Clinical use of mesenchymal stem cells (MSCs) requires a uniform cell population, and their harvesting is invasive and produces a limited number of cells. Human embryonic stem cell-derived MSCs (hESC-MSCs) can differentiate into three germ layers and possess immunosuppressive effects in vitro. Anticancer treatment is a well-known risk factor for premature ovarian failure (POF). In this study, we investigated the effect of hESC-MSC on recovery of ovarian function in cisplatin-induced POF in mice. Female mice received intraperitoneal cisplatin for 10 days. On day 12, CHA15-derived hESC-MSCs were transplanted into the mice by tail vein injection. An injection of PBS served as the negative control. Ovaries were removed 28 days after transplantation for assessment of ovarian histology, immunostaining, and fertility testing by superovulation and in vitro fertilization. hESC-MSC transplantation into mice with cisplatin-induced damage restored body weight and ovary size. Mean primary and primordial follicle counts in the hESC-MSC group were significantly improved compared to the PBS group (P < 0.05), and counts of zona pellucida remnants, an apoptotic sign in ovarian follicles, were significantly reduced (P < 0.05). TUNEL assays and cleaved PARP immunostaining indicated apoptosis, which led to loss of ovarian stromal cells in negative control mice, while Ki-67 was higher in the hESC-MSC group and in non-cisplatin-treated controls than in the PBS group. Ovulation was reduced in the PBS group but recovered significantly in the hESC-MSC group. Rates of blastocyst formation from ovulated eggs and live births per mouse also recovered significantly in the hESC-MSC group. hESC-MSC restored structure and function in the cisplatin-damaged ovary. Our study provides new insights into the great clinical potential of human hESC-MSC in treating POF.

中文翻译：

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人类胚胎干细胞来源的间充质干细胞在顺铂诱导的小鼠卵巢早衰中恢复卵巢功能。

间充质干细胞（MSCs）的临床使用需要均匀的细胞群，并且其收获是侵入性的，并且会产生数量有限的细胞。人胚胎干细胞来源的MSC（hESC-MSC）可以分化为三个胚层，并在体外具有免疫抑制作用。抗癌治疗是卵巢早衰（POF）的众所周知的危险因素。在这项研究中，我们调查了hESC-MSC对顺铂诱导的POF小鼠卵巢功能恢复的影响。雌性小鼠腹膜内接受顺铂治疗10天。在第12天，通过尾静脉注射将衍生自CHA15的hESC-MSC移植到小鼠中。注射PBS作为阴性对照。移植后28天摘除卵巢，以评估卵巢组织学，免疫染色，通过超排卵和体外受精进行生育力测试。hESC-MSC移植到具有顺铂诱导的损伤的小鼠中，可恢复体重和卵巢大小。与PBS组相比，hESC-MSC组的平均初级和原始卵泡计数显着改善（P <0.05），并且透明带残留（卵巢卵泡中的凋亡信号）的计数显着降低（P <0.05）。TUNEL分析和裂解的PARP免疫染色表明，凋亡可导致阴性对照小鼠卵巢基质细胞丢失，而hESC-MSC组和未用顺铂处理的对照组的Ki-67高于PBS组。PBS组排卵减少，而hESC-MSC组排卵明显恢复。在hESC-MSC组中，由排卵卵形成的胚泡形成率和每只小鼠的活产率也显着恢复。hESC-MSC在顺铂损伤的卵巢中恢复了结构和功能。我们的研究为人类hESC-MSC在治疗POF中的巨大临床潜力提供了新的见解。