PKD Connection Blog

Research

The PKD Research Experience

In response to recent findings of mini-kidney organoids, Dr. Benjamin Freedman recounts his research experience.

benjamin-freedmanI 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 freedman-microscopeprogress, 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.”

mini-kidney

Mini-kidney from a patient’s cells (1-mm diameter)

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.

mini-kidney-cyst

Cyst (1.5-mm diameter) from a mini-kidney with PKD mutations

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

Comments

  1. Christine Richer says:

    Dear Dr. Freedman,

    Your research is totally amazing and totally exciting from my viewpoint as a PKD patient! I do hope you can continue to do more research on finding a drug that can slow or stop the growth of the cysts. And just the idea of turning heart cells into kidney cells – whoa! Does that have any possibility of growing your own new kidney for transplant? Thank you very much for doing such important and lifesaving research!

    1. Your research is totally amazing and totally exciting from my viewpoint as a PKD patient!

      Thanks Christine! Great to hear that you are excited about this. We get some great feedback from patients and some great ideas, too.

      And just the idea of turning heart cells into kidney cells – whoa! Does that have any possibility of growing your own new kidney for transplant?

      The cells we started with to make the kidney organoids were skin cells, which we ‘reprogrammed’ into special cells called pluripotent stem cells. These pluripotent cells have ‘turned back the clock’ to a very early stage in embryonic development, before the organs were formed. They can turn into any type of cell in the body – heart, kidney, you name it.

      So yes, there is the potential here to ‘grow your own kidney’, or at least kidney tissue, on-demand from your own cells. But, I need to emphasize that we are only in the infancy of this technology. We can make some primitive kidney tissue, but we haven’t yet figured out how to make very mature tissue or to connect it with the patient’s blood supply and bladder. We need to make sure these tissues are safe for use, and test their ability to replace kidney function. These are key questions that will take years to figure out.

      You may find additional information on our lab website, including how non-scientists can help advance this research.

  2. ann buttle says:

    i have this kidney but lucikly my second tranplant has been with me for.years bless.you for your resesrch awesome to have read your story may god bless your support ann buttle

  3. mary arredondo says:

    My heart skipped a beat reading your article. It is a beginning and maybe hope at the end of the tunnel. My daughter was dx PKD and was told it was a spontaneous mutation, so lets hope your discovery will bring more discoveries. Thank you Dr. Freedman, you are amazing!

  4. Maria Casas says:

    My heart skipped too when I read this article and the amazing news. I feel so proud of you and the excellent work you are doing. I am a PKD patient who required a liver transplant 12 years ago due to severity of the PKD. Now on hemodialysis, waiting for a kidney transplant or any new treatment with your stem cells work. Keep on trying for us and future generations. God bless you!

  5. Karla Hope says:

    I am so grateful for your research and your new findings! The news is so exciting for individuals and families who suffer from PKD. I had a kidney transplant at the age of 44 and I am extremely happy that my son will potentially have new treatment opportunities when the day comes for him. Thank you! Keep up the awesome research! God is good.

  6. Elizabeth says:

    I donated my PKD kidneys hen they were removed prior to my transplant. I hope they have contributed to research into this disease.

  7. Eugenia says:

    Thanks for the note. With the aid of the mouse animal model why is there so little pharmokinetic progress? Further, why will no one make a definitive stand on the efficicacy of Tolvaptan? I have PKD and understand about cell physiology and sodium channels, why do my questions go unanswered? The need as a society for supporting academic research and fellowships are painfully obvious, in the absence of supporting science and medical innovation we become little more than barbarians. Yet being painfully honest concerning the extent of any real progress is also important. Good luck with your future medical and academic pursuits.

  8. Eugenia says:

    Addendum: Ben – I’ll soon be growing my own kidney at home, DIY, hope I get it completed in time, LOL. Unfortunately Medicare has refused my claim for developing a stem cell lab. Thanks for your interest and sincere efforts.

  9. Robert says:

    I’m 43 waiting on a transplant now I would be happy to donate my kidneys there is no kidney tissue left in either kidney once I recieve my new kidney I would hope it helps with these amazing studies to make positive strides to find a cure.

  10. Helen Schwarz says:

    Thank you for all the long hard hours in PZkD research. This discovery is so fantastic and hopefully will help find a cure or at least help slow the progression of PKD! I had a sister die from PKD, a brother had a transplant many years ago because of PKD and I had two 8 lb kidneys removed and a kidney transplant two years sgo snd a 18 lb Polycystic liver removeed and liver transplant 18 months ago as well as thre brain aneurisms clipped 12 years ago all a result of this mysterious disease. Thank you and praise God for determined people like you. Never give up!

