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Weizmann Institute scientists have created a functioning human kidney in the bodies of mice

Tissues of human or porcine kidney cells grown in a similar manner in the human body may help alleviate the shortage of kidney donors

Avi Blizovsky

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Instead of waiting a long time for the donation of a used kidney, it may be possible to grow new tissue of kidney cells in the body of patients who need a kidney transplant. This possibility arises from a pioneering study by Prof. Yair Reisner and the research student, doctor Dr. Benny Dekal from the Department of Immunology at the Weizmann Institute of Science, whose findings are published today in the scientific journal "Nature Medicine". Also participating in the research team were Prof. Justen Paswell, and Prof. Gideon Raffi from the Haim Sheba Medical Center in Tel Hashomer.

The researchers were able to cause embryonic tissue cells, which constitute the first stage of kidney formation, to undergo a process of differentiation and develop into functioning kidney cells, all in the bodies of mice, in the laboratory. In another experiment, the same process was also carried out in pig embryonic cells. Ultimately, the scientists hope that it will be possible to grow human kidney cells (or even pig cells) in the bodies of people who need kidney transplants, which will solve the severe shortage of kidney donors that exists today, all over the world.

More than 50,000 people are currently registered, in the US alone, on the waiting list for kidney transplants. More than 2,000 of them have died this year, while waiting. The wait may last years, and even after a donor is found, and the kidney is transplanted into the patient's body, there is a risk that the body will reject the transplanted organ. For example, on the website of the Israeli Ministry of Health it is stated that most transplanted kidneys do not function throughout the life of the transplant recipient, and that after years they may stop functioning gradually, in a process called chronic rejection. Patients suffering from this phenomenon need dialysis treatments again, or another transplant.

Prof. Yair Reisner and his colleagues located tissues of embryonic cells (both human and porcine) which constitute the first stage in the formation of a kidney (these cells are called kidney precursor cells). These cells were implanted under the kidney box in mice, and they were allowed to continue to differentiate and develop for eight weeks, until they matured and became functioning kidney cells. The result: both the human tissues and the porcine tissues developed in the bodies of the mice and formed perfect, functioning (urine producing) kidneys the size of a mouse kidney. The blood vessels of the mice grew into the kidneys and provided them with the blood necessary for their development and operation, which significantly reduces the chance of rejection of the kidney that developed from the transplant.
These findings hint at the possibility that human or porcine kidney precursor cells could develop and create a functioning kidney in the human body as well. Tissues from porcine cells, unlike whole organs from a pig, may be absorbed and function in the human body without the acute rejection that characterizes organ transplants between different species. The scientists hope, therefore, that pig kidney progenitor stem cells can be successfully transplanted into humans in need of a kidney transplant.

To ensure a supply of renal precursor stem cells, the scientists located the stage of fetal development where the chances of these cells developing into a functioning kidney are the best, and at the same time, they will not yet cause rejection by the body where they will be transplanted. Prof. Reisner says that human tissues of kidney precursor cells should be transplanted when they are seven to eight weeks old, while tissues of porcine cells should be transplanted when they are four weeks old. Younger tissues have not yet passed the stage from which they develop into kidneys, while more mature and developed tissues may attract more acute resistance and rejection by the body in which they will be transplanted. In a series of experiments, Prof. Reisner and the members of his research group were able to show that human tissue that was ten weeks old or more, or pig tissue that was six weeks old or more, indeed provoked an acute immune rejection reaction.

Prof. Reisner and the members of his research group found that the tissues that are in this window of opportunity do not yet contain cells that may stimulate the immune system to an acute rejection response. These cells, which originate from the blood system, reach the developing kidney only after ten weeks. Therefore, the window of opportunity for integrating the fetal tissue into the patient's body is when the fetal tissue is only seven to eight weeks old, and not beyond ten weeks.

After successfully growing human and pig kidney tissues in the mice, the scientists injected human immune system cells into the mice (which lack their own immune system). The result: the human immune cells did not attack the transplanted kidney tissues in the described window of opportunity.

Now the scientists plan to do some more tests. If these tests, which will last a year or more, go well, it will be possible, in the future, to continue testing the method in clinical trials (in humans).

For the news published today in New Scientist
They knew innovations in medicine

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