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Friday, December 08, 2023
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Rhesus monkeys, left to right, Canto, 27, and on a restricted diet, and Owen, 29, and a control subject on an unrestricted diet, are pictured at the Wisconsin National Primate Research Center at the University of Wisconsin-Madison on May 28, 2009. The two are among the oldest surviving subjects in a pioneering long-term study of the links between diet and aging in Rhesus macaque monkeys, which have an average life span of about 27 years in captivity. Lead researcher Richard Weindruch, a professor of medicine in the UW School of Medicine and Public Health, and co-author Ricki Colman, associate scientist at the Wisconsin National Primate Research Center, report new findings in the journal Science that a nutritious, but reduced-calorie, diet blunts aging and delays the onset of such aged-related disorders as cancer, diabetes, cardiovascular disease and brain atrophy.

Advancements in kidney transplantation prove optimistic in new UW-Madison research study

Dr. Dixon Kaufman, director of UW Health’s Transplant Research Center, worked with a team of UW-Madison researchers and specialists at Stanford University to optimize compatibility between host and recipient transplants.

The journey of a kidney transplant survivor is turbulent, with necessary and lasting lifelong medications that impede a patient’s quality of life. 

Dr. Dixon Kaufman and his team are working at the University of Wisconsin-Madison to avoid these complications and increase the success and frequency of life-saving transplant surgeries. 

“[It’s] what we commonly refer to as the holy grail: we would like to do transplants without the need for the patient to have a lifelong commitment to these medications,” Kaufman told The Daily Cardinal.

The project he and his team have worked on seeks to develop a “new system of transplant” that allows recipients’ immune systems to accept organs “with little or no anti-rejection medicines needed.”

Kidney transplants are not an uncommon occurrence — over 24,000 were performed in 2022 in the United States. However, there remains the lingering possibility of organ rejection, an aspect Kaufman’s team has specifically targeted. 

“There’s over a half million people on dialysis that need transplants, and we can only transplant about 24,000 a year. There is a big unmet need,” Kaufman said. “We need more human organs, and for the people here who do offer to become organ donors, they should know that we’re trying to do everything we can to get the most lifespan out of those organs.”

The project’s founding was in partnership with specialists at Stanford University who had done similar work in small animals — namely, monkeys.

Kaufman contacted them to bring their “monkey model” to UW-Madison and find ways to better match human donor recipients with “one of two strings of tissue typing,” which works to verify compatibility of alleles between donor and recipient organs. From there, they put together the project and received funding. 

Over the course of many years, Kaufman’s team performed surgeries and daily testing on monkeys at the Wisconsin National Primate Research Center. The monkeys were well taken care of and closely monitored at the center, he said. 

“One surgical team would remove one of the two kidneys from the donor monkey,” Kaufman explained. “And then the other surgical team would, in the recipient, take out their two native kidneys and then put in the transplanted kidney, so it was dependent on just that transplanted kidney.”

From there, scientists tried to achieve kidney success by experimenting with chimerism — the development of the recipient and donor’s immune systems in the recipient host — and total lymphoid radiation.  

“On Friday, they would get this special treatment called total lymphoid radiation through a machine called tomotherapy,” Kaufman said. “In the afternoon, we would infuse cells from that donor monkey’s immune cells into the recipient animal to create a dual-immune system.” 

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After many years of hard work, the project finally proved effective, potentially changing the way transplants will be carried out. Its long-term survival — more than four years of kidney transplant success without anti-rejection medicines — is “probably the longest anyone had ever reported you could achieve,” especially given that working with monkeys is more challenging than with humans, Kaufman said.

There are still many unknowns. However, the study demonstrates future hope for the field and paves a way for easier and more effective transplantation, Kaufman said. 

“If we could reach the day where we could just technically, operatively put the kidney in without having to rely on the medicines, that would be truly miraculous,” Kaufman said. “[It] would help people do even better than they are currently doing with transplants.”

Yet, their work isn’t done. Kaufman highlighted a UW-Madison project to transplant gene-edited pig organs into other large animals and eventually to people. 

“It may be possible one day to create tolerance to the xenotransplant,” Kaufman said. A xenotransplant is any procedure involving the “transplantation, implantation or infusion” of live cells, tissues or organs from a non-human animal source or human “body fluids, cells, tissues or organs” that have made contact with live non-human animal sources outside of a human body, according to the Food and Drug Administration.

By doing gene therapy and editing on pig DNA, the team is attempting to create certain “strains” of pigs whose organs would be less likely to be registered as foreign and less likely to be rejected. 

“There would be potentially an unlimited number of organs from these special breeds of pigs,” Kaufman said. 

Dr. Kaufman said he drew on the community and environment at Madison to achieve his potentially life-changing outcomes. He hopes his work will have a national and global impact.

“You want to do big, bold things that not only help our community but our nation at large. That’s why we’re here, that’s what draws us here,” Kaufman said.

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