Su Wenjun, Zhang Hao, Jia Zhuqing, Zhou Chunyan, Wei Yingjie, Hu Shengshou
Research Center for Cardiovascular Regenerative Medicine, the Ministry of Health, and Department of Cardiovascular Surgery, Cardiovascular Institute and Fu-Wai Hospital, CAMS and PUMC, West District, Beijing 100037, People's Republic of China.
Stem Cells. 2006 Feb;24(2):349-56. doi: 10.1634/stemcells.2005-0168. Epub 2005 Oct 20.
Human cartilage is reported to contain multipotent stromal cells. We evaluated the effect of human cartilage-derived stromal cells (CDSCs) on heart function when transplanted into the infarcted myocardium of rats. CDSCs were isolated and cultured from human articular cartilage and subjected to fluorescence-activated cell sorting (FACS) analysis. The CDSCs were consistently negative for CD14, CD34, CD38, CD45, CD49f, CD104, CD105, CD106, CD117, HLA-DR, and ABCG-2, and positive for CD10, CD44, CD71, CD73, CD90, CD147, and HLA-A, -B, and -C by FACS analysis. Myocardial infarction (MI) was created in rats by ligation of the left anterior descending artery. Three weeks after MI, the CDSCs labeled with Hoechst stain were injected into the infarct and border zone. Echocardiography, histological examination, and reverse transcription-polymerase chain reaction (RT-PCR) were performed 4 weeks after cell transplantation. Echocardiography indicated that CDSC transplantation could improve heart function. The number of capillaries increased in the injection regions in the transplantation group. Histological examination showed that Hoechst-labeled CDSCs in islands within the infarcted region were stained positively for desmin and smooth muscle actin but negatively for alpha-sarcomeric actin and troponin-I. RT-PCR results indicated the expression level of collagen I, collagen III, tissue inhibitor of metalloproteinase-1, transforming growth factor-beta1, and vascular endothelia growth factor were much higher in the scar tissue in the transplantation group than in the medium and control groups. Our findings suggested that CDSCs might promote angiogenesis, prevent left ventricular remodeling, and improve the heart function when transplanted into injured heart in the rat model of myocardial infarction.
据报道,人软骨含有多能基质细胞。我们评估了人软骨来源的基质细胞(CDSCs)移植到大鼠梗死心肌后对心脏功能的影响。从人关节软骨中分离并培养CDSCs,并进行荧光激活细胞分选(FACS)分析。FACS分析显示,CDSCs对CD14、CD34、CD38、CD45、CD49f、CD104、CD105、CD106、CD117、HLA-DR和ABCG-2持续呈阴性,而对CD10、CD44、CD71、CD73、CD90、CD147以及HLA-A、-B和-C呈阳性。通过结扎左前降支在大鼠中制造心肌梗死(MI)。MI发生三周后,将用Hoechst染色标记的CDSCs注入梗死区和边缘区。细胞移植4周后进行超声心动图、组织学检查和逆转录聚合酶链反应(RT-PCR)。超声心动图表明,CDSCs移植可改善心脏功能。移植组注射区域的毛细血管数量增加。组织学检查显示,梗死区内岛状的Hoechst标记的CDSCs对结蛋白和平滑肌肌动蛋白呈阳性染色,但对α-肌节肌动蛋白和肌钙蛋白-I呈阴性染色。RT-PCR结果表明,移植组瘢痕组织中I型胶原、III型胶原、金属蛋白酶组织抑制剂-1、转化生长因子-β1和血管内皮生长因子的表达水平远高于培养基组和对照组。我们的研究结果表明,在大鼠心肌梗死模型中,CDSCs移植到受损心脏后可能促进血管生成,防止左心室重构,并改善心脏功能。