首页> 外文期刊>Stem cells international >The Paracrine Effect of Transplanted Human Amniotic Epithelial Cells on Ovarian Function Improvement in a Mouse Model of Chemotherapy-Induced Primary Ovarian Insufficiency
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The Paracrine Effect of Transplanted Human Amniotic Epithelial Cells on Ovarian Function Improvement in a Mouse Model of Chemotherapy-Induced Primary Ovarian Insufficiency

机译:移植的人羊膜上皮细胞对化疗诱导的原发性卵巢功能不全的小鼠模型卵巢功能改进的旁静脉作用

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摘要

Human amnion epithelial cells (hAECs) transplantation via tail vein has been reported to rescue ovarian function in mice with chemotherapy-induced primary ovarian insufficiency (POI). To test whether intraperitoneally transplanted hAECs could induce therapeutic effect and to characterize the paracrine effect of transplanted hAECs, we utilized a chemotherapy induced mice model of POI and investigated the ability of hAECs and conditioned medium collected from cultured hAECs (hAECs-CM) to restore ovarian function. We found that transplantation of hAECs or hAECs-CM either 24 hours or 7 days after chemotherapy could increase follicle numbers and partly restore fertility. By PCR analysis of recipient mice ovaries, the presence of SRY gene was only detected in mice transplanted with male hAECs 24 hours following chemotherapy. Further, the gene expression level of VEGFR1 and VEGFR2 in the ovaries decreased, although VEGFA increased 2 weeks after chemotherapy. After treatment with hAECs or hAEC-CM, the expression of both VEGFR1 and VEGFR2 increased, consistent with the immunohistochemical analysis. In addition, both hAECs and hAECs-CM treatment enhanced angiogenesis in the ovaries. The results suggested that hAECs-CM, like hAECs, could partly restore ovarian function, and the therapeutic function of intraperitoneally transplanted hAECs was mainly induced by paracrine-mediated ovarian protection and angiogenesis.
机译:据报道,通过尾静脉移植通过尾静脉移植以拯救卵巢功能,以诱导的原发性卵巢不足(POI)。为了测试腹膜内移植的HAEC是否可以诱导治疗效果并表征移植的HAECs的旁静脉作用,我们利用了化疗诱导的POI小鼠模型,并研究了从培养的HAECS(HAECS-CM)中收集的HAECS和条件培养基的能力恢复卵巢功能。我们发现化疗后24小时或7天移植HAECs或HAECS-CM可以增加卵泡数并部分恢复生育能力。通过PCR分析卵巢分析,仅在化疗后24小时移植的小鼠中检测到Sry基因的存在。此外,卵巢中VEGFR1和VEGFR2的基因表达水平降低,但在化疗后2周增加2周。在用HAECS或HAEC-CM处理后,VEGFR1和VEGFR2的表达增加,与免疫组化分析一致。此外,HAECs和HAECS-CM治疗均有增强卵巢的血管生成。结果表明,如HAECs,可以部分恢复卵巢功能,并且腹膜内移植的HAECs的治疗功能主要由旁静脉介导的卵巢保护和血管生成诱导。

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