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| 1 | Bone marrow derived stem cells for the treatment of end-stage liver disease显示文摘End-stage disease due to liver cirrhosis is an important cause of death worldwide. Cirrhosis results from progressive, extensive fibrosis and impaired hepatocyte regeneration. The only curative treatment is liver transplantation, but due to the several limitations of this procedure, the interest in alternative therapeutic strategies is increasing. In particular, the potential of bone marrow stem cell(BMSC) therapy in cirrhosis has been explored in different trials. In this article, we evaluate the results of 18 prospective clinical trials, and we provide a descriptive overview of recent advances in the research on hepatic regenerative medicine. The main message from the currently available data in the literature is that BMSC therapy is extremely promising in the context of liver cirrhosis. However, its application should be further explored in randomized, controlled trials with large cohorts and long follow-ups. | Cristina Margini Ranka Vukotic Lucia Brodosi Mauro Bernardi Pietro Andreone | 2014 | World Journal of Gastroenterology2014，20，27： | 18 |
| 2 | 自体外周血CD34+造血干细胞移植治疗晚期肝硬化的远期疗效显示文摘目的 探讨自体外周血CD34+造血干细胞移植治疗晚期肝硬化的远期临床疗效.方法 采用回顾性横断面研究方法.收集2010年7月至2015年7月四川省人民医院收治的42例晚期肝硬化患者的临床病理资料.患者行自体外周血CD34+造血干细胞移植治疗:每日皮下注射集落刺激因子5μg/kg,治疗3~5d,采集外周血干细胞,采集的干细胞行流式细胞检测CD34+造血干细胞数量达(1.8±1.7)×10^6/kg.采集后第2天在DSA检查下行经股动脉超选肝动脉植入术或手术经胃网膜右静脉置管至门静脉主干注入,术中监测门静脉压力.术后积极降低门静脉压力,保护肝肾功能;第3天给予抗凝治疗,防止门静脉系统血栓形成.观察指标:(1)治疗情况:CD34+造血干细胞移植后患者基本情况、术后并发症.(2)随访情况:患者生存率、肝功能Child评分、终末期肝病模型(MELD)评分、肝脏活组织病理学检查结果、组织学Knodell评分、慢性肝病健康相关生存质量(HRQL)评分.采用门诊、电话及邮件方式随访,随访内容为检查患者肝肾功能、凝血功能;B超及CT检查患者腹腔积液情况;行肝功能Child及MELD评分;行B超引导下肝脏穿刺取活组织检查;调查患者慢性肝病生存质量.随访时间截至2015年7月.正态分布的计量资料以-x±s表示,组间比较采用配对设计t检验.偏态分布的计量资料以M(范围)表示.采用Kaplan-Meier法绘制生存曲线.结果 (1)治疗情况:42例患者经自体外周血CD34+造血干细胞移植治疗后,患者精神、睡眠、食欲、大小便情况及症状均有不同程度改善.10例患者发生术后并发症,其中上消化道大出血3例,Ⅰ度肝性脑病3例,术后1个月及3个月各发生肝肾综合征1例均死亡,术后6个月发生门静脉血栓1例,自发性腹膜炎1例,其余患者经对症支持治疗后治愈或好转.(2)随访情况:42例患者获得随访,随访中位时间为57个月(1~60个月),5年生存率为95.23%.患者术后5年肝功能Child评分及MELD评分分别为(7.1±1.1)分和(14±4)分,与术前的(9.4±1.8)分和(19±5)分比较,差异均有统计学意义(t=1.672,3.773,P<0.05).患者肝脏活组织病理学检查结果:移植前患者肝小叶结构紊乱,被纤维切割,肝细胞水肿变性,呈毛玻璃样变,有点状及碎屑坏死;可见汇管区-汇管区桥接坏死,汇管区内有纤维组织增生,其内有中等量淋巴细胞、单核细胞浸润,假小叶形成.移植后5年患者正常肝小叶形成明显增多,且分布更加趋近正常,肝细胞水肿变性,见少量点状坏死,未见明显碎屑坏死;汇管区内纤维组织增生较前明显好转,纤维组织明显减少,染色明显变淡.移植后5年患者Knodell评分为(9.9±2.7)分,与移植前的(14.1±4.1)分比较,差异有统计学意义(t=4.142,P<0.05);HRQL评分为(167±21)分,与移植前的(134±15)分比较,差异有统计学意义(t=3.142,P<0.05).结论 自体外周血CD34+造血干细胞移植能长期有效地改善晚期肝硬化患者的肝功能、肝组织形态学以及提高患者的生命质量. | 骆乐 薛华 罗兰云 姚豫桐 邹海波 王冠 向光明 魏玲玲 杨卯竹 张天 谢坪 徐钢 邓绍平 黄孝伦 | 2016 | 中华消化外科杂志2016，15，7： | 10 |
