Researchers in Tokyo report a new, specialized technique for easier and more efficient growth of mini intestinal organoids in the lab, raising hopes for regenerative medicine and advancing the understanding of gut diseases. 

Organoids are organ-like balls of cells that are grown in the lab from spheroids of human cells and mimic the properties of the organ from which the “seed” cell was taken. They are valuable tools for studying organ function in a lab setting and could one day be used to grow organs for transplant. Notably, the method by researchers from Tokyo Medical and Dental University (TMDU) successfully grew intestine-like tissues of predictable size and composition.

“There are established methods for growing human intestinal organoids (HIOs) from induced pluripotent stem cells (iPSCs),” says Junichi Takahashi, first author of the study, published recently in Cell Reports Methods. “However, these techniques are challenging to perform. They result in spheroids of varying sizes and are limited by the growth conditions, which can result in deformed and unhealthy spheroids over time.”

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To develop a more robust and consistent way to generate HIOs, the researchers explored the use of cell culture plates made with an ultra-low attachment polymer to encourage the cells to detach and grow in suspension. They also tested the effects of growing the resulting spheroids in a bioreactor, a specialized incubator that keeps the growth medium constantly flowing to improve the health of the cells.

“Using our technique, we were able to grow spheroids of a predictable, consistent size that could be modified by modulating the number of cells seeded into the plates,” says Tomohiro Mizutani, corresponding author. “Furthermore, transferring the spheroids to a bioreactor allowed them to grow even larger, into healthy HIOs.”

The TMDU organoids were surrounded by mesenchyme, a type of tissue found between organs in the human body. Importantly, when the organoids were transplanted into mice, they continued to grow and differentiate, developing a complex tissue architecture reflecting that of mature intestine.