UCSF resumes human embryo stem cell work

UCSF scientists are attempting to use controversial cloning techniques to generate human embryonic stem cell lines, resuming an effort shelved as a failure five years ago. At least half a dozen other groups in the United States and abroad also are getting involved in such work, signaling a renewed global push to achieve what experimenters in South Korea falsely claimed to have done last year. The ultimate goal ranks among the most important in experimental biology: to create "patient-specific" stem cell lines to study how diseases develop and to make transplant cells matched to a patient's own genes, thus avoiding the usual risks of rejection. UCSF's project is the only one of its kind on the West Coast, although this type of work also is being pursued by researchers in San Diego and is expected to be a key priority of the California Proposition 71 program. The first stage of the work at UCSF is being backed by private donations, and the experimental protocol has passed all the necessary ethical approvals. The research team is led by Renee Reijo Pera, a UCSF associate professor of obstetrics, gynecology and reproductive sciences. She also is co-director of the UCSF Human Embryonic Stem Cell Center. The human eggs required to carry out the work are being obtained now through UCSF's in vitro fertilization clinic. Key pieces of laboratory equipment have been ordered and are expected to arrive in June. The first of the donated eggs are expected to be transferred to the researchers as early as Monday. Scientists said they had no way to predict how long it might take to complete the experiments or what chance they have to succeed. Researchers plan to use a cloning method known as somatic cell nuclear transfer, or SCNT. Cloning solely done to produce stem cells, also known as "therapeutic cloning," is allowed in California under Prop. 71, the voter-approved 2004 stem cell initiative, but still is considered politically sensitive. Some politicians -- including President Bush -- want to outlaw the research on the grounds that it could encourage illicit attempts at reproductive cloning. And besides long-standing religious objections, pro-choice advocates worry about the potential harm to women who provide the human eggs involved. In somatic cell nuclear transfer, a person's donated DNA from an ordinary skin cell or other body cell is inserted into an egg, also called an oocyte, from which the nucleus has been removed. The hollowed-out egg is thought to retain the mysterious ability to reprogram the inserted DNA, causing it to behave as a new nucleus, producing a cloned embryo. Scientists would then try to coax the cloned embryo into dividing just long enough to produce stem cells, a process that usually takes about four or five days. All the stem cells produced this way would carry the DNA imprint of the donor. Partly to avoid the difficulty of having to solicit new egg donors, the UCSF researchers will start by using only eggs that failed to fertilize in IVF procedures. Typically, such eggs are discarded. None of the UCSF donors is being compensated, officials said, and the donors must sign consent forms that detail what will happen to their eggs. If an IVF patient used another egg donor, that donor must also consent before her oocytes can be diverted to cloning research. For now, the same IVF patients providing the eggs also are donating the adult-cell DNA, which the researchers plan to obtain by scraping a few cells from inside each donor's cheek. If the early efforts succeed, scientists would try DNA from someone with a particular genetic disease -- to produce the long-sought patient-specific cells for such mystery conditions as Alzheimer's or ALS. Disease researchers currently often rely on mouse or other animal models that may not accurately reflect the human disease process. Stem cell cloning offers "a terrific advantage," said Dr. Arnold Kriegstein, director of UCSF's Institute for Stem Cell and Tissue Biology, who is overseeing the latest research. "Those animal models of disease are not perfect examples of what happens in human cases. Here we have the advantage of actually studying human disease in human cells. The stem cell approach allows us to study these diseases in ways we just aren't able to any other way. To us that's one of the most attractive features of this approach," he said. The experimental protocol was approved by a special bioethics committee created by the university to study any project in which reproductive tissues are involved. A separate panel endorsed the project's scientific merits. The project has roots in an effort conducted at UCSF in 1999 and early 2001 that failed to produce any of the prized stem cell lines. The lead researcher at that time, Roger Pedersen, eventually relocated to the United Kingdom. In May 2005, a team in South Korea led by veterinarian Woo Suk Hwang, announced to great acclaim that it had produced cloned embryonic stem cell lines using SCNT, and moreover had done so with far fewer human eggs than anyone thought possible. Those successes proved illusory -- the results were faked. Now, scientists are hoping to achieve genuine success through improved techniques. In fact, some of the cloning methods developed in South Korea may turn out to be useful, Kriegstein said, when coupled with better cell-culture methods. Separate teams are pursuing essentially the same goal as UCSF, including scientists at the Harvard Stem Cell Institute in Cambridge, Mass. A formal announcement is expected within a few weeks. The effort reportedly will go beyond UCSF's project by recruiting young women to donate their eggs, an invasive procedure that involves hormonal stimulation of the ovaries, posing "a much more difficult and complex" set of ethical issues, said Dr. Bernard Lo, who chaired the UCSF bioethics review. Besides the health risks to donors, some critics worry that cloned embryos might somehow be misdirected into reproductive attempts, even though UCSF scientists insist that would never work in the case of the eggs they are using. Some religious analysts say all human cloning is inherently immoral. "What is ultimately being proposed in therapeutic cloning is the generation of very young beings that are human so that desirable cells may be removed from them, thereby always destroying those young human beings," said the Rev. Tad Pacholczyk, director of education at the National Catholic Bioethics Center in Philadelphia. The UCSF experiment, he added, creates "a situation where the ethical objections are about as serious as they could be." "Source":[ http://www.sfgate.com/cgi-bin/article.cgi?file=/c/a/2006/05/06/MNGUUIMR5D1.DTL]

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