多能干细胞源性肝细胞和类器官的培养

Culture of pluripotent stem cell-derived hepatocytes and organoids

肝脏是人体最重要的器官之一,肝脏疾病也是威胁人类健康和寿命的主要原因之一。由于各种原因,肝失代偿的治疗相当困难,体外肝支持装置无法解决这一问题,原位肝移植供体严重短缺。用多能干细胞诱导肝细胞和肝类器官不仅可以研究肝细胞的命运决定、肝发育、肝再生机制和肝脏疾病的病理生理学,而且也可用于筛选药物,并为未来的移植治疗提供稳定的功能性肝细胞来源。与肝脏发育类似,多能干细胞衍生的肝细胞和类器官的培养是一个自组织过程:从几个关键因素的变化开始,最终形成具有复杂功能的细胞/器官。现介绍目前多能干细胞来源的肝细胞和类器官培养的主要方法和进展,以期为今后的研究提供线索。

Liver is one of the most important organs in the human body.Liver diseases are also a major threat to human health and longevity.Hepatic decompensation treatment is quite difficult due to multiple reasons.Extracorporeal liver support devices are unable to solve this problem,and there is a severe shortage of orthotopic liver transplant donors.Study of pluripotent stem cell-derived hepatocytes and organoids can determine not only hepatocyte fate,but also liver development,regeneration mechanisms,and pathophysiology.Furthermore,it can be used for drug screening in order to provide a stable source of functional hepatocytes for future transplantation therapy.Culture of pluripotent stem cell-derived hepatocytes and organoids has a self-organizing process similar to liver development,i.e.,starting with changes in several key factors,and eventually forming functionally complex cells/organs.This paper introduces the main methods and progress of pluripotent stem cell-derived hepatocytes and organoids,with hope to provide clues for future research.