Baig Maria Tayyab, Ali Gibran, Awan Sana Javaid, Shehzad Umara, Mehmood Azra, Mohsin Sadia, Khan Shaheen N, Riazuddin Sheikh
a Centre of Excellence in Molecular Biology , University of Punjab , Lahore , Pakistan.
b Cardiovascular Research Centre, Lewis Katz School of Medicine at Temple University , Philadelphia , PA , USA.
Growth Factors. 2017 Oct;35(4-5):144-160. doi: 10.1080/08977194.2017.1392945. Epub 2017 Nov 7.
Cellular therapies hold promise to alleviate liver diseases. This study explored the potential of allogenic serum isolated from rat with acute CCl injury to differentiate adipose derived stem cells (ADSCs) towards hepatic lineage. Acute liver injury was induced by CCl which caused significant increase in serum levels of VEGF, SDF1α and EGF. ADSCs were preconditioned with 3% serum isolated from normal and acute liver injury models. ADSCs showed enhanced expression of hepatic markers (AFP, albumin, CK8 and CK19). These differentiated ADSCs were transplanted intra-hepatically in CCl-induced liver fibrosis model. After one month of transplantation, fibrosis and liver functions (alkaline phosphatase, ALAT and bilirubin) showed marked improvement in acute injury group. Elevated expression of hepatic (AFP, albumin, CK 18 and HNF4a) and pro survival markers (PCNA and VEGF) and improvement in liver architecture as deduced from results of alpha smooth muscle actin, Sirius red and Masson's trichome staining was observed.
细胞疗法有望缓解肝脏疾病。本研究探索了从急性四氯化碳（CCl）损伤大鼠中分离出的异体血清将脂肪来源干细胞（ADSCs）诱导分化为肝系细胞的潜力。CCl诱导急性肝损伤，导致血清中血管内皮生长因子（VEGF）、基质细胞衍生因子1α（SDF1α）和表皮生长因子（EGF）水平显著升高。将ADSCs分别用从正常和急性肝损伤模型中分离出的3%血清进行预处理。ADSCs表现出肝脏标志物（甲胎蛋白、白蛋白、细胞角蛋白8和细胞角蛋白19）表达增强。将这些分化后的ADSCs肝内移植到CCl诱导的肝纤维化模型中。移植一个月后，急性损伤组的纤维化程度和肝功能（碱性磷酸酶、谷丙转氨酶和胆红素）均有显著改善。观察到肝脏标志物（甲胎蛋白、白蛋白、细胞角蛋白18和肝细胞核因子4α）和促生存标志物（增殖细胞核抗原和VEGF）表达升高，并且根据α平滑肌肌动蛋白、天狼星红和Masson三色染色结果推断肝脏结构有所改善。
