骨髓动员对骨髓造血干细胞在心肌梗死后心脏中定植及分化的影响

INFLUENCE OF BONE MARROW MOBILIZATION ON BONE MARROW HEMATOPOIETIC STEM CELLS' ENGRAFTMENT AND DIFFERENTIATION IN MOUSE INFARCTED HEART

目的观察小鼠心肌梗死后骨髓造血干细胞在心脏内的分化及细胞因子的影响。方法C57/BL6小鼠60只分为骨髓动员组和对照组,先后行脾切除、骨髓移植(骨髓供体为增强绿色荧光蛋白转基因小鼠)、骨髓动员及建立心肌梗死模型。心肌梗死后3周将小鼠心脏取出并切片行组织学及激光共聚焦显微镜免疫荧光检查。结果骨髓动员可以增加EGFP阳性细胞在心脏中梗死区和边缘区的定植,但绝大多数EGFP阳性细胞都同时表达CD45。仅发现有极少数骨髓来源的心肌细胞、成纤维细胞及血管内皮细胞,且与骨髓动员无相关性。结论骨髓动员能够明显促进骨髓来源细胞定植入小鼠心脏的梗死区;极少数骨髓造血干细胞可以分化为心肌细胞,其数量远不足以修复梗死心肌及改善心功能;骨髓造血干细胞不参与梗死区疤痕形成的病理过程。

Objective To observe the differentiation of bone marrow hematopoietic stem cells （BMHSCs） in murine infarcted heart and identify the cytokines＇ influence on the differentiation. Methods Sixty C57/BL6 mice were randomly grouped and treated with splenectomy and bone marrow transplantation from EGFP transgenic donor. Bone marrow was mobilized by granulocyte clone stimulating factor （G-CSF） and stem cell factor （SCF） and myocardial infarction was induced successively. The infarcted hearts were taken out and sectioned for histological study and immuno-fluorescenc staining observed by＇ confocal laser scanning technique. Results Cytokines enhanced the engraftment of EGFP positive cells in infarcted and border zones, but most of these cells were CIM5 positive. Only a few BMHSC-originated cardiomyocyte-like cells, fibroblast and endothelial cells were found＇in the infarcted heart, independent of cytokines treatment. Conclusion Bone marrow mobilization can significantly enhance the engraftment of bone marrow derived cells （mainly leukocyte） in the infarcted area of the heart. Only a few BMHSCs were found to differentiate into cardiomyocyte-like cells which are too few to repair the infarcted myocardium and improve the heart function. The BMHSCs per se may not take part in the pathological process of scar formation after myocardial infarction.