Hong, Seokheon Oh, Seung Ja Choi, Dongho Hwang, Yongsung Kim, Sang-Heon 2024-01-19T17:30:26Z 2024-01-19T17:30:26Z 2021-09-04 2020-07 1661-6596 https://pubs.kist.re.kr/handle/201004/118504 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 1 alpha (HIF1 alpha)-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 HIF1 alpha-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. English MDPI MESENCHYMAL STEM-CELLS 3-DIMENSIONAL COCULTURE MOUSE FIBROBLASTS TISSUE HEPATOCYTES MICROENVIRONMENTS DIFFERENTIATION MAINTENANCE EXPRESSION CLUSTERS Self-Organized Liver Microtissue on a Bio-Functional Surface: The Role of Human Adipose-Derived Stromal Cells in Hepatic Function Article 10.3390/ijms21134605 1 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.21, no.13 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 21 13 scie scopus 000550265000001 2-s2.0-85087112007 Biochemistry & Molecular Biology Chemistry, Multidisciplinary Biochemistry & Molecular Biology Chemistry Article MESENCHYMAL STEM-CELLS 3-DIMENSIONAL COCULTURE MOUSE FIBROBLASTS TISSUE HEPATOCYTES MICROENVIRONMENTS DIFFERENTIATION MAINTENANCE EXPRESSION CLUSTERS multicellular hepatic microtissue human adipose stem cell induced hepatocyte hypoxia-inducible factor 1 alpha hepatocyte maturation