POS8-0852

Development of an LSS/HepaRG Hybrid Spheroid System for Liver Toxicity Evaluation

Topic

S8. Frontiers of Functional Polymers in Biology and Medicine

When and Where

Sep 30, 2026 08:30 - 09:30

Room 301 (Grand Ballroom)

Session Chairs

Heesuk KIM

Jinhye BAE

Presenter(s)

Yoonhyuck Lee (Department of Biomedical Sciences & Systems Biology, Dankook University, Cheonan 31116, Korea)

Co-Author(s)

No co-authors

Abstract

Reliable in vitro liver models are essential for predicting drug-induced hepatotoxicity during preclinical drug development. Conventional two-dimensional (2D) hepatocyte cultures are widely used because of their simplicity and reproducibility; however, they rapidly lose hepatic phenotype, metabolic activity, and liver-specific functions, resulting in poor physiological relevance. Three-dimensional (3D) hepatic spheroids have emerged as promising alternatives due to their enhanced cell-cell interactions and improved maintenance of liver functions. Nevertheless, conventional spheroids often suffer from limited oxygen and nutrient diffusion, leading to hypoxic or necrotic cores, heterogeneous cellular microenvironments, and reduced functionality during long-term culture. In addition, the absence of tissue-like structural support within spheroids limits their ability to recapitulate the native hepatic microenvironment. To address these challenges, we developed a porous leaf-stacked structure (LSS) particle designed to serve as an internal scaffold within hepatic spheroids. The highly porous architecture of the LSS particle was expected to facilitate cell attachment, improve mass transport, and provide a more physiologically relevant microenvironment for hepatocyte culture. By co-culturing HepaRG cells with LSS particles, we prepared LSS/HepaRG hybrid spheroids and hypothesized that the incorporation of LSS particles would enhance hepatic functionality while minimizing diffusion-related limitations commonly observed in conventional spheroids. To evaluate its applicability as an in vitro hepatotoxicity model, acetaminophen was used as a model hepatotoxic compound. The hybrid spheroid was assessed cell viability, cytochrome P450 (CYP) activity, lactate dehydrogenase (LDH) release, and albumin secretion.

Keywords: Leaf stacked structure, Cell spheroid, Liver toxicity, HepaRG, Acetaminophen

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