UNR Stem Cell Research Focuses on Sheep

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A flock of sheep grazing on the outskirts of Reno could hold the key that one day ends the anguish of people waiting for organ donors and provides a new way to treat genetic defects in unborn children.

The sheep are the subjects of stem-cell research being conducted by a team led by Esmail Zanjani, head of the Department of Animal Biotechnology at the University of Nevada, Reno.

Human stem cells taken from the bone marrow of adult volunteers or from one of the federally approved embryo lines are injected into sheep fetuses before the unborn animals' immune systems have developed enough to reject the human cells, Zanjani said.

The sheep, kept at UNR's Agricultural Experiment Station southeast of Reno, make good test models because their stem-cell behavior is similar to humans.

"We found that if we transplanted adult stem cells, human cells developed everywhere in the sheep fetus - in the skin, the liver, the heart and the pancreas, which did make insulin," Zanjani said.

The sheep fetuses could one day provide options for people who have diseased organs, such as a pancreas for those who suffer from diabetes or a liver damaged by hepatitis, Zanjani said.

If the fetuses indeed produce normal, viable human cells, they could be extracted, placed in a culture to multiply and then injected into the diseased liver to regenerate healthy tissue. Or the entire part-animal, part-human organ could be harvested and implanted in the patient who donated the original bone marrow cells transplanted into the sheep fetus.

"So your body is going to reject the sheep part of the liver and destroy it, but your body would accept the human part, and that little bit of liver that is accepted has the ability to regenerate," Zanjani said. "Then you take the diseased part of the liver out."

In both cases, since the new liver cells or the human portion of the sheep liver were developed from stem cells taken from the bone marrow of the human donor, the donor's body won't reject them, he said.

"This isn't science fiction," Zanjani said. "I'm very hopeful this will work. I think in the next five to 10 years, it will happen."

The fact the sheep fetuses used in his research are born with human cells doesn't make them part human, according to Zanjani, since only 7 percent to 15 percent of their organs are composed of human cells.

One concern is that viruses specific to sheep could mutate into a form that could infect humans.

"That's the real limitation," Zanjani said. "Whether there will be viruses that could then be transferred into humans and what effect that could have, I don't know the answer."

Zanjani's research originally began decades ago when he was searching for ways to treat genetic defects in unborn children by injecting the fetus with healthy stem cells.

Stem cells already have been implanted into human fetuses to correct genetic immunodeficiency, but Zanjani hopes his sheep models will advance in utero treatment to deal with a number of genetic diseases, including hemophilia and the metabolic defect known as Hurler's syndrome.

Zanjani's work has earned him "a remarkable reputation" among researchers internationally, said David Thawley, dean of the College of Agriculture, Biotechnology and Natural Resources.

"There are very few people in the world doing what he is doing," Thawley said. "He really is a superstar, but he hides his light under a bushel."

Thawley said Zanjani is aided by other talented researchers, including Graca Almeida-Porada and her husband, Christopher Porada, both members of the animal biotechnology department.

A native of Iran, Zanjani earned his doctorate in experimental hematology at New York University. He became a professor at UNR in 1987 while he also was conducting research at the Veterans Affairs Medical Center.