Vitamin C improves the therapeutic potential of human amniotic epithelial cells in premature ovarian insufficiency disease
Vitamin C improves the therapeutic potential of human amniotic epithelial cells in premature ovarian insufficiency disease
复制标题
维生素C提高人羊膜上皮细胞对卵巢早衰疾病的治疗潜力
DOI：
10.1186/s13287-020-01666-y
复制
发表时间：
2020-04-22
影响因子：
7.5
通讯作者：
Li, Hong
中科院分区：
文献类型：
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作者：
Hou, Shunyu;Ding, Chenyue;Li, Hong
背景人羊膜上皮细胞（human amniotic epithelial cell，hAEC）移植在治疗卵巢功能不全（premature ovarian insufficiency，POI）方面具有广阔的应用前景。然而，hAECs的某些生物学特性限制了其应用。然后，测定VC处理的hAEC（VC-hAEC）的增殖能力、迁移能力、多能性和自我更新能力。接着，将hAECs和VC-hAECs移植到环磷酰胺（CTX）诱导的POI模型小鼠的卵巢中。移植后通过计数卵泡数和测定AMH、E2和FSH水平评价POI小鼠的卵巢功能。通过与CTX损伤的人卵巢颗粒细胞（hGCs）共培养并分析相关标志物表达来揭示VC-hAECs和hAECs的拯救作用。此外，在移植后检测POI小鼠中的卵巢标志物表达和移植物存活，以验证VC-hAEC的有益效果。的细胞因子的VC-hAECs和hAECs的细胞因子档案进行细胞因子阵列和ELISA显示其旁分泌functions.ResultsOur结果表明，VC促进增殖，迁移，多能性，和自我更新的hAECs在体外。VC的最佳浓度为50 μg/ml。在移植到POI小鼠模型中后，VC-hAEC比hAEC更有力地逆转卵巢功能。与hAECs相比，与VC-hAECs共培养后，CTX损伤的hGCs中的人颗粒细胞标志物表达增加。在POI小鼠的卵巢中，VC-hAEC移植后卵巢标志物的表达高于hAEC移植后。VC-hAEC显示出比hAEC更高的移植存活率。此外，VC-hAECs分泌更多的生长因子比hAECs.ConclusionTreatment与VC促进hAECs的增殖，迁移，自我更新，和旁分泌功能。此外，VC提高了hAEC在治疗POI中的治疗潜力。
BackgroundHuman amniotic epithelial cell (hAEC) transplantation holds great promise in treating premature ovarian insufficiency (POI). However, some deficient biological characteristics of hAECs restrict their application.MethodsVitamin C (VC) was added to the culture media of hAECs for 2 weeks. Then, the proliferative ability, migration ability, pluripotency, and self-renewal of VC-treated hAECs (VC-hAECs) were determined. Next, hAECs and VC-hAECs were transplanted into the ovaries of cyclophosphamide (CTX)-induced POI model mice. The ovarian function of POI mice was evaluated after transplantation by counting follicle numbers and measuring the blood levels of AMH, E2, and FSH. The rescue effects of VC-hAECs and hAECs were unveiled by coculturing with CTX-damaged human ovarian granulosa cells (hGCs) and analyzing relative marker expression. Additionally, ovarian marker expression and transplant survival were detected in POI mice after transplantation to verify the beneficial effect of VC-hAECs. The cytokine profiles of VC-hAECs and hAECs were revealed by performing a cytokine array and an ELISA to show their paracrine function.ResultsOur results indicated that VC promoted the proliferation, migration, pluripotency, and self-renewal of hAECs in vitro. The most effective concentration of VC was 50 μg/ml. After transplantation into the POI mouse model, VC-hAECs reversed ovarian function more powerfully than hAECs. Human granulosa cell marker expression in CTX-damaged hGCs was increased after coculture with VC-hAECs compared with hAECs. In the ovaries of the POI mice, ovarian marker expression was greater after VC-hAEC transplantation than after hAEC transplantation. VC-hAECs showed higher transplant survival than hAECs. Furthermore, VC-hAECs secreted more growth factors than hAECs.ConclusionTreatment with VC promoted the proliferation, migration, self-renewal, and paracrine functions of hAECs. Additionally, VC elevated the therapeutic potential of hAECs in treating POI.