Three-quarters of patients with kidney transplants who receive stem cells from their organ donors have successfully stopped taking immunosuppressive drugs for more than two years – a medical achievement that can change the way transplants are managed.
The results of the Phase III clinical trial, published in the American Journal of Transplant, offer hope for thousands of transplant recipients who are currently facing the harsh side effects of resisting drugs.
This innovative approach combines kidney transplantation with injecting donor stem cells, essentially, the immune system of the recipient receives new organs. Of the 20 participants who received this dual therapy, 19 successfully terminated all immunosuppressive drugs, about one year after transplantation.
Current treatment challenges
Traditional organ transplants require recipients to take immunosuppressive drugs indefinitely to prevent their immune system from attacking the transplanted organ. These drugs have huge costs: increasing sensitivity to infections and cancer, and the side effects from headaches and tremors to more severe complications.
“I’ve been in transplant research for over 30 years and we’ve done a lot of amazing things. But, in the planning of things, this research is the most important thing,” said Dr. Mark Stegall, co-author of the Mayo Clinic study. “It’s a goal – being able to safely get the transplant recipient out of immunosuppression – for longer than I did.”
How treatment works
The study involved kidney recipients and their sibling donors whose tissue types were closely matched with two human leukocyte antigen haplotypes. Recipients received a carefully planned regimen that included low-dose radiation therapy and donor stem cell infusion 11 days after transplantation.
Stem cell products called MDR-101 were collected from the same donor that provided the kidneys. The recipient received a conditional protocol for rabbit anti-inhibitor globulin and total lymphatic radiation before stem cell infusion.
Research results:
- More than 2 years
- 95% of people successfully stop all medications for one year
- No death, graft loss or graft-versus-host disease occurred
- Participants showed improved quality of life compared to standard treatment
- Four patients eventually recovered from rejection or recurrence of the disease
Patient’s opinion
Minnesota native Mark Welter attended the trial four years ago, demonstrating the potential of treatment. Diagnosed with polycystic kidney disease, he received kidney and stem cells from his sister Cindy Kendall. Today, he has been taking immunosuppressive drugs for more than three years.
“I feel great. Actually, I feel like I’ve done it before the transplant, and that’s the greatest thing,” Welt reflects. “It’s almost like no transplantation happened.”
His sister Cindy observed the shift: “It was amazing to be able to see him get rid of these drugs. He just tried his best to live his life. He had been able to see both of his daughters getting married and meeting his grandson.”
The science behind success
This treatment is a way to establish what researchers call “donor hybrid chimericism”, in which the blood cells of the recipient and the donor coexist peacefully. When the donor hematopoietic chimerism reaches at least 5%, the doctor can safely reduce tacrolimus gradually.
This approach represents a fundamental shift from suppressing the immune system to retraining it. Stem cell therapy does not permanently weaken the body’s defense capabilities, but rather selective tolerance created for transplanted organs.
The direction of the future
While promising, current protocols require siblings with tightly matched organizational types, limiting their immediate applicability. Researchers are investigating whether the method can be used with less-matched donors, potentially expanding access to such a treatment.
“Even in close-fitting siblings, immunosuppression is required for life. We have stopped the drug eight to ten years after transplantation and can lead to rejection,” explains Dr. Andrew Bentell, a Mayo Clinic transplant adrenalist. “Our goal is to find ways to reduce or stop post-transplant immunosuppressive drugs so patients can have longer lasting kidneys with fewer side effects.”
The study forms part of the Mayo Clinic Transformation Transplant Program, which aims to ensure that everyone who needs a transplant can receive it once while making the surgery more successful. With the continuous development of cell therapy, this study provides a crucial proof of concept that immune tolerance in organ transplantation is not only possible, but also achievable.
Related
If our report has been informed or inspired, please consider donating. No matter how big or small, every contribution allows us to continue to deliver accurate, engaging and trustworthy scientific and medical news. Independent news takes time, energy and resources – your support ensures that we can continue to reveal the stories that matter most to you.
Join us to make knowledge accessible and impactful. Thank you for standing with us!
