Faculty, Staff and Student Publications
Publication Date
3-26-2024
Journal
Cell Reports
DOI
10.1016/j.celrep.2024.113918
PMID
38451817
Abstract
Maximizing the potential of human liver organoids (LOs) for modeling human septic liver requires the integration of innate immune cells, particularly resident macrophage Kupffer cells. In this study, we present a strategy to generate LOs containing Kupffer cells (KuLOs) by recapitulating fetal liver hematopoiesis using human induced pluripotent stem cell (hiPSC)-derived erythro-myeloid progenitors (EMPs), the origin of tissue-resident macrophages, and hiPSC-derived LOs. Remarkably, LOs actively promote EMP hematopoiesis toward myeloid and erythroid lineages. Moreover, supplementing with macrophage colony-stimulating factor (M-CSF) proves crucial in sustaining the hematopoietic population during the establishment of KuLOs. Exposing KuLOs to sepsis-like endotoxins leads to significant organoid dysfunction that closely resembles the pathological characteristics of the human septic liver. Furthermore, we observe a notable functional recovery in KuLOs upon endotoxin elimination, which is accelerated by using Toll-like receptor-4-directed endotoxin antagonist. Our study represents a comprehensive framework for integrating hematopoietic cells into organoids, facilitating in-depth investigations into inflammation-mediated liver pathologies.
Keywords
Humans, Kupffer Cells, Induced Pluripotent Stem Cells, Liver, Liver Diseases, Organoids, Sepsis, Endotoxins, Cell Differentiation
Published Open-Access
yes
Recommended Citation
Li, Yang; Nie, Yunzhong; Yang, Xia; et al., "Integration of Kupffer Cells Into Human iPSC-Derived Liver Organoids for Modeling Liver Dysfunction in Sepsis" (2024). Faculty, Staff and Student Publications. 4765.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4765
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