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用骨髓细胞进行治疗可减轻慢性感染曼氏血吸虫的小鼠的肝脏病变。

Therapy with bone marrow cells reduces liver alterations in mice chronically infected by Schistosoma mansoni.

作者信息

Oliveira Sheilla Andrade, Souza Bruno-Solano-Freitas, Guimaraes-Ferreira Carla-Adriana, Barreto Elton-Sa, Souza Siane-Campos, Freitas Luiz-Antonio-Rodrigues, Ribeiro-Dos-Santos Ricardo, Soares Milena-Botelho-Pereira

机构信息

Centro de Pesquisas Goncalo Moniz, Fundacao Oswaldo Cruz, Rua Waldemar Falcao 121, Brotas, Salvador 40295-001, BA, Brazil.

出版信息

World J Gastroenterol. 2008 Oct 14;14(38):5842-50. doi: 10.3748/wjg.14.5842.

Abstract

AIM

To investigate the potential of bone marrow mononuclear cells (BM-MCs) in the regeneration of hepatic lesions induced by Schistosoma mansoni (S.mansoni) chronic infection.

METHODS

Female mice chronically infected with S.mansoni were treated with BM-MCs obtained from male green fluorescent protein (GFP) transgenic mice by intravenous or intralobular injections. Control mice received injections of saline in similar conditions. Enzyme-linked immunosorbent assay (ELISA) assay for transforming growth factor-beta (TGF-beta), polymerase chain reaction (PCR) for GFP DNA, immunofluorescence and morphometric studies were performed.

RESULTS

Transplanted GFP(+) cells migrated to granuloma areas and reduced the percentage of liver fibrosis. The presence of donor-derived cells was confirmed by fluorescence in situ hybridization (FISH) analysis for detection of cells bearing Y chromosome and by PCR analysis for detection of GFP DNA. The levels of TGF-beta, a cytokine associated with fibrosis deposition, in liver fragments of mice submitted to therapy were reduced. The number of oval cells in liver sections of S.mansoni-infected mice increased 3-4 fold after transplantation. A partial recovery in albumin expression, which is decreased upon infection with S.mansoni, was found in livers of infected mice after cellular therapy.

CONCLUSION

In conclusion, transplanted BMCs migrate to and reduce the damage of chronic fibrotic liver lesions caused by S.mansoni.

摘要

目的

探讨骨髓单个核细胞(BM-MCs)在曼氏血吸虫(S.mansoni)慢性感染所致肝损伤再生中的潜力。

方法

用从雄性绿色荧光蛋白(GFP)转基因小鼠获得的BM-MCs,通过静脉注射或小叶内注射对慢性感染曼氏血吸虫的雌性小鼠进行治疗。对照小鼠在相似条件下接受盐水注射。进行了转化生长因子-β(TGF-β)的酶联免疫吸附测定(ELISA)、GFP DNA的聚合酶链反应(PCR)、免疫荧光和形态学研究。

结果

移植的GFP(+)细胞迁移至肉芽肿区域,降低了肝纤维化的百分比。通过检测携带Y染色体细胞的荧光原位杂交(FISH)分析和检测GFP DNA的PCR分析,证实了供体来源细胞的存在。接受治疗的小鼠肝脏碎片中与纤维化沉积相关的细胞因子TGF-β水平降低。移植后,曼氏血吸虫感染小鼠肝脏切片中的卵圆细胞数量增加了3 - 4倍。在细胞治疗后的感染小鼠肝脏中,发现白蛋白表达部分恢复,白蛋白表达在感染曼氏血吸虫后会降低。

结论

总之,移植的BMCs迁移至并减轻了曼氏血吸虫所致慢性纤维化肝损伤的损害。

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