Organoids and Organ Regeneration: Cracking the Code in the Field of Regenerative Medicine

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Beno Freedman, Ph.D., says that the human system is a "black box"—researchers have no way of knowing what's going on inside until they get in and see it up close. That's why, Freedman says, organoids have had a profound effect on our understanding of human biology—particularly in his field, regenerative medicine.

As in vitro models that mimic in vivo conditions, stem cell organoid disease models have helped Freedman and his lab at the University of Washington create biological scenarios that could someday crack the code on organ regeneration.

"You can genome-engineer cells so that they have any type of genetic composition you want," Freedman said. "You can essentially create forms of life that don't naturally occur and use that to test out why certain genes are there."

Doing so has helped the Freedman Lab uncover new insights on the frontiers of nephrology. The team recently discovered a role for an essential pathway in human kidney development that they hadn't noticed before.

That's just one example of how organoids can help researchers crack open the black box of disease pathologies to discover possible regenerative solutions. Organoids offer promise for virtually every organ in the human system, but the kidney is especially dear to Freedman. After watching his uncle battle kidney disease, he saw the need to improve nephrology with organoid models.

Recreating a Disease in a Dish

Organoid research could change how we treat polycystic kidney disease — a common genetic disorder in which cysts interfere with kidney function. Treating the disease often requires long-term dialysis, which impairs quality of life and comes with complications.

Many people with polycystic kidney disease ultimately require an organ transplant. That's tough to hear if you're a patient. Waitlists can take years to get through, and donated organs don't last forever: Nearly half of transplanted kidneys stop working within 10 years, the National Kidney Foundation reports.

There is no cure for polycystic kidney disease. But Freedman and his lab aim to change that using organoids and high-throughput technologies.

"For many years, researchers have been limited to taking cells from patients with polycystic kidney disease and looking at them in vitro," Freedman said. "But they haven't been able to figure out what's happening with the disease because cells change when you take them out of the body. They don't recreate the disease in a dish, but organoids do. Organoids can go from being a normal organoid with tiny tubules to a cystic organoid that looks like a jellyfish swimming around because the tubule has swelled up with fluid."

Using those tiny, jellyfish-like diseased organoids, scientists can automate and run thousands of therapeutic simulations on the organoids to find the right treatment for the right patient.

"It's a game-changer," Freedman said. "Organoids are special in their ability to recreate disease in a dish at tissue scale. And what that means for regenerative medicine is that we could discover personalized therapeutics by using the petri dish as a surrogate for the patient. So before anyone would ever try the drug, we'd already know whether their tissue would respond well."

Because the cellular expansion of those organoids is essential for this type of work, extracellular matrices that contain growth factors and collagen IV—such as Corning Matrigel marix —can be particularly helpful as a scaffolding choice. Corning ultra-low attachment (ULA) plates are also very helpful for studying the polycystic kidney disease organoids.

The Holy Grail of Organ Regeneration

In the short term, using organoids in the lab achieves pharmacological objectives—that is, it helps researchers find a curative mix of therapies based on a patient's makeup. But then there's the million-dollar question: When will people not need drugs because they can just get a new organ made from their own cells?

"We're all very excited about the potential for kidney regeneration in the long term," Freedman said. "That's the holy grail for the field. We've seen that organoids have the ability to get halfway there—in terms of when you implant them in the body, there's a potential for maturation. Whether these can function and compare with existing organ transplants, the current answer is no. But if we as a culture push this idea forward, the potential of regenerative medicine as a whole is vast enough to make it a real possibility in the future."

Science and medicine are getting closer to blasting the black box wide open. We might still be decades away from organ regeneration, but organoids have helped researchers peek inside that box and bridge gaps in pathologies and therapies for a myriad of diseases. Someday, we'll do more than we ever thought possible.

"We need a 21st-century solution to kidney diseases," Freedman said. "And this type of research is critical to making it happen. Because this isn't just a dream—it's something we should all continue to work toward. If we put our minds to it and press forward with regenerative therapies, we've got a lot to be hopeful for in the years ahead."

The revolutionary potential of in vitro disease modeling with 3D cell cultures don't end at the kidneys. Discover how neural organoids, gastrointestinal organoids, and other organoid types are opening up the possibilities for personalized medicine.