colon organoids.

These colon organoids developed by Jorge Munera, James Wells and colleagues move scientists a step closer to mimicking an entire GI tract.

Scientists at Cincinnati Children’s, working with a variety of research partners, have recently published significant steps forward in developing organoids that mimic colon and liver functions. 

These projects, combined with previously reported progress at producing stomach and intestinal organoids, moves the medical center closer to being able to mimic an entire human gastrointestinal system—a potentially powerful tool for drug development and disease research.

Growing colons from stem cells

A team including Jorge Munera, PhD, James Wells, PhD, and Michael Helmrath, MD, reported a breakthrough in coaxing human pluripotent stem cells to form colon organoids. In mice, transplanted organoids went on to form larger structures that mimicked several key properties of the human colon. Detailed findings were published June 22, 2017, in Cell Stem Cell.

Someday, such organoids may become useful for producing tissue transplants based on a patient’s own cells. Shorter-term, however, the new organoids may support improved studies of colitis, colon cancer, irritable bowel syndrome, Hirschsprung’s disease and more. 

“We’ve been limited in how we can study these diseases, in significant part because animal models like mice don’t precisely recreate human disease processes in the gastrointestinal tract,” Wells says. “This system allows us to very effectively model human diseases and human development.”

Budding liver organoids

liver buds.

These liver buds developed by Takanori Takebe and colleagues could advance efforts to grow healthy human liver tissue.

Meanwhile, Cincinnati Children’s scientist Takanori Takebe, MD, worked with the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, to bioengineer human liver “buds” that revealed previously unknown networks of genetic-molecular crosstalk that control organ development. 

The findings, reported online June 14, 2017, in Nature, could advance efforts to generate healthy human liver tissue from human pluripotent stem cells.

Using single-cell RNA sequencing, the team observed a dramatic change in how the cells behave when they all develop together in a 3D microenvironment. More fine-tuning will be needed to produce liver tissues that could be used in clinical trials, but if the team can produce self-organizing human tissues, it would provide new hope to people with end-stage liver disease who currently depend upon transplants from limited numbers of donated organs.

“The ability to bioengineer transplantable livers and liver tissues would be a great benefit,” Takebe says. “Our data give us a new, detailed understanding of the intercellular communication between developing liver cells, and shows we can produce human liver buds that come remarkably close to recapitulating fetal cells from natural human development.”

Mimicking the GI tract

Since 2009, Wells and colleagues have reported successes at producing functional intestinal organoids, as well as connecting them to a nervous system. The team also has produced organoids that display the cell types and functions of the antrum and fundus regions of the human stomach.

The researchers have much more work ahead of them, but the latest findings advance a larger goal of mimicking an entire human digestive tract in the lab—and to do so for individual patients. This could become a highly useful tool for evaluating new oral medications and planning drug regimens for a wide range of diseases.