Cincinnati Children's Hospital researchers grow mini liver, pancreas and biliary ducts from stem cells

petri dishes in a lab
Cincinnati Children's researchers have a goal of someday using organoids to develop transplantable tissues grown in labs. (science photo/Shutterstock)

Scientific researchers at Cincinnati Children's Hospital see a future where no patient risks dying while waiting for an organ transplant. 

Developments with bioengineered miniature organs called organoids are not quite there yet. But a multidisciplinary team at the hospital's Center for Stem Cell & Organoid Medicine (CuSTOM) say they have made a breakthrough discovery that brings them a step closer.

Cincinnati Children's Hospital's CuSTOM teammade up of scientists, clinicians, geneticists, surgeons and bioengineers—has grown the world’s first-ever set of three functional organoids, liver, pancreas and biliary ducts, to function as one system. The team's results were published in Nature Wednesday.

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Organoids are tiny 3D formations of human tissue that perform the functions of multiple cells found in full-sized organs. Cincinnati Children's CuSTOM launched two years ago to accelerate the transfer of stem cell-organoid technology from the research lab to a practical clinical tool.

The biggest potential for organoids is to help treat and cure disease. These advances in developmental biology and stem cell technologies also will drive a big leap in personalized medicine and improve patient care, the team said.

RELATED: Mini esophagus grown from stem cells could yield treatments for GI diseases

Organoids can be developed using a specific patient's stem cells to then test how a patient might respond to a drug or to create personalized treatments, lead scientist Takanori Takebe, M.D., and assistant professor at Cincinnati Children’s, told FierceHealthcare.

Approximately 113,000 people in the U.S. are on the national transplant waiting list and 20 people die each day waiting for a transplant, according to data from the Human Resources and Services Administration.

"Organoids are not ready for transplantation therapies yet but they are incredibly useful as patient avatars," James Wells, Ph.D., chief scientific officer at Cincinnati Children's CuSTOM, said last year during a TEDxCincinnati presentation (video).

close up photo of a two-month-old human esophageal organoid bioengineered by scientists
Microscopic image of esophageal organoid
(Cincinnati Children's Hospital)

"With cancer, one drug might cure cancer in one patient and create great harm in another patient. My lab is growing organoids from cancer patients and giving them to cancer biologists who are using them to test whether a drug might actually work on that type of cancer for that patient," Wells said.

To create these mini organs in a lab dish, scientists use pluripotent stem cells, which can form any tissue type in the body, to replicate much of the complexity. Organoid experts at Cincinnati Children's have previously grown intestines and an esophagus, and stomach organoids that produce digestive acids. Recently the team successfully bioengineered human liver organoids that faithfully mimic key features of fatal liver disease in the laboratory.

What's next

The first organoid that the team developed was about the size of a pea and now they are developing ones about the average size of a person's thumb, Wells said.

The most recently developed organoids, a living connected “gut” of multiple organsrepresent the first connected system, according to the team.

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Single organoids provide a sophisticated tool for research, but this advancement allows scientists to study how human tissues work together as a complete system.

"Over the past 10 years, we have tried to connect different organ domains, but never succeeded," Takebe said. He said the team took a different bioengineering approach with this latest organoid development.

"What we have done is to take nature’s capacity to self-develop and we designed the best timing for the cells to trigger their intrinsic development capacity. That was exciting," he said.

Advancements with organoids provide scientists with a powerful tool to study organ development and to one day provide more precise diagnosis and customized treatments for patients, Takebe said.

"One of the coolest ways of using organoid is to diagnose patients with complicated diseases when the normal barrage of tests fail to uncover the cause," Wells said in the TEDxCincinnati video. Scientists and physicians were able to use these bioengineered tissues to help a patient who came into Cincinnati Children's Hospital Medical Center with a highly complicated disease affecting the pancreas, stomach, and intestine.

"The physicians did a great job of figuring out what was wrong with the pancreas but none of these invasive tests were able to figure out what was wrong with stomach and intestines. A scientist in my lab made organoids from that patient and in the laboratory figured out what was wrong with that patient," he said.

The team is now working with physicians to come up with a new treatment strategy that is specifically designed for that patient.

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Cincinnati Children's team of organoid experts also are working to make the miniature organs bigger and more functional, more like real organs. 

"We're working to make them with more functional tissues. We're engineering in complexity like nerves, muscles, blood vessels even immune cells," Wells said. And the team is collaborating closely with surgeons to test whether the bio-engineered organ tissue can actually cure disease, testing it first in an animal model.

In the short term, the use of organoids could begin reducing the need for animal-based medication studies. Longer-term, it could someday lead to transplantable tissues grown in labs. 

"The ultimate goal that nobody should be told that they may die while waiting for an organ for transplantation," Wells said.

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