Optimization of 3D hydrogel microenvironment for enhanced hepatic functionality of primary human hepatocytes

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Title
Optimization of 3D hydrogel microenvironment for enhanced hepatic functionality of primary human hepatocytes
Author(s)
Ho-Joon Lee; Jiwon AhnCho Rok Jung; Yun-Ji Jeung; Hyun Soo ChoMyung Jin SonKyung-Sook Chung
Bibliographic Citation
Biotechnology and Bioengineering, vol. 117, no. 6, pp. 1864-1876
Publication Year
2020
Abstract
Although primary human hepatocytes (PHHs) are the gold standard in drug efficacy and metabolism studies, long-term survival of PHHs and maintenance of their hepatic function are still challenging. In this study, we focused on the effect of the initial microenvironment on upregulation and long-term preservation of hepatic function of PHHs encapsulated within biodegradable hydrogel systems. PHHs were encapsulated in RGD-functionalized hybrid hydrogels with various degrees of degradability, and their hepatic functionality was analyzed. Regardless of the hydrogel elastic modulus, the combination with nondegradable hydrogels had a predominantly negative effect on the prompt engraftment of PHHs, whereas a degradable hydrogel with intermediate initial degradability was most effective in maintaining hepatic function. Efficient network formation by PHHs and cocultured cells, along with the control of hydrogel degradation, governed the hepatic functionality at an early stage and upon long-term cultivation. Under optimized conditions, expression of genes involved in biological processes such as focal adhesions, cell survival, cytoskeleton formation, and extracellular matrix interactions was significantly higher than that in a control with relatively delayed initial degradation. Thus, we suggest that the orchestrated control of initial cellular remodeling may play an important role in the maintenance of hepatic function in a three-dimensional PHH culture.
Keyword
cellular remodelingdegradable hydrogelinitial microenvironmentlongterm cultureprimary human hepatocytes
ISSN
0006-3592
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/bit.27328
Type
Article
Appears in Collections:
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
Division of Research on National Challenges > 1. Journal Articles
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