Laboratory-grown liver organoids acquire blood vessels for the first time

Scientists have successfully created liver organoids with functional blood vessels that closely mimic the specialized capillaries found in the real liver. The advance payment solves the major challenges of tissue engineering and provides potential treatments for blood-friendly blood clotting disease.

The liver organoids developed by researchers at the Tokyo Institute of Science and Cincinnati Children’s Hospital Medical Center are the first time scientists replicate the complex blood vessel network of the liver under laboratory conditions. These tiny dome-shaped structures measure only a 3 mm range, but contain the necessary types of blood vessels to make the liver function properly.

Build better blood vessels

The key innovation lies in creating the liver sinusoidal endothelial cells – specialized cells of the liver’s unique blood vessels. Unlike other organs, the capillaries of the liver have tiny pores that can quickly exchange nutrients and waste between blood and liver cells.

Using a novel 3D culture method called the Countdown Multilayer Air Interface (IMALI), the researchers coaxed four different cell types to self-organize as functional organoids. The process mimics the way the liver develops naturally, and cells arrange themselves into appropriate buildings without external guidance.

Treatment applications

The organ demonstrates its medical potential by treating hemophilia A in laboratory mice. After transplantation, they produced basic coagulation factors for up to five months, which significantly improved bleeding symptoms. Key therapeutic benefits include:

• Continuous production of Factor VIII and other coagulation proteins
• In some tests, better than current treatment
• Reduced bleeding time and blood loss in animal models
• The potential of personalized medical approaches

Molecular crosstalk drive development

This study reveals key communication between different cell types during organ formation. Hepatic endothelial cells release Wnt2 protein, which promotes hepatocyte maturation and encourages vascular branching. This molecular dialogue has proven to be crucial for the creation of functional liver tissue.

Professor Takanori Takebe, who leads the research team, explained: “This technology provides a fundamental approach to embedding organ-specific vascular structures into organs, facilitating understanding of human biology and disease.”

Clinical potential

Compared with current hemophilia treatment, organoids exhibit excellent coagulation activity, even with the presence of inhibitory antibodies, affecting 20-30% of patients with severe hemophilia A. This suggests that this approach can help patients who have poor responses to existing therapies.

In addition to hemophilia, the technology also provides the possibility for studying liver disease, testing drug responses, and possibly treating end-stage liver failure. The researchers stressed that their enhanced organoids could support regenerative therapies and personalized medical approaches.

The team plans to explore the long-term stability and safety of clinical applications while extending insights to other organ types. This work represents an important step in creating functional alternative organizations for human transplantation.

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