What does this advance mean?
Aaron Zorn, PhD, Director of the Center for Stem Cell and Organoid Medicine (CuSTOM) at Cincinnati Children’s says this advance will be useful in multiple ways.
“The real breakthrough here was to be able to make an integrated organ system,” Zorn says. “From a research perspective this is an unprecedented opportunity to study normal human development.”
However, Takebe and colleagues were able to grow these organoids only so far.
For the long-term hope of growing organ tissues large enough to be useful in human transplantation, Takebe says more work is needed. He and his colleagues already have started working on ways to add in immune cells along with cell lines needed to form blood vessels, connective tissues, and more.
But for research and diagnostic purposes, this discovery may have more immediate implications.
In precision medicine, doctors are starting to use genomic data and other information to determine exactly which treatments would work best for patients with serious disease, at what dose, and with the least amount of possible side effects.
A living “gut” of multiple organs would provide scientists with a powerful tool for studying exactly how gene variations and other factors affect organ development during pregnancy, and to develop better targeted drugs to treat conditions after babies are born.
A connected system of “generic” human organoids would offer much more information than having three organoids in disconnected dishes. Growing a set of gut organoids for a specific patient could allow even more precise diagnosis and customized treatment.
“Current liver regenerative medicine approaches suffer from the absence of bile duct connectivity,” Takebe says. “While much work remains before we can begin human clinical trials, our multi-organoid transplant system is poised to solve this issue and may someday provide a life-long cure for patients with liver diseases.”
Someday may not be so far away
While much more work remains ahead, Takebe and colleagues already report one step toward a practical application.
The team already has grown a set of gut organoids that lack the gene HES1. This is one of several known genes that play a major role in triggering biliary atresia, a condition that destroys the biliary duct system, which leads to liver failure and death unless a transplant can be provided. This condition is the leading cause of liver transplants for children.
The new study demonstrates how the gut organoids are harmed by the lack of HES1. If scientists can find a way to compensate for that genetic variation, they may be able to find a medication or cell transplant that would preserve biliary function in newborns and possibly avoid the need for hard-to-obtain liver transplants.
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