Frozen organ transplant gives hope for humans

SHERYL UBELACKER

Toronto Canadian Press

A new way of freezing tissue has allowed researchers to successfully remove, store and re-implant ovaries in sheep, providing hope the procedure could one day be used for women at risk of losing their fertility.

Furthermore, the freezing process may offer a way to preserve scarce donor organs, such as hearts, kidneys and livers, which now must be transplanted into recipients within hours of retrieval, the scientists say.

“This is the first time an intact organ was frozen, thawed and came back to full function,” said Dr. Amir Arav, a biologist at Israel's Agricultural Research Organization.

Dr. Arav and his team were then able to retrieve eggs from the transplanted ovaries, which were chemically induced to begin cell-division — the process triggered naturally by sperm fertilization that turns them into embryos.

“What was most surprising was that when we opened the animals and collected the oocytes (eggs), they looked fine and we were able to activate them and produce embryos from these eggs,” said Dr. Arav, lead author of a paper published Thursday in Human Reproduction.

“We really wanted to know if these eggs that we have are able to become embryos. Probably next time we'll do fertilization as well (to produce a lamb).”

The scientists removed one ovary from each of eight sheep in 2001. The reproductive organs were then frozen for different periods of time — from a week to a month — then transplanted back into the animals.

In five of the animals, blood began to circulate to the ovary immediately after the operation. Two of the sheep who resumed hormone production are still “cyclic” after four years, Dr. Arav said by phone from near Tel Aviv.

“The method of freezing is a new technique, a new concept in thermodynamics, where we can control the ice crystal propagation and we can freeze very, very slowly,” he said. “This is what makes all the (ovarian) cells survive.”

Mature eggs, which are sensitive to any kind of freezing in liquid nitrogen, did not survive the process, but less mature eggs “were fine,” Dr. Arav noted.

Scientists have removed ovaries from women undergoing chemotherapy or radiation for cancer, later implanting slices of the organ under the skin of the arm, for instance, or in the pelvic cavity, to restore limited reproductive function.

With that method, eggs are retrieved and the women undergo in-vitro fertilization. At least two women are reported to have given birth after the procedure.

Dr. Arav said the new technique used on sheep would be much easier in women because their blood vessels feeding the ovaries are much larger and easier to work with than are those in the animals.

“It's a huge opportunity for women who are going into chemotherapy and radiotherapy and they lose most of their eggs in the follicles,” he said. “With this way, it would be possible to remove one ovary previous to the treatment, freeze it in liquid nitrogen and after everything is OK and the treatment is done, it would be possible to put it back and to get normal function.”

Co-author Yehudit Nathan of Core Dynamics, the biotech company that funded and provided technological expertise for the project, said the next goal is to attempt to transplant ovaries in women at risk of losing their fertility.

“There is a lot of research still to be done, but we hope that it will not take more than a few years for this to become a practicable option for women, such as young cancer patients, who would otherwise be left infertile after their treatment,” she said.

Dr. Roger Gosden, director of research in reproductive biology at Cornell University's Weill Medical College in New York, said he is delighted to hear that the Israeli team has successfully frozen and transplanted a whole ovary, calling it a milestone in reproductive technology.

“The attraction of doing this with the whole ovary is that if you're successful with the surgery and the freezing, you should be able to restore to the natural state completely, that is not just to have a few cycles for a year or two or three — which is feasible with the tissue slices — but to have a full reproductive lifespan,” said Dr. Gosden, formerly of Montreal's McGill University.

“I think there's a good chance it may eventually work in humans,” said Dr. Gosden, who was part of the U.S. team that transplanted an ovary to a sterile women from her fully reproductive identical twin. The woman subsequently gave birth.

However, he said Dr. Arav's technique is unlikely to be practised in humans for some years.

Dr. Arav said the freezing process also could be used to store donor organs for longer periods, so they don't go to waste while tissue and blood-type matching is done and the organs are tested for communicable diseases.

Donor hearts, for instance, are relatively rare and can only be kept on ice for about four hours, limiting screening and transportation time, he said.

“If we were able to keep organs long-term, it would be a revolution in this area. I believe it will also increase the number of donor organs.”

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