A1AT-loaded nanoparticles for liver organoids immune modulation
Embargo Date
2028-02-20
OA Version
Citation
Abstract
End-stage liver disease and ALF often require OLT as the only viable treatment option. However, the limited availability of donor livers presents a significant challenge, driving researchers to investigate organoid-based liver regeneration as a potential alternative. Despite this promise, both OLT and liver organoid transplantation can trigger inflammatory immune responses. Due to their relatively small size, transplanted liver organoids are particularly vulnerable to destruction in such conditions. In this study, we utilized dextran-based nanoparticles loaded with A1AT, a protein with potent immunomodulatory properties, and incorporated these nanoparticles into our liver organoids. To simulate in vivo inflammatory conditions, the organoids were exposed to a pro-inflammatory cytokine cocktail (cytomix), after which their viability and function were assessed using various assays. Our results showed that liver organoids containing A1AT-NPs demonstrated significantly improved viability under inflammatory conditions. Additionally, these organoids maintained their gene and protein expression profiles, as well as enzymatic function, compared to controls. These findings suggest that A1AT-NPs provide a protective effect against inflammation-induced damage, offering a promising strategy to enhance the survival and functionality of transplanted liver organoids.
Description
2025