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人胎肝来源的干细胞移植作为支持手段治疗终末期失代偿性肝硬化。

Human fetal liver-derived stem cell transplantation as supportive modality in the management of end-stage decompensated liver cirrhosis.

机构信息

Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, Andhra Pradesh, India.

出版信息

Cell Transplant. 2010;19(4):409-18. doi: 10.3727/096368910X498241.

DOI:10.3727/096368910X498241
PMID:20447340
Abstract

Liver transplantation is the only existing modality for treating decompensated liver cirrhosis. Several factors, such as nonavailability of donors, combined with operative risks, complications associated with rejection, usage of immunosuppressive agents, and cost intensiveness, make this strategy available to only a few people. With a tremendous upsurge in the mortality rate of patients with liver disorders worldwide, there is a need to search for an alternative therapeutic tool that can combat the above limitations and serve as a supportive therapy in the management of liver diseases. Cell therapy using human fetal liver-derived stem cells can provide great potential to conservatively manage end-stage liver diseases. Therefore, the present investigation aimed to study and prove the safety and efficacy of human fetal liver-derived stem cell transplantation in patients with end-stage liver cirrhosis. Twenty-five patients with liver cirrhosis of different etiologies were infused with human fetal liver-derived stem cells (EpCAM+ve) labeled with Tc-HMPAO through hepatic artery. Our high throughput analysis using flow cytometry, RT-PCR, and cellular characterization exemplifies fetal liver cells with their high proliferation rate could be the best source for rejuvenating the diseased liver. Further, no episodes related to hepatic encephalopathy recurred in any of the subjects following hepatic stem cell transplantation. There was marked clinical improvement observed in terms of all clinical and biochemical parameters. Further, there was decrease in mean MELD score (p < 0.01) observed in 6 months follow-up in all patients. Therapy using human fetal liver stem/progenitor cells offers a potentially supportive modality to organ transplantation in the management of liver diseases.

摘要

肝移植是治疗肝功能失代偿期肝硬化的唯一方法。由于供体不足、手术风险、排斥相关并发症、免疫抑制剂的使用和费用高昂等多种因素,这种策略仅适用于少数人。由于全球范围内肝功能障碍患者的死亡率急剧上升,因此需要寻找一种替代治疗工具,以克服上述限制,并在肝脏疾病的治疗中提供辅助治疗。用人胎肝来源的干细胞进行细胞治疗为保守治疗终末期肝病提供了巨大的潜力。因此,本研究旨在研究并证明人胎肝来源的干细胞移植治疗终末期肝硬化患者的安全性和有效性。25 例不同病因的肝硬化患者通过肝动脉输注人胎肝来源的干细胞(EpCAM+ve),并用 Tc-HMPAO 标记。我们使用流式细胞术、RT-PCR 和细胞特征分析的高通量分析证明,具有高增殖率的胎肝细胞可能是修复患病肝脏的最佳来源。此外,肝干细胞移植后,所有患者均未出现与肝性脑病相关的发作。所有临床和生化参数均有明显的临床改善。此外,所有患者在 6 个月的随访中平均 MELD 评分均有下降(p<0.01)。用人胎肝干细胞/祖细胞进行治疗为器官移植提供了一种潜在的支持方式,可用于肝脏疾病的治疗。

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