Scientists develop advanced liver organoids, boosting rodent survival rates

Scientists have recently achieved a significant breakthrough by developing a new "multi-zone" human liver organoid that has dramatically improved the survival rate of mice with damaged livers. This advance hinges on the successful simulation of the liver's three key "zones," each responsible for different functions essential to its efficiency in clearing waste from the blood. Previously, researchers struggled to cultivate liver organoids in the lab that accurately replicated the liver's complex zonal structure. The team at Stanford University, led by bioengineering professor John Lynn, overcame this challenge by innovating a novel cultivation method that encourages these organoids to form multi-zone structures spontaneously. The results of the experiment, published in October 2023 in the prestigious scientific journal *Nature*, show that these new liver organoids excel in promoting liver repair in damaged mice, leading to a notable increase in their survival rate. John Lynn explains that the success of these liver organoids is primarily due to the advanced cultivation techniques they used. They optimized the nutrient medium to include specific growth factors and nutrients that support the long-term survival and differentiation of liver cells. Additionally, the team developed a unique 3D support material that mimics the in vivo environment, providing a more natural growth condition for the liver cells. This approach not only increased the volume of the organoids to over ten times the previous lab record but also enhanced their metabolic functions and drug responsiveness, making them more closely resemble real livers. The implications of this research are profound. These multi-zone liver organoids can be used for foundational studies, allowing scientists to gain deeper insights into liver functions and disease mechanisms. They also hold significant potential for clinical applications, offering a new treatment option for patients in need of liver transplants. The organoids can be employed to test new drugs more accurately, simulating human liver responses and accelerating the drug development and clinical trial processes. Furthermore, they may enable personalized medicine, where doctors can tailor treatment plans to individual patients, reducing drug side effects and improving outcomes. Livers play a crucial role in metabolic control, converting nutrients into glucose, storing fat, and breaking down toxins. However, over one-third of the global population suffers from various liver diseases, including Metabolic-associated Fatty Liver Disease (MASLD), which can progressively threaten the liver's core functions. To speed up drug development and advance regenerative medicine, scientists have been working on liver organoids—miniature 3D liver models. The Stanford team's breakthrough in liver organoid growth involves not only increasing the volume to unprecedented levels but also preserving and enhancing the organoid's functional capabilities. By achieving a tenfold increase in volume and improved metabolic and drug response properties, these organoids are a step closer to being used in clinical settings. The enhanced size and functionality of these organoids make them more suitable for both research and practical applications. Industry experts and organizations have lauded this achievement. Sarah Thomson, the executive director of the American Liver Research Association, notes that Stanford's breakthrough offers new hope for liver disease research and treatment. She believes that these liver organoids can significantly shorten the drug development cycle and improve treatment outcomes in the short term, particularly in the realm of personalized medicine. Stanford University, a world-renowned research institution, is known for its leading bioengineering department, which has made substantial contributions to the fields of tissue engineering and regenerative medicine. This study reinforces Stanford's position at the forefront of biotechnology and has the potential to create far-reaching impacts on liver disease research and treatment globally. The development of multi-zone liver organoids not only showcases the university's expertise but also opens new avenues for advancing medical science and improving patient care.