Integrated mesenchymal and extracellular cues drive bioengineered liver tissue formation and function.

Area of Science:

• Biotechnology
• Regenerative Medicine
• Tissue Engineering

Background:

• Human tissue engineering aims to create physiological models but struggles with complexity.
• Existing methods often lack cellular complexity, extracellular matrix (ECM) mimicry, and dynamic stimuli.

Purpose of the Study:

• To bioengineer functional liver tissues (BLTs) by incorporating key bioengineering factors.
• To address limitations in current tissue engineering approaches for liver tissue development.

Main Methods:

• Utilized human intrahepatic cholangiocyte organoids (ICOs), hepatic stellate cells (HSCs), and mesenchymal stromal cells (MSCs).
• Employed a synthetic polyisocyanide (PIC)-based hydrogel and dynamic suspension culture (DS).
• Performed transcriptomic analyses to understand cellular and ECM cue integration.

Main Results:

• Mesenchymal cells (HSCs and MSCs) accelerated organoid growth and promoted BLT formation.
• Dynamic suspension culture (DS) and PIC hydrogel improved BLT formation and functionality.
• Transcriptomic data confirmed integrated cellular and extracellular cues in BLT development.

Conclusions:

• Organoids with mesenchymal cells in defined hydrogels yield functional BLTs for disease modeling, drug screening, and toxicity testing.
• This bioengineering strategy provides a basis for developing larger liver tissues for transplantation.
• The approach is adaptable for engineering other tissues and studying bioengineering factor interactions.