Vitamin C plus hydrogel facilitates bone marrow stromal cell-mediated endometrium regeneration in rats.
Vitamin C plus hydrogel facilitates bone marrow stromal cell-mediated endometrium regeneration in rats.
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维生素 C 加水凝胶促进大鼠骨髓基质细胞介导的子宫内膜再生
DOI：
10.1186/s13287-017-0718-8
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发表时间：
2017-11-21
影响因子：
7.5
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Yang H;Wu S;Feng R;Huang J;Liu L;Liu F;Chen Y
研究背景宫腔粘连（IUA）是一种常见的宫腔疾病，可由机械性损伤引起，最终可导致不孕和妊娠异常。由于治疗药物的效果令人失望，细胞治疗已成为子宫内膜再生的替代选择。本研究的目的是探讨水凝胶Pluronic F-127（PF-127）、维生素C（Vc）和骨髓基质细胞（BMSC）混合物的组合是否是改善子宫内膜再生的可行策略在大鼠IUA机械损伤模型中。方法首先，使用Annexin V/碘化丙啶（PI）凋亡试验、细胞计数试剂盒（CCK）生长试验和酶联免疫吸附试验（ELISA）在体外检测PF-127细胞毒性和Vc的作用。为了建立大鼠IUA模型，在子宫上端制备2 mm横切口，刮取1.5- 2.0cm的子宫内膜损伤。将大鼠随机分为假手术组、IUA对照组、PF-127 + Vc组、IUA BMSC + Vc组、IUA PF-127 + Vc组，观察联合用药对IUA子宫再生的影响。在制作IUA模型的同时，将细胞混合物注入子宫角。细胞移植后8周，处死大鼠，解剖子宫进行分析。子宫内膜厚度，腺体数量，纤维化面积，和子宫内膜的标志蛋白的表达进行了检查，苏木精-伊红染色，Masson染色，免疫组化。ResultsVc促进PF-127封装的BMSCs在体外的生存和健康。当这种组合物在体内移植时，子宫内膜显示出更好的恢复，因为子宫内膜膜变得更厚，并且具有更多的腺体和更少的纤维化区域。细胞角蛋白，血管性血友病因子（vWF）的表达，也得到恢复。促炎细胞因子白细胞介素-1 β（IL-1β）显著低于对照组（control group.ConclusionsVc增强PF-127的细胞毒性作用，促进大鼠BMSC包裹细胞的存活和生长。因此，含有生物材料支架、BMSC和调节因子Vc的细胞治疗策略促进受损的IUA子宫内膜的恢复。
BackgroundIntrauterine adhesion (IUA) is a common uterine cavity disease which can be caused by mechanical damage that may eventually lead to infertility and pregnancy abnormalities. Since the effect of therapeutic drugs appears disappointing, cell therapy has emerged as an alternative choice for endometrium regeneration. The aim of this study is to investigate whether the combination of hydrogel Pluronic F-127 (PF-127), Vitamin C (Vc), and a bone marrow stromal cell (BMSC) mixture could be a feasible strategy to improve the endometrial regeneration in a mechanical damage model of IUA in rats.MethodsFirstly, PF-127 cytotoxicity and the effect of Vc was tested in vitro using the Annexin V/propidium iodide (PI) apoptosis test, cell count kit (CCK) growth test, and enzyme-linked immunosorbent assay (ELISA). For the establishment of the rat IUA model, a 2-mm transverse incision in the uterus was prepared at the upper end, and 1.5- to 2.0-cm endometrial damage was scraped. Rats were randomly assigned to five groups to investigate the combined strategy on IUA uterine regeneration: a sham group, an IUA control group, an IUA BMSC encapsulated in PF-127 plus Vc group, an IUA BMSC plus Vc group, and an IUA PF-127 plus Vc group. A cell mixture was injected into the uterine horn while making the IUA model. Eight weeks after cell transplantation, the rats were sacrificed and the uterine was dissected for analysis. Endometrial thickness, gland number, fibrosis area, and the expression of marker proteins for endometrial membrane were examined by hematoxylin and eosin staining, Masson’s staining, and immunohistochemistry.ResultsVc promoted the survival and health of PF-127-encapsulated BMSCs in vitro. When this combination was transplanted in vivo, the endometrium showed better restoration as the endometrium membrane became thicker and had more glands and less fibrosis areas. The expression of cytokeratin, von Willebrand Factor (vWF), was also restored. The proinflammatory cytokine interleukin-1β (IL-1β) was significantly lower compared with the control group.ConclusionsVc alleviates the cytotoxic effect of PF-127 and promotes cell survival and growth in rat BMSC encapsulation. Thus, a cell therapy strategy containing biomaterial scaffold, BMSCs and the modulatory factor Vc promotes the restoration of damaged IUA endometrium.
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影响因子：
14
作者：
Matthew, JE;Nazario, YL;Bhatia, SR
通讯作者：
Bhatia, SR
影响因子：
5.9
作者：
D'Aniello C;Habibi E;Cermola F;Paris D;Russo F;Fiorenzano A;Di Napoli G;Melck DJ;Cobellis G;Angelini C;Fico A;Blelloch R;Motta A;Stunnenberg HG;De Cesare D;Patriarca EJ;Minchiotti G
通讯作者：
Minchiotti G
影响因子：
--
作者：
Wang, Jianmei;Ju, Baohui;Zhang, Yujuan
通讯作者：
Zhang, Yujuan
DOI：
10.1016/j.ijporl.2005.04.026
发表时间：
2005-11-01
影响因子：
1.5
作者：
Idrus, RBH;Chua, K;Bin Saim, A
通讯作者：
Bin Saim, A
DOI：
10.1111/j.1752-8062.2009.00096.x
发表时间：
2009-06
期刊：
Clinical and translational science
影响因子：
--
作者：
Nelson TJ;Behfar A;Yamada S;Martinez-Fernandez A;Terzic A
通讯作者：
Terzic A