Keio University scientists have achieved a significant breakthrough by successfully generating human adult hepatocyte organoids exhibiting mature metabolic functions. These 3D liver cell cultures demonstrate complex liver activities, marking a substantial advancement in liver disease research. These organoids effectively replicate the intricate biology of the liver outside the human body.
The research team, led by Ryo Igarashi and Mayumi Oda, utilized cryopreserved adult human hepatocytes and discovered that treatment with oncostatin M, a cytokine involved in inflammatory signaling pathways, triggered a million-fold expansion in organoid numbers. This finding addresses previous limitations in cell growth observed in laboratory settings, where hepatocytes often transformed into cholangiocyte-like cells with limited functional lifespans.
These hepatocyte organoids maintained viability for over three months, with some surviving up to six months. Post-differentiation, the organoids expressed key liver functions, including the synthesis of glucose, urea, cholesterol, and bile acid. Moreover, they formed bile canaliculi-like networks, mimicking the liver's native architecture. When transplanted into immunocompromised mice with impaired liver function, the organoids successfully engrafted, replacing lost liver cells and restoring fundamental liver functionalities. This development addresses the critical scarcity of donor organs in liver transplantation.
These organoids hold great promise for pharmaceutical research and disease modeling, providing a renewable and consistent source of metabolically active human liver cells. The team also replicated pathological states, such as ornithine transcarbamylase (OTC) deficiency, using gene-editing techniques, further expanding the potential applications of this innovative technology.