Long-Term Growth of Stem Cell-Derived Liver Organoids Enhanced by Bile Acid Support
Japanese researchers have developed long-term growing liver organoids from human stem cells enhanced by bile acid support, opening new possibilities for liver disease research and therapy.
Researchers from Japan have achieved a significant breakthrough in liver regenerative medicine by developing three-dimensional hepatic organoids derived from human induced pluripotent stem cells (iPSCs) that demonstrate sustained growth and maintained hepatocyte-like features over extended periods. The key to this advancement was the addition of bile acids, which act as farnesoid X receptor (FXR) agonists, to the culture medium, fostering the organoids' proliferation and structural integrity. These organoids exhibited a distinctive grape-like morphology and could be cultivated for more than three months, unlike traditional spherical or cyst-like structures seen without bile acids.
The study, published in Cell Reports, involved forming two-dimensional cultures of iPS-Heps from human iPSCs, then embedding them into basement membrane to create three-dimensional structures. The innovative culture medium, called human iPSC-derived hepatic (iHO) medium, included bile acids alongside growth factors, supporting the organoids' growth. Gene expression analyses revealed these organoids closely resembled fetal hepatocytes, with FXR signaling playing a pivotal role in maintaining their hepatic characteristics.
Additionally, experimental inhibition of FXR resulted in a marked decrease in the formation of grape-like organoids, confirming FXR's importance. The researchers also demonstrated that these organoids can support hepatitis C virus infection, hinting at their potential for disease modeling and drug testing. This research paves the way for future studies on chronic liver diseases and opens new avenues for developing therapeutic strategies. The findings underscore the potential of stem cell-derived liver organoids as versatile tools for understanding liver pathology and treating liver disorders.
Source: https://medicalxpress.com/news/2025-07-stem-cell-derived-liver-organoids.html
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