Mesenchymal stem cell-derived liver-on-a-chip reconstitutes human liver structure and function

Area of Science:

• Regenerative Medicine
• Organ-on-a-Chip Technology
• Hepatobiliary Research

Background:

• Current microfluidic liver models often lack a complete biliary component, limiting their ability to fully replicate human liver excretory functions.
• Developing in vitro models with functional integrity is crucial for advancing liver research and enabling personalized therapeutic strategies.

Purpose of the Study:

• To engineer a microfluidic liver-on-a-chip model that incorporates a functional hepatobiliary network, including a biliary component.
• To utilize a single source of human mesenchymal stem cells to derive all necessary liver cell types (endothelial cells, hepatocytes, cholangiocytes).
• To create a model capable of recapitulating integrated organ-level responses, such as xenobiotic metabolism and excretion, and modeling liver injury.

Main Methods:

• Development of a microfluidic device integrating endothelial cells, hepatocytes, and cholangiocytes derived from human mesenchymal stem cells.
• Reconstruction of a simplified liver unit comprising a sinusoid, hepatocyte compartment, and bile duct, supported by barrier integrity and controlled fluid flow.
• Assessment of integrated organ-level responses to xenobiotics and modeling of ischemic liver injury with therapeutic cell recruitment.

Main Results:

• Successfully created a stem cell-derived liver-on-a-chip with a functional hepatobiliary network, including a bile duct.
• The model demonstrated integrated organ-level responses, including hepatic uptake and biliary excretion of xenobiotics.
• The platform effectively modeled ischemic liver injury and showed potential for therapeutic cell recruitment.

Conclusions:

• The developed microfluidic liver-on-a-chip, derived from a single source of human stem cells, successfully reconstructs key liver functions, including excretion.
• This technology offers a platform for personalized organ-level modeling, advancing the study of tissue development and targeted therapies for liver injury.
• The model holds significant potential for drug screening, toxicity testing, and personalized medicine applications in hepatology.