干細(xì)胞移植在肝硬化治療中的應(yīng)用

1、n美國(guó)美國(guó)6161名諾貝爾獲得者及其他科學(xué)家名諾貝爾獲得者及其他科學(xué)家20002000年年4 4月月 聯(lián)名要求美國(guó)政府對(duì)干細(xì)胞研究給予全面支持聯(lián)名要求美國(guó)政府對(duì)干細(xì)胞研究給予全面支持 n20002000年年8 8月美國(guó)政府批準(zhǔn)投入政府經(jīng)費(fèi)支持干細(xì)月美國(guó)政府批準(zhǔn)投入政府經(jīng)費(fèi)支持干細(xì) 胞研究，美各州陸續(xù)制定新政策支持干細(xì)胞研究胞研究，美各州陸續(xù)制定新政策支持干細(xì)胞研究 n20052005年年1010月，美國(guó)食品和藥物管理局月，美國(guó)食品和藥物管理局 （FDAFDA）批準(zhǔn)將神經(jīng)干細(xì)胞移植入人體大腦。批準(zhǔn)將神經(jīng)干細(xì)胞移植入人體大腦。 20052005年年1111月，美國(guó)心臟協(xié)會(huì)報(bào)道了一項(xiàng)月，美國(guó)心臟協(xié)會(huì)

2、報(bào)道了一項(xiàng)三個(gè)國(guó)家多中心用三個(gè)國(guó)家多中心用干細(xì)胞治療心肌梗塞干細(xì)胞治療心肌梗塞204204例例的臨床病例研究報(bào)告，其結(jié)論是干的臨床病例研究報(bào)告，其結(jié)論是干細(xì)胞對(duì)心臟功能的改善是沒(méi)有任何現(xiàn)有細(xì)胞對(duì)心臟功能的改善是沒(méi)有任何現(xiàn)有臨床藥物能達(dá)到的。臨床藥物能達(dá)到的。 國(guó)務(wù)院（國(guó)務(wù)院（2006202020062020年）年）國(guó)家中長(zhǎng)國(guó)家中長(zhǎng)期科學(xué)和技術(shù)發(fā)展規(guī)劃綱要期科學(xué)和技術(shù)發(fā)展規(guī)劃綱要 n中國(guó)干細(xì)胞治療實(shí)踐處于世界前沿地位中國(guó)干細(xì)胞治療實(shí)踐處于世界前沿地位 n干細(xì)胞技術(shù)日益成熟、普及干細(xì)胞技術(shù)日益成熟、普及 n患者對(duì)干細(xì)胞治療的接受程度逐步提高患者對(duì)干細(xì)胞治療的接受程度逐步提高 n干細(xì)胞治療蘊(yùn)含廣闊的

3、醫(yī)療前景干細(xì)胞治療蘊(yùn)含廣闊的醫(yī)療前景 細(xì)胞損傷性疾病臨床上有許多細(xì)胞損傷性疾病缺乏臨床上有許多細(xì)胞損傷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頭壞死脊髓損傷腎功能損害老年癡呆癥紅斑狼瘡閉塞性脈管炎下肢壞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肝硬化患者例自體骨髓干細(xì)胞移植前后實(shí)驗(yàn)室指標(biāo)變化肝硬化患者例自體骨髓干細(xì)胞移植前后實(shí)驗(yàn)室指標(biāo)變化血清白蛋白血清白蛋白(g/L)(g/L)谷丙轉(zhuǎn)氨酶谷丙轉(zhuǎn)氨酶(U/L)(U/L)谷草轉(zhuǎn)氨酶谷草轉(zhuǎn)氨酶(U/L)(U/L)總膽紅素總膽紅素(mol/L)(mol/L)凝血酶原時(shí)間凝血酶原時(shí)間( (秒秒) )纖維蛋白原纖維蛋白原(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郭曉鐘等郭曉鐘等郭曉鐘等郭曉鐘等n移植時(shí)機(jī)的問(wèn)題移植時(shí)機(jī)的問(wèn)題n移植數(shù)量的問(wèn)題移植數(shù)量的問(wèn)題n細(xì)胞移植后肝內(nèi)定位跟蹤的問(wèn)題細(xì)胞移植后肝內(nèi)定位跟蹤的問(wèn)題n調(diào)控肝臟干細(xì)胞的增殖、分化的途徑和機(jī)制尚不調(diào)控肝臟干細(xì)胞的增殖、分化的途徑和機(jī)制尚不完全清楚完全清楚n起步階段，實(shí)驗(yàn)規(guī)模較小，臨床研究缺乏對(duì)照起步階段，實(shí)驗(yàn)規(guī)模較小，臨床研究缺乏對(duì)照肝干細(xì)胞移植的應(yīng)用前景肝干細(xì)胞移植的應(yīng)用前景n干細(xì)胞移植將使肝硬化門(mén)靜脈高壓癥及肝干細(xì)胞移植將使肝硬化門(mén)靜脈高壓癥及肝衰竭這一難治療的衰竭這一難治療的“頑疾頑疾”發(fā)生革命性的發(fā)生革命性的變化。其未來(lái)的應(yīng)用前景十分廣闊。此外，變化。其未來(lái)的應(yīng)用前景十分