  11. @ann, @mary, @Maria, @Karla, @Elizabeht, @Eugenia, @Robert, @Helen,

    Thanks for your comments and the kind words. It keeps me motivated to continue the research and unite in our fight against PKD. The hope you all express is inspiring.

    @Eugenia, I want to address a few of the questions you are asking, which I am sure are also on others’ minds.

    With the aid of the mouse animal model why is there so little pharmokinetic progress?

    Mouse genetic models of PKD have led to many very important findings over the last two decades. We now understand much better about how PKD works and have new drug candidates to test. However, mice are probably more resilient to PKD compared to humans, and the mouse models are not perfect replicas of human disease. Mouse research is also pricey and can be controversial. Hopefully our little human organoids can help complement animal studies. But I would say overall that we need more mouse research, not less.

    Further, why will no one make a definitive stand on the efficicacy of Tolvaptan? I have PKD and understand about cell physiology and sodium channels, why do my questions go unanswered?

    The jury is still out on Tolvaptan from the academic medicine side. Even if it works, it needs to be tested against other approaches (for instance, drinking a lot of water). PKD is a slowly progressing disease which has made the interpretation of human trials a challenge. Still, I think we can all see the development of drugs against PKD to be a positive overall development. It is important to raise awareness of this very common disease to pharmaceutical companies.

    Yet being painfully honest concerning the extent of any real progress is also important.

    I can sympathize with the frustration that you must feel. This is a marathon and not a sprint when it comes to curing a disease like PKD. We are only beginning to understand molecular medicine, and it’s still a rather small group that is working on this. That being said, there has been progress on PKD, even in our lifetimes, thanks to science. One example is in vitro fertilization. With preimplantation genetic diagnosis, it is now possible to identify the mutations that are likely to be responsible for PKD in a family, and do IVF to avoid passing on the disease to the next generation. This would have been unthinkable a couple generations ago, but is now possible because of research efforts.

    I’ll soon be growing my own kidney at home, DIY, hope I get it completed in time, LOL. Unfortunately Medicare has refused my claim for developing a stem cell lab.

    Academic research is non-profit and is primarily funded by the public through the National Institutes of Health. I would encourage you to think of your local research organization as your tax dollars at work and work with them if you are interested in participating in experimental therapies. Raising money for the PKD Foundation is a great way to help and is critical for supplementing scant federal funds for research. Always avoid non-university clinics touting miraculous ‘stem cell therapies’, even if listed on clinicaltrials.gov – these may be predatory organizations.

  12. moslyn says:

    I wanna thank u for ur research. Pkd has hit every generation of my family and only God know how we pray for a cure. We thank you and ur research team. Continue because we have generations to come. Thanks. Please cure PKD!!!!

  13. priyanka says:

    thank u so much for ur research,
    article and the discussion is very imformative of new possibilities , hopeful and positive
    there was a time when i found out that my only brother n mother are blessed with this mutation which we were not even aware of… since then every new research that comes out makes us very hopeful that smday soon these will b available to change our life…
    wish u all the best for ur clinical trials
    n my blessing goes out to each n every individual working for the cause

  14. Linda C. in AZ says:

    You are AMAZING!! As part of my participation in the Tolvaptan study, I agreed to allow for my DNA to be used for 15 years for PKD research. Although I withdrew from the study this week due to the extreme side effects i experienced, I fully support any and all research and study to assist those of us who suffer from this horrific disease. It is my sincere belief that scientists such as you are tackling the complexities and seeking solutions Thank you, thank you!

  15. Linda C. in AZ says:

    I am most willing to participate in any future studies for myself, my 3 sons, and my 2 grandchildren,

    1. Alexis Denny says:

      Hi Linda!

      If you are interested in learning about clinical studies, you can find information about them on our website here: pkdcure.org/research/clinical-studies

      Please let me know if you have any questions!

      alexisd@pkdcure.org

  16. Judith A Bradley says:

    I to have polycystic kidney disease and in my liver , my mom had it and has passed on . I am now in the process of going on a donor list and I am to say the least scared by this entire ordeal …..no matter what I have done I have not been successful in slowing down the progression …..my having it I spent my life eating organic watching what I put on my skin , cleaning supplies to only natural and nothing is working ….I am so frustrated and feel helpless , nothing seems to stop the cyst from growing , your research gives me hope for my grown son , who by the way has not been tested as he feels nothing can be done ….thank you for all you are doing ….having to wait for two years for a kidney means I will go on dialist which I was hoping to avoid all together ….

  17. Maureen says:

    Thank you for giving me hope!
    I’ve been in 3 clinical trials at Mayo with Dr Torres and my DNA is being used worldwide. You are critical in the research loop to end this disease and find a cure.
    Keep up the amazing work!

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