Organ rejection no more?https://indianexpress.com/article/news-archive/web/organ-rejection-no-more/

Organ rejection no more?

Stem cells transplant can ‘trick’ immune system into accepting organs from mismatched,unrelated donor

Scientists have found a way to trick the immune system into accepting organs from a mismatched,unrelated organ donor,a finding that could help patients avoid a lifetime of drugs to prevent rejection of the donated organ.

Of eight kidney transplant patients who have been treated with this new approach,five have managed to avoid taking anti-rejection drugs a year after their surgery,according to the study published on Wednesday in Science Translational Medicine.

And one patient,47-year-old Lindsay Porter of Chicago,is completely free of anti-rejection drugs nearly two years after her kidney transplant.

“I hear about the challenges recipients have to face with their medications and it is significant. It’s surreal when I think about it because I feel so healthy and normal,” she said in a statement.

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With conventional transplants,recipients need to take pills to suppress immune systems for the rest of their lives. These drugs can cause side effects,including high blood pressure,diabetes,infection,heart disease and cancer.

“This new approach would potentially offer a better quality of life and fewer health risks for recipients,” Dr Suzanne Ildstad,director of the Institute of Cellular Therapeutics at the University of Louisville in Kentucky,who developed the new approach,said.

But some experts say the procedure,in which patients undergo a bone marrow transplant from an unmatched organ donor,is too risky,especially given the relative safety of kidney transplants. “We have to think about the risks and benefits. Since the current treatment is so stable,it really has to be safe,” said Dr Tatsuo Kawai,a transplant surgeon at Harvard Medical School,who wrote a commentary on the new approach.

The new technique draws on research by Australian immunologist Sir Frank Macfarlane Burnet and Brazilian-born British zoologist Peter Medawar,who won the 1960 Nobel Prize for discovering that the immune system in animals can be trained to acquire tolerance of foreign tissue.

“But it has been a long road to bring this about in people,” says Dr Joseph Leventhal,a transplant surgeon at Northwestern Memorial Hospital in Chicago,where the transplants took place.

To get recipients to accept the organ,the team needs to “condition” them by suppressing their bone marrow with chemotherapy and radiation before transplanting the donor’s bone marrow. Bone marrow contains immature blood-forming stem cells that give rise to all blood cells,including immune system cells.

“The idea here is to try to use donor-derived stem cells to achieve engraftment,a state we call chimerism,” Leventhal,a co-author of the study,said. “Here what we are trying to do is get donor and recipient cells to peacefully coexist.”

About a month before transplant surgery,kidney donors must inject themselves with a medication for several days that forces stem cells and other key cells called “facilitating cells” into their bloodstream,from where they can be collected and sent off to the University of Louisville for processing.

Leventhal said these “facilitating cells” are naturally occurring cells that help create a more favourable environment for the stem cells and allow engraftment to occur safely.

Ildstad has developed a process for enriching these cells and formed a company called Regenerex LLC,which is developing the patented technology.

Meanwhile,the transplant recipient is given radiation and chemotherapy to suppress the immune system,a process intended to prepare them for accepting the donor’s stem cells.

The patient then undergoes a kidney transplant,and a day later gets transplanted with the enriched mix of the donor’s stem cells and facilitating cells with the hope of forming two bone marrow systems that can exist and function in one person.

Following those procedures,the recipient starts off taking anti-rejection drugs but is gradually weaned off them with the goal of stopping entirely a year after the transplant.

Leventhal said patients developed tolerance to the graft,eliminating the need for anti-rejection drugs,even when donors and recipients were mismatched and unrelated. The team is enrolling patients in the clinical trial,which aims to include 40 subjects.

The ‘trick’

With conventional transplants,organ recipients need to take pills to suppress their immune system for the rest of their lives. These drugs can cause serious side effects,including heart disease,diabetes and cancer.

In The new approach,the recipient is given radiation and chemotherapy to suppress the immune system,a process intended to prepare them for accepting the donor’s stem cells.

Then the donor’s bone marrow is transplanted.

The patient then undergoes a kidney transplant,and a day later gets transplanted with the enriched mix of the donor’s stem cells and facilitating cells.

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Following this,the transplant recipient starts off taking anti-rejection drugs but is gradually weaned off them with the goal of stopping entirely a year after the transplant.