Fertility Center of CHA Gangnam Medical Center, CHA University, 569 Nonhyun-ro, Gangnam-Gu, Seoul, 06125, South Korea.
Department of Biomedical Science, CHA University, Seongnam-si, South Korea.
Stem Cell Res Ther. 2020 Jun 26;11(1):255. doi: 10.1186/s13287-020-01769-6.
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.
间充质干细胞（MSCs）的临床应用需要一个均匀的细胞群体，而其采集具有侵入性且只能产生有限数量的细胞。人胚胎干细胞来源的间充质干细胞（hESC-MSCs）可分化为三个胚层，并在体外具有免疫抑制作用。癌症治疗是导致卵巢早衰（POF）的一个众所周知的危险因素。在这项研究中，我们研究了 hESC-MSC 对顺铂诱导的 POF 小鼠卵巢功能恢复的影响。
雌性小鼠接受腹腔内顺铂治疗 10 天。在第 12 天，通过尾静脉注射将 CHA15 衍生的 hESC-MSCs 移植到小鼠体内。注射 PBS 作为阴性对照。移植后 28 天取出卵巢，进行卵巢组织学、免疫染色和通过超排卵和体外受精进行的生育能力测试。hESC-MSC 移植到顺铂损伤的小鼠体内恢复了体重和卵巢大小。
与 PBS 组相比，hESC-MSC 组的原始卵泡和初级卵泡计数明显增加（P<0.05），卵母细胞透明带残余物（卵巢卵泡凋亡的一个标志）计数明显减少（P<0.05）。TUNEL 检测和 cleaved PARP 免疫染色表明凋亡导致阴性对照组卵巢基质细胞丢失，而 hESC-MSC 组和未用顺铂处理的对照组的 Ki-67 水平高于 PBS 组。PBS 组的排卵减少，但 hESC-MSC 组明显恢复。从排卵卵形成囊胚的率和每只小鼠的活产率在 hESC-MSC 组也明显恢复。
hESC-MSC 恢复了顺铂损伤卵巢的结构和功能。我们的研究为 hESC-MSC 在治疗 POF 方面的巨大临床潜力提供了新的见解。
