脂肪间充质干细胞联合内皮祖细胞治疗小鼠溃疡性结肠炎

Co-transplantation of adipose mesenchymal stem cells and endothelial progenitor cells in ulcerative colitis mice

背景:已有研究表明间充质干细胞具有治疗溃疡性结肠炎的效果,内皮祖细胞对溃疡性结肠炎是否有治疗效果尚不明确,二者都是生物组织工程重要的种子细胞,均可进行移植。目的:探索脂肪间充质干细胞和内皮祖细胞联合移植治疗溃疡性结肠炎的效果。方法:C57BL/6J小鼠随机分为6组,每组24只:正常对照组、脂肪间充质干细胞组、内皮祖细胞组、联合移植组、糖皮质激素组、模型对照组。除正常对照组外,其他5组小鼠采用葡聚糖硫酸钠诱导建立溃疡性结肠炎模型。造模第7,10天各组小鼠分别经尾静脉注射脂肪间充质干细胞和/或内皮祖细胞、地塞米松磷酸钠、磷酸盐缓冲液。造模第12天处死小鼠,比较各组小鼠疾病活动指数、组织学病理评分、结肠长度、血清肿瘤坏死因子α水平等。结果与结论:①糖皮质激素组具有治疗溃疡性结肠炎的效果,与模型对照组比较差异有显著性意义(P<0.05);②脂肪间充质干细胞组具有治疗溃疡性结肠炎的效果,优于糖皮质激素组,差异有显著性意义(P<0.05);③内皮祖细胞组治疗溃疡性结肠炎的效果不显著,与模型对照组比较,差异无显著性意义(P>0.05);④脂肪间充质干细胞联合内皮祖细胞移植治疗溃疡性结肠炎的效果优于其他各组,显著改善结肠缩短程度、疾病活动指数、组织学病理评分、血清肿瘤坏死因子α水平。

BACKGROUND:Mesenchymal stem cell transplantation has been proved to be effective for ulcerative colitis,while the effect of endothelial progenitor cells in ulcerative colitis treatment is still unknown.They are both promising cells for tissue engineering,which can be used for cell transplantation.OBJECTIVE:To explore whether co-transplantation of endothelial progenitor cells and adipose mesenchymal stem cells can relieve ulcerative colitis in a mouse model.METHODS:C57BL/6J mice were randomly divided into six groups(n=24 per group):co-transplantation group,mesenchymal stem cell transplantation group,endothelial progenitor cell transplantation group,glucocorticoid treatment group,transplantation control group and normal control group.Murine ulcerative colitis model was established in all groups except for the normal control group.At 7 and 10 days after modeling,transplantation groups were respectively injected via tail vein with adipose mesenchymal stem cells and/or endothelial progenitor cells,glucocorticoid or PBS.Mice were sacrificed at 12 days after modeling.Colon length,disease activity index,histological score and the serum level of tumor necrosis factor-αwere compared between groups.RESULTS AND CONCLUSION:Treatment with glucocorticoid was significantly effective for ulcerative colitis relative to the transplantation control group(P<0.05).Adipose mesenchymal stem cells were proved to have better effects than glucocorticoids in the murine ulcerative colitis model(P<0.05).No significant differences were found between endothelial progenitor cell transplantation group and transplantation control group(P>0.05).Co-transplantation of adipose mesenchymal stem cells and endothelial progenitor cells was better than the other treatments,which significantly improved the shortening of the colon,disease activity index,histological score,and serum level of tumor necrosis factor-α.