| 3 | Clinical Outcome of Autologous Hematopoietic Stem Cell Infusion via Hepatic Artery or Portal Vein in Patients with End-stage Liver Diseases显示文摘Objective To investigate the efficacy of hematopoietic stem cell(HSC) transplantation via the hepatic artery vs.the portal vein for end-stage liver disease(ESLD).Methods Patients with hepatic decompensation were prospectively recruited from September 2010 to September 2012 to receive HSC transplantation via the hepatic artery or the portal vein.Liver function was examined at 3,6,and 12 months after transplantation.Liver biopsy results were analyzed using the Knodell score.Results Eighty patients(58 males and 22 females) were enrolled in the study.The Child-Pugh score was grade B in 69 cases,and grade C in the remaining 11 cases.HSC transplantation was performed via the portal vein in 36 patients and via the hepatic artery in 44 patients.ALT levels decreased while serum albumin levels increased significantly in both groups at 6 and 12 months after HSC transplantation(P<0.05 compared with pre-transplantation levels).Total bilirubin levels decreased significantly in both groups at 3,6,and 12 months after HSC transplantation(P<0.05 compared with pre-transplantation levels).Additionally,prothrombin time decreased in both groups at 12 months after HSC transplantation(P<0.05 compared with pre-transplantation level).There were no significant differences in ALT,total bilirubin and prothrombin time between the two groups either before or after transplantation.Moreover,Knodell score decreased significantly at 6 and 12 months.Histological examination showed that liver cell edema,degeneration,necrosis,and inflammation were significantly relieved at 3,6,and 12 months after transplantation.The incidence of portal vein thrombosis,upper gastrointestinal bleeding,and hepatic encephalopathy were 1.25%,3.75%,and 2.5% respectively.The one-year survival rate was 100%.Conclusions Autologous HSC transplantation improves liver function and histology in ESLD patients.The administration route of HSC has no significant impact on the efficacy of transplantation. | Xiao-lun Huang Le Luo Lan-yun Luo Hua Xue Ling-ling Wei Yu-tong Yao Hai-bo Zou Xiao-bing Huang Yi-fan Zhu Tian Zhang Ping Xie Mao-zhu Yang Shao-ping Deng | 2014 | Chinese Medical Sciences Journal2014，29，1： | 4 |
