Department of Biomedical Engineering, Northwestern University, Evanston, Illinois.
Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.
Biotechnol Bioeng. 2018 Aug;115(8):2075-2086. doi: 10.1002/bit.26721. Epub 2018 May 14.
Cancer survivorship rates have drastically increased due to improved efficacy of oncologic treatments. Consequently, clinical concerns have shifted from solely focusing on survival to quality of life, with fertility preservation as an important consideration. Among fertility preservation strategies for female patients, ovarian tissue cryopreservation and subsequent reimplantation has been the only clinical option available to cancer survivors with cryopreserved tissue. However, follicle atresia after transplantation and risk of reintroducing malignant cells have prevented this procedure from becoming widely adopted in clinics. Herein, we investigated the encapsulation of ovarian follicles in alginate hydrogels that isolate the graft from the host, yet allows for maturation after transplantation at a heterotopic (i.e., subcutaneous) site, a process we termed in vivo follicle maturation. Survival of multiple follicle populations was confirmed via histology, with the notable development of the antral follicles. Collected oocytes (63%) exhibited polar body extrusion and were fertilized by intracytoplasmic sperm injection and standard in vitro fertilization procedures. Successfully fertilized oocytes developed to the pronucleus (14%), two-cell (36%), and four-cell (7%) stages. Furthermore, ovarian follicles cotransplanted with metastatic breast cancer cells within the hydrogels allowed for retrieval of the follicles, and no mice developed tumors after removal of the implant, confirming that the hydrogel prevented seeding of disease within the host. Collectively, these findings demonstrate a viable option for safe use of potentially cancer-laden ovarian donor tissue for in vivo follicle maturation within a retrievable hydrogel and subsequent oocyte collection. Ultimately, this technology may provide novel options to preserve fertility for young female patients with cancer.
由于肿瘤治疗效果的提高，癌症患者的存活率大幅上升。因此，临床关注点已从单纯关注生存转变为生活质量，而生育力保存是一个重要的考虑因素。在女性患者的生育力保存策略中，卵巢组织冷冻保存和随后的再植入是唯一可供有冷冻组织的癌症幸存者选择的临床方案。然而，移植后卵泡闭锁和引入恶性细胞的风险阻止了该程序在临床上广泛采用。在此，我们研究了将卵巢卵泡包封在藻酸盐水凝胶中，该水凝胶将移植物与宿主隔离，但允许在异位（即皮下）部位移植后成熟，我们将此过程称为体内卵泡成熟。通过组织学证实了多种卵泡群体的存活，其中明显发育了窦卵泡。收集的卵母细胞（63%）表现出极体排出，并通过胞浆内精子注射和标准的体外受精程序进行受精。成功受精的卵母细胞发育到原核（14%）、二细胞（36%）和四细胞（7%）阶段。此外，在水凝胶内共移植带有转移性乳腺癌细胞的卵巢卵泡，可回收卵泡，且在去除植入物后，没有小鼠发生肿瘤，证实水凝胶可防止疾病在宿主内播散。总之，这些发现表明，对于有癌症风险的卵巢供体组织，使用可回收水凝胶进行体内卵泡成熟和随后卵母细胞采集是一种可行的安全选择。最终，这项技术可能为年轻的癌症女性患者提供新的生育力保存选择。
