Souza Bruno S d F, Azevedo Carine M, d Lima Ricardo S, Kaneto Carla M, Vasconcelos Juliana F, Guimarães Elisalva T, dos Santos Ricardo R, Soares Milena B P
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil; Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, Salvador, Brazil.
Int J Exp Pathol. 2014 Oct;95(5):321-9. doi: 10.1111/iep.12089. Epub 2014 Jun 30.
Infection by Trypanosoma cruzi, the aetiological agent of Chagas disease, causes an intense inflammatory reaction in several tissues, including the myocardium. We have previously shown that transplantation of bone marrow cells (BMC) ameliorates the myocarditis in a mouse model of chronic Chagas disease. We investigated the participation of BMC in lesion repair in the heart and skeletal muscle, caused by T. cruzi infection in mice. Infection with a myotropic T. cruzi strain induced an increase in the percentage of stem cells and monocytes in the peripheral blood, as well as in gene expression of chemokines SDF-1, MCP1, 2, and 3 in the heart and skeletal muscle. To investigate the fate of BMC within the damaged tissue, chimeric mice were generated by syngeneic transplantation of green fluorescent protein (GFP(+) ) BMC into lethally irradiated mice and infected with Trypanosoma cruzi. Migration of GFP(+) BMC to the heart and skeletal muscle was observed during and after the acute phase of infection. GFP(+) cardiomyocytes and endothelial cells were present in heart sections of chimeric chagasic mice. GFP(+) myofibres were observed in the skeletal muscle of chimeric mice at different time points following infection. In conclusion, BMC migrate and contribute to the formation of new resident cells in the heart and skeletal muscle, which can be detected both during the acute and the chronic phase of infection. These findings reinforce the role of BMC in tissue regeneration.
克氏锥虫是恰加斯病的病原体，其感染会在包括心肌在内的多个组织中引发强烈的炎症反应。我们之前已经表明，在慢性恰加斯病小鼠模型中，骨髓细胞（BMC）移植可改善心肌炎症状。我们研究了BMC在小鼠因克氏锥虫感染而导致的心脏和骨骼肌损伤修复中的作用。感染亲心肌性克氏锥虫菌株会导致外周血中干细胞和单核细胞百分比增加，同时心脏和骨骼肌中趋化因子SDF-1、MCP1、2和3的基因表达也会增加。为了研究受损组织内BMC的命运，通过将绿色荧光蛋白（GFP(+)）BMC同基因移植到经致死剂量照射的小鼠体内并感染克氏锥虫，构建了嵌合小鼠。在感染急性期及之后，观察到GFP(+) BMC迁移至心脏和骨骼肌。在嵌合型恰加斯病小鼠的心脏切片中存在GFP(+)心肌细胞和内皮细胞。在感染后的不同时间点，在嵌合小鼠的骨骼肌中观察到了GFP(+)肌纤维。总之，BMC会迁移并有助于心脏和骨骼肌中新驻留细胞的形成，在感染的急性期和慢性期均可检测到。这些发现强化了BMC在组织再生中的作用。
