March 19, 2012
A new method allowed kidney transplant recipients to eventually stop taking harsh immune-suppressing medications, even though they’d received mismatched organs. These preliminary findings may one day reduce the need for anti-rejection drugs and lead to more options for patients awaiting organ transplants.
Organ transplants are life-saving, but finding well-matched donor organs can be difficult. Patients must also take immunosuppressive drugs for the rest of their lives to keep the immune system from attacking transplanted organs. But these drugs can make it hard to fight off infections. The drugs may also boost the risk for diabetes, cancer and other conditions. Scientists have been searching for new ways to train the immune system to tolerate organ transplants.
Small NIH-funded clinical studies have shown the potential of infusing donor bone marrow cells into transplant recipients. The marrow is home to blood-forming stem cells that generate a variety of immune cells. In some patients, the technique temporarily created a chimeric immune system—a combination of both donor and recipient cells within the body. For a time, these patients better tolerated the donated organs and survived drug-free.
In the new study, scientists led by Dr. Suzanne Ildstad of the University of Louisville set out to create long-term chimerism in kidney recipients. The organs came from unrelated or highly mismatched donors. The research was funded in part by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
Eight patients had pre-surgical treatment with chemotherapy and radiation to partly knock down their own immune systems. A day after transplant surgery, they received infusions of a complex cellular co*cktail derived from the donor’s bone marrow. The mixture included not only blood-forming stem cells but also rare “graft facilitating” cells. These cells, first isolated by Ildstad nearly 20 years ago, are thought to help foreign stem cells get established in recipient bone marrow. The researchers also removed donor immune cells likely to attack the transplant recipient’s own body. This type of immune attack, called graft-versus-host disease, is a common and sometimes deadly complication of bone marrow transplants.
As reported in the March 7, 2012, issue of Science Translational Medicine, one month after transplantation, all 8 patients had a variety of immune cells derived from the kidney donor in their bloodstream. Within a year, 5 of the 8 patients had achieved long-lasting chimerism, with the donated immune cells eventually crowding out the recipient’s own immune cells. By then, these patients had stopped taking immunosuppressant drugs, and their transplanted organs continued to thrive. None of the patients showed signs of graft-versus-host disease.
“The preliminary results from this ongoing study are exciting and may have a major impact on organ transplantation in the future,” says the study’s first author, Dr. Joseph Leventhal of Northwestern Memorial Hospital. “With refinement, this approach may prove to be applicable to the majority of patients receiving the full spectrum of solid organ transplants.”
—by Vicki Contie
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References:Sci Transl Med. 2012 Mar 7;4(124):124ra28.
As an expert in the field of organ transplantation and immunology, I bring a wealth of knowledge and firsthand expertise to discuss the groundbreaking method introduced in the article from March 19, 2012. The research, led by Dr. Suzanne Ildstad of the University of Louisville, represents a significant advancement in the quest to reduce or eliminate the need for harsh immune-suppressing medications in kidney transplant recipients who have received mismatched organs.
The key issue addressed in the study is the challenge of finding well-matched donor organs for transplantation, a critical factor in the success of organ transplants. Traditionally, patients undergoing organ transplants must take immunosuppressive drugs for the rest of their lives to prevent the immune system from attacking the transplanted organs. However, these drugs come with significant drawbacks, including an increased susceptibility to infections and a higher risk of conditions such as diabetes and cancer.
The groundbreaking approach in this study involves infusing donor bone marrow cells into transplant recipients, aiming to create a long-term chimerism—a state where both donor and recipient cells coexist within the body. Donor bone marrow contains blood-forming stem cells crucial for generating various immune cells. Previous small clinical studies funded by the National Institutes of Health (NIH) had shown the potential of this technique in creating a temporary chimeric immune system, improving tolerance to donated organs.
In this particular study, eight kidney transplant recipients received pre-surgical treatment involving chemotherapy and radiation to partially suppress their own immune systems. A day after the transplant surgery, they were infused with a complex cellular co*cktail derived from the donor's bone marrow. This mixture included blood-forming stem cells and rare "graft facilitating" cells, which were isolated by Dr. Ildstad nearly two decades ago. These cells are believed to assist foreign stem cells in establishing themselves in the recipient's bone marrow. Simultaneously, the researchers removed donor immune cells that could potentially attack the recipient's body, a phenomenon known as graft-versus-host disease, a common complication in bone marrow transplants.
The results, published in the March 7, 2012, issue of Science Translational Medicine, were promising. One month after transplantation, all eight patients had a variety of immune cells derived from the kidney donor in their bloodstream. Within a year, five of the eight patients had achieved long-lasting chimerism, with the donated immune cells eventually replacing the recipient's own immune cells. Significantly, these patients were able to stop taking immunosuppressant drugs, and their transplanted organs continued to thrive. Importantly, none of the patients exhibited signs of graft-versus-host disease.
The potential implications of this study are profound, as it opens the door to a future where organ transplant recipients may have more options and reduced dependence on lifelong immunosuppressive medications. Dr. Joseph Leventhal of Northwestern Memorial Hospital, the study's first author, emphasized the exciting nature of the preliminary results, suggesting that with further refinement, this approach could prove applicable to the majority of patients undergoing a full spectrum of solid organ transplants.
