Researchers from Northwestern Medicine And University of Louisville are in the midst of a clinical trial to examine the use of stem cell infusions to re-educate the immune system of recipients of transplanted organs. Such re-education of the immune system might completely eliminate the need for anti-rejection medicines.
Organ transplant recipient must take several pills each day for the remainder of their lives. These medicines are drugs that suppress the immune system, and these drugs have many undesirable side effects. Prolonged use of these drugs can cause high blood pressure, diabetes, infections, heart disease, and cancer. Therefore a stem cell-based approach that obviates the need for drugs that inhibit the immune system would offer transplant recipients better quality of life and few health risks for transplant patients.
Joseph Leventhal, a transplant surgeon at Northwestern Memorial Hospital said, “The preliminary results are exciting and may have a major impact on organ transplantation in the future. With refinement, this approach may prove to be applicable to the majority of patients receiving the full spectrum of solid organ transplants.” Leventhal is the main author of this study in collaboration with Suzanne Ildstad, who is the director of the Institute of Cellular Therapeutics at the University of Louisville. The study is, in fact, one of the first of its kind, since it does not require that the organ donor and recipient do not have to be tissue matched.
For standard kidney transplants, the organ donor, who has agreed to donate a kidney, provides their kidney for transplantation to the recipient. In this study, the organ donor not only provides a kidney, but also a small quantity of blood cells. Approximately one month before the transplant, the organ donor gives some bone marrow by means of a procedure called “apheresis.”
Apheresis removes whole blood from a patient, and then uses a centrifuge-like instrument to separate blood components. These separated portions are removed and the remaining components used for retransfusion. The blood components are separated into fluids, otherwise known as plasma, platelets, and white blood cells. From the white cell fraction, a group of cells that the study cells “facilitating cells” are isolated. The organ recipient’s bone marrow is partially ablated with radiation.
The kidney is then transplanted into the recipient’s body, and one day later, the facilitating cells are given to the recipient. Because the organ recipient’s bone marrow has been semi-ablated, the facilitating cells have space to grow without competition from the recipient’s bone marrow. The goal of this is to make within the recipient two bone marrow stem cell systems that are completely functional in one person. The patient is given anti-immune system drugs, but he or she is slowly weaned off them, with the goal of all anti-rejection drugs being ended within one year of the transplant. To qualify for this study, patients must have compatible blood types
Ildstad provided this insight, “This is something I have worked for my entire life.” Ildstad pioneered the discovery of the “facilitating cell.” This trial is ongoing, but the initial results are immensely encouraging, since some transplant patients seem to not need their anti-rejection medicines anymore even though they now have a kidney inside them that was not tissue matched. Specifically, five of eight people who underwent this treatment protocol were able to stop all immunosuppressive therapy within a year after their kidney and stem-cell transplants,. Note that four of these five patients received kidneys that came from unrelated donors. Notably, all of these patients maintained entirely donor-derived immune systems with no signs of Graft-versus-Host disease. Ildstad and her team have since treated seven more people. “We continue to see good results,” she says. This could easily revolutionize solid organ transplantation.