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Simple Maturation of Direct-Converted Hepatocytes Derived from Fibroblasts

Title
Simple Maturation of Direct-Converted Hepatocytes Derived from Fibroblasts
Author
최동호
Keywords
Mouse induced hepatocytes; Maturation; Dimethyl sulfoxide; Direct conversion
Issue Date
2017-06
Publisher
KOREAN TISSUE ENGINEERING REGENERATIVE MEDICINE SOC
Citation
TISSUE ENGINEERING AND REGENERATIVE MEDICINE, v. 14, no. 5, page. 579-586
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 HNF4 alpha 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.
URI
https://link.springer.com/article/10.1007%2Fs13770-017-0064-zhttps://repository.hanyang.ac.kr/handle/20.500.11754/114384
ISSN
1738-2696
DOI
10.1007/s13770-017-0064-z
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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