'Adult' stem cells could skirt embryos' ethical dilemmas
Published 4:00 am, Saturday, June 25, 2005
In the emerging field of stem cell research, much of the promise -- and most of the controversy -- involves the breathtaking notion that replacement parts for our bodies one day may be grown from multipurpose cells derived from human embryos.
But scientists also are learning that embedded in our skin, flowing in our blood and stored in the deep reaches of our bones and brains are less versatile breeds of "adult" stem cells that may yet be coaxed into producing the same sort of medical advances without disturbing the ethical waters.
Because adult stem cells can be harvested without destroying a human embryo, they are the technology of choice among those, like President Bush, who have moral objections to research involving embryonic stem cells.
At a White House gathering last month, the president reaffirmed his opposition to such research but said his administration strongly supported the use of "alternative sources" of stem cells such as bone marrow and umbilical cord blood. "With the right policies and the right techniques, we can pursue scientific progress while still fulfilling our moral duties," he said.
Adult stem cells do not have the ability to turn into virtually any organ or tissue in the human body -- that is a trick reserved for their embryonic counterparts. Adult stem cells are also harder to study, because they do not renew themselves indefinitely in the lab, as embryonic stem cells do.
Despite those limits, new therapies using adult stem cells are likely to turn up in the clinic long before embryonic stem cells are tried. About 3,000 researchers are gathered in San Francisco for the third annual meeting of the International Society for Stem Cell Research, which ends today, and the majority of presentations on the program will deal with adult stem cells, conference organizers said.
Although adult stem cells do not have the ability to produce all kinds of cells, they still pack a wallop -- they can be the raw materials for entire systems, such as the hematopoietic stem cells in bone marrow that build red and white blood cells that nourish the body and create immunity from foreign microbes.
One limitation of adult stem cells is that they carry the biological markers of an individual and are likely to cause a dangerous immune reaction if they are transplanted into another person. Therefore, most adult stem cell transplants would have to be carried out using a patient's own cells.
Although embryonic stem cells in theory would not provoke such an immune rejection, they have their own hazardous tendencies that must be tamed. With a few chemical signals in a petri dish, embryonic stem cells can be turned into neurons -- the stuff of brain tissue. But these same stem cells injected in animals have produced teratomas -- grotesque tumors containing rudimentary skin, bone and hair.
Adult stem cell therapy is already being tested on patients. In fact, bone marrow transplantation -- pioneered three decades ago -- is adult stem cell therapy by another name.
The marrow contains reserves of adult stem cells that can divide and redivide to form every type of cell in human blood. A transplant of human bone marrow to a cancer patient can regenerate an immune system that has been destroyed by chemotherapy.
Bone marrow transplants have provided the "proof of principle" that stem cells have therapeutic potential, said Dr. Arnold Kriegstein, director of the Program in Stem Cell and Developmental Biology at UCSF.
Although the stem cells in bone marrow were first identified in the 1960s, Kriegstein said our understanding of adult and embryonic stem cells is still in its early stages. "We need to make progress on both types," he said.
At the Texas Heart Institute in Houston, controversial clinical trials are already under way, using adult stem cells in older patients with failing hearts whose only alternative is a hard-to-come-by transplant.
Using a technique he has already tried on 21 patients in Brazil, Dr. Emerson Perin injects a mixture of a patient's own bone marrow cells into the damaged heart. Perin calls it a "shotgun approach," acknowledging that only a fraction of the injected cells are actually adult stem cells.
The controversy involves a dispute as to whether the healthier cells subsequently detected in the heart are truly regenerated heart muscle or a fusion of the stem cells in the marrow with existing heart tissue. It is also possible that the stem cells simply die off but secrete chemical signals that promote healing of the damaged heart tissue before they disappear.
"We're not killing anybody," Perin said. "The bottom line is, these guys seem to do better."
Despite encouraging signs of improvement in some patients, the trial is only halfway completed -- 15 of 30 selected patients have undergone the procedure or been injected with a placebo to gauge whether the improvements are just the result of chance. Perin expects to complete the trial by year's end and to have analyzed the data six months later.
Adult stem cells have been isolated in blood, bone marrow, the brain, liver, skin and skeletal muscle. Although some researchers -- such as University of Minnesota Stem Cell Institute director Dr. Catherine Verfaillie -- have found they can coax bone marrow stem cells to produce other types of organ tissue, those results have not been replicated in other labs, said David Traver, a UC San Diego stem cell researcher.
"The more conservative thing to say is that each human organ probably has a specific stem cell system behind it, and there probably isn't a lot of 'cross-talk' between them," he said.
Traver, a speaker at this week's stem cell conference in San Francisco, uses the versatile zebra fish to study how adult stem cells normally develop - - a complex process of chemical signaling that leads the cells, step by step, to produce one type of tissue and not another.
Zebra fish produce hundreds of embryos, develop from egg to adult in a short time frame and are easy to observe because they are transparent. Researchers can knock out selected genes in the zebra fish's blood-producing stem cells and see how it affects their subsequent development.
"The bottom line is that we haven't learned much from studying human stem cells," Traver said. "Most of what we know comes from studying mice, fish and flies."
Theo Palmer, a neuroscientist at Stanford University School of Medicine, said there were biological reasons why embryonic stem cells should be easier to work with than the adult version. "They are a blank slate," he said. "They do not know what their role is."
Adult stem cells, on the other hand, already have been programmed to perform certain functions -- to form blood cells, bone cells or nerve tissue. "An adult stem cell has enormous potential that's already been realized," he said. "We don't know how to reprogram them yet."
On the other hand, he said that theoretically it might be possible, once the complexities of stem cell function are better understood, to reprogram an adult stem cell to make tissues as easily as an embryonic stem cell can. The catch is it will take years of research on embryonic stem cells to yield those insights, Palmer said.
"Embryonic stem cells will become increasingly outmoded as we find more directed ways of causing the body to heal itself," he said. "But only if you have enough information can you begin to approach the problem."
To learn more about stem cells
The UCSF Mini Medical School program will feature a lecture open to the public on "Stem Cells: Exploring Human Development and New Strategies in Medicine," given by Dr. Arnold Kriegstein, director of the UCSF Developmental and Stem Cell Biology Program.
The event will be from 7 to 9 p.m. Wednesday at Cole Hall, Medical Sciences Building, 513 Parnassus Ave., San Francisco. Participants can register at the door for the lecture for $15.
Parking is available in the UCSF campus garage for $3.
For more information, call (415) 476-2557.