Kidney transplant patients given a mixture of stem cells from their organ donor were able to quit taking anti-rejection medicine in a small study, suggesting that life-long reliance on the toxic drugs may be avoidable.
Five of eight patients treated were able to stop taking about a dozen pills a day to suppress their immune systems. The drugs, which prevent rejection and stop tissue from a donated kidney from attacking the patient, can damage the transplant and cause diabetes, infections, heart disease and cancer.
The breakthrough, reported in the journal Science Translational Medicine, mixed stem cells from the donor’s infection-fighting immune system with the patient’s natural immune system. The result enabled tissue from both to co-exist in the transplant patient without either being seen as “foreign” by the immune system, researchers said.
The results “may potentially have an enormous, paradigm-shifting impact on solid-organ transplantation,” wrote James Markmann and Tatsuo Kawai from Massachusetts General Hospital in Boston, in an editorial accompanying the study. “Although only a taste of things to come, few transplant developments in the past half-century have been more enticing than these that put transplantation tolerance within our grasp.”
The findings are particularly striking since the patients weren’t perfect tissue matches with the living donors. The mismatch traditionally makes it more difficult for the donated organ to survive since the patient’s immune system perceives the unfamiliar tissue as a threat.
‘Road to Tolerance’
“It’s been a longstanding goal in transplantation to achieve tolerance, to get the recipient to see the donor organ as part of itself,” said Joseph Leventhal, a surgeon at Northwestern Memorial Hospital in Chicago and the lead author. “A road to tolerance” now exists, he said.
Having two immune systems blend into one is called a “chimerism.” The long-lasting effect seen in the study may stem from the manipulation of stem cells taken from the donor in advance of the surgery, according to the report.
The cells were sent to Suzanne Ildstad, director of the Institute of Cellular Therapeutics at the University of Louisville in Kentucky. There “facilitating cells” that help transplants take hold were identified and used to enrich the mixture, which was given to the patient the day after surgery.
The researchers didn’t provide details on how they crafted the stem cell mix, which may make it difficult for other investigators to confirm the findings, Markmann and Kawai wrote.
Two of the study’s 10 authors are officers in Regenerex LLC, a startup biotechnology company based in Louisville, Kentucky, that is involved in processing the donor cells. Ildstad has an equity interest in the company and is an author on a patent for the facilitator cells, which she discovered.
While patients who stopped taking anti-rejection drugs have been off the medicine for at least a year, the researchers plan to continue following them to ensure the donor organ thrives, said Leventhal, who is also the director of kidney and pancreas transplantation at Northwestern University Feinberg School of Medicine. The study, in the second of three phases needed to win U.S. regulatory approval, will eventually include as many as 40 patients getting kidney transplants from living donors, he said.
Additional work is needed to expand the technique to transplants from deceased donors and for more complex organs including the liver, heart and lung, Markmann and Kawai wrote. Nonetheless, the findings are building on evidence first gathered in 1953 that found newborn mice could support an intermingling of two immune systems, they said.
The findings “add to advances in the last few years that suggest that the six-decade old quest for tolerance for kidney transplant patients may finally be nearing its end,” they said.
The study was funded by the U.S. National Institutes of Health, the Department of the Army, the National Foundation to Support Cell Transplant Research, the W. M. Keck Foundation and the American Society of Transplant Surgeons.