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Article

Self-Organized Liver Microtissue on a Bio-Functional Surface: The Role of Human Adipose-Derived Stromal Cells in Hepatic Function

1
Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Korea
2
Department of Surgery, Hanyang University College of Medicine, Seoul 04763, Korea
3
Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan-si, Chungcheongnam-do 31151, Korea
4
Department of Bio-Med Engineering, KIST school, Korea University of Science and Technology, Seoul 02792, Korea
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(13), 4605; https://doi.org/10.3390/ijms21134605
Received: 6 June 2020 / Revised: 24 June 2020 / Accepted: 25 June 2020 / Published: 29 June 2020
(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 2.0)
The maintenance of hepatocyte function is a critical research topic in liver tissue engineering. Although an increasing number of strategies have been developed, liver tissue engineering using hepatocytes as a therapeutic alternative remains challenging owing to its poor efficacy. In this study, we developed a multicellular hepatic microtissue to enhance the function of induced hepatic precursor cells. Mouse induced hepatic precursor cells (miHeps) were self-organized in 3D with human adipose-derived stem cells (hASCs) on a bio-functional matrix. We found that hepatic phenotypes, such as levels of albumin, asialoglycoprotein receptor-1, and cytochrome P450, were enhanced in miHeps-hASC microtissue comprising miHeps and hASCs relative to two-dimensional-cultured miHeps-hASCs. Additionally, the secretome of 3D-cultured hASCs increased the hepatic function of mature miHeps. Furthermore, hepatic gene expression was reduced in mature miHeps treated with conditioned media of hypoxia-inducible factor 1α (HIF1α)-depleted hASCs relative to that with conditioned media of control hASCs. Our results suggested that the hepatic function of 3D-co-cultured miHeps could be enhanced by HIF1α-dependent factors secreted from stromal cells. This study provides an insight into the factors regulating hepatic function and shows that self-organized hepatic microtissue could act as liver spheroids for liver regenerative medicine and liver toxicity tests. View Full-Text
Keywords: multicellular hepatic microtissue; human adipose stem cell; induced hepatocyte; hypoxia-inducible factor 1α; hepatocyte maturation multicellular hepatic microtissue; human adipose stem cell; induced hepatocyte; hypoxia-inducible factor 1α; hepatocyte maturation
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MDPI and ACS Style

Hong, S.; Oh, S.J.; Choi, D.; Hwang, Y.; Kim, S.-H. Self-Organized Liver Microtissue on a Bio-Functional Surface: The Role of Human Adipose-Derived Stromal Cells in Hepatic Function. Int. J. Mol. Sci. 2020, 21, 4605. https://doi.org/10.3390/ijms21134605

AMA Style

Hong S, Oh SJ, Choi D, Hwang Y, Kim S-H. Self-Organized Liver Microtissue on a Bio-Functional Surface: The Role of Human Adipose-Derived Stromal Cells in Hepatic Function. International Journal of Molecular Sciences. 2020; 21(13):4605. https://doi.org/10.3390/ijms21134605

Chicago/Turabian Style

Hong, Seokheon, Seung J. Oh, Dongho Choi, Yongsung Hwang, and Sang-Heon Kim. 2020. "Self-Organized Liver Microtissue on a Bio-Functional Surface: The Role of Human Adipose-Derived Stromal Cells in Hepatic Function" International Journal of Molecular Sciences 21, no. 13: 4605. https://doi.org/10.3390/ijms21134605

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