Authors
Da-Hyun Kim, Yongju Lee, Min-Ji Kim, Amos Chungwon Lee, Sunghoon Kwon, Kyung-Sun Kang
Published in
Science advances. Volume 12. Issue 32. Pages eaea3814. Aug 07, 2026. Epub Aug 05, 2026.
Abstract
Liver tissue engineering offers a promising alternative for end-stage liver disease, yet the recreation of functional vasculature remains a major bottleneck to clinical translation. Here, we developed vascularized liver organoids by integrating human induced pluripotent stem cell (iPSC)-derived hepatoblasts and endothelial cells into decellularized scaffolds functionalized with an anti-CD31 aptamer-based vascular coating agent (VCA). This facilitated spatially coordinated organization of vasculature and parenchyma. Spatial transcriptomic profiling and subsequent functional perturbation demonstrated IGF2-IGF1R-AKT/MAPK signaling as a key axis governing spatial organization and functional maturation of the liver organoids. Furthermore, exogenous IGF2 synergized with the VCA to augment the structural and functional refinement of liver organoids, which translated into markedly improved therapeutic outcomes following transplantation into a chronic liver failure mouse model. Collectively, these findings establish a comprehensive framework for generating physiologically relevant liver tissues from iPSCs and demonstrate the utility of spatial transcriptomics for uncovering regenerative mechanisms. This approach advances the feasibility of autologous, transplantable liver grafts for personalized regenerative therapy.
PMID:
42555733
Bibliographic data and abstract were imported from PubMed on 06 Aug 2026.
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