生长因子诱导骨髓间充质干细胞肝向分化抑制慢性肝纤维化

Hepatic differentiation of bone marrow mesenchymal stem cells induced by additional growth factors inhibits chronic liver fibrosis

背景:骨髓间充质干细胞在改善肝纤维化或肝硬化所致肝损伤中的作用仍存在争议,骨髓间充质干细胞移植对慢性肝纤维化的治疗作用是否与其分化程度相关,尚有待进一步研究。目的:通过体外诱导骨髓间充质干细胞肝向分化并进行体内植入,观察其对肝脏慢性纤维化的治疗作用。方法:分离、培养、纯化大鼠骨髓间充质干细胞,通过体外诱导骨髓间充质干细胞肝向分化,获得肝样细胞。采用四氯化碳构建大鼠慢性肝纤维化模型,将骨髓间充质干细胞或肝样细胞通过尾静脉注射法行体内植入,观察并比较各组间大鼠生存率、肝纤维化程度、肝功能指标。结果与结论:(1)骨髓间充质干细胞具有体外分化潜能,经诱导成功分化为肝样细胞;(2)将肝样细胞移植到慢性肝纤维化大鼠体内,大鼠4周生存率提高至66.7%,肝纤维化程度减轻至(14.69±0.37)%,白蛋白水平提高至(29.4±0.7)mg/L,谷草转氨酶水平降低至(347.0±11.3)U/L,优于模型组及骨髓间充质干细胞移植组(P<0.05);(3)结果提示,骨髓间充质干细胞经肝向诱导分化后行体内移植,能够改善慢性肝纤维化大鼠的肝脏功能,减轻纤维化程度,并提高生存率。

BACKGROUND:The use of bone marrow mesenchymal stem cells to improve hepatic fibrosis or cirrhosis is still controversial.Whether the effect of bone marrow mesenchymal stem cell transplantation for chronic liver fibrosis is related to the degree of differentiation remains to be further studied.OBJECTIVE:To explore the effect of hepatic-differentiated bone marrow mesenchymal stem cell transplantation in the treatment of chronic liver fibrosis.METHODS:Rat bone marrow mesenchymal stem cells were separated,cultured and purified by differential adherent culture.A 3-step protocol including sequential addition of growth factors,cytokines and hormones was used to induce the bone marrow mesenchymal stem cells to differentiate into hepatocyte-like cells.An animal model of chronic liver fibrosis was constructed by using tetrachloride.The bone marrow mesenchymal stem cells or hepatic-like cells were then implanted through the tail vein injection.The survival rate,liver fibrosis degree and liver function of rats were compared between groups.RESULTS AND CONCLUSION:Bone marrow mesenchymal stem cells had the potential of differentiation in vitro and successfully differentiated into hepatic-like cells.After transplantation of hepatocyte-like cells,the 4-week survival rate of rats increased to 66.7%,the degree of liver fibrosis was significantly reduced to(14.69±0.37)%,the albumin level increased to(29.4±0.7)mg/L,and the level of glutamate transaminase decreased to(347.0±11.3)IU/L,which were significantly improved as compared with the model group and bone marrow mesenchymal stem cell transplantation group.To conclude,transplantation of hepatic-differentiated bone marrow mesenchymal stem cells can improve the liver function,reduce liver fibrosis and improve the survival rate of chronic liver fibrosis rats.