Jelicks Linda A, Tanowitz Herbert B, Peters Vera Maria, Mendez-Otero Rosalia, de Carvalho Antonio C Campos, Spray David C
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil.
Dept. of Neuroscience, Albert Einstein College of Medicine, NY, USA.
Microbes Infect. 2014 Nov;16(11):923-935. doi: 10.1016/j.micinf.2014.08.016. Epub 2014 Sep 16.
Chagasic cardiomyopathy, resulting from infection with the parasite Trypanosoma cruzi, was discovered more than a century ago and remains an incurable disease. Due to the unique properties of mesenchymal stem cells (MSC) we hypothesized that these cells could have therapeutic potential for chagasic cardiomyopathy. Recently, our group pioneered use of nanoparticle-labeled MSC to correlate migration with its effect in an acute Chagas disease model. We expanded our investigation into a chronic model and performed more comprehensive assays. Infected mice were treated with nanoparticle-labeled MSC and their migration was correlated with alterations in heart morphology, metalloproteinase activity, and expression of several proteins. The vast majority of labeled MSC migrated to liver, lungs and spleen whereas a small number of cells migrated to chagasic hearts. Magnetic resonance imaging demonstrated that MSC therapy reduced heart dilatation. Additionally metalloproteinase activity was higher in heart and other organs of infected mice. Protein expression analyses revealed that connexin 43, laminin γ1, IL-10 and INF-γ were affected by the disease and recovered after cell therapy. Interestingly, MSC therapy led to upregulation of SDF-1 and c-kit in the hearts. The beneficial effect of MSC therapy in Chagas disease is likely due to an indirect action of the cells of the heart, rather than the incorporation of large numbers of stem cells into working myocardium.
恰加斯病性心肌病由寄生虫克氏锥虫感染引起，一个多世纪前就已被发现，至今仍是一种无法治愈的疾病。鉴于间充质干细胞（MSC）的独特特性，我们推测这些细胞可能对恰加斯病性心肌病具有治疗潜力。最近，我们小组率先使用纳米颗粒标记的间充质干细胞，在急性恰加斯病模型中关联其迁移与其效果。我们将研究扩展到慢性模型并进行了更全面的分析。用纳米颗粒标记的间充质干细胞治疗感染的小鼠，并将其迁移与心脏形态、金属蛋白酶活性和几种蛋白质的表达变化相关联。绝大多数标记的间充质干细胞迁移到肝脏、肺和脾脏，而少数细胞迁移到恰加斯病心脏。磁共振成像显示间充质干细胞疗法减轻了心脏扩张。此外，感染小鼠心脏和其他器官中的金属蛋白酶活性更高。蛋白质表达分析表明，连接蛋白43、层粘连蛋白γ1、白细胞介素-10和干扰素-γ受疾病影响，并在细胞治疗后恢复。有趣的是，间充质干细胞疗法导致心脏中基质细胞衍生因子-1和c-kit上调。间充质干细胞疗法对恰加斯病的有益作用可能是由于心脏细胞的间接作用，而不是大量干细胞融入工作心肌。
