March 6, 2019

Right now, kidney transplant recipients are required to undergo a lifelong regimen of immunosuppressive medications so their white blood cells won’t reject the new organ. But scientists at the Wisconsin National Primate Research Center (WiNPRC) at the University of Wisconsin-Madison (UW) are working to create conditions in recipients that will allow their bodies to accept transplants without the need for drugs.

In an ongoing study utilizing nonhuman primates, hematopoietic stem cells (HSC; cells that can become any other blood cell) are driven from the bone marrow of the potential donor into the blood. They are then collected from the blood and frozen, using methods like those used in humans to harvest cells for transplantation into cancer patients. Next, the kidney is transplanted from donor to recipient. Then, the recipients undergo targeted treatments for two weeks with immune-depleting agents and radiation to prevent rejection. After the last radiation treatment, the donor’s set-aside blood containing the HSCs is infused into the recipient.

If these cells are accepted along with the kidney, this is called a state of mixed chimerism; the resulting immune system is part-donor and part-recipient. The subjects are then placed on immunosuppressive drugs for eight months, during which time the investigators examine whether the transplanted kidney is doing its job, and whether the infused HSCs are actually multiplying.

“We are seeing that the donor HSCs survive and differentiate to join the components of the recipient’s immune system,” said Dixon B. Kaufman, MD, PhD, one of the researchers and chair of the UW Division of Transplantation. “This combined system appears to be much more accommodating to the new organ than what we observe in traditional transplantation.”

A critical next step, according to the researchers, is to come up with a new standard of care that works for most, if not all patients, as everyone’s immune system reacts differently to disease, surgery and postoperative care.  

“We hope to provide a successful system for other major organ transplants (as well),” Kaufman said. “Saving lives, along with reducing the cost to patients and the healthcare system with a one-and-done transplant approach, where the patient need not take a regimen of drugs, nor have to worry about a second organ transplant if the first gives out, is the holy grail of this work.”

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