Organoid Animation | Cincinnati Children's

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Organoid Animation | Cincinnati Children's

Scientists at Cincinnati Children’s use stem cells to grow connected, functioning set of miniature human liver, pancreas, biliary ducts.

Imagine trying to paint a forest when all the artist has is a leaf and a piece of bark versus having a living, growing tree as a model. Seeing how the parts fit together can make all the difference.

That’s the level of advancement in organoid science that researchers at Cincinnati Children’s have achieved with findings published today in the prestigious journal Nature. Instead of growing mini human organs independently in separate lab dishes, a team led by Takanori Takebe, MD, succeeded at growing a connected set of three organs: the liver, pancreas and biliary ducts.

Organoids, grown from stem cells, are tiny 3D formations of human tissue that actually perform the functions of multiple cells types found in full-sized organs. Organoid experts at Cincinnati Children’s have already grown intestines that feature nutrient-absorbing villi, stomach organoids that produce digestive acids, and more.

By themselves, human organoids already provide a sophisticated tool for research. But this advance allows scientists to study how human tissues work in concert. This major step forward could begin reducing the need for animal-based medication studies, sharply accelerate the concept of precision medicine, and someday lead to transplantable tissues grown in labs.

“The connectivity is the most important part of this,” Takebe says. “What we have done is design a method for producing pre-organ formation stage tissues so that they can develop naturally. We are maximizing our capacity to make multiple organs much like or body does.”

A 5-YEAR QUEST ACHIEVES KEY GOAL

Takebe, age 32, joined Cincinnati Children’s in 2016 and holds a dual appointment at Tokyo Medical and Dental University (TMDU) in Japan. He graduated from medical school in 2011 with plans to become a liver transplant surgeon. But as he learned about the yawning gap between the supply and demand for donor organs, Takebe shifted gears to focus on organ supply.

In previous research, Takebe has demonstrated a method to produce large supplies of liver “buds,” an early-stage form of a liver organoid. He also has grown liver organoids that reflect disease states, including steatohepatitis, a dangerous form of liver scarring and inflammation that occurs in some people with obesity.

His work to date has been hailed by the Imperial Prince of Japan, who presented Takebe with an honor in 2018 from the Japan Society for the Promotion of Science. Discover magazine also listed Takebe’s organoid work as No. 5 in its list of the top 100 science achievements of 2013.

But Takebe says this project is his highest-impact work yet.

“We noted this point in organ differentiation some time ago. But it took five years to tune up the culture system to allow this development to occur,” Takebe says.

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