Challenges on the road to a multicellular bioartificial liver

Area of Science:

• Regenerative Medicine
• Biotechnology
• Hepatology

Background:

• Significant progress has been made in developing bioartificial livers (BALs) for extracorporeal devices and transplantable organs.
• However, critical characteristics for clinical application, such as multicellularity and sinusoidal microarchitecture, remain insufficiently addressed.
• Existing BALs often lack the complexity to fully replicate the diverse functions of a native liver.

Purpose of the Study:

• To review the challenges in developing clinically applicable bioartificial livers (BALs).
• To highlight the importance of multicellularity and sinusoidal microarchitecture for BAL functionality.
• To discuss advancements in cell sourcing, microarchitecture reconstruction, and other BAL design aspects.

Main Methods:

• Literature review of recent studies on bioartificial liver development.
• Analysis of current sources and applications of nonparenchymal liver cells in BALs.
• Discussion of strategies for reconstructing liver sinusoid microarchitecture and vascular/biliary networks.

Main Results:

• Defined sources of nonparenchymal liver cells (endothelial cells, cholangiocytes, macrophages) are available for BAL development.
• Recent studies show progress in reconstructing complex liver sinusoid microarchitecture using various cell types.
• Key aspects like liver zonation and vascular/biliary network formation are being investigated for improved substrate delivery and waste removal.

Conclusions:

• Achieving multicellularity and a functional sinusoidal microarchitecture are crucial for developing effective BALs.
• Further research into liver zonation and network formation is necessary for BALs to meet clinical demands.
• Multicellular BALs offer potential benefits for the pharmaceutical industry, particularly in drug testing and development.