Primordial Follicle Transplantation within Designer Biomaterial Grafts Produce Live Births in a Mouse Infertility Model.
Primordial Follicle Transplantation within Designer Biomaterial Grafts Produce Live Births in a Mouse Infertility Model.
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DOI：
10.1038/srep17709
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发表时间：
2015-12-03
影响因子：
4.6
通讯作者：
Shea LD
中科院分区：
文献类型：
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作者：
Kniazeva E;Hardy AN;Boukaidi SA;Woodruff TK;Jeruss JS;Shea LD
化疗和放疗的促性腺毒性作用可能导致绝经前肿瘤患者卵巢早衰。虽然卵巢组织的自体移植已经导致成功的活产，但重新引入潜在的恶性细胞诱导复发是一个重要的问题。在这篇报道中，我们研究了分离卵泡移植的生物材料移植物的设计，作为保持生育能力的一种手段。从年轻雌性小鼠中提取原始和初级卵巢卵泡并包封成生物材料，随后移植到成年小鼠中。在测试的配方中，相对于纤维蛋白-海藻酸盐和纤维蛋白-胶原复合材料，包裹在纤维蛋白内的聚集性卵泡在移植后的存活率和与宿主组织的整合度都有所提高。所有移植了纤维蛋白包裹的卵泡的小鼠都恢复了循环，只有在vegf -负载的纤维蛋白珠内移植的卵泡才能实现活产。这些手术在一定程度上减少了分离卵泡中转移性乳腺癌细胞的存在，相对于完整的卵巢，癌细胞的数量显著减少。这种通过移植分离的原始和初级卵泡获得活产的能力，同时也降低了相对于卵巢组织移植的重新播种疾病的风险，可能最终为保持绝经前肿瘤患者的生育能力提供了一种手段。
The gonadotoxic effects of chemotherapy and radiation may result in premature ovarian failure in premenopausal oncology patients. Although autotransplantation of ovarian tissue has led to successful live births, reintroduction of latent malignant cells inducing relapse is a significant concern. In this report, we investigated the design of biomaterial grafts for transplantation of isolated ovarian follicles as a means to preserve fertility. Primordial and primary ovarian follicles from young female mice were extracted and encapsulated into biomaterials for subsequent transplantation into adult mice. Among the formulations tested, aggregated follicles encapsulated within fibrin had enhanced survival and integration with the host tissue following transplantation relative to the fibrin-alginate and fibrin-collagen composites. All mice transplanted with fibrin-encapsulated follicles resumed cycling, and live births were achieved only for follicles transplanted within VEGF-loaded fibrin beads. The extent to which these procedures reduce the presence of metastatic breast cancer cells among the isolated follicles was evaluated, with significantly reduced numbers of cancer cells present relative to intact ovaries. This ability to obtain live births by transplanting isolated primordial and primary follicles, while also reducing the risk of re-seeding disease relative to ovarian tissue transplantation, may ultimately provide a means to preserve fertility in premenopausal oncology patients.