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Updated: Jul 19, 2025
Robust Generation of Hepatocyte-like Cells from Human Embryonic Stem Cell Populations
Published on: October 26, 2011
Generation of functional liver sinusoidal endothelial-like cells from human bone marrow-derived mesenchymal stem
Seiji Mitani1, Yu Onodera1, Chihiro Hosoda1
1Advanced Medical Science of Thrombosis and Hemostasis, Nara Medical University, Kashihara, Nara 634-8521, Japan.
Introduction:
Liver sinusoidal endothelial cells (LSECs) are specialized vascular endothelial cells that play an important role in the maintenance of biological homeostasis. However, the lack of versatile human LSECs has hindered research on LSECs and development of medical technologies for liver diseases including hemophilia A. In this study, we developed a technique to induce LSEC differentiation from human bone marrow-derived mesenchymal stem cells (BM-MSCs).
Methods:
To induce LSECs from human BM-MSCs, cytokines and chemical compounds associated with signaling implicated in LSEC differentiation and liver development were screened. Then LSEC-related genes and proteins expression in the differentiated cells were analyzed by qPCR and flow cytometry analysis, respectively. LSEC-related functions of the differentiated cells were also examined.
Results:
We found that the gene expression of LSEC markers, such as LYVE1, was considerably increased by culturing human BM-MSCs with bone morphogenetic protein 4, fibroblast growth factor 8b, transforming growth factor-β signal inhibitor, and cyclic AMP. Furthermore, the differentiated cells expressed LSEC marker proteins and clearly demonstrated LSEC-specific functions, such as the uptake of hyaluronic acid.
Conclusions:
Our result indicate that the functional LSEC-like cells were successfully generated from human BM-MSCs using our established protocol.
