Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis
Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis
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DOI：
10.1016/j.clinbiochem.2007.04.017
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发表时间：
2007-08-01
影响因子：
2.8
通讯作者：
Hasan, N. M.
中科院分区：
文献类型：
--
作者：
Aziz, M. T. Abdel;Atta, H. M.;Hasan, N. M.
目的：目的：研究骨髓间充质干细胞（MSC）对大鼠实验性肝纤维化的影响。分离MSC，使其生长并在培养物中增殖4周，并在形态学上和通过RT-PCR检测CD 29来表征。然后将它们输注到接受CC 14注射的雌性大鼠的尾静脉中以诱导肝纤维化。大鼠分为4组：对照组、CC 14组、CC 14 + MSC组和MSC组。对所有组的肝组织进行组织病理学检查，并估计肝功能（ALT和血清白蛋白）。通过PCR评估雌性大鼠肝脏组织中的Y染色体基因（sry），以确认雄性干细胞的摄入。结果表明，MSC具有显著的抗肝纤维化作用，CC 14/MSC组肝组织中胶原基因表达显著降低，羟脯氨酸含量显著降低（p < 0.001）。RT-PCR检测到CC 14/MSC组细胞中存在Y染色体基因（sry），而对照组及其他各组细胞中均未检测到。CD 29基因在MSC培养物中表达，这证实了MSC在培养物中分离和增殖的效率。关于肝功能，与CC 14组相比，CC 14/MSC组中的血清白蛋白也有显著改善和升高（p < 0.05）。至于肝酶ALT，与CC 14组相比，CC 14/MSC组中其水平降低。然而，这在统计学上是不显著的（p > 0.05）。总之，MSC通过它们在最小化胶原沉积方面的作用以及它们分化成肝细胞的能力而对纤维化过程具有潜在的治疗作用。(c)2007年加拿大临床化学家协会。爱思唯尔公司出版All rights reserved.
Objective: To study the effect of mesenchymal stem cells (MSC) on experimental liver fibrosis in rats.Design and method: MSC were derived from bone marrow obtained from femoral and tibia] bones of male albino rats. MSC were separated, grown, and propagated in culture for 4 weeks and were characterized morphologically and by detection of CD29 by RT-PCR. They were then infused into the tail vein of female rats that received CC14 injection to induce liver fibrosis. Rats were divided into 4 groups: control, CC14, CC14 plus MSC, and MSC. Liver tissue was examined histopathologically and liver functions (ALT and serum albumin) were estimated for all groups. Y-chromosome gene (sry) was assessed by PCR in liver tissue of the female rats to confirm uptake of the male stem cells. Hydroxyproline content in liver tissue was assessed by chemical methods and expression of the collagen gene (type 1) was detected as a marker for liver fibrosis.Results of the present study showed that MSC have a significant antifibrotic effect as evidenced by the significant decrease in liver collagen gene expression as well as the decrease in hydroxyproline content in the CC14/MSC group (p < 0.001) compared to the CC14 group. The Y-chromosome gene (sry) was detected by RT-PCR in the CC14/MSC group, but was not detected in control group and other groups. The CD29 gene was expressed in MSC culture, and this confirmed the efficiency of isolation and propagation of MSC in culture. With regard to liver function, there was also a significant improvement and elevation of serum albumin in the CC14/MSC group compared to the CC14 group (p < 0.05). As regard to the liver enzyme ALT, there was a decrease of its level in the CC14/MSC group compared to the CC14 group. However, this was statistically nonsignificant (p > 0.05).In conclusion, MSC have a potential therapeutic effect against the fibrotic process through their effect in minimizing collagen deposition in addition to their capacity to differentiate into hepatocytes. (c) 2007 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.