Intraovarian Transplantation of Female Germline Stem Cells Rescue Ovarian Function in Chemotherapy-Injured Ovaries.
Intraovarian Transplantation of Female Germline Stem Cells Rescue Ovarian Function in Chemotherapy-Injured Ovaries.
复制标题
女性生殖干细胞的卵巢内移植可挽救化疗损伤卵巢的卵巢功能
DOI：
10.1371/journal.pone.0139824
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Xiong J;Lu Z;Wu M;Zhang J;Cheng J;Luo A;Shen W;Fang L;Zhou S;Wang S
女性癌症患者化疗后常出现绝经早和不孕。对于这些患者，卵母细胞/胚胎冷冻保存或卵巢组织冷冻保存是目前的生育力保存方式。然而，上述方法在长期保护卵巢功能，特别是生育能力方面受到限制（到目前为止，很少有癌症女性用冷冻保存的卵巢组织或卵子实现怀孕）。此外，上述方法受其范围限制（没有丈夫的女性或没有成熟卵母细胞的青春期前女性）。因此，许多患有癌症的女性不会在CTx前后采用上述方法，因为它们的不确定性，安全性和成本效益。因此，数以百万计的妇女在彻底的CTx治疗后获得了长期生存，并希望用经济、持久和可靠的方法挽救她们的卵巢功能和生育能力。近年来，有研究表明，通过卵巢内注射外源性雌性生殖系干细胞（FGSCs），CTx致不孕小鼠可以产生正常的后代。虽然外源性FGSC可以从同一品系的小鼠中无免疫排斥反应地获得，但人类雌性生殖系干细胞（hFGSC）的获得比较困难，而且不同个体之间可能发生免疫排斥反应。在这项研究中，CTx导致小鼠不育，并评估了FGSC恢复卵巢功能甚至产生后代的能力。我们已经成功地从CTx后两周的成年雌性小鼠中分离和纯化了FGSC。感染携带GFP的病毒后，将FGSC移植到CTx致不孕小鼠的卵巢中。最后，卵巢功能恢复，受体长期生育后代。这些发现表明，CTx小鼠具有FGSC，恢复卵巢功能并避免外源种系干细胞的免疫排斥。
Early menopause and infertility often occur in female cancer patients after chemotherapy (CTx). For these patients, oocyte/embryo cryopreservation or ovarian tissue cryopreservation is the current modality for fertility preservation. However, the above methods are limited in the long-term protection of ovarian function, especially for fertility preservation (very few females with cancer have achieved pregnancy with cryopreserved ovarian tissue or eggs until now). In addition, the above methods are subject to their scope (females with no husband or prepubertal females with no mature oocytes). Thus, many females who suffer from cancers would not adopt the above methods pre- and post-CTx due to their uncertainty, safety and cost-effectiveness. Therefore, millions of women have achieved long-term survival after thorough CTx treatment and have desired to rescue their ovarian function and fertility with economic, durable and reliable methods. Recently, some studies showed that mice with infertility caused by CTx can produce normal offspring through intraovarian injection of exogenous female germline stem cells (FGSCs). Though exogenous FGSC can be derived from mice without immune rejection in the same strain, it is difficult to obtain human female germline stem cells (hFGSCs), and immune rejection could occur between different individuals. In this study, infertility in mice was caused by CTx, and the ability of FGSCs to restore ovarian function or even produce offspring was assessed. We had successfully isolated and purified the FGSCs from adult female mice two weeks after CTx. After infection with GFP-carrying virus, the FGSCs were transplanted into ovaries of mice with infertility caused by CTx. Finally, ovarian function was restored and the recipients produced offspring long-term. These findings showed that mice with CTx possessed FGSCs, restoring ovarian function and avoiding immune rejection from exogenous germline stem cells.