| 4 | 移植人脐带干细胞改善乙型肝炎失代偿肝硬化患者的肝功能(英文)显示文摘背景:失代偿肝硬化是危机生命的慢性肝疾病并发症,是肝移植的主要指标之一。目的:探索人脐带间充质干细胞治疗乙肝肝硬化失代偿患者的安全性和有效性。方法:间充质干细胞治疗组包括17例乙肝肝硬化失代偿患者及对照组包含17例匹配的乙肝失代偿患者。所有患者接受标准乙肝肝硬化治疗,包括口服抗病毒核酸类似物。间充质干细胞治疗组接受肘静脉注射人脐带间充质干细胞。结果与结论:间充质干细胞移植患者肝功能有所改善,白蛋白、胆红素、乳酸脱氢酶及碱性磷酸酶水平有所恢复,且患者Child-Pugh及MELD评分明显恢复。表明人脐带间充质干细胞静脉注射入乙肝肝硬化失代偿患者体内可改善肝功能。 | 傅青春 金银鹏 王晓今 李莉 王皙 李洪超 汪照静 周丰 臧祖胜 施莉琴 李震宇 陈成伟 | 2018 | 中国组织工程研究2018，22，25： | 4 |
| 5 | Human induced pluripotent stem cells derived hepatocytes:rising promise for disease modeling,drug development and cell therapy显示文摘Recent advances in the study of human hepatocytes derived from induced pluripotent stem cells(iPSC)represent new promises for liver disease study and drug discovery.Human hepatocytes or hepatocyte-like cells differentiated from iPSC recapitulate many func-tional properties of primary human hepatocytes and have been demonstrated as a powerful and efficient tool to model human liver metabolic diseases and fa-cilitate drug development process.In this review,we summarize the recent progress in this field and discuss the future perspective of the application of human iPSC derived hepatocytes. | Fei Yi Guang-Hui Liu Juan Carlos Izpisua Belmonte | 2012 | Protein & Cell2012，3，4： | 3 |
| 6 | 干细胞向肝细胞诱导分化机制的研究进展显示文摘终末期肝病是急性或慢性肝病的终末阶段,常伴有肝衰竭的临床表现。目前,原位肝移植术是治疗终末期肝病最有效的方法,虽然近期疗效较好,但因其成本高及排斥反应等不足使其临床广泛应用受到了一定的限制。干细胞是具有自我更新和多向分化潜能的细胞群体,研究显示干细胞可在特定条件下分化为肝细胞,且能支持受损肝脏的再生,在治疗终末期肝病中具有广阔的前景。 | 孙文静 王军 胡辂 兰春慧 陈东风 | 2010 | 医学综述2010，16，9： | 2 |
| 7 | 造血干细胞移植对终末期肝病患者ICGR15的影响及意义显示文摘目的观察自体外周血CD^(34+)造血干细胞移植治疗不同Child-Pugh分级的终末期肝病(end-stage liver disease,ESLD)患者移植前及移植后3、6、12、36和60个月的吲哚氰绿15 min滞留率(indocyanine green retention rate at 15 min,ICGR15)变化情况。方法对内科严格保守治疗无效且已达到肝移植适应证的不同Child-Pugh分级的60例晚期肝硬化患者,采用自体外周血CD^(34+)造血干细胞移植,分别在移植前及移植后3、6、12、36和60个月进行ICGR15测定,并对各Child-Pugh分级组内的各时间点结果进行比较,以及比较各ChildPugh分级级组之间的ICGR15值变化率。结果各Child-Pugh分级组ICGR15值随时间延长均呈下降趋势,其中Child-Pugh A级组内:移植后6个月、12个月、36个月及60个月组与术前及移植后3个月组比较差异均具有统计学意义(P<0.05),但移植后3个月组与术前比较差异无统计学意义(P>0.05),而移植后12个月组与移植后60个月组比较差异有统计学意义(P<0.05)。Child-Pugh B级组内:移植后6个月、12个月、36个月及60个月组与术前及移植后3个月组比较差异均有统计学意义(P<0.05),移植后3个月组与术前比较差异也有统计学意义(P<0.05),移植后6个月组与12个月、36个月及60个月组比较差异均有统计学意义(P<0.05)。Child-Pugh C级组内:移植后6个月、12个月、36个月及60个月组与术前及移植后3个月组比较差异均有统计学意义(P<0.05),但移植后3个月组与术前比较差异无统计学意义(P>0.05),而移植后6个月组与12个月、36个月及60个月组比较差异均有统计学意义(P<0.05)。各Child-Pugh分级组之间ICGR15变化率比较差异无统计学意义(P>0.05)。结论自体外周血CD^(34+)造血干细胞移植能长期有效地改善ESLD患者的肝功能储备能力,提高手术安全性。 | 骆乐 姚豫桐 魏玲玲 邓绍平 黄孝伦 | 2017 | 中国普外基础与临床杂志2017，24，4： | 1 |
| 8 | 间充质干细胞在肝再生中运用的研究进展显示文摘许多肝脏疾病都可造成肝脏功能紊乱,最终可能导致肝功能衰竭。肝移植虽是目前治疗终末期肝病的主要手段,但受到供肝缺乏,手术损伤,免疫排斥等因素的影响,而受到一定限制。调查显示,2005年需要肝移植的患者中仅约1/3的患者最终得到移植。因此,如何对损伤肝脏进行修复已成为研究的热点。随着干细胞研究的不断深入,以干细胞为基础的细胞治疗已成为肝脏疾病治疗的新途径。 | 杨阳(综述) 李江(综述) 刘斌(审校) | 2010 | 医学新知2010，20，1： | 0 |
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