Self-Organized Liver Microtissue on a Bio-Functional Surface: The Role of Human Adipose-Derived Stromal Cells in Hepatic Functionopen access
- Authors
- Hong, Seokheon; Oh, Seung Ja; Choi, Dongho; Hwang, Yongsung; Kim, Sang-Heon
- Issue Date
- Jul-2020
- Publisher
- MDPI
- Keywords
- multicellular hepatic microtissue; human adipose stem cell; induced hepatocyte; hypoxia-inducible factor 1 alpha; hepatocyte maturation
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.21, no.13, pp.1 - 21
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- Volume
- 21
- Number
- 13
- Start Page
- 1
- End Page
- 21
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/9679
- DOI
- 10.3390/ijms21134605
- ISSN
- 1661-6596
- Abstract
- 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.
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