Intracarotid administration of human bone marrow mononuclear cells in rat photothrombotic ischemia.

Jens Minnerup, Florian H Seeger, Katharina Kuhnert, Kai Diederich, Matthias Schilling, Stefanie Dimmeler, Wolf-Rüdiger Schäbitz
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引用次数: 16

Abstract

Background: Increasing evidence suggests that cell therapy improves functional recovery in experimental models of stroke and myocardial infarction. So far only small pilot trials tested the effects of cell therapy in stroke patients, whereas large clinical trials were conducted in patients with ischemic heart disease. To investigate the therapeutic benefit of cell therapy to improve the recovery after stroke, we determined the efficacy of bone marrow derived mononuclear cells, which were shown to improve the recovery in experimental and clinical acute myocardial infarction studies, in a rat stroke model.

Methods: Adult male Wistar rats were randomly assigned to receive either five million human bone marrow mononuclear cells (hBMC) or placebo intraarterially 3 days after photothrombotic ischemia. For immunosuppression the animals received daily injections of cyclosporine throughout the experiment, commencing 24 hours before the cell transplantation. A battery of behavioral tests was performed before and up to 4 weeks after ischemia.

Results: Body temperature and body weight revealed no difference between groups. Neurological deficits measured by the Rotarod test, the adhesive-removal test and the cylinder test were not improved by hBMC transplantation compared to placebo.

Conclusions: This study demonstrates that hBMC do not improve functional recovery when transplanted intraaterially 3 days after the onset of focal cerebral ischemia. A possible reason for the failed neurological improvement after cell therapy might be the delayed treatment initiation compared to other experimental stroke studies that showed efficacy of bone marrow mononuclear cells.

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人骨髓单核细胞在大鼠光血栓性缺血中的应用。
背景:越来越多的证据表明,细胞治疗可以改善脑卒中和心肌梗死实验模型的功能恢复。到目前为止,只有小规模的试点试验测试了细胞疗法对中风患者的影响,而大型临床试验是在缺血性心脏病患者中进行的。为了研究细胞疗法对提高中风后恢复的疗效,我们在大鼠中风模型中确定了骨髓来源的单个核细胞的疗效,骨髓来源的单个核细胞在实验和临床急性心肌梗死研究中被证明可以改善恢复。方法:成年雄性Wistar大鼠在光血栓性缺血3天后,随机分配500万人类骨髓单个核细胞(hBMC)或安慰剂动脉内注射。为了抑制免疫,动物在整个实验过程中每天注射环孢素,从细胞移植前24小时开始。在缺血前和缺血后4周进行一系列行为测试。结果:两组间体温、体重无明显差异。与安慰剂相比,hBMC移植没有改善Rotarod试验、黏合剂去除试验和圆柱体试验测量的神经功能缺损。结论:本研究表明,在局灶性脑缺血发生后3天内移植hBMC并不能改善功能恢复。细胞治疗后神经系统改善失败的一个可能原因可能是与其他显示骨髓单核细胞疗效的实验性中风研究相比,治疗开始时间较晚。
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