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

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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 l

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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