Northwestern trials involve manipulation of donor stem cells to trick recipient's immune system
By Steven Ross Johnson, Special to the Tribune
March 28, 2012
Since she was first diagnosed with polycystic kidney disease at age 19, Lindsay Porter, now 47, has had to face the reality that she would someday need a kidney transplant.
"It really didn't affect me very much at all until my early 30s, when I developed high blood pressure," said Porter, who lives on Chicago's Northwest Side. "In my 40s, I started feeling really tired, and my abdomen just started growing huge by leaps and bounds. Eventually, my function declined to the point where I knew I was going to have to have a transplant."
Scheduled for June 2010, Porter's surgery was delayed until July, which she said turned out to be a stroke of good fortune.
"I knew that Northwestern (Memorial Hospital) was doing these trials. But at the time that (a friend) offered to donate the kidney, the trial wasn't open," Porter said. "The trial opened again on July 1, and I ended up being the first person in the trial."
The trial Porter referred to was the testing of a new kidney transplant method that has the potential to someday allow organ recipients to live a life free of anti-rejection medication.
The method, published this month in the journal Science Translational Medicine, suggested that through the manipulation of donor stem cells, the recipient's immune system might be tricked into accepting the new organ as a natural part of the body, thereby eventually eliminating the need for immunosuppressant drugs.
Study co-author Dr. Joseph Leventhal said the procedure has marked the first success at making a recipient's immune system accept a mismatched organ — one with a high rate of rejection — or from those donors who are unrelated, which made up the majority of the roughly 28,000 organ transplants conducted in the U.S. last year.
"We think this approach has very broad applicability to the larger number of patients receiving a solid organ transplant by virtue of the fact that it has been successful in mismatched, unrelated individuals, which is the usual scenario when you're doing a solid organ transplant," said Leventhal, a transplant surgeon at Northwestern Memorial Hospital.
Transplant recipients often must take a number of medications for the rest of their lives in order to prevent the body's immune system from rejecting their new organ.
As a result, the immune system is left susceptible to viruses and bacteria that it could easily fight off prior to surgery, which in turn requires the need to take a number of anti-viral drugs along with immunosuppressants.
But prolonged exposure to such drugs can have serious side effects, including high blood pressure, diabetes, cancer and damage to the new organ. That damage often requires the patient to eventually undergo another transplant.
On average, kidneys that are transplanted from living donors can last up to 15 to 20 years, with kidneys from deceased donors lasting anywhere from 5 to 10 years, Leventhal said. He felt the new procedure could prolong the life span of the new organ, eliminating the need for additional transplants.
"Many of the individuals who are coming onto the transplant waiting list — be it for a kidney, or for a heart, or for a liver — are people who have received a previous transplant and that transplant is failing," Leventhal said. "By achieving better control of the immune system without the need for drugs that can have negative side effects, we think that this is going to further prolong how the organs will last."
Dr. Suzanne Ildstad, a co-author of the study, said the process, which she called immune system tolerance, requires the kidney donor to also donate part of his or her immune system. The bone marrow stem cells that are collected are then enriched for "facilitating cells," which is believed to help transplants succeed.
During the monthlong process, the recipient undergoes radiation and chemotherapy to suppress his or her own bone marrow in order to provide enough space for the donor's stem cells to grow once they have been transplanted, said Ildstad, who is director of the University of Louisville's Institute of Cellular Therapeutics.
Conditioning of the stem cells takes about two days, which makes it possible to use only kidneys that come from living donors because bone marrow taken out of the body has already begun to degrade after such time, Ildstad said.
Ildstad and Leventhal said they hope the new transplant procedure might become a standard alternative in three to five years. For now, additional trials were needed to see whether the process could be used to treat patients who receive organs from deceased donors.
For physicians such as Dr. Dorry Segev, an associate professor of surgery at Johns Hopkins University School of Medicine, such a discovery has been what many in his field have waited to become a reality for years.
"Organ transplantation without anti-rejection medication is the holy grail that transplant folks have been dreaming about for decades," Segev said. "So if this can work, this would be a major breakthrough in our field."
Now two years removed from her surgery, Porter has remained drug-free and said living free of medications has vastly improved her quality of life.
"I feel great, I feel fantastic," Porter said. "I kind of feel like I got into a time machine, and it suddenly took me back about 10 or 15 years."