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The following excerpts are from ; Science Magazine Online June 8, 2001 It offers replies from the scientists to the arguments that adult stem cell research is sufficient. It also responds to the media hype over the use of fat cells and of cadavers as a source of stem cells, with the facts about the reported research. And it explains the difference between peer reviewed, published research results from NIH and university sponsored studies and the non-reviewed results announced by commercial firms -- The two main points of the article; -- most scientists who work in the field agree that both embryo and adult stem cell research are needed to eventually advance to clinical applications and actually being able to cure diseases -- especially true for neurological diseases. -- these clinical applications are still years away. linda STEM CELL POLICY: Can Adult Stem Cells Suffice? BY Gretchen Vogel ' ... most scientists in the field--including those who work with adult-derived cells--caution that recent advances, although promising, do not mean that adult cells can replace the need for those derived from embryos or fetal tissue. For some diseases, they say, adult cells may indeed turn out to be the better choice. But for other applications, embryo-derived cells have some distinct advantages. Scientists working mostly with ES cells derived from mice have found that they multiply more readily in the lab than do their adult counterparts, providing as many cells as needed, and they seem far more proficient in producing certain specialized cell types, such as dopamine-producing neurons and insulin-producing cells. "It's incorrect to say that these published papers show that the adult cells are equivalent to embryonic stem cells for treating diabetes and Parkinson's," says Ron McKay of the National Institute of Neurological Disorders and Stroke (NINDS) in Bethesda, Maryland. Fat and Frankenstein Both types of cells could prove to be a tremendous boon to medicine. ...Eventually, scientists would like to use stem cells to replace damaged or worn-out tissues--for instance, to treat paralyzing spinal cord injuries. This might work if scientists can figure out how to guide the growth of stem cells--immature cells that can replicate themselves and give rise to mature daughter cells. The stem cells themselves are found in many tissues in the body and also in developing embryos and fetuses. Those isolated from embryos are pluripotent--meaning that, with the correct cues, they can give rise to any kind of cell in the body. Stem cells in adult tissue are often multipotent--they can produce many, but not all, cell types. ...One recent paper captured the public's imagination as few others have. In the April issue of Tissue Engineering, surgeon Marc Hedrick of the University of California, Los Angeles, and his colleagues reported that fat cells isolated after liposuction could become cells resembling cartilage, bone, and muscle. The paper has prompted numerous sound bites, with several politicians volunteering to give up some of their fat to further research. But although the image of liposuction as an altruistic operation might be attractive, developmental biologist Douglas Melton of Harvard University says the study leaves several key questions unanswered. He speculates, for instance, that the team may have cultured a circulating hematopoietic stem cell, rather than a fat cell. That may be so, says co-author Adam Katz of the University of Pittsburgh, but he suspects people will prefer liposuction to bone marrow donation any day. Cell biologist Bruce Spiegelman of the Dana-Farber Cancer Institute in Boston is similarly circumspect. He points out that the four cell types the team described--fat, cartilage, muscle, and bone--are all part of the mesenchymal cell family and have already been derived from several stem cell sources. The paper reports no sign that the cells could become nerve cells or the much-sought-after pancreatic cells. Fat cells might be abundant, Spiegelman says, but "they are a far cry from being the answer to everything we need." The next paper to make a major splash described isolating stem cells from cadavers. "Frankenstein cells," several headlines proclaimed. As described in the 3 May issue of Nature, neuroscientist Fred Gage of the Salk Institute for Biological Studies in La Jolla, California, and his colleagues cultured neural progenitor cells from brain tissue taken from cadavers shortly after death. Gage notes that the team members were careful to call their cells neural "progenitors" instead of neural "stem cells." The cells could divide and differentiate in culture, but the team didn't show that they could both replicate themselves and produce mature daughter cells--the true test of a bona fide stem cell. The cells also had a limited lifetime in culture--a major disadvantage for scientists trying to coax cells to become a particular tissue type. In short, says Gage, the technique is a long way from clinical application. At least two companies have announced--but not published--that they have identified or produced pluripotent cells without using embryos or fetal tissue. Although the claims got plenty of play in the press, most stem cell scientists are dubious. In April, a company called Anthrogenesis, located in Cedar Knolls, New Jersey, announced via a telephone press conference