Researchers at Cincinnati Children’s are creating increasingly sophisticated organoids of the small intestine, colon, stomach, esophagus and liver. The miniature, three-dimensional organs, created from human induced pluripotent stem cells (hPSCs), provide unprecedented opportunities for scientific discovery. But for that to happen on a large scale, researchers face a conundrum: how to monitor organoid activity during lab experiments. A team of scientists, led by stem cell biologist Takanori Takebe, MD, found a solution by turning to the same technology that helps airlines track luggage and department stores catch shoplifters: radio-frequency identification (RFID).

The proof-of-principle study involved using blood samples from healthy and diseased donors to create 96 liver organoids. Each organoid was embedded with a 0.4 mm RFID chip, and as the cells assembled into three-dimensional structures, all but one organoid successfully incorporated the chip. The remaining 95 organoids maintained their shape, secreted normal liver proteins, and transported bile as expected—even after being frozen. The researchers also developed a high-speed, RFID-based detection system, which was able to identify the organoids that derived from stem cells of donors with fatty liver disease.

Planned upgrades

"Combining organoids with digital technologies helps us expand their potential for drug development, personalized medicine and transplant applications,” says Takebe, associate director of commercial innovation at the Center for Stem Cell and Organoid Medicine (CuSTOM) at Cincinnati Children’s. “The microchips we used were able to identify organoids and record signal intensity, but once we combine that technology with fluorescence imaging and sensing capabilities, we will be able to track data related to the organoid’s state, such as lipid volume, morphology, other stress signals and so on.”

Research that spans two continents

Takebe is one of many researchers at Cincinnati Children’s focusing on organoid research. He joined the faculty in 2016, and maintains a large research lab at Yokohama City University, where he is a professor. In 2018, he and collaborators at both institutions published research on a variety of topics related to organoid medicine. One study successfully bioengineered a vascularized pancreatic organoid that effectively rescued severe diabetes; another identified a new and unlimited source of progenitors useful for intestine, liver and pancreas generation. A third study developed a mass-production platform for human liver organoids that could be applied to transplant medicine.

“This year, we are working with an industry partner to build an organoid-level drug testing platform, with a major focus on drug-induced liver injury and steatohepatitis,” Takebe says. “It is the kind of dynamic collaboration that is bringing us closer to the day we can generate larger, functional organ tissues to fix and/or replace damaged and diseased organs.”

The RFID study appeared in the journal iScience in May 2018.