A groundbreaking discovery has emerged in the field of organoid research, offering new hope for regenerative medicine and drug testing. Scientists have identified a key mechanism by which placenta-derived factors can significantly enhance the growth of liver organoids, miniature replicas of human organs used to study diseases and develop treatments. This advancement could revolutionize medical research by providing more effective models for understanding organ development and dysfunction.
In an innovative study conducted at The Institute of Medical Science, The University of Tokyo, Japan, researchers led by Dr. Yoshiki Kuse and Prof. Hideki Taniguchi uncovered how specific biological signals from the placenta promote liver organoid expansion. By replicating conditions observed during early fetal development, including localized blood flow and low-oxygen environments, they successfully stimulated unprecedented growth in lab-grown liver tissues derived from human induced pluripotent stem cells (hiPSCs).
This achievement builds on previous knowledge about the critical role of the placenta in supporting fetal organ growth. During embryonic development, the placenta supplies essential proteins and oxygen necessary for cell proliferation. Focusing on this interaction, the team isolated a protein called IL1α, which plays a pivotal role in enhancing the proliferation of hepatoblasts, the precursor cells of the liver. Through meticulous experimentation, they demonstrated that introducing IL1α under controlled hypoxic conditions followed by gradual oxygenation resulted in liver organoids growing up to five times larger than conventional ones. Moreover, these enhanced organoids exhibited improved functional traits, such as increased production of liver-specific proteins.
To further elucidate the underlying mechanisms, the researchers employed single-cell RNA sequencing techniques. Their findings revealed that IL1α influences hepatoblast expansion via the SAA1-TLR2-CCL20-CCR6 signaling pathway. This insight not only deepens our understanding of external factors regulating liver development but also opens doors for developing advanced organoid-based disease models and even lab-grown organs for transplantation.
Although challenges remain in fully replicating the dynamic in vivo conditions of fetal liver development, this study represents a major leap forward in overcoming current limitations in organoid research. Future investigations will likely focus on designing perfusion-based culture systems capable of continuously supplying placenta-derived factors and oxygen, thereby better mimicking physiological conditions during organ formation.
Dr. Kuse emphasizes that their results highlight the importance of using placenta-derived factors under hypoxic conditions as an efficient technique for inducing progenitor cell expansion in human liver organoids. By integrating principles from developmental biology, this pioneering work advances our comprehension of liver growth processes while illuminating novel pathways to improve scalability and functionality in hiPSC-derived organoids. These advancements hold immense potential for transforming personalized medicine and regenerative therapies across multiple organ systems.