Liver Tissueoid on-a-Chip Modeling Liver Regeneration and Allograft Rejection

Area of Science:

• * Biomedical Engineering
• * Regenerative Medicine
• * Transplantation Immunology

Background:

• * Current in vitro models lack physiological relevance for liver transplantation research.
• * Organ-on-a-chip technology offers a promising avenue for developing clinically translatable in vitro models.
• * There is a need for advanced models to study liver regeneration and allograft rejection.

Purpose of the Study:

• * To engineer a vascularized liver tissueoid-on-a-chip (LToC) model that replicates human liver tissue.
• * To utilize the LToC model for studying liver regeneration and allograft rejection.
• * To establish a platform for immunosuppressive drug testing and personalized transplant medicine.

Main Methods:

• * Engineered a microfluidic device with human hepatic progenitor cells and endothelial cells in a fibrin matrix.
• * Maintained dynamic culture for 49 days to promote self-assembly into vascularized liver tissueoids.
• * Assessed tissueoid architecture, cell viability, vascular integrity, hepatic function, and cellular composition.

Main Results:

• * The LToC model self-assembled into a perfusable microvascular network with lobule-like architecture.
• * Demonstrated high cell viability (>95%), stable vascular integrity, and active hepatic functions.
• * Successfully modeled allogeneic T cell-induced liver rejection, including decreased viability, endothelial disruption, and inflammatory responses.

Conclusions:

• * The LToC model provides a physiologically relevant platform for studying liver regeneration and immune-mediated injury.
• * This organ-on-a-chip system can be used to investigate liver allograft rejection.
• * The LToC model holds potential for drug screening and advancing personalized transplant medicine.