that it had isolated stem cells from human placentas that might be the equivalent of human pluripotent stem cells. These placental cells can differentiate into nerves and blood vessels, the company says, although chief scientific officer Robert Hariri says they are still characterizing the cells. "These claims ... were just absolutely absurd," says John Gearhart of Johns Hopkins University, who isolated pluripotent stem cells from fetal tissue in late 1998. "If you don't have published research reports, how are [colleagues] supposed to judge a claim?" Hariri says the company has submitted several papers describing the cells, although none have been published yet. ... Strong signs from bones In one tissue, at least, scientists agree that the results are encouraging. In the past few months, a series of papers has strengthened the idea that cells in the bone marrow can respond to cues from damaged tissue and help repair it. Until recently, doctors had only attempted to use bone marrow stem cells to reconstitute the blood or immune system. But late last year, two teams reported that mouse cells derived from bone marrow could become neuronlike cells (Science, 1 December 2000, pp. 1775 and 1779). In April, another two groups reported that bone marrow-derived cells could help repair damaged heart muscle. In one study, Piero Anversa of New York Medical College in Valhalla and Donald Orlic of the National Perhaps most impressive, in the 4 May issue of Cell, scientists reported that a single cell from the bone marrow of an adult mouse can multiply and contribute to the lung tissue, liver, intestine, and skin of experimental mice. Researchers knew that a tiny subset of cells purified from bone marrow had the potential to multiply and give rise to all the blood cell types, but isolating those cells has been very difficult. To increase their chances of capturing the elusive cells, Diane Krause of Yale University School of Medicine and Neil Theise of New York University Medical School and their colleagues performed a double bone marrow transplant. They first injected bone marrow cells from a male mouse, tagged with green fluorescent protein, into the bloodstream of female mice that had received a lethal dose of radiation. Two days later, they killed the recipient mice and isolated a handful of green-tagged cells that had taken up residence in the bone marrow. (Previous studies had suggested that the most primitive transplanted cells lodge in bone marrow.) They then injected irradiated mice with just one of the green-tagged cells accompanied by untagged, female-derived bone marrow cells that survive about a month. When the scientists killed the surviving mice 11 months after the second transplant, they found progeny from the cells in lung, skin, intestine, and liver as well as bone and blood. "Bone marrow stem cells can probably form any cell type," says Harvard's Melton. Even so, Krause says her work highlights the need for more work on ES cells rather than suggesting a replacement: "We basically have a black box. We put the cells in at the beginning and look at the mice" several months later. Because only six of the 30 mice that received a single-cell transplant survived, Krause estimates that one-fifth of cells harvested from the first transplant recipients have such broad potential. The scientists don't know why the most versatile cells go to the bone marrow in the first transplant, nor can they predict which ones might have the potential to multiply and differentiate. Melton also notes that cells from bone marrow have one major drawback: Although they are fairly easy to collect from donors, the cells do not grow well outside the body--and not for lack of trying. "Biotech companies have spent tens of millions of dollars on that problem," Melton says. "I don't think it's going to happen very easily." ... Two are better than one Most researchers say they need access to both embryonic and adult stem cells. McKay points out that embryonic cells have one huge advantage over adult-derived cells: their ability to divide in culture. "The ES cell will be the basis for how you will get large numbers of cells," he says. Gearhart of Johns Hopkins adds that the ability of embryonic and fetal cells to divide in the lab makes them a vital tool for learning how differentiating cells behave. "Answers to the problems of how you would do things with adult stem cells will probably come from the embryonic and fetal cells," he says. "There's no other way you're going to get that information." But ES cells have plenty of limitations, too. For one, murine ES cells have a disturbing ability to form tumors, and researchers aren't yet sure how to counteract that. And so far reports of pure cell populations derived from either human or mouse ES cells are few and far between--fewer than those from adult cells. Even if adult-derived cells do become the favorite for some treatments, such applications are years away, says McKay. The long-term consequences of stem cell therapies are completely unknown, as few animal studies have looked at results longer than a year after transplants. And scientists need to know more about the process of cell differentiation before anyone will be able to tell which cells hold the most hope for curing disease, McKay notes. "All of these cells," he says, "are partial solutions for the moment." ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn