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The Sacramento Bee Stem cell team avoids ethics tangle: Long-running Nevada research makes strides using human placental blood, not embryos. By Edie Lau - Bee Science Writer (Published Aug. 19, 2001) Scoot over, Dolly. A flock of sheep growing in Reno may be as biologically astonishing as the Scottish sheep clone. Inside the white, fleecy bodies of the Nevada sheep is evidence of the power of stem cells. The animals look and bleat like regular sheep, but they're composed partly of human cells. There are human cells in their livers, their hearts, their lungs, their skin, in the linings of their guts, and even in their brains. These human-sheep chimeras, as they're called, were brought to life with funding from the U.S. government. A long-term goal of the research is to find ways to repair defects in babies in the womb. The difference between this University of Nevada, Reno, research on stem cells and the studies that have elicited so much debate recently is that the human components of the sheep came from stem cells derived not from embryos, but from blood in human placentas. "It's really an amazing thing," said Esmail Zanjani, the professor of medicine and physiology who leads the Reno studies demonstrating the broad versatility of the neonatal stem cells. "They really have tremendous potential." Stem cell research is one of the hottest fields in medicine -- and a hot potato politically and ethically. Stem cells are immature cells in the body that have the ability to develop into a variety of cell types with specific functions. Theoretically, the cells could be manipulated to repair diseased or injured organs and tissues. The body possesses stem cells at all stages of development, from before birth to death. The cells have been found in bone marrow, the blood of placentas and umbilical cords, and in embryos. Generally, it's been thought that embryos yield the most malleable -- and therefore the most promising -- cells, and there is the rub: Gathering the cells kills the embryo. Some people who object to using embryonic stem cells support as an alternative research using stem cells from the blood of placentas and umbilical cords, arguing they may be just as useful. These cells typically are discarded with the rest of the afterbirth following a baby's delivery. Advocates of placental stem cell research include the Vatican, which is supporting a new placental/cord blood bank at Sacre Cuore University in Rome, and President Bush, who cited the possible value of umbilical cord and placental stem cells when he announced this month that limited federal funding would be available for embryonic stem cell research. Bush decided that only studies using existing lines of embryonic cells may obtain taxpayer money. So far, there's been little controversy over research on stem cells from animals other than humans, from human adults, and from afterbirth -- these studies have been funded all along. Zanjani, in Reno, said he has received grants from the National Institutes of Health for 30 years. His experiments in making human-sheep chimeras, which began 12 years ago, largely are supported by the federal government, on the order of $200,000 to $300,000 a year, he said. The injection of human placenta stem cells into sheep demonstrates that stem cell research not involving embryos can raise tough ethical questions, as well. At the very least, "this one scores high on the 'yuck' factor," said Arthur Caplan, a bioethicist at the University of Pennsylvania and frequent commentator on cloning, stem cells, artificial reproduction and related topics. "We think about Minotaurs and centaurs, where they've got human heads on animal bodies," Caplan said. But from a biologist's point of view, he said, putting animal cells in people or vice versa "is more or less trivial, unless they're carrying a (disease)." Biologists use the term "chimera" to describe an organism with two or more genetically different cell types. In Greek mythology, chimeras are monsters. Zanjani, an easygoing man with a quick smile and a cap of snowy hair, expresses no doubts about the appropriateness of his work. "We're not doing anything bad," he said. "What we do even the anti-abortion people like because what we're trying to do is save babies." The aim of Zanjani's research is to develop strategies for correcting genetic defects in babies before they're born. He and his colleagues hope healthy stem cells eventually could be injected into unhealthy human fetuses and used by their bodies. To test the safety and efficacy of the procedure, Zanjani first is experimenting with laboratory animals. He is interested in determining whether it's possible to successfully transplant stem cells into fetuses, and whether those cells can be used to heal. He first experimented with transplanting