Abdul Wali Khan University Mardan, Department of Biochemistry, Stem Cell Regenerative Medicine Lab, Khyber Pakhtunkhwa, Pakistan.
Bacha Khan University Charsadda, Department of Agriculture, Khyber Pakhtunkhwa, Pakistan.
Braz J Biol. 2022 Mar 16;84:e253061. doi: 10.1590/1519-6984.253061. eCollection 2022.
Liver fibrosis is initial stage of any chronic liver disease and its end stage is develops into cirrhosis. Chronic liver diseases are a crucial global health issue and the cause of approximately 2 million deaths per year worldwide. Cirrhosis is currently the 11th most common cause of death globally. Mesenchymal stem cell (MSCs) treatment is the best way to treat acute and chronic liver disease. The aim of this study is to improve the therapeutic potential of MSCs combined with melatonin (MLT) to overcome CCl4-induced liver fibrosis and also investigate the individual impact of melatonin and MSCs against CCl4-induced liver impairment in animal model. Female BALB/c mice were used as CCL4-induced liver fibrotic animal model. Five groups of animal model were made; negative control, Positive control, CCl4+MSCs treated group, CCl4+MLT treated group and CCl4+MSCs+MLT treated group. Cultured MSCs from mice bone marrow were transplanted to CCl4-induced liver injured mice model, individually as well as together with melatonin. Two weeks after MSCs and MLT administration, all groups of mice were sacrificed for examination. Morphological and Histopathological results showed that combined therapy of MSCs+MLT showed substantial beneficial impact on CCl4-induced liver injured model, compared with MSCs and MLT individually. Biochemically, considerable reduction was observed in serum bilirubin and ALT levels of MLT+MSC treated mice, compared to other groups. PCR results shown down-regulation of Bax and up-regulation of Bcl-xl and Albumin, confirm a significant therapeutic effect of MSCs+MLT on CCI4-induced liver fibrosis. From the results, it is concluded that combined therapy of MSCs and MLT show strong therapeutic effect on CCL4-induced liver fibrosis, compared with MSCs and MLT individually.
肝纤维化是任何慢性肝病的初始阶段，其终末期发展为肝硬化。慢性肝病是一个全球性的重大健康问题，全球每年约有 200 万人因此死亡。肝硬化是目前全球第 11 大常见死因。间充质干细胞（MSCs）治疗是治疗急性和慢性肝病的最佳方法。本研究旨在提高 MSCs 联合褪黑素（MLT）治疗 CCl4 诱导的肝纤维化的治疗潜力，并研究褪黑素和 MSCs 单独对抗 CCl4 诱导的肝损伤的个体影响在动物模型中。雌性 BALB/c 小鼠被用作 CCL4 诱导的肝纤维化动物模型。制作了五组动物模型：阴性对照、阳性对照、CCl4+MSCs 治疗组、CCl4+MLT 治疗组和 CCl4+MSCs+MLT 治疗组。从老鼠骨髓中培养的 MSCs 被移植到 CCl4 诱导的肝损伤小鼠模型中，单独或与褪黑素一起。MSCs 和 MLT 给药两周后，所有组别的小鼠均被处死进行检查。形态学和组织病理学结果表明，与 MSCs 和 MLT 单独治疗相比，MSCs+MLT 的联合治疗对 CCl4 诱导的肝损伤模型具有显著的有益影响。从生化角度来看，与其他组相比，MLT+MSC 治疗组的血清胆红素和 ALT 水平有显著降低。PCR 结果显示 Bax 下调和 Bcl-xl 和白蛋白上调，证实 MSCs+MLT 对 CCI4 诱导的肝纤维化具有显著的治疗作用。结果表明，与 MSCs 和 MLT 单独治疗相比，MSCs 和 MLT 的联合治疗对 CCL4 诱导的肝纤维化具有更强的治疗作用。
