Researchers explore new therapies to prevent organ rejection without immunosuppressive drugs

While immunosuppressive medications are critical to prevent rejection of transplant organs, they also come with plenty of downsides. They can cause harsh side effects, like headaches and tremors, and increase the risk for infection and cancer. But what if there was a way to prevent organ rejection without using these medications?

That goal fuels the work of Mark Stegall, M.D., a longtime Mayo Clinic transplant researcher. He leads a team of researchers developing pioneering therapies to prevent organ rejection without the need for immunosuppression. A recently published study in the American Journal of Transplantation is offering hope for patients.

Using stem cells to prevent organ rejection

Mayo Clinic participated in the multisite phase 3 clinical trial detailed in the study. The goal was to see whether people who simultaneously received both a kidney and stem cell transplant from a closely matched sibling could discontinue all immunosuppressive medications after a year. The results were promising. The study found that 75% of participants were able to stop taking the medication for more than two years. At Mayo Clinic, three patients participated, with two off immunosuppression medications for over three years and one on a low dose.

I've been involved in transplant research for more than 30 years, and we've done quite a few amazing things. But in the scheme of things, this research is right at the very top. It's been a goal - to be able to safely get transplant recipients off immunosuppression - for longer than I've been doing this. We're very excited about it."

Dr. Mark Stegall, co-author of the study

The research being done across Mayo Clinic is part of a growing trend in transplant to explore ways to use cellular therapies to prevent organ rejection. It is also a cornerstone of Mayo Clinic's Transforming Transplant Initiative, which has the bold goal of ensuring everyone who wants a transplant can get one and to make transplants more successful.

To qualify for the clinical trial, the transplant recipients and donors needed to be siblings whose tissue types closely matched. The donor agreed to donate their stem cells in addition to their kidney to their sibling. The recipient receives the transplant, undergoes radiation and then receives the stem cell transplant. The goal was to wean recipients off immunosuppression medication after a year.

'Almost like the transplant didn't happen'

For Minnesota native Mark Welter, the results have been better than he imagined. Four years ago, he needed a kidney transplant due to polycystic kidney disease, an inherited condition that causes cysts to grow on the kidneys. The Mayo Clinic patient volunteered to be a part of the clinical trial in hopes of not having to worry about immunosuppression medication the rest of his life. His younger sister Cindy Kendall immediately stepped forward to donate a kidney and her stem cells to help her brother.

"Being able to see him get off those medications has been amazing," Cindy says. "He just gets to live his life to the fullest. He has been able to see both of his daughters get married and meet his grandchildren."

Mark has not taken immunosuppression medication for more than three years.

"I feel fantastic. I actually feel like I did before the transplant, which has been the greatest thing," Mark says. "It's almost like the transplant didn't happen."

There is still plenty of work to be done to advance this research. This clinical trial only involved siblings with closely matching tissue types. Researchers want to know if stem cell transplants can prevent rejection in recipients paired with a less closely matched donor.

"Even in closely matched siblings, immunosuppression is needed lifelong. We have seen stopping medications even at eight to 10 years post-transplant leads to rejection. Our goal is to find ways to reduce or stop immunosuppressive medications after transplant so patients can have longer lasting kidneys with fewer side effects," says Andrew Bentall, M.B., Ch.B., M.D., a Mayo Clinic transplant nephrologist.