The restorative effects of adipose-derived mesenchymal stem cells on damaged ovarian function.

The restorative effects of adipose-derived mesenchymal stem cells on damaged ovarian function.
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DOI:
10.1038/labinvest.2012.167
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发表时间:
2013-02
期刊:
Laboratory investigation; a journal of technical methods and pathology
影响因子:
--
通讯作者:
--
中科院分区:
其他
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人脂肪源性间充质干细胞(MSCs)作为治疗顽固性疾病或创伤性组织损伤的临床应用备受关注。为了研究重新激活受损卵巢的能力,我们使用抗癌剂环磷酰胺(CTX)制备了受损卵巢的大鼠模型。然后,我们研究了脂肪来源的间充质干细胞(A-MSCs)对卵巢功能的恢复作用和安全性。MSCs具有诱导血管生成、恢复卵巢卵泡和黄体数量的作用。F1和F2大鼠未见畸形、肿瘤形成和死亡,说明卵巢局部注射MSCs无明显副作用。此外,通过将雄性A-MSCs注入卵巢,采用荧光原位杂交法研究Y染色体的定位;结果,Y染色体不是定位于卵泡,而是定位于鞘层。ELISA结果显示,A-MSCs比尾成纤维细胞分泌更高水平的血管内皮细胞生长因子(VEGF)、胰岛素样生长因子-1 (IGF-1)和肝细胞生长因子(HGF)。实时荧光定量PCR和免疫组化结果显示,A-MSC移植后,ctx处理的卵巢中VEGF、IGF-1和HGF的表达水平较高。这些发现表明间充质干细胞可能在恢复受损卵巢功能方面发挥作用,并可能对再生医学有用。
The clinical application of human adipose-derived mesenchymal stem cells (MSCs) as treatment for intractable diseases or traumatic tissue damage has attracted attention. To address the ability of reactivating injured ovaries, we prepared a rat model with damaged ovaries by using an anticancer agent, cyclophosphamide (CTX). We then investigated the restorative effects on ovarian function and the safety of adipose-derived MSCs (A-MSCs). MSCs were shown to be capable of inducing angiogenesis and restoring the number of ovarian follicles and corpus lutea in ovaries. No deformities, tumor formation or deaths were observed in F1 and F2 rats, indicating that the local injection of MSCs into the ovary did not have any obvious side effects. In addition, the localization of the Y chromosome was investigated using the fluorescent in situ hybridization method by injecting male A-MSCs into the ovaries; as a result, the Y chromosomes were localized not in the follicles, but in the thecal layers. ELISA revealed that A-MSCs secreted higher levels of vascular endothelial cell growth factor (VEGF), insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) than tail fibroblast cells. Quantitative real-time PCR and immunohistochemistry showed that higher expression levels of VEGF, IGF-1 and HGF were observed in CTX-treated ovaries after A-MSC transplantation. These findings suggest that MSCs may have a role in restoring damaged ovarian function and could be useful for regenerative medicine.
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