Mesenchymal stem cell-derived angiogenin promotes primodial follicle survival and angiogenesis in transplanted human ovarian tissue.
Mesenchymal stem cell-derived angiogenin promotes primodial follicle survival and angiogenesis in transplanted human ovarian tissue.
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间充质干细胞来源的血管生成素促进移植的人卵巢组织中原始卵泡的存活和血管生成
DOI：
10.1186/s12958-017-0235-8
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发表时间：
2017-03-09
期刊：
影响因子：
--
通讯作者：
Qiao J
中科院分区：
文献类型：
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作者：
Zhang Y;Xia X;Yan J;Yan L;Lu C;Zhu X;Wang T;Yin T;Li R;Chang HM;Qiao J
背景我们最近报道了人骨髓间充质干细胞（MSCs）促进异种移植的人卵巢组织中的血管生成并防止卵泡丢失。然而，这种影响的机制仍有待阐明。因此，确定旁分泌配置文件，并确定在与卵巢移植物共同移植的间充质干细胞的关键分泌因子是必不可少的，为未来的应用MSCs.MethodsIn这项研究中，我们使用细胞因子微阵列，以确定差异表达的蛋白质与血管生成在冷冻解冻的卵巢组织共同移植间充质干细胞。通过靶向阻断短发夹状RNA干扰和使用单克隆中和抗体，研究了与人卵巢组织共移植的MSC中特异性分泌因子的功能。结果显示，血管生成素（ANG）是表达上调最强烈的蛋白之一（在我们筛选的42种蛋白中，有37种蛋白表达上调）。值得注意的是，有针对性的ANG与短发夹RNAi（shANG）或添加抗ANG单克隆中和抗体（ANG Ab）的消耗显着逆转MSC刺激的血管生成，增加卵泡数量和保护作用对卵泡apoptosis.ConclusionOur结果表明，ANG在调节血管生成和卵泡存活在异种移植人卵巢组织中起着至关重要的作用。我们的研究结果提供了重要的见解的分子机制，骨髓间充质干细胞促进血管生成和移植卵巢组织中的卵泡存活，从而提供了理论基础，其进一步的应用。
BackgroundWe have recently reported that human bone marrow-derived mesenchymal stem cells (MSCs) facilitate angiogenesis and prevent follicle loss in xenografted human ovarian tissues. However, the mechanism underlying this effect remains to be elucidated. Thus, determining the paracrine profiles and identifying the key secreted factors in MSCs co-transplanted with ovarian grafts are essential for the future application of MSCs.MethodsIn this study, we used cytokine microarrays to identify differentially expressed proteins associated with angiogenesis in frozen-thawed ovarian tissues co-transplanted with MSCs. The function of specific secreted factors in MSCs co-transplanted with human ovarian tissues was studied via targeted blockade with short-hairpin RNAi and the use of monoclonal neutralizing antibodies.ResultsOur results showed that angiogenin (ANG) was one of the most robustly up-regulated proteins (among 42 protein we screened, 37 proteins were up-regulated). Notably, the targeted depletion of ANG with short-hairpin RNAi (shANG) or the addition of anti-ANG monoclonal neutralizing antibodies (ANG Ab) significantly reversed the MSC-stimulated angiogenesis, increased follicle numbers and protective effect on follicle apoptosis.ConclusionOur results indicate that ANG plays a critical role in regulating angiogenesis and follicle survival in xenografted human ovarian tissues. Our findings provide important insights into the molecular mechanism by which MSCs promote angiogenesis and follicle survival in transplanted ovarian tissues, thus providing a theoretical basis for their further application.