sheep bone marrow stem cells into the bellies of fetal lambs, and then turned to cells from human bone marrow. In the blood and bone marrow of the resulting lambs, the researchers found human cells. The cells were functioning -- producing human proteins -- and the sheep were OK. "They have no illness (resulting from the transplants), they act like sheep, they're cute as anything," Zanjani said. His team has gone on to transplant human placental/cord blood stem cells into fetal lambs, producing more than 1,500 human-sheep chimeras. The cells are taken up by the fetuses and appear to be incorporated seamlessly into their bodies. The lambs are injected at the end of the first trimester in gestation, when their immune systems can be fooled into accepting the foreign cells as their own. Might the presence of a few human neurons in the sheep give them humanlike minds? Zanjani can't say. "They don't talk," he jokes. They sheep are kept in pens and pastures with views of the eastern Sierra. The scientists are monitoring some of the sheep for their lifetimes (up to 14 years) to see whether the human cell grafts remain stable and functional. Zanjani estimates that the sheep have 2 percent to 3 percent human cells overall, with some organs possessing a greater percentage. He said he would not try to significantly boost the share of human cells. "I don't think that's compatible with the animals' life," he said. The Rev. Charles S. McDermott, who handles medical ethics questions for the Catholic Diocese of Sacramento, said the ethical propriety of the procedure is, to his mind, not a matter of absolutes, but of proportion. The operative question is: Does such research create a human hybrid? Deciding what proportion of human cells would constitute a hybrid is for scientists and ethicists to work out together, McDermott said. "I would say that the lower the number of cells, the less unacceptable it would be." Zanjani's sheep are unusual for possessing functioning human cells over the long term, but they are not unique as experimental animals injected with human cells. Marcus Muench, a hematology researcher at the University of California, San Francisco, has contributed to studies testing human blood stem cells in mice. Muench said others have done similar work, but to date no one has grown human cells in another animal species to the extent Zanjani's team has. Other types of animal chimeras have been made for years in the study of developmental biology. Gary Anderson, chairman of the animal science department at the University of California, Davis, said that in 1980, he and colleagues combined a sheep embryo with a goat embryo. "You get a normal critter that has patches of wool, patches of hair," he said. Apart from the ethical questions, the human-sheep chimeras are a scientific feat. They suggest that stem cells from the blood of placentas and umbilical cords may be almost as versatile as embryonic stem cells, able to develop into a variety of cell types. For years, it was thought that stem cells, except for those from an embryo, could generate only a particular kind of cell. So blood stem cells (those from bone marrow as well as placentas) would make only blood cells, liver stem cells liver cells, gut-lining stem cells gut-lining cells, and so on. But recent studies suggest that these stem cells may be more flexible. It was thought, too, that people didn't grow any more brain cells after birth, but that's become outdated dogma. Now, the search is on for the source of neuronal stem cells. The creation of Dolly the sheep contributed profoundly to the understanding that old cells can be taught new lessons. Born in 1996, Dolly was the first animal cloned from an adult cell -- a 6-year-old udder cell. Placentas, as almost limitless sources of neonatal blood and tissue, are an increasingly popular focus of research. The biotech company Anthrogenesis Corp. in New Jersey has hooked up placentas to "life support" machinery in an attempt to find and cultivate stem cells from the tissue itself, not the blood. Whatever the ultimate utility of the cells, research with them is a potentially big business. In Rancho Cordova, the company Thermogenesis makes kits to collect placental/cord blood, along with robotic freezers for storage. A unit able to hold the blood of 3,626 placentas sells for $200,000. Among customers requesting a quote on a Thermogenesis system, said CEO Phil Coelho, is the Vatican, for its new cord blood bank. The growing profile of placental stem cells is good for the company, Coelho said. "We think it is likely that it will be the preferred source of stem cells." The Bee's Edie Lau can be reached at (916) 321-1098 or [log in to unmask] SOURCE: The Sacramento Bee http://www.sacbee.com/news/news/local02_20010819.html * * * ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn