A groundbreaking discovery in the field of organoid research has brought scientists closer to replicating the intricate functions of the human liver. Researchers at Keio University School of Medicine have developed a novel method to cultivate hepatocyte organoids derived from cryopreserved adult human liver cells. By utilizing oncostatin M, a signaling protein linked to inflammatory processes, these organoids demonstrated unprecedented growth and functionality over extended periods. The team observed that the organoids maintained their ability to differentiate for up to six months while exhibiting robust proliferation rates.
This innovative approach not only enhances the scalability of organoid production but also ensures the preservation of critical liver functions. Upon differentiation, the organoids exhibited all major metabolic activities characteristic of the liver, such as glucose and urea synthesis, bile acid secretion, and cholesterol production. Remarkably, the levels of albumin secretion surpassed those achieved in previous studies, reaching concentrations comparable to native human hepatocytes. Additionally, the organoids formed intricate networks of ducts that facilitated bile acid transport, mimicking natural liver architecture.
The implications of this research extend far beyond laboratory advancements. When transplanted into immunocompromised mice with impaired liver function, the human hepatocyte organoids successfully integrated and restored liver capabilities. This breakthrough holds immense promise for addressing the global shortage of transplantable livers, which often degrade rapidly post-harvest. Furthermore, the technology could significantly reduce costs associated with drug toxicity testing by providing consistent, functional hepatocyte models. These organoids also serve as superior platforms for studying liver diseases, accurately modeling conditions like MASLD and genetic disorders such as ornithine transcarbamylase deficiency. As research progresses, scaling up organoid production and incorporating additional liver cell types will further enhance their utility in regenerative medicine and pharmaceutical development, paving the way for transformative therapies and treatments.