Glowing liver spheroids in a futuristic lab, representing stem cell research.

Lab-Grown Liver Tissue: A New Hope for Treating Liver Disease?

Rhea Morgan in Health & Wellness December 2025 • 4 min read.

"Stem cell-derived 'mini-livers' show promise for research and potential future therapies."

In a recent issue of Archives of Toxicology, Hassan Rashidi and his team from the University of Edinburgh unveiled a study detailing the creation of 3D liver tissue spheroids derived from pluripotent stem cells. These spheroids, essentially miniature versions of liver tissue, hold immense potential for advancing our understanding and treatment of liver diseases.

The team utilized various human pluripotent stem cell lines, including H9, Man12, FSPS13B, and P106, to generate these 3D structures. The process involved differentiating the stem cells into hepatoblasts (precursor liver cells) and then further into hepatocyte-like cells (HLCs) using specific growth factors (HGF and OSM) in a culture environment that encouraged spheroid formation. These spheroids could be maintained in the lab for up to a year, showcasing their stability and potential for long-term study.

The resulting spheroids exhibited high expression of key liver proteins like HNF4A and albumin, confirming their liver-like characteristics. Importantly, the expression of specific liver enzymes (CYP3A4, SULT1, and MRP1) was observed primarily in the periphery of the spheroids, mirroring certain aspects of liver tissue organization. The success of this method across different stem cell lines (hESC and hiPSC) further strengthens its potential for wider application.

Why are Liver Spheroids a Big Deal?

Glowing liver spheroids in a futuristic lab, representing stem cell research.

The creation of these liver spheroids addresses a critical need in the field of liver research. For years, scientists have been working to develop reliable in vitro (lab-based) systems for studying liver function and toxicity. Traditional methods often fall short of accurately replicating the complexity of the human liver, making it difficult to predict how drugs and other substances will affect the organ in vivo (in a living organism).

These 3D liver spheroids offer several advantages over traditional 2D cell cultures:

Improved Liver Function: 3D structures allow cells to interact with each other in a more natural way, leading to better representation of liver-specific functions like metabolism and enzyme induction.
Long-Term Studies: The ability to maintain these spheroids for extended periods (up to a year) enables long-term toxicity studies and investigations into chronic liver diseases.
Omics Applications: Spheroids can be used for advanced “omics” studies (genomics, proteomics, metabolomics) to analyze the effects of various compounds on liver cells at a molecular level.
Personalized Medicine Potential: iPS cells from individuals with genetic liver diseases can be used to generate spheroids, creating models for studying and potentially treating these specific conditions.

While current differentiation protocols still result in 'hepatocyte-like cells' (HLCs) that aren't perfect replicas of primary human hepatocytes, the Rashidi et al. technique is a significant step forward, particularly regarding potential in vivo applications. However, the authors acknowledge a need for unbiased characterization via genome-wide expression analysis to confirm HLC differentiation status compared to primary human hepatocytes.

Future Directions: From Lab to Clinic?

The development of liver spheroids represents a significant advancement in liver research, offering a more realistic and versatile model for studying liver function, toxicity, and disease.

However, further research is needed to fully characterize these HLCs and optimize their differentiation to more closely resemble primary human hepatocytes. Specifically, future studies should focus on:

Determining whether the supportive effect of HLC-spheroids in mouse models of partial hepatectomy have a clinical perspective, and if this may lead to applications for transplants.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1007/s00204-018-2347-0, Alternate LINK

Title: Highlight Report: Spheroids From Stem Cell-Derived Hepatocyte-Like Cells

Subject: Health, Toxicology and Mutagenesis

Journal: Archives of Toxicology

Publisher: Springer Science and Business Media LLC

Authors: Patrick Nell

Published: 2018-11-16

Everything You Need To Know

Why is the creation of liver spheroids considered a significant advancement in liver research?

Liver spheroids are significant because they provide a more realistic in vitro model for studying liver function, toxicity, and disease. Traditional 2D cell cultures often fail to replicate the complexity of the human liver, limiting their usefulness in predicting how drugs and substances affect the organ. Spheroids, being 3D structures, allow for more natural cell interactions, leading to better representation of liver-specific functions like metabolism and enzyme induction.

How are these 3D liver tissue spheroids created from stem cells?

The 3D liver tissue spheroids are created from human pluripotent stem cell lines like H9, Man12, FSPS13B, and P106. These stem cells are differentiated into hepatoblasts (precursor liver cells) and then further into hepatocyte-like cells (HLCs) using specific growth factors such as HGF and OSM in a culture environment. This environment encourages the cells to self-assemble into 3D spheroids, which can then be maintained for long-term study.

Do these lab-grown liver spheroids actually function like real liver tissue?

Yes, the liver spheroids created in the study exhibited key characteristics of liver tissue. They showed high expression of essential liver proteins like HNF4A and albumin. Additionally, specific liver enzymes like CYP3A4, SULT1, and MRP1 were observed, primarily in the periphery of the spheroids, mirroring aspects of the liver's natural organization.

What are the key advantages of using liver spheroids compared to traditional methods for studying liver disease and toxicity?

The liver spheroids offer several advantages. They enable improved liver function representation, allowing cells to interact in a more natural way. They also allow for long-term studies, with the capability to maintain spheroids for up to a year. Spheroids also support advanced 'omics' studies (genomics, proteomics, metabolomics) to analyze the effects of compounds on liver cells at a molecular level. Moreover, iPS cells from individuals with genetic liver diseases can be used to generate spheroids, creating models for personalized medicine.

Are the lab-grown 'mini-livers' perfect replicas of a real liver, and what further research is needed?

While the created hepatocyte-like cells (HLCs) are not perfect replicas of primary human hepatocytes, it's a significant advancement, especially for potential in vivo applications. Further research is needed, involving unbiased characterization via genome-wide expression analysis, to confirm the HLC differentiation status more precisely compared to primary human hepatocytes. This is important to ensure the HLCs accurately represent the functions and responses of real liver cells.