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Friday, March 16, 2012

Study of Immune System Tricked to Accept Donor Organs

Kidney transplant or other organs has become one of the therapeutic treatment of a disease. Now the researchers found a way to trick the immune system (immunity) of the body, so that is not suitable donor organ can be accepted. This finding is considered very important because it helps patients who had organ transplants must take drugs for life to prevent rejection of organ donors.

According to a study published in the journal Science Translational Medicine, from eight renal transplant patients treated with the new method, five of them stopped taking anti-rejection drugs a year after their surgery organ.

In fact, one patient, Lindsay Porter, completely free of anti-rejection drugs for nearly two years after undergoing a kidney transplant.

Kidney Transplant.
(Picture from: http://www.kundankidneycare.com/)

"I heard about the challenges that organ recipients to take drugs. But this method shows the opposite, I feel very healthy and normal," said 47-year-old woman from Chicago, some time ago.

During this organ transplant recipients require organ konvensfonal drugs to suppress their immune system. Though the drug can cause serious side effects, including high blood pressure, diabetes, infections, heart disease, and cancer.

"This new method will offer a better quality of life and fewer health risks to the donor organ recipients," said Suzanne Ildstad, director of the Institute of Cellular Therapeutics at the University of Louisville in Kentucky, United States, which developed the current method.

But, not all organ transplants can use this method Ildstad findings. Some experts say this method can not be applied in patients undergoing bone marrow transplantation.

"It's too risky. In contrast to kidney transplantation is relatively safe," said Tatsuo Kawai, a transplant surgeon at Harvard Medical School.

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 transplant recipients to accept the donor organ, the team needs to condition" them by suppressing their body's bone marrow with chemotherapy and radiation before transplanting the donor's bone marrow, the soft fatty tissue inside bones. 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 in a telephone interview. Here what we are trying to do is get donor and recipient cells to peacefully coexist in the transplant recipient."

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 favorable 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.

In the study, five out of eight patients reached this one-year goal. Two patients had a partial response and have been placed on a reduced dose of immunosuppressive drugs.

One patient developed sepsis and lost the new kidney, but has since received a conventional kidney transplant. 

The study is the first to try to create chimeric tolerance in patients using the facilitating cells created by Regenerex.

By use of this stem cell product, we have been able to show we can safely achieve engraftment of donor stem cells," Leventhal said.

He said patients developed tolerance to the graft, eliminating the need for anti-rejection drugs, even when donors and recipients were mismatched and unrelated.

Kawai of Harvard called the results amazing," but he said it is hard to tell from the study how much of a difference the facilitating cells made because there was no control arm, in which patients underwent the procedure without getting the enriched facilitating cells.

And because these cells are not fully described in the paper, he said it is impossible for other labs to replicate the results.

At Harvard, Kawai and colleagues achieved temporary chimeric tolerance - in which two immune systems coexisted in one body - in a separate study published in 2008 in the New England Journal of Medicine.

Patients in that study did not have their immune systems suppressed by chemotherapy and radiation, and the donor immune system cells died off after a few weeks. But at least one patient still has a working donor organ 10 years after the procedure and does not need to take anti-rejection medications.

Kawai worries that patients in the recent trial are taking too much risk. Their approach is to totally destroy the host immune system by medication and radiation," he said.

Kawai said he would like to see the approach tested first in patients with blood cancers or other disorders who would need a bone marrow transplant -- patients for whom there are no other options, and therefore in whom this harsh treatment" is justified.

Leventhal said the team is still enrolling patients in the clinical trial, which aims to include as many as 40 subjects.

To qualify, donors and recipients need to have compatible blood types and a negative cross-match, which means the recipient does not have antibodies in the blood that could cause rejection of the kidney. *** [REUTERS | MAHARDIKA SATRIA HADI | KORAN TEMPO 3821]
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