脐带间充质干细胞联合骨髓干细胞移植治疗失代偿期肝硬化:1年随访对照

Umbilical cord mesenchymal stem cells with bone marrow stem cells in the treatment of decompensated cirrhosis:a 1-year follow-up study

背景:骨髓干细胞应用于治疗失代偿期肝硬化有较多单中心研究报道,效果均不理想,其原因可能与肝硬化患者年龄大、体质弱,骨髓造血功能差,能够获取的干细胞数量少,再生和增殖能力弱有关,而脐带间充质干细胞具有易获得、来源广、免疫原性弱等特点。二者联合移植有可能提高其对失代偿期肝硬化患者的治疗效果。目的:探讨脐带间充质干细胞联合骨髓干细胞治疗失代偿期肝硬化的疗效及安全性。方法:失代偿期肝硬化患者32例随机分为两组,对照组19例单纯内科综合治疗,干细胞组13例在内科治疗基础上进行脐带间充质干细胞联合骨髓干细胞移植。跟踪观察随访1年,分别于治疗后4,12,52周观察并详细记录患者肝功能(丙氨酸转氨酶、总胆红素、白蛋白)、凝血酶原时间、Child-Pugh评分、MELD评分、患者1年生存率、临床生活质量评分(QOL)及干细胞治疗相关不良反应。结果与结论:在治疗后4,12,52周,干细胞组和对照组肝功能、凝血酶原时间、Child-Pugh评分、MELD评分等指标较治疗前均有改善,但两组对比差异无显著性意义(P>0.05);移植后4周患者临床症状及临床生活质量评分(QOL)有较快改善,与对照组相比差异有显著性意义(P<0.05),在治疗后12,52周时差异无显著性意义(P>0.05);两组患者1年生存率无明显差异,未发生与细胞治疗相关的严重并发症。结果表明脐带间充质干细胞联合骨髓干细胞移植能够较快地改善失代偿期肝硬化患者临床症状,安全性好,但对其确切疗效有待扩大样本量进一步深入研究。

BACKGROUND： There are most single-center studies about bone marrow stem cells applied to treat decompensated cirrhosis, but the therapeutic results are not ideal. It is possibly related to aging, physical weakness, poor bone marrow hematopoietic function, less available number of stem cells and feeble ability of regeneration and proliferation in liver cirrhosis patients. Umbilical cord mesenchymal stem cells are characterized of easy to obtain, wide source and weak immunogenicity. Co-transplantation of bone marrow stem cells and umbilical cord mesenchymal stem cells may improve the therapeutic effects on decompensated cirrhosis patients.OBJECTIVE： To investigate the efficacy and safety of co-transplantation of umbilical cord mesenchymal stem cells and bone marrow stem cells on decompensated cirrhosis.METHODS： Thirty-two decompensated cirrhosis patients were randomly divided into two groups： in stem cellgroup, 13 patients received co-transplantation of umbilical cord mesenchymal stem cells and bone marrow stem cells based on regular medical treatment; in control group, 19 patients only underwent the regular medical treatment. All the patients were follow-up for 1 year. Alanine aminotransferase, albumin, total bilirubin, prothrombin time, Child-Pugh score and Model for End-Stage Liver Disease score, 1-year survival rate, Quality of Life score and adverse reactions related to stem cell therapy were observed and recorded in the two groups at 4, 12, 52 weeks after treatment.RESULTS AND CONCLUSION： At 4, 12, 52 weeks after treatment, improvements in the liver function, prothrombin time,Child-Pugh score and Model for End-Stage Liver Disease score were found in the two groups, but there was no difference between the two groups（P〉0.05）. At 4 weeks after transplantation, the clinical symptoms and Quality of Life score in the stem cell group were significantly improved, which were better than those in the control group（P〈0.05）. But at 12 and 52 weeks after treatment, no difference was found between the two groups（P〉0.05）. In addition, the 1-year survival rate showed no difference between the two groups, and no severe adverse reactions related to stem cell therapy occurred during the follow-up. Co-transplantation of umbilical cord mesenchymal stem cells and bone marrow stem cells is safe and effective to improve the clinical symptoms of decompensated cirrhosis patients. However, further studies with larger samples are warranted to better clarify the co-transplantation effects.