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成年干细胞的全身递送可改善自发性高血压大鼠的心脏功能。

Systemic delivery of adult stem cells improves cardiac function in spontaneously hypertensive rats.

作者信息

Braga Luisa M G de Macedo, Rosa Kaleizu, Rodrigues Bruno, Malfitano Christiane, Camassola Melissa, Chagastelles Pedro, Lacchini Silvia, Fiorino Patricia, De Angelis Kátia, Schaan Beatriz D'Agord, Irigoyen Maria C, Nardi Nance Beyer

机构信息

Department of Genetics, Federal University of Rio Grande do Sul, and State Foundation of Production and Research in Health of Rio Grande do Sul, Porto Alegre, Brazil.

出版信息

Clin Exp Pharmacol Physiol. 2008 Feb;35(2):113-9. doi: 10.1111/j.1440-1681.2007.04820.x. Epub 2007 Oct 31.

Abstract
  1. Heart regeneration after myocardial infarction (MI) can occur after cell therapy, but the mechanisms, cell types and delivery methods responsible for this improvement are still under investigation. In the present study, we evaluated the impact of systemic delivery of bone marrow cells (BMC) and cultivated mesenchymal stem cells (MSC) on cardiac morphology, function and mortality in spontaneously hypertensive rats (SHR) submitted to coronary occlusion. 2. Female syngeneic adult SHR, submitted or not (control group; C) to MI, were treated with intravenous injection of MSC (MI + MSC) or BMC (MI + BM) from male rats and evaluated after 1, 15 and 30 days by echocardiography. Systolic blood pressure (SBP), functional capacity, histology, mortality rate and polymerase chain reaction for the Y chromosome were also analysed. 3. Myocardial infarction induced a decrease in SBP and BMC, but not MSC, prevented this decrease. An improvement in functional capacity and ejection fraction (38 +/- 4, 39 +/- 3 and 58 +/- 2% for MI, MI + MSC and MI + BM, respectively; P < 0.05), as well as a reduction of the left ventricle infarcted area, were observed in rats from the MI + BM group compared with the other three groups. Treated animals had a significantly reduced lesion tissue score. The mortality rate in the C, MI + BM, MI + MSC and MI groups was 0, 0, 16.7 and 44.4%, respectively (P < 0.05 for the MI + MSC and MI groups compared with the C and MI + BM groups). 4. The results of the present study suggest that systemic administration of BMC can improve left ventricular function, functional capacity and, consequently, reduce mortality in an animal model of MI associated with hypertension. We speculate that the cells transiently home to the myocardium, releasing paracrine factors that recruit host cells to repair the lesion.
摘要
  1. 心肌梗死(MI)后心脏再生可在细胞治疗后发生,但其改善的机制、细胞类型及递送方法仍在研究中。在本研究中,我们评估了骨髓细胞(BMC)和培养的间充质干细胞(MSC)全身递送对接受冠状动脉闭塞的自发性高血压大鼠(SHR)心脏形态、功能及死亡率的影响。2. 雌性同基因成年SHR,分为接受或未接受(对照组;C)MI,经静脉注射雄性大鼠的MSC(MI + MSC)或BMC(MI + BM)进行治疗,并在1、15和30天后通过超声心动图进行评估。还分析了收缩压(SBP)、功能能力、组织学、死亡率及Y染色体的聚合酶链反应。3. 心肌梗死导致SBP降低,而BMC可预防这种降低,但MSC不能。与其他三组相比,MI + BM组大鼠的功能能力和射血分数有所改善(MI组、MI + MSC组和MI + BM组分别为38±4%、39±3%和58±2%;P < 0.05),左心室梗死面积减小。治疗动物的病变组织评分显著降低。C组、MI + BM组、MI + MSC组和MI组的死亡率分别为0、0、16.7%和44.4%(MI + MSC组和MI组与C组和MI + BM组相比,P < 0.05)。4. 本研究结果表明,BMC全身给药可改善左心室功能、功能能力,从而降低与高血压相关的MI动物模型的死亡率。我们推测这些细胞短暂归巢至心肌,释放旁分泌因子招募宿主细胞修复损伤。

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