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自体骨髓间充质干细胞对二甲基甲酰胺中毒肝衰竭患者肝功能恢复的促进作用

Accelerating effect of autologous bone marrow mesenchymal stem cells for restoration of liver function in a patient with acute liver failure induced by dimethylformamide
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摘要 目的探讨自体骨髓间充质干细胞(BM-MSCs)对二甲基甲酰胺(DMF)中毒致急性肝衰竭后肝功能延迟恢复患者的疗效和安全性。方法 1例DMF中毒性急性肝衰竭患者,在人工肝为主的内科综合治疗后肝功能持续得不到恢复时,采取患者骨髓,分离、培养制备BMMSCs,经肝动脉介入输注到患者肝内,观察其临床表现、肝功生化、凝血、肝脏影像学、肝组织病理学等改变及BM-MSCs近期不良反应和远期的安全性。结果 BM-MSCs治疗后,患者持续不见好转的肝功生化指标开始改善,凝血功能恢复速度加快,凝血酶原活动度(PTA)逐渐恢复到40﹪以上,上腹部CT见肝脏再生结节较前增大,Child-Pugh分级由C级转为A级,终末期肝病模型(MELD)评分由21分降到7分;干细胞输注早期未出现相关的不良反应,8周后再生结节穿刺活检其病理特征为:肝细胞变性、坏死、纤维化、胆汁淤积与再生并存。随访3年患者肝功生化正常、肝硬化结节影像学观察无明显变化,未发生癌变。结论 BM-MSCs肝动脉介入治疗对DMF中毒致急性肝衰竭肝功能延迟恢复患者的肝功能改善具有一定促进作用,近期无明显不良反应,中远期安全性好。 Objective To investigate the efficacy and safety of autologous bone marrow mesenchymal stem cells(BM-MSCs)in a patient with delayed liver function recovery after acute liver failure caused by dimethylformamide(DMF).Methods The liver function continued to be restored in a patient with acute liver failure induced by DMF after treated with artificial liver support system based comprehensive therapy,BM-MSCs were prepared and cultured in vitro,and then infused into the liver via the hepatic artery.The clinical manifestations,biochemistries,coagulation function,liver imaging,liver histopathology of the patient were observed as well as recent adverse events and longterm safety after transplantation.Results After the treatment of BM-MSCs,no significant adverse events were observed,unchanged liver function indexes improved,the recovery of coagulation function was accelerated,the prothrombin activity(PTA)gradually increased to more than 40﹪,Child-Pugh classification improved from grade A to grade B and score of Model for end-stage liver disease decrease from 21 to 7.The abdominal CT showed that the liver regeneration nodules increased at 4 weeks post-transplant.Liver cell degeneration,necrosis,fibrosis,cholestasis and regeneration co-existed in regenerative nodules as shown by a liver biosy.In the 3-year follow-up,the patient remained normal liver function.Neither significant changes in liver cirrhosis nodules nor ocurrence of cancer was observed.Conclusion BM-MSCs can promote the restoration of liver function in patient with delayed liver function recovery after acute liver failure caused by DMF.Transplantation of BMMSCs into the liver via the hepatic artery results in mild adverse events.
作者 吴海聪 李东良 方坚 张志强 夏磊 刘邦 Wu Haicong;Li Dongliang;Fang Jian;Zhang Zhiqiang;Xia Lei;Liu Bang(Fuzhou General Hospital Clinical Medical School,Fujian Medical University,Fuzhou 350025,China)
出处 《中华细胞与干细胞杂志(电子版)》 2018年第1期29-34,共6页 Chinese Journal of Cell and Stem Cell(Electronic Edition)
基金 南京军区军事医学重大专项(14ZX24)
关键词 骨髓间充质干细胞 肝衰竭 二甲基甲酰胺 疗效 安全性 Bone marrow mesenchymal stem cells Liver failure Dimethylformamide Efficacy Safety
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