Organoids have emerged as valuable tools for modeling human organs, offering potential advancements in research and therapy. However, limitations in their growth and functionality have hindered their full potential. A recent breakthrough study conducted by researchers at The University of Tokyo sheds light on a novel approach to enhance the growth of human liver organoids using placenta-derived factors.
Published in Nature Communications, the study led by Dr. Yoshiki Kuse and Prof. Hideki Taniguchi explores the role of placental IL1α in promoting the expansion of liver progenitor cells within stem cell-derived liver organoids. By replicating the hypoxic conditions and growth factors present during fetal development, the researchers achieved remarkable growth in the organoids, surpassing previous barriers in organoid research.
The team’s investigation into mouse embryo development revealed the critical role of placental factors in liver growth. By isolating IL1α and introducing it to hiPSC-derived liver organoids under controlled conditions, the researchers observed a fivefold increase in organoid size and improved functional characteristics. This groundbreaking approach offers new insights into the mechanisms governing organoid growth and provides a promising avenue for regenerative medicine.
Through single-cell RNA sequencing analysis, the researchers identified the SAA1-TLR2-CCL20-CCR6 signaling pathway as the key mechanism through which IL1α promotes hepatoblast expansion. These findings not only enhance our understanding of liver development but also offer a potential strategy for enhancing the scalability and functionality of organoid models.
The implications of this research are vast, with potential applications extending beyond liver organoids to other organ types. By refining techniques to deliver placenta-derived factors in a controlled manner, researchers may unlock new possibilities for disease modeling and organ transplantation. The study paves the way for future research focusing on perfusion-based culture systems to better mimic the in vivo conditions of organ development.
In conclusion, this groundbreaking study showcases the power of leveraging insights from developmental biology to advance organoid research. By unraveling the intricate interplay of external factors in organ growth, the research team at The University of Tokyo has opened up new avenues for enhancing the utility of organoid models in medical research and regenerative therapies.