Is hepatic differentiation of embryonic stem cells induced by valproic acid and cytokines?

Embryonic stem (ES) cells, known for their capacity to proliferate indefinitely and differentiate into almost all types of cells including hepatocytes, have raised the hope of cellular replacement therapy for liver failure. There have been several protocols available for hepatic fate specification from ES cells, however, most of the protocols currently used result in low yield or purity of functional hepatocytes. Valproic acid (VPA), a histone deacetylase inhibitor, has been demonstrated to facilitate the hepatic differentiation of mesenchymal stem cells. However, little is know about whether VPA could induce the hepatic differentiation of ES cells.

A research team from China reported such research and the development of a protocol for direct hepatic lineage differentiation, from early developmental progenitors to a population of mature hepatocytes, based on sequential induction with VPA and cytokines. Results showed that VPA can direct the hepatic specification of ES cells and largely participates in the differentiation of ES cells into hepatic progenitors. Further differentiation of hepatic progenitors into mature hepatocytes requires supplementation with cytokines. Their study will be published on November 7, 2009 in the World Journal of Gastroenterology.

Their research may not only be helpful for the clinical application of hepatocyte transplantation, but also provide an in vitro research model for the better investigation and understanding of the entire developmental process of hepatocytes, from ES cells to hepatic progenitors, and then to mature hepatocytes. Furthermore, as VPA is an epigenetic modulator, their results may also be of benefit to the research of mechanisms of epigenetic modifications during liver development.

Reference: Dong XJ, Zhang GR, Zhou QJ, Pan RL, Chen Y, Xiang LX, Shao JZ. Direct hepatic differentiation of mouse embryonic stem cells induced by valproic acid and cytokines. World J Gastroenterol 2009; 15(41): 5165-5175

http://www.wjgnet.com/1007-9327/15/5165.asp

Correspondence to: Jian-Zhong Shao, Professor, College of Life Sciences, Zhejiang University, Hangzhou 310058, Zhejiang Province, China. dxj9666@163.com

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World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H. pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2008 IF: 2.081. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.