未来人类治疗中的可行性至关重要。 随着不孕不育发病率的上升和妇女继续推迟生育，需要更多的生育保护选择。如果建立了这种OSC方法，所有女性都可以在年轻时将卵巢干细胞储存起来，供以后使用。这种方法将减少与年龄相关的生育延迟风险，并为不可预见的未来特发性或医源性卵巢早衰提供生育保护。

Premature ovarian failure/Primary ovarian insufficiency occurs due to idiopathic causes or following chemotherapy or radiation, and results in the inability of a woman to have her own genetic offspring. Currently, donor eggs from younger women are the only option for these women, given a lack of pharmacologic or surgical treatments to restore ovarian function. Recently, several new stem cell advances have occurred which could be used in future strategies to treat women with premature ovarian aging. Until recently, it was thought that female ovarian germline stem cells (aka ovarian stem cells, oogonial stem cells, OSCs, egg precursor cells, or EggPCs) did not exist. However, these cells have now been isolated in both a murine and human models using magnetic beads and FACS with antibodies against the germ line marker Ddx4 (aka Mouse Vasa Homologue), cultured ex vivo with mitotic expansion, and transplanted in murine and human xenograft models. Adult OSCs were able to enter into meiosis after transplantation back into a donor ovary, where they gave rise to offspring in mice, raising the possibility of therapeutic potential. The goal of this project is to translate technical advances in stem cell research into ways to help women with reproductive disorders. The overall goal of lab is to rapidly translate these reproductive stem cell breakthroughs to clinical trials. However, significant differences in reproductive physiology exist between rodents and primates (e.g. menstrual cycles and hemachorial placentation), which make it critical to perform proof of concept studies in non human primate (NHP) to determine the viability of this approach for future human therapy. As the incidence of infertility rises and women continue to delay reproduction, more fertility preservation options are needed. If this OSC approach is established, all women could bank ovarian stem cells at young ages for later use. This approach would mitigate age related risks of delayed reproduction and provide fertility preservation for unforeseen future idiopathic or iatrogenic premature ovarian failure.