Engineering a perfusable 3D human liver platform from iPS cells.

Area of Science:

• Biotechnology
• Regenerative Medicine
• In Vitro Modeling

Background:

• In vitro human tissue models are vital for disease study and drug development.
• Existing single-organ models lack multi-organ interaction capabilities for drug metabolism and toxicity assessment.

Purpose of the Study:

• To develop a perfusable liver chip using patient-specific induced pluripotent stem cells (iPS cells).
• To create a robust model compatible with other tissue chips for multi-organ studies.
• To enable patient-specific in vitro liver response analysis.

Main Methods:

• Forming hepatocyte aggregates from iPS cells using a novel interrupted differentiation protocol.
• Encapsulating 3D organoids in PEG hydrogel for stable culture within a C-trap microfluidic chip.
• Culturing and characterizing liver organoid function under perfusion for at least 28 days.

Main Results:

• Successful formation and encapsulation of iPS cell-derived hepatocyte organoids.
• Robust culture of organoids in a perfusable microfluidic platform across various flow rates.
• Demonstrated stable liver function of the iHep organoid chip for a minimum of 28 days.

Conclusions:

• The developed liver chip utilizes patient-specific iPS cells and 3D organoids for in vitro disease modeling.
• This perfusable platform supports long-term liver function and can be integrated with other tissue chips.
• The strategy offers a novel approach for studying patient-specific liver responses and drug effects in vitro.