Tissue Eng Regen Med.  2017 Oct;14(5):579-586. 10.1007/s13770-017-0064-z.

Simple Maturation of Direct-Converted Hepatocytes Derived from Fibroblasts

Affiliations
  • 1Department of Emergency Medicine, Korea University Guro Hospital, Seoul 02841, Korea.
  • 2HY Indang Center of Regenerative Medicine and Stem Cell Research, Hanyang University College of Medicine, Seoul 04763, Korea. jmj1103@gmail.com, crane87@hanyang.ac.kr
  • 3Department of Surgery, Hanyang University College of Medicine, Seoul 04763, Korea.
  • 4Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Science, Seoul 01812, Korea.
  • 5Bioinformatics Department, Macrogen Corp, Rockville, MD 20850, USA.
  • 6Department of Obstetrics and Gynecology, Hanyang University College of Medicine, Seoul 04763, Korea.

Abstract

Target cells differentiation techniques from stem cells are developed rapidly. Recently, direct conversion techniques are introduced in various categories. Unlike pluripotent stem cells, this technique enables direct differentiation into the other cell types such as neurons, cardiomyocytes, insulin-producing cells, and hepatocytes without going through the pluripotent stage. However, the function of these converted cells reserve an immature phenotype. Therefore, we modified the culture conditions of mouse direct converted hepatocytes (miHeps) to mature fetal characteristics, such as higher AFP and lower albumin (ALB) expression than primary hepatocytes. First, we generate miHeps from mouse embryonic fibroblasts (MEFs) with two transcription factors HNF4α and Foxa3. These cells indicate typical epithelial morphology and express hepatic proteins. To mature hepatic function, DMSO is treated during culture time for more than 7 days. After maturation, miHeps showed features of maturation such as exhibiting typical hepatocyte-like morphology, increased up-regulated ALB and CYP enzyme gene expression, down-regulated AFP expressions, and acquired hepatic function over time. Thus, our data provides a simple method to mature direct converted hepatocytes functionally and these cells enable them to move closer to generating functional hepatocytes.

Keyword

Mouse induced hepatocytes; Maturation; Dimethyl sulfoxide; Direct conversion

MeSH Terms

Animals
Dimethyl Sulfoxide
Fibroblasts*
Gene Expression
Hepatocytes*
Methods
Mice
Myocytes, Cardiac
Neurons
Phenotype
Pluripotent Stem Cells
Stem Cells
Transcription Factors
Dimethyl Sulfoxide
Transcription Factors
Full Text Links
  • TERM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr