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KMID : 1377020170140050579
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Tissue Engineering and Regenerative Medicine
2017 Volume.14 No. 5 p.579 ~ p.586
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Simple Maturation of Direct-Converted Hepatocytes Derived from Fibroblasts
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Cho Young-Duck
Yoon Sang-Tae
Kang Kyo-Jin
Kim Yo-Han
Lee Seung-Bum
Seo Dae-Kwan
Ryu Ki-Young
Jeong Jae-Min
Choi Dong-Ho
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Abstract
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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 HNF4a 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.
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KEYWORD
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Mouse induced hepatocytes, Maturation, Dimethyl sulfoxide, Direct conversion
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