静脉及心肌注射骨髓间充质基质细胞未能改善慢性心肌梗死大鼠的心脏功能

Intravenous and intramyocardial administration of bone marrow mesenchymal stromal cells cannot improve heart function in a rat model of chronic myocardial infarction

背景:有多项研究证明,经静脉或经心肌表面注射移植间充质基质细胞促进了急性心肌梗死后心功能的改善。然而,目前尚缺乏有关经静脉联合经心肌注射移植间充质基质细胞对慢性心肌梗死心脏功能影响的研究。目的:探讨静脉联合心肌注射骨髓间充质基质细胞对慢性心肌梗死模型大鼠心脏功能的影响及其机制。方法:体外培养扩增Lewis大鼠的骨髓间充质基质细胞。将3×106Brd U标记过的骨髓间充质基质细胞分别经股静脉和经心肌表面注射移植于慢性心肌梗死模型大鼠,对照组注射等量PBS。4周后检测两组大鼠心功能的变化,并对大鼠心脏组织行免疫组化染色,观察细胞分化情况及毛细血管数量。结果与结论:骨髓间充质基质细胞移植4周后,细胞移植组与对照组心功能无明显差别,免疫组化染色提示存留于心肌组织内的移植细胞未分化为心肌细胞,心梗瘢痕区血管密度在细胞移植组和对照组间没有明显差别。结果表明经静脉联合经心肌注射骨髓间充质基质细胞未能改善慢性心肌梗死模型大鼠的心脏功能。

BACKGROUND： It has been demonstrated to be effective for the improvement of heart function after acute myocardial infarction with intravenous or intramyocardial administration of bone marrow mesenchymal stromal cells.However, little is known regarding the effect of the combination of intravenous and intramyocardial administration of mesenchymal stromal cells on the heart function of a chronic myocardial infarction model.OBJECTIVE： To study the effect of intravenous and intramyocardial administration of bone marrow mesenchymal stromal cells on the heart function of a rat chronic myocardial infarction model and the relevant mechanism.METHODS： Bone marrow mesenchymal stromal cells isolated from Lewis rats were expanded ex vivo.Brd U-labeled bone marrow mesenchymal stromal cells（3×106） were administered via the femoral vein and themyocardial surface respectively into rat models of chronic myocardial infarction in cell transplantation group. The equal volume of PBS was injected into the same place in control group. Four weeks after injection, echocardiography was performed to evaluate the heart function, and then the heart tissues were harvested for immunohistochemistry examination. The total blood vessel density in the scar area was evaluated.RESULTS AND CONCLUSION： At 4 weeks after cell implantation, the left ventricular function was not improved in the two groups. The immunohistochemistry staining showed that（1） the mesenchymal stromal cells in the myocardium did not differentiate to myocardial cells;（2） there was no significant difference in the total blood vessel density in the scar area between the cell transplantation and control groups. Taken together, the combined intravenous and intramyocardial administration of bone marrow mesenchymal stromal cells cannot improve heart function in a rat chronic myocardial infarction model.