Minnerup Jens, Seeger Florian H, Kuhnert Katharina, Diederich Kai, Schilling Matthias, Dimmeler Stefanie, Schäbitz Wolf-Rüdiger
Department of Neurology, University of Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany.
Exp Transl Stroke Med. 2010 Feb 2;2(1):3. doi: 10.1186/2040-7378-2-3.
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.
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.
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.
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.
越来越多的证据表明,细胞疗法可改善中风和心肌梗死实验模型中的功能恢复。到目前为止,仅有小型试点试验测试了细胞疗法对中风患者的影响,而大型临床试验则在缺血性心脏病患者中进行。为了研究细胞疗法对改善中风后恢复的治疗益处,我们在大鼠中风模型中确定了骨髓来源的单核细胞的疗效,在实验性和临床急性心肌梗死研究中已证明这些细胞可改善恢复情况。
成年雄性Wistar大鼠在光血栓性缺血3天后被随机分配接受动脉内注射500万个人类骨髓单核细胞(hBMC)或安慰剂。为了进行免疫抑制,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。在缺血前及缺血后长达4周的时间内进行了一系列行为测试。
两组之间的体温和体重没有差异。与安慰剂相比,通过转棒试验、去粘连试验和圆筒试验测量的神经功能缺损在hBMC移植后没有改善。
本研究表明,在局灶性脑缺血发作3天后动脉内移植hBMC并不能改善功能恢复。细胞治疗后神经功能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有效性的实验性中风研究相比,治疗开始延迟。