In a study published in Nature, Keio University researchers unveiled a method to proliferate these hard-to-grow organoids by a million-fold in just 3–4 weeks while maintaining key liver functions. “These organoids are potentially the closest laboratory representations of the liver and its multifunctionality,” says senior author Professor Toshiro Sato of the Keio University School of Medicine.
Keio University’s Liver Organoid Breakthrough in May of 2025
Key Innovation:
Researchers achieved a million-fold expansion of human hepatocyte organoids in just 3–4 weeks, maintaining essential liver functions. This advancement addresses previous challenges where organoids would lose functionality after a short period.
Methodology:
- Cell Source: Human adult hepatocytes obtained from patients.
- Growth Inducer: Oncostatin M, a signaling protein involved in inflammation, was used to stimulate proliferation.
- Differentiation: Hormonal treatments guided the cells to differentiate into functional liver cells.Nature
Functional Outcomes:
- Metabolic Activities: Organoids produced glucose, urea, bile acids, cholesterol, and triglycerides.
- Protein Secretion: Albumin secretion levels surpassed previous studies, reaching those comparable to human liver cells.
- Structural Formation: Development of bile canaliculi-like structures, allowing bile acid transport.Keio University
In Vivo Application:
When transplanted into mice with compromised immune systems and liver dysfunction, the organoids integrated into the liver, replacing damaged cells and restoring function.
Implications:
- Drug Development: Provides a more consistent and cost-effective model for testing liver-related drugs.
- Disease Modeling: Offers a platform to study liver diseases like MASLD and genetic disorders such as ornithine transcarbamylase deficiency.
- Regenerative Medicine: Potential to scale up organoid production for human liver regeneration, addressing transplant shortages.
This breakthrough represents a significant step forward in liver research, with the potential to revolutionize drug testing, disease modeling, and regenerative therapies.
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