干细胞移植在肝硬化治疗中的应用

1、n美国美国6161名诺贝尔获得者及其他科学家名诺贝尔获得者及其他科学家20002000年年4 4月月 联名要求美国政府对干细胞研究给予全面支持联名要求美国政府对干细胞研究给予全面支持 n20002000年年8 8月美国政府批准投入政府经费支持干细月美国政府批准投入政府经费支持干细 胞研究，美各州陆续制定新政策支持干细胞研究胞研究，美各州陆续制定新政策支持干细胞研究 n20052005年年1010月，美国食品和药物管理局月，美国食品和药物管理局 （FDAFDA）批准将神经干细胞移植入人体大脑。批准将神经干细胞移植入人体大脑。 20052005年年1111月，美国心脏协会报道了一项月，美国心脏协会

2、报道了一项三个国家多中心用三个国家多中心用干细胞治疗心肌梗塞干细胞治疗心肌梗塞204204例例的临床病例研究报告，其结论是干的临床病例研究报告，其结论是干细胞对心脏功能的改善是没有任何现有细胞对心脏功能的改善是没有任何现有临床药物能达到的。临床药物能达到的。 国务院（国务院（2006202020062020年）年）国家中长国家中长期科学和技术发展规划纲要期科学和技术发展规划纲要 n中国干细胞治疗实践处于世界前沿地位中国干细胞治疗实践处于世界前沿地位 n干细胞技术日益成熟、普及干细胞技术日益成熟、普及 n患者对干细胞治疗的接受程度逐步提高患者对干细胞治疗的接受程度逐步提高 n干细胞治疗蕴含广阔的

3、医疗前景干细胞治疗蕴含广阔的医疗前景 细胞损伤性疾病临床上有许多细胞损伤性疾病缺乏临床上有许多细胞损伤性疾病缺乏有效有效治愈的方法治愈的方法I型糖尿病糖尿病足股骨头坏死脊髓损伤肾功能损害老年痴呆症红斑狼疮闭塞性脉管炎下肢坏死帕金森氏病抗衰老等抗衰老等肝炎、肝硬化心肌梗塞Figure 1. Adult human HSCs generate significant numbers of hepatocytes in a noninjury fetal model. (A) Control sheep liver section (nontransplanted) stained with an

4、antibody antihuman hepatocyte. (B-C) Liver sections obtained at 3 weeks (B) and 4 months (C) after transplantation a higher number of human hepatocytes in the latter (C). (D) Liver section obtained at 11 months after transplantation .Human hepatocytes in all sections can be identified by the dark br

5、own coloration.Improved Liver Function in Patients with Liver Cirrhosis After Autologous Bone Marrow Cell Infusion Therapy We here report nine liver cirrhosis (LC) patients that underwent autologous bone marrow cell infusion (ABMI) from the peripheral vein. Subjects were patients with LC with total

6、bilirubin of less than 3.0 mg/dl, platelet count of morethan 5 (1010/l). Autologous bone marrow (BM; 400 ml) was isolated from the ilium under general anesthesia. Mononuclearcells (MNCs) were separated by cell washing and were infused via the peripheral vein. MNC characteristics were confirmed by fl

7、uorescence-activated cell sorting analysis. After ABMI therapy, liver function was monitored by blood examination for 24 .After washing, 5.200.63 109 MNCs were infused intopatients with LC. Significant improvements in serum albumin levels and total protein were observed at 24 weeks after ABMI therap

8、y (p .05). Significantly improved Child-Pugh scores were seen at 4 and 24 weeks (p .05). Fetoprotein and proliferating cell nuclear antigen (PCNA) expression in liver biopsy tissue was significantly levated after ABMI therapy (p .05). No major adverse effects were noted. Inconclusion, ABMI therapy s

9、hould be considered as a noveltreatment for atients with decompensated LC. STEMCELLS 2006;24:22922298表表1 90肝硬化患者例自体骨髓干细胞移植前后实验室指标变化肝硬化患者例自体骨髓干细胞移植前后实验室指标变化血清白蛋白血清白蛋白(g/L)(g/L)谷丙转氨酶谷丙转氨酶(U/L)(U/L)谷草转氨酶谷草转氨酶(U/L)(U/L)总胆红素总胆红素(mol/L)(mol/L)凝血酶原时间凝血酶原时间( (秒秒) )纤维蛋白原纤维蛋白原(g/L)(g/L)移植前移植前28.2728.274.294.2

10、9109.17109.1789.7489.7494.5794.5753.2853.2837.3937.3926.8726.8718.2318.234.584.581.961.960.890.89移植后移植后37.0937.096.156.1577.2777.2719.5719.5760.0760.0717.3817.3835.8135.8123.9023.9016.7216.724.334.332.422.421.011.01P值值P P0.010.01P P0.050.05P P0.050.05P P0.050.05P P0.050.05P P0.010.01郭晓钟等郭晓钟等郭晓钟等郭晓钟等n移植时机的问题移植时机的问题n移植数量的问题移植数量的问题n细胞移植后肝内定位跟踪的问题细胞移植后肝内定位跟踪的问题n调控肝脏干细胞的增殖、分化的途径和机制尚不调控肝脏干细胞的增殖、分化的途径和机制尚不完全清楚完全清楚n起步阶段，实验规模较小，临床研究缺乏对照起步阶段，实验规模较小，临床研究缺乏对照肝干细胞移植的应用前景肝干细胞移植的应用前景n干细胞移植将使肝硬化门静脉高压症及肝干细胞移植将使肝硬化门静脉高压症及肝衰竭这一难治疗的衰竭这一难治疗的“顽疾顽疾”发生革命性的发生革命性的变化。其未来的应用前景十分广阔。此外，变化。其未来的应用前景十分