高效诱导多能干细胞生成人肝细胞样细胞。

Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells.

机构信息

Department of Cell Biology, Division of Pediatric Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

出版信息

Hepatology. 2010 Jan;51(1):297-305. doi: 10.1002/hep.23354.

Abstract

UNLABELLED

There exists a worldwide shortage of donor livers available for orthotropic liver transplantation and hepatocyte transplantation therapies. In addition to their therapeutic potential, primary human hepatocytes facilitate the study of molecular and genetic aspects of human hepatic disease and development and provide a platform for drug toxicity screens and identification of novel pharmaceuticals with potential to treat a wide array of metabolic diseases. The demand for human hepatocytes, therefore, heavily outweighs their availability. As an alternative to using donor livers as a source of primary hepatocytes, we explored the possibility of generating patient-specific human hepatocytes from induced pluripotent stem (iPS) cells.

CONCLUSION

We demonstrate that mouse iPS cells retain full potential for fetal liver development and describe a procedure that facilitates the efficient generation of highly differentiated human hepatocyte-like cells from iPS cells that display key liver functions and can integrate into the hepatic parenchyma in vivo.

摘要

未加标签

全世界都缺乏可用于同种异体肝移植和肝细胞移植治疗的供体肝脏。除了具有治疗潜力外,原代人肝细胞还促进了对人类肝脏疾病的分子和遗传方面的研究,为药物毒性筛选和鉴定具有广泛治疗代谢疾病潜力的新型药物提供了一个平台。因此,对人肝细胞的需求远远超过了其供应。作为使用供体肝脏作为原代肝细胞来源的替代方法,我们探讨了从诱导多能干细胞(iPS)细胞产生患者特异性人肝细胞的可能性。

结论

我们证明了小鼠 iPS 细胞保持着胎肝发育的全部潜能,并描述了一种能够从 iPS 细胞中高效产生具有高度分化的人肝样细胞的方法,这些细胞显示出关键的肝脏功能,并能在体内整合到肝实质中。

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