Yu Yue, Wang Xuehao, Nyberg Scott L
Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province 210029, China.
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
J Clin Med. 2014 Sep 5;3(3):997-1017. doi: 10.3390/jcm3030997.
Tens of millions of patients are affected by liver disease worldwide. Many of these patients can benefit from cell therapy involving living metabolically active cells, either by treatment of their liver disease, or by prevention of their disease phenotype. Cell therapies, including hepatocyte transplantation and bioartificial liver (BAL) devices, have been proposed as therapeutic alternatives to the shortage of transplantable livers. Both BAL and hepatocyte transplantation are cellular therapies that avoid use of a whole liver. Hepatocytes are also widely used in drug screening and liver disease modelling. However, the demand for human hepatocytes, heavily outweighs their availability by conventional means. Induced pluripotent stem cells (iPSCs) technology brings together the potential benefits of embryonic stem cells (ESCs) (i.e., self-renewal, pluripotency) and addresses the major ethical and scientific concerns of ESCs: embryo destruction and immune-incompatibility. It has been shown that hepatocyte-like cells (HLCs) can be generated from iPSCs. Furthermore, human iPSCs (hiPSCs) can provide an unlimited source of human hepatocytes and hold great promise for applications in regenerative medicine, drug screening and liver diseases modelling. Despite steady progress, there are still several major obstacles that need to be overcome before iPSCs will reach the bedside. This review will focus on the current state of efforts to derive hiPSCs for potential use in modelling and treatment of liver disease.
全球数以千万计的患者受到肝脏疾病的影响。这些患者中的许多人可以从涉及具有代谢活性的活细胞的细胞疗法中受益，无论是通过治疗他们的肝脏疾病，还是通过预防他们的疾病表型。细胞疗法，包括肝细胞移植和生物人工肝（BAL）装置，已被提议作为可移植肝脏短缺的治疗替代方案。BAL和肝细胞移植都是避免使用全肝的细胞疗法。肝细胞也广泛用于药物筛选和肝脏疾病建模。然而，对人肝细胞的需求远远超过了通过传统方法获得的肝细胞数量。诱导多能干细胞（iPSC）技术结合了胚胎干细胞（ESC）的潜在优势（即自我更新、多能性），并解决了ESC的主要伦理和科学问题：胚胎破坏和免疫不相容性。已经证明可以从iPSC生成肝细胞样细胞（HLC）。此外，人iPSC（hiPSC）可以提供无限的人肝细胞来源，并在再生医学、药物筛选和肝脏疾病建模中具有巨大的应用前景。尽管取得了稳步进展，但在iPSC应用于临床之前，仍有几个主要障碍需要克服。本综述将重点关注为潜在用于肝脏疾病建模和治疗而衍生hiPSC的当前研究进展。
