Liver fibrosis is the excessive extracellular matrix accumulation of proteins, such as collagen, which follows the chronic liver diseases. Advanced liver fibrosis leads to cirrhosis and liver failure. Nilotinib is a second-generation tyrosine kinase inhibitor, which showed antifibrotic efficacy. Stem cell therapy still has some limitations such as oncogenesis, unexpected differentiation, and ethical consideration. Stem cells secrete cytokines and growth factors that showed paracrine-mediated antifibrotic and anti-inflammatory effects in vivo and in vitro. Thus, stem cell-conditioned medium (SC-CM), which contains the secretory proteins of stem cells, may have an antifibrotic role. This study was carried out to examine the antifibrotic effect of Nilotinib and stem cell exosomes on CCl₄-induced liver fibrosis in rats. Male Wistar rats were injected intraperitoneally with CCl₄ twice a week for 9 weeks and given daily treatments of Nilotinib (20 mg/kg), stem cell exosomes (0.5 ml/rat), and the combination treatment of Nilotinib and stem cell exosomes during the last 5 weeks of CCl₄ intoxication. Liver fibrosis and also antifibrotic efficacy of the treatments were estimated with liver function tests, oxidative stress parameters, apoptotic parameters, histopathological examination, and hydroxyproline contents. Results showed that the combination of Nilotinib and stem cell-conditioned media had more antifibrotic effects than each one alone ( value < 0.001).

中文翻译：

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尼罗替尼和干细胞条件培养基结合对CCl4诱导的肝纤维化的抗纤维化作用。

肝纤维化是蛋白质（例如胶原蛋白）在细胞外基质中积累过多，继而引起慢性肝病。晚期肝纤维化会导致肝硬化和肝衰竭。Nilotinib是第二代酪氨酸激酶抑制剂，具有抗纤维化功效。干细胞疗法仍存在一些局限性，例如致癌作用，意外分化和伦理考虑。干细胞分泌的细胞因子和生长因子在体内和体外均表现出旁分泌介导的抗纤维化和抗炎作用。因此，包含干细胞分泌蛋白的干细胞条件培养基（SC-CM）可能具有抗纤维化作用。进行了这项研究，以研究尼洛替尼和干细胞外泌体对CCl ₄的抗纤维化作用。引起的大鼠肝纤维化。每周两次向雄性Wistar大鼠腹腔注射CCl ₄，持续9周，并在治疗期间每天给予尼洛替尼（20 mg / kg），干细胞外泌体（0.5 ml /大鼠）以及尼洛替尼和干细胞外泌体的联合治疗。最后5周CCl ₄中毒。通过肝功能测试，氧化应激参数，凋亡参数，组织病理学检查和羟脯氨酸含量评估了治疗的肝纤维化以及抗纤维化功效。结果显示，尼洛替尼和干细胞条件培养基的组合比单独使用的组合具有更大的抗纤维化作用（值<0.001）。