University of Minnesota researchers are reporting a breakthrough in what has long been viewed as a holy grail in the field of organ transplantation — success without the permanent need for immunosuppressive drugs.
Their technique could greatly increase the number and safety of organ transplants because the anti-rejection drugs required today can have harmful long-term side effects.
While their experimental transplants only involved monkeys, university researchers said the next logical step is to show that the technique could work in people.
“If we could show that, we could change the practice of transplantation across the world,” said Dr. Bernhard Hering, a U diabetes researcher who led the study.
Immunosuppressive drugs have been essential because they prevent recipients’ immune systems from rejecting the foreign organs or cells that are transplanted into their bodies. But their effectiveness tends to wear out, meaning that patients must eventually undergo second or third transplants with new donor organs.
In addition daily, long-term use of the anti-rejection medications can take a toll that includes hypertension, cancer risks, fatigue and extreme susceptibility to infections.
“You really are suppressing one of the key systems in your body,” Hering said. “Yes, you do it for the purpose of preventing transplant rejection, but you do it and then you have to hold your breath.”
The U researchers performed five transplants of islets, clusters of cells in the pancreas that produce insulin. Each monkey received infusions of stem cells before and after transplants to persuade their immune systems to accept the donor islets.
The donor stem cells were modified to undergo apoptosis, which is the natural death and replacement of cells that occurs in the body each day.
These apoptotic cells created a state of immune tolerance that prevented the monkeys’ immune systems from rejecting the subsequent islet transplants, Hering said.
Results of the federally funded study were published this week in the journal Nature Communications by researchers from the U and Northwestern University in Chicago.
The researchers followed the monkeys for at least one year after surgery and found no signs of rejection, Hering said. The monkeys did receive anti-rejection drugs for the first three weeks after their transplants out of caution, but Hering said he isn’t sure that was necessary.
The discovery is the latest in a series by U researchers regarding pancreatic and islet transplants, which are used to replace the failing insulin-producing systems in people who have severe diabetes.
This latest process could have applications beyond islets and diabetes, though. Hering said, the approach could be used to improve transplants of lungs and livers from deceased donors as well as kidneys from living donors.
Eliminating the need for immunosuppressive drugs in some of those transplants could have the additional benefit of shortening the daunting wait that many transplant patients face, he added. If patients didn’t need as many second or third transplants, that would save organs for patients awaiting their first procedures.
In Minnesota, more than 2,500 people are waiting for transplants of kidneys, livers, pancreases or lungs, according to the federal Organ Procurement and Transplantation Network.
Nearly 200 people on the waiting list died in 2018 because organs did not become available in time.