In response to recent findings of mini-kidney organoids, Dr. Benjamin Freedman recounts his research experience.
I remember the moment clearly. I was staring through the microscope, as I had done countless of times before, expecting to see beating heart cells. Instead, I saw beautiful, convoluted tubules that somehow reminded me of a kidney. With just a small change in protocol, my stem cells had turned into kidney tissue instead of heart. And my own heart skipped a beat.
Only a few weeks later, the microscope surprised me yet again. I did the same experiment, but this time I started with cells carrying a genetic mutation that causes polycystic kidney disease (PKD). The idea that these cells would re-create PKD in a petri dish seemed like a long shot. But there I was, staring into the microscope, watching little cysts form off of the tubules. Our PKD mini-kidneys were acting just like the kidneys in PKD patients.
Eureka moments such as these are vanishingly rare for scientists like me. On most days, we are satisfied with much smaller victories. We make incremental progress, struggling to see the unseeable, deciphering like detectives the tiny shreds of evidence that cells leave behind. Every experiment is a new challenge, and most of the time they don’t work. The work is hard, the hours are long, and there’s a lot of delayed gratification. But that process of trial-and-error learning also opens the door to discovery. As Pasteur famously said, “Chance favors the prepared mind.”
We live for those moments where all the years of work suddenly crystallize into something greater. I’d been telling family members and patients for years that we were trying to make kidney tissue from stem cells. Now, we have done just that. We don’t know whether these mini-kidneys can produce urine, or when they will be safe for clinical use – getting there will take years of follow-up research. What we have done, though, is establish a starting point for regenerating new kidney tissues on-demand from our body’s own cells, which would not require immunosuppression.
What really takes this research to the next level is that these mini-kidneys can be genetically engineered to mimic PKD. PKD is a very mysterious disease, which is difficult to study. Now, we can study PKD in these tiny mini-kidneys. We can use fancy gene-editing techniques to correct PKD mutations, similar to the one we used to make PKD mini-kidneys. We can test thousands of drugs side-by-side to see which ones prevent cysts – perform PKD ‘clinical trials in a dish’ for a fraction of the cost of a real clinical trial.
I feel lucky to have had those moments at the microscope. They remind me of how much is still left to be discovered. It is fulfilling to give back to the community by sharing our findings with patients and supporters. Sometimes, nature surprises us, and in those surprises we can find hope for the future.
Dr. Benjamin Freedman is an Assistant Professor of Medicine at the University of Washington Division of Nephrology, Kidney Research Institute, and Institute for Stem Cell and Regenerative Medicine, in Seattle.
Images were freely shared without modification via a Creative Commons License (CC BY 4.0) from Nature Communications, doi: 10.1038/ncomms9715
Photo of author by Francie Fitzpatrick