Adipose Tissue-Derived Stem Cells as a Regenerative Therapy for a Mouse Steatohepatitis-Induced Cirrhosis Model
Adipose Tissue-Derived Stem Cells as a Regenerative Therapy for a Mouse Steatohepatitis-Induced Cirrhosis Model
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DOI：
10.1002/hep.26470
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发表时间：
2013-09-01
期刊：
影响因子：
13.5
通讯作者：
Kaneko, Shuichi
中科院分区：
文献类型：
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作者：
Seki, Akihiro;Sakai, Yoshio;Kaneko, Shuichi
肝硬化是一种慢性肝病，损害肝功能并导致晚期纤维化。间充质干细胞作为一种再生疗法，因为它们具有免疫调节功能，最近得到了普及。我们发现，注射的脂肪组织来源的干细胞（ADSC）驻留在肝脏中。注射ADSC还恢复了肝实质细胞中白蛋白的表达，并改善了小鼠肝硬化非酒精性脂肪性肝炎模型中的纤维化。肝脏的基因表达分析鉴定了基因的上调和下调，表明ADSC注射后的再生/修复和抗炎过程。ADSC治疗还减少了肝内浸润的CD 11b（+）和Gr-1（+）细胞的数量，并降低了肝脏炎症细胞中CD 8（+）/CD 4（+）细胞的比例。这与肝脏炎症细胞中与抗原呈递和辅助性T细胞活化相关的基因下调一致。结论：这些结果表明ADSC治疗对肝硬化有益，因为它可以修复和恢复受损肝脏的功能。（肝病学2013;53：1133-1142）
Cirrhosis is a chronic liver disease that impairs hepatic function and causes advanced fibrosis. Mesenchymal stem cells have gained recent popularity as a regenerative therapy since they possess immunomodulatory functions. We found that injected adipose tissue-derived stem cells (ADSCs) reside in the liver. Injection of ADSCs also restores albumin expression in hepatic parenchymal cells and ameliorates fibrosis in a nonalcoholic steatohepatitis model of cirrhosis in mice. Gene expression analysis of the liver identifies up- and down-regulation of genes, indicating regeneration/repair and anti-inflammatory processes following ADSC injection. ADSC treatment also decreases the number of intrahepatic infiltrating CD11b(+) and Gr-1(+) cells and reduces the ratio of CD8(+)/CD4(+) cells in hepatic inflammatory cells. This is consistent with down-regulation of genes in hepatic inflammatory cells related to antigen presentation and helper T-cell activation. Conclusion: These results suggest that ADSC therapy is beneficial in cirrhosis, as it can repair and restore the function of the impaired liver. (Hepatology 2013;53:1133-1142)