Researchers have developed advanced liver organoids capable of supporting regenerative therapies for liver failure and coagulation disorders, with potential to improve drug discovery and disease modeling.

These organoids, created using a novel 3D culture system called inverted multilayered air–liquid interface (IMALI), can self-organize into dome-shaped structures approximately 3 mm in diameter, incorporating multiple cell types.

The team successfully produced liver sinusoidal endothelial progenitors (LSEPs) from human-induced pluripotent stem cells, overcoming previous challenges in organoid development.

Genetic analysis revealed that these organoids develop four distinct blood vessel cell types, with sinusoidal vessel cells becoming dominant over time, mimicking natural liver vasculature.

The organoids demonstrated the ability to produce essential clotting factors, including Factor VIII, which is vital for hemophilia A patients, and successfully improved bleeding symptoms in a mouse model for up to five months.

This breakthrough addresses the challenge of replicating the liver’s complex vasculature, crucial for its metabolic and detoxification functions, and may serve as a source of coagulation factors for patients with inhibitors or at risk of bleeding.

The study, led by Dr. Takanori Takebe and published on June 25, 2025, in Nature Biomedical Engineering, involved multiple institutions, including Tokyo's Institute of Science and Takeda Pharmaceutical Co.

The research describes a reliable method to produce liver sinusoidal endothelial progenitors from human iPSCs and a novel 3D culture system that enables four precursor cell types to self-organize into functional liver organoids.

The organoids not only demonstrated key liver functions but also showed promise in regenerative medicine by potentially aiding in liver repair and recovery from damage.

This research marks a significant step forward in creating lab-grown liver tissues with internal blood vessels, addressing a major challenge in organoid development and opening avenues for treating hemophilia and liver diseases.

Future research will focus on evaluating the long-term stability and safety of these organoids for clinical applications, with potential insights extending to other organ types.