Bone marrow multipotent mesenchymal stromal cells do not reduce fibrosis or improve function in a rat model of severe chronic liver injury
Bone marrow multipotent mesenchymal stromal cells do not reduce fibrosis or improve function in a rat model of severe chronic liver injury
复制标题
DOI：
10.1634/stemcells.2007-0941
复制
发表时间：
2008-05-01
期刊：
影响因子：
5.2
通讯作者：
Goldenberg, Regina C. S.
中科院分区：
文献类型：
--
作者：
Carvalho, Adriana B.;Quintanilha, Lutz Fernando;Goldenberg, Regina C. S.
我们的研究目的是评估骨髓间充质间质细胞（MSC）在严重慢性肝损伤大鼠模型中的治疗潜力。14只雌性Wistar大鼠只喂含酒精的液体饲料，并在15周内每隔一天接受四氯化碳腹腔注射。在此期间，8只动物（MSC组）在门静脉注射1 × 10(7)个细胞，6只动物（安慰剂组）接受载药。在细胞治疗前、细胞输注或安慰剂输注后1个月和2个月进行血液分析以评估谷丙转氨酶（ALT）、天冬氨酸转氨酶（AST）和白蛋白。在细胞或安慰剂注射前和注射后1个月通过肝活检评估肝纤维化。细胞递送2个月后，处死动物，进行肝脏组织学分析。组织形态学定量测定纤维化程度。细胞输注前的活检显示强烈的胶原沉积和间隔相互连接的再生结节。细胞注射一个月后，这一结果没有改变，在MSC组和安慰剂组之间没有发现纤维化量化的差异。细胞输注或安慰剂输注2周后ALT、AST恢复正常，实验组间差异无统计学意义。在细胞或安慰剂注射两个月后，白蛋白也恢复到正常值，组织学结果保持不变，MSC组和安慰剂组之间同样没有差异。因此，在我们的实验条件下，MSC不能减少严重慢性肝损伤大鼠模型的纤维化或改善肝功能。
The objective of our study was to evaluate the therapeutic potential of bone marrow mesenchymal stromal cells (MSC) in a rat model of severe chronic liver injury. Fourteen female Wistar rats were fed exclusively an alcoholic liquid diet and received intraperitoneal injections of carbon tetrachloride every other day during 15 weeks. After this period, eight animals (MSC group) had 1 x 10(7) cells injected into the portal vein while six animals (placebo group) received vehicle. Blood analysis was performed to evaluate alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin before cell therapy and 1 and 2 months after cell or placebo infusion. Fibrosis was evaluated before and 1 month after cell or placebo injection by liver biopsies. Two months after cell delivery, animals were sacrificed and histological analysis of the livers was performed. Fibrosis was quantified by histomorphometry. Biopsies obtained before cell infusion showed intense collagen deposition and septa interconnecting regenerative nodules. One month after cell injection, this result was unaltered and differences in fibrosis quantification were not found between MSC and placebo groups. ALT and AST returned to normal values 2 weeks after cell or placebo infusion, without significant differences between experimental groups. Two months after cell or placebo injection, albumin had also returned to normal values and histological results were maintained, again without differences between MSC and placebo groups. Therefore, under our experimental conditions, MSC were unable to reduce fibrosis or improve liver function in a rat model of severe chronic liver injury.