Time course of myocardial stromal cell-derived factor 1 expression and beneficial effects of intravenously administered bone marrow stem cells in rats with experimental myocardial infarction

Time course of myocardial stromal cell-derived factor 1 expression and beneficial effects of intravenously administered bone marrow stem cells in rats with experimental myocardial infarction
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DOI:
10.1007/s00395-005-0521-z
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发表时间:
2005-05-01
影响因子:
9.5
通讯作者:
Zou, YZ
Zou, YZ
中科院分区:
医学1区
文献类型:
--
作者:
Ma, J;Ge, JB;Zou, YZ

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目的趋化因子基质细胞衍生因子-1(SDF-1)参与骨髓细胞向损伤部位的归巢。我们研究了心肌梗死(MI)大鼠心肌SDF-1表达的时间过程和静脉注射骨髓间充质干细胞(MSC)的影响。方法采用逆转录聚合酶链反应(RT-PCR)和蛋白质印迹法(Western blot)检测假手术组和梗死组心肌组织中SDF-1的表达。供体大鼠骨髓间充质干细胞用BrdU标记。在上述时间点,通过尾静脉注射2.5 mL PBS中的总共5 x 10(6)个细胞或单独的等体积PBS。注射后3天计数梗死心脏中标记的MSC的数量。注射后28天评估心脏功能和血管数量。结果假手术组心肌组织SDF-1表达增加,并在MI后第1天达高峰,此后逐渐下降,但无明显变化。移植1d组心肌内MSCs的富集和血管生成明显高于其他各组(P < 0.01)。仅在MI后4天内接受静脉注射MSC的大鼠中心功能得到改善,而PBS注射对心功能没有影响。结论心肌梗死后早期心肌SDF-1表达增加。在MI早期静脉输注MSCs可募集到受损心脏,促进血管生成,改善心功能。
Objective The chemokine stromal cell-derived factor-1 (SDF-1) has been implicated in homing of bone marrow cells to sites of injury. We investigated the time course of myocardial SDF-1 expression and effects of intravenously administered bone marrow mesenchymal stem cells ( MSC) in rats with myocardial infarction (MI). Methods SDF-1 expression was measured by RT-PCR and Western blot in sham operated or infarcted hearts at 1/2, 1, 2, 4, 8 and 16 days post operation. MSCs from donor rats were labeled with BrdU. A total of 5 x 10(6) cells in 2.5 mL of PBS or equal volume PBS alone were injected through the tail vein at above mentioned time points. The number of the labeled MSCs in the infarcted hearts was counted 3 days post injection. Cardiac function and vessel numbers were assessed 28 days post injection. Results Myocardial SDF-1 expression increased and peaked at the first day and decreased thereafter post MI and remained unchanged in sham operated hearts. The MSCs enrichment and angiogenesis in the host hearts were more abundant in the 1 day transplantation group than in the other groups ( P < 0.01). Cardiac function was only improved in rats received intravenous MSCs injection within 4 days post MI and not affected by PBS injection. Conclusions Myocardial SDF-1 expression was increased only in the early phase post MI. MSCs intravenous infused at the early phase of MI were recruited to injured heart, enhanced angiogenesis and improved cardiac function.