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肝干细胞:治疗肝硬化的一种可行方法。

Hepatic stem cells: A viable approach for the treatment of liver cirrhosis.

作者信息

Habeeb Md Aejaz, Vishwakarma Sandeep Kumar, Bardia Avinash, Khan Aleem Ahmed

机构信息

Md Aejaz Habeeb, Sandeep Kumar Vishwakarma, Avinash Bardia, Aleem Ahmed Khan, Center for Liver Research and Diagnostics, Deccan College of Medical Sciences, Hyderabad 500058, Andhra Pradesh, India.

出版信息

World J Stem Cells. 2015 Jun 26;7(5):859-65. doi: 10.4252/wjsc.v7.i5.859.

Abstract

Liver cirrhosis is characterized by distortion of liver architecture, necrosis of hepatocytes and regenerative nodules formation leading to cirrhosis. Various types of cell sources have been used for the management and treatment of decompensated liver cirrhosis. Knowledge of stem cells has offered a new dimension for regenerative therapy and has been considered as one of the potential adjuvant treatment modality in patients with end stage liver diseases (ESLD). Human fetal hepatic progenitor cells are less immunogenic than adult ones. They are highly propagative and challenging to cryopreservation. In our earlier studies we have demonstrated that fetuses at 10-18 wk of gestation age contain a large number of actively dividing hepatic stem and progenitor cells which possess bi-potent nature having potential to differentiate into bile duct cells and mature hepatocytes. Hepatic stem cell therapy for the treatment of ESLD is in their early stage of the translation. The emerging technology of decellularization and recellularization might offer a significant platform for developing bioengineered personalized livers to come over the scarcity of desired number of donor organs for the treatment of ESLD. Despite these significant advancements long-term tracking of stem cells in human is the most important subject nowadays in order to answer several unsettles issues regarding the route of delivery, the choice of stem cell type(s), the cell number and the time-point of cell delivery for the treatment in a chronic setting. Answering to these questions will further contribute to the development of safer, noninvasive, and repeatable imaging modalities that could discover better cell therapeutic approaches from bench to bed-side. Combinatorial approach of decellularization and nanotechnology could pave a way towards the better understanding in determination of cell fate post-transplantation.

摘要

肝硬化的特征是肝脏结构扭曲、肝细胞坏死和再生结节形成,进而导致肝硬化。多种类型的细胞来源已被用于失代偿期肝硬化的管理和治疗。干细胞知识为再生治疗提供了新的维度,并被视为终末期肝病(ESLD)患者潜在的辅助治疗方式之一。人胎儿肝祖细胞的免疫原性低于成人肝祖细胞。它们具有高度增殖性,且冷冻保存具有挑战性。在我们早期的研究中,我们已经证明,妊娠10 - 18周的胎儿含有大量活跃分裂的肝干细胞和祖细胞,这些细胞具有双潜能特性,有可能分化为胆管细胞和成熟肝细胞。肝干细胞治疗ESLD尚处于转化的早期阶段。脱细胞和再细胞化的新兴技术可能为开发生物工程个性化肝脏提供一个重要平台,以克服治疗ESLD所需供体器官数量不足的问题。尽管取得了这些重大进展,但对人体干细胞进行长期追踪是当今最重要的课题,以便回答有关给药途径、干细胞类型选择、细胞数量以及在慢性情况下治疗的细胞给药时间点等几个未解决的问题。回答这些问题将进一步有助于开发更安全、无创且可重复的成像模式,从而能够发现从实验室到床边更好的细胞治疗方法。脱细胞和纳米技术的组合方法可能为更好地理解移植后细胞命运的确定铺平道路。

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