Hepatotoxicity Evaluation by iPSC-derived Hepatocyte Spheroids

Hepatotoxicity is a significant concern in drug development and safety assessment. Traditional in vitro hepatotoxicity screening methods rely on 2D monolayer cultures, which often fail to replicate the complex microenvironment and functionality of the liver. Creative Biolabs launches induced pluripotent stem cell (iPSC)-derived hepatocyte spheroid as a tool to evaluate hepatotoxicity.

Formation of iPSC-derived Hepatocyte Spheroids

The first step in creating iPSC-derived hepatocyte spheroids involves reprogramming somatic cells into pluripotent stem cells, followed by directed differentiation into hepatocyte-like cells. These cells are then aggregated into spheroids utilizing various techniques such as hanging drop, microfluidics, bioprinting, or scaffold-based methods. The resulting spheroids exhibit enhanced liver-specific functions and maintain cellular heterogeneity similar to native liver tissue.

Fig.1 Scheme of generation of iPSCs from healthy controls and RA patients with MTX-induced hepatotoxicity.¹

Fig.2 Cytotoxicity test using hepatocyte-like cells treated with MTX for 6 days.¹

Advantages of the iPSC-derived Hepatocyte Spheroids Compared to Traditional Animal Models

• IPSC-derived hepatocyte spheroids closely mimic the native liver tissue, providing a more physiologically relevant environment for drug metabolism and toxicity assessment. The increased cell-cell and cell-matrix interactions within spheroids contribute to improved cell viability and functionality.
• IPSC-derived hepatocyte spheroids exhibit enhanced drug-metabolizing enzyme activity, making them more suitable for studying drug metabolism and toxicological responses.
• The expression of key hepatocyte markers, such as albumin, cytochrome P450 enzymes, and transporters, are preserved in spheroids, further validating their relevance in hepatotoxicity evaluation.
• Measuring hepatocyte-specific functions like albumin secretion, urea synthesis, and bile acid transport can provide insights into drug-induced liver injury and toxicological responses.
• Prolonging the lifespan of iPSC-derived hepatocytes with the ability to measure long-term toxicity or drug efficacy.

Applications of the iPSC-derived Hepatocyte Spheroids

The utilization of iPSC-derived hepatocyte spheroids marks a significant advancement in regenerative medicine and drug discovery. The 3D structure provides a more physiologically relevant platform, revolutionizing our ability to model liver biology, study hepatic diseases, and enhance drug screening processes. The diverse applications include but are not limited to:

1. The evaluation of hepatotoxicity, which includes assessing markers of cell viability, such as lactate dehydrogenase release and ATP production.
2. Nanomaterials detection application.
3. Drug-induced chronic liver disease research. Such as fatty degeneration, cholestasis, etc.

Hepatotoxicity Evaluation

iPSC-derived hepatocyte spheroids offer a promising platform for evaluating hepatotoxicity in drug discovery and safety assessment. Creative Biolabs offers highly specialized iPSC-derived hepatocyte spheroids to meet your needs. Please contact us for more information.

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