Some bone marrow cells could prevent rejection of transplanted kidney in recipients: Study

By Dr. Ananya Mandal, MDMar 8 2012

In an experimental technique researchers have found a way that could free some kidney transplant patients from having to take anti-rejection drugs.

After a kidney transplant usually the recipient of the transplant needs to take these medications lifelong to prevent their body from rejecting the new organ as a foreign entity.

Researchers transplanted certain cells from the kidney donor’s bone marrow along with the new organ. Five of eight transplant recipients who tried the method so far were off immune-suppressing medication up to 2½ years later, the researchers reported Wednesday. The preliminary results were considered important enough to be published in the journal Science Translational Medicine even though the study still is under way, because the technique worked for patients who didn’t have well-matched or related donors.

The idea is that if a sort of twin immune system takes root and lasts, it can allow the patient’s body to accept the foreign organ and not attack it, said study co-author Suzanne Ildstad of the University of Lousville. Scientists call it chimerism. “The most reliable indicator of really being successful at taking someone off immune-suppressing drugs is durable chimerism,” says Ildstad, who teamed with doctors at Chicago’s Northwestern Memorial Hospital for the research.

In Greek mythology, a chimera was a creature with parts from several different kinds of animals. In the human immune system, chimerism requires contributions from just two people - a donor and a recipient - but mixing immune systems is asking for trouble. The recipient might react against the donor organ (which is what happens in rejection), or donor immune cells in the transplant might declare war on their new host (what’s called graft-versus-host disease). But properly achieved, chimerism might actually prevent hostilities.

“Chimerism is a condition wherein two different genetic cell populations are present in the body, and both cell types are tolerated,” said Dr. Anthony Atala, director of the Institute for Regenerative Medicine at Wake Forest Baptist Medical Center, who was not involved in the study. “This has been the holy grail for solid organ transplantation for more than half a century,” said Dr. Joseph Leventhal study co-author and a Northwestern transplant surgeon. “It has been an elusive goal to be able to do this in mismatched donor and recipient combos.”

Other scientists are attempting to tap bone marrow to induce immune tolerance, with varying success. Ildstad’s approach transfuses a special mix of bone marrow cells including blood-producing stem cells and another type named “facilitating cells” that are thought vital for a successful transplant. She filters out still other cells that can become too aggressive and cause a life-threatening disorder named graft-versus-host disease.

Transplant recipients had radiation and chemotherapy, not destroying their own bone marrow but toning it down to make space for the donated cells, explained Leventhal. “By having these new cells in the bloodstream, it is like a draw at the OK Corral,” said Atala, also chairman of the urology department at Wake Forest Baptist Medical Center. “Neither cell type in the bloodstream will attack the other and tolerance of the cells in the bloodstream, and also of the organ, occurs.”

Five of eight transplant recipients who weren’t spot-on matches with their donors. The five tapered off suppressants designed to prevent organ rejection and have stayed free of the drugs for at least six months. One is nearly two years out since quitting the medicines, researchers at the University of Louisville in Kentucky and Northwestern University School of Medicine in Chicago report.

“Immunosuppressants increase risk of cancer, certain infections and have other side effects,” said Leventhal, an associate professor of surgery at Northwestern University Feinberg School of Medicine. “They can promote diabetes, hypertension and bone disease. They're toxins.”

Much more study is needed to find the best approach but “the results are striking,” Tatsuo Kawai of Massachusetts General Hospital wrote in an accompanying editorial. He is part of a team that in 2008 reported the only other success with a small number of mismatched transplants. “It’s a remarkable feat,” says David Sachs, a transplant surgeon at Harvard Medical School in Boston who coauthored the earlier study. The new findings are surprising and even amazing, they both acknowledge, but since the technique is proprietary, “it will be hard to reproduce,” Sachs says. “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,” wrote James F. Markmann and Tatsuo Kawai in the editorial. They are transplant experts at Massachusetts General Hospital.

“It's another big step towards understanding how to achieve tolerance, so that's good,” said Dr. Bryan Becker, spokesperson for the National Kidney Foundation and chief medical officer at the University of Illinois. “With that said, this is a lot to put a patient through. You're talking about the same type of treatment you'd give a patient who has leukemia...That's not usual for a patient with kidney failure.”