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Updated: Feb 28, 2026

3D Imaging of the Liver Extracellular Matrix in a Mouse Model of Non-Alcoholic Steatohepatitis
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Reconstructing Liver Fibrosis: 3D Human Models, Microbiome Interfaces, and Therapeutic Innovation.

Dileep G Nair1,2, Divya B Nair2, Ralf Weiskirchen1

  • 1Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany.

Current Issues in Molecular Biology
|February 27, 2026
PubMed
Summary
This summary is machine-generated.

Advanced 3D liver models offer new hope for understanding and treating liver fibrosis. These innovative models better mimic human disease, aiding drug discovery and aligning with new regulatory approaches.

Keywords:
cirrhosisextracellular matrixliver fibrosismetabolic dysfunction-associated steatohepatitismetabolic dysfunction-associated steatotic liver disease

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Area of Science:

  • Hepatology and Regenerative Medicine
  • Biotechnology and Advanced Cell Culture Models
  • Drug Discovery and Development

Background:

  • Liver fibrosis, a precursor to cirrhosis, results from chronic liver injury (viral hepatitis, alcohol, metabolic dysfunction) and is a major global health burden.
  • Current therapies for liver fibrosis are limited, and traditional in vitro and animal models inadequately replicate human disease complexity, including cellular interactions and immune modulation.
  • The limitations of existing models hinder the development of effective treatments for progressive liver fibrosis.

Purpose of the Study:

  • To review the pathophysiology of liver fibrosis and its global impact.
  • To summarize the current landscape of advanced three-dimensional (3D) human liver models.
  • To examine the role of microbiome interfaces in modulating liver fibrogenesis and their implications for anti-fibrotic drug screening.

Main Methods:

  • Review of current scientific literature on liver fibrosis pathophysiology and advanced 3D cell culture models.
  • Analysis of emerging technologies such as organoids, spheroids, bioprinted constructs, and organ-on-a-chip systems.
  • Exploration of multi-organ models incorporating microbiome cues and multi-omics readouts for mechanistic dissection.

Main Results:

  • Three-dimensional (3D) cell culture models (organoids, spheroids, bioprinted constructs, organ-on-a-chip) are superior in reconstructing cellular diversity and mechanical microenvironments compared to traditional models.
  • Emerging multi-organ models integrate microbiome influences and advanced analytical techniques (multi-omics, imaging) for more predictive screening.
  • These advanced models align with evolving regulatory frameworks like FDA's Modernization 3.0 and New Approach Methodologies (NAMs).

Conclusions:

  • Advanced 3D human liver models represent a significant leap forward in understanding liver fibrosis pathophysiology.
  • These models facilitate more accurate drug discovery and development for liver fibrosis and cirrhosis.
  • Incorporating microbiome interactions into these models enhances their predictive power for anti-fibrotic therapies.