Human CD133+ bone marrow-derived stem cells promote endometrial proliferation in a murine model of Asherman syndrome
Human CD133+ bone marrow-derived stem cells promote endometrial proliferation in a murine model of Asherman syndrome
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DOI：
10.1016/j.fertnstert.2015.08.032
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发表时间：
2015-12-01
影响因子：
6.7
通讯作者：
Simon, Carlos
中科院分区：
文献类型：
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作者：
Cervello, Irene;Gil-Sanchis, Claudia;Simon, Carlos
目的：研究超顺磁性氧化铁纳米颗粒（SPIOs）标记的人CD133（+）骨髓源性干细胞（BMDSCs）在Asherman综合征（AS）动物模型中的植入和增殖情况。设计：前瞻性实验动物研究。环境：大学研究实验室。动物：非肥胖糖尿病小鼠（品系代码394；NOD）。CB17-Prkdc(scid)/NcrCrl)，根据已发表的方案诱导AS。干预措施：从接受自体细胞治疗的难治性AS和子宫内膜萎缩患者中获得人CD133(+) BMDSCs，用SPIOs标记，在动物模型中通过子宫内注射（n = 5）或通过尾静脉全身注射（n = 5）。主要观察指标：三色染色检测胶原积累和糖胺聚糖沉积。普鲁士蓝染色法测定人spios标记CD133（+）骨髓间充质干细胞移植的百分比和定位。使用Ki67和逆转录聚合酶链反应（PCR）对特定旁分泌因子进行细胞增殖试验。结果：三色染色显示，小鼠损伤角中胶原蛋白和糖胺聚糖沉积的积累证实了AS的诱导作用。人spio标记的CD133(+) BMDSCs归巢分别占子宫内或尾静脉注射后角中细胞总数的0.59%和0.65%。移植细胞定位于子宫内膜血管周围，通过Ki67和旁分泌因子血小板反应蛋白1和胰岛素样生长因子1的调控，诱导周围细胞增殖。结论：在小鼠AS模型中注射人spio标记的CD133(+) BMDSCs证实，这些细胞在子宫内膜血管周围植入，通过旁分泌分子如血栓反应蛋白1和胰岛素样生长因子1诱导周围细胞增殖。(C) 2015年美国生殖医学学会。
Objective: To investigate the engraftment and proliferation of superparamagnetic iron oxide nanoparticles (SPIOs)-labeled human CD133(+) bone marrow-derived stem cells (BMDSCs) in an animal model of Asherman syndrome (AS).Design: Prospective experimental animal study.Setting: University research laboratories.Animal(s): Nonobese diabetic mice (strain code 394; NOD. CB17-Prkdc(scid)/NcrCrl) in which AS was induced according to a published protocol.Intervention(s): Human CD133(+) BMDSCs were obtained from patients undergoing autologous cell therapy in refractory AS and endometrial atrophy, labeled with SPIOs and injected either intrauterinely (n = 5) or systemically through the tail vein (n = 5) in the animal model. Main Outcome Measure(s): Accumulation of collagen and glycosaminoglycan deposits detected by trichrome staining. Percentage and localization of engrafted human SPIOs-labeled CD133(+) BMDSCs by Prussian blue staining. Cell proliferation assay using Ki67 and reverse transcriptase-polymerase chain reaction (PCR) for specific paracrine factors.Result(s): The induction of the AS in the murine model was demonstrated by the accumulation of collagen and glycosaminoglycan deposits in the damaged horns by trichrome staining. Human SPIOs labeled CD133(+) BMDSCs homing represents 0.59% and 0.65% of total number of cells present in the horns after intrauterine or tail vein injections, respectively. Engrafted cells were localized around endometrial blood vessels, inducing proliferation in surrounding cells based on Ki67 and regulation of the paracrine factors thrombospondin 1 and insulin-like growth factor 1.Conclusion(s): The injection of human SPIOs labeled CD133(+) BMDSCs in a murine model of AS confirms that these cells engraft around endometrial vessels, inducing proliferation of surrounding cells through paracrine molecules such as thrombospondin 1 and insulin-like growth factor 1. (C) 2015 by American Society for Reproductive Medicine.