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A r t i c l e # 1 Alternative to Embryonic Stem Cells "Master Cell" Found in Adult Bone Marrow By Dave Andrusko Thanks to research coming out of the University of Minnesota's Stem Cell Institute, what had seemed to be a logjam in the debate over both cloning and embryonic stem cell research that requires the destruction of human embryos may have been broken. Dr. Catherine M. Verfaillie and her colleagues have discovered a type of adult stem cell found in bone marrow that holds out the possibility of growing into any kind of tissue in the body. The work of Dr. Verfaillie and her colleagues is part of a broader pattern of recent discoveries which challenge the conventional wisdom - - that because stem cells found in human embryos are "unspecialized," they have a monopoly on the ability to become any tissue type found in the human body. Dubbed "multipotent adult progenitor cells" (MAPCs), the adult stem cells isolated by Dr. Verfaillie's team appear to offer the best of all possible worlds. They seem to possess all the advantages attributed to embryonic cells but avoid the two major drawbacks researchers have encountered with embryonic stem cells: (1) Coming from the patient's own body, the immune system would not attack the tissue as foreign invaders; and (2) the MPACs don't turn cancerous! As reported first in the November 1, 2001, edition of the journal Blood and then amplified in a piece that appeared January 26 in the journal New Scientist, Verfaillie et al. have shown that MAPCs can be coaxed into turning into muscle, bone, liver, cartilage, and a variety of types of neurons and brain cells. In addition, at least in the lab, these cells went about their business without showing any signs of slowing down. (According to the Boston Globe, "MAPCs express an enzyme called telomerase that keeps cells from aging.") "The work is very exciting," said Ihor Lemischka of Princeton University. Irving Weissman of Stanford University said, "It's very dramatic the kinds of observations Verfaillie is reporting. The findings, if reproducible, are remarkable." Even Rudolph Jaenisch of MIT, a vocal proponent of research that requires the destruction of human embryos to obtain their stem cells, admitted to the New York Times, "I haven't seen the data, but if they did it, that's pretty good." An intriguing technical question is what exactly MAPCs are. For instance, are they "rare cells present in the bone marrow that can be fished out through a series of enriching steps," as the British Broadcasting Company described it "a small population of embryonic stem cells [that linger] on in the adult, morphing into the various types of adult stem cell as needed," in the words of the New York Times? Or had Dr. Verfaillie "somehow reprogramed the cells back to a semi-embryonic state," as the Times speculated? In fact, the news about the capacities of adult stem cells is not new. Verfaillie's work is just the latest evidence that adult stem cells are much friskier than first advertised. Initially, the argument was that only human embryos possessed stem cells that were sufficiently "versatile" or "malleable" or "plastic" to potentially be capable of becoming any tissue in the human body. That was a powerful weapon in the arsenal of those who wanted federal funding (and the respectability that comes from tapping into the federal spigot) to underwrite research that required the destruction of human embryos. However, more and more research of late has shown that adult stem cells possess similar properties. Those wedded to procuring stem cells that require the destruction of human embryos grudgingly concede that adult stem cells "had their place," but insist that the real action is in embryonic stem cells. But as a public relations statement describing Verfaillie's work sent out by the University of Minnesota stated, the team had found an adult stem cell with characteristics "much like embryonic stem cells." Beyond the potential benefit to people with various diseases--everything from Parkinson's and Alzheimer's through degenerative diseases such as osteoporosis to single gene disorders such as hemophilia--this breakthrough is hugely important for another reason. As the Associated Press discreetly put it, "Using embryonic stem cells is controversial, because embryos must be destroyed to harvest them." As the New Scientist article explains, the Stem Cell Institute's results are not unique. Two other labs say they have made similar cells in mice "and one biotech company, MorophoGen Pharmaceuticals of San Diego, says it has found them in skin and muscle as well as human bone marrow." The difference (the New Scientist writes) is Verfaillie "appears" to be the first to carry out the kind of experiments that back up a claim that these adult stem cells are as "versatile" as embryonic stem cells. According to the New Scientist, "Crucially, using a technique called retroviral marking, Verfaillie has shown that the descendants of a single cell can turn into all these different cell types; a key experiment in proving that MAPCs are truly versatile." Also Verfaillie's group has done the tests that are perhaps the gold standard in assessing a cell's plasticity. She placed single MAPCs from humans and mice into very early mouse embryos, when they are just a ball of cells. Analyses of mice born after the experiment reveal that a single MAPC can contribute to all the body's tissues." With a historic debate over cloning about to begin in the Senate, Verfaillie's discoveries also undercut the primary advantage that proponents of cloning attribute to stem cells that are extracted from cloned embryos. Proponents maintain that stem cells taken from an embryonic human being and used in another human being would trigger an attack by the recipient's immune system. But, they tell us, if an individual creates his/her own clone, supposedly by definition, an attack on "foreign" tissue is impossible. Proponents place great weight on what they call the "compatibility" argument. But a Wired News story quite accurately summarized the potential bombshell: "If Verfaillie's research were reproducible, it would eliminate any need to use embryos, as well as the need to clone embryos. Stem cells could be taken from one's own bone marrow, eliminating the potential for rejection." Proponents agree. According to Wired News, the director of the Reproductive Cloning Network e-mailed a fellow cloning advocate this message: " All I could think about while reading this story is that if it were true, we would lose our greatest arguing point," wrote Randolfe Wicker. "I have always believed that the compatibility argument was our 'ace in the hole' that they could never really defeat." A r t i c l e # 2 Adult Stem Cells Offer Hope Without Hype By Victoria White Since the discovery of their unique restorative properties, stem cells have been touted as miracle makers...but are they up to the challenge? And is there a source for them other than embryonic tissue and all the ethical baggage it carries? Dennis Steindler is staking his career on it. Steindler and his colleagues at the University of Florida are pioneers in the discovery and use of adult brain cells to achieve many of the same results as their more controversial cousins. He is optimistic that, like stem cells taken from embryos, adult stem cells can be coaxed into supplying the right material for the job at hand, whether its repairing injured brains or spinal cords or providing healthy cells to replace diseased ones. These adult tissues dont appear to be as restricted as we once thought they were, says Steindler, a professor of neuroscience and neurosurgery at UFs College of Medicine who also is affiliated with UFs McKnight Bain Institute and the UFs Shands Cancer Center. In some ways, they may not have the same potential as embryonic cells, but once we figure out their molecular genetics, we should be able to coax them into becoming almost anything we want them to be, he adds. Douglas K. Anderson, chair of UFs Department of Neuroscience and a key player in UFs efforts to understand the biological response to spinal cord injury, says of Steindlers team: What makes them so unique is their focus on adult tissues. They can take stem cells from cadavers, obviating the need for having to deal with the controversies associated with embryonic tissue. Theyve also shown that they can get stem cells by dedifferentiating them, a way of essentially turning old cells young again.1 1 Victoria White, Brain Marrow: Adult Stem Cells Offer Hope Without Hype, Explore: Research at the University of Florida, University of Florida, Fall, 2001. A r t i c l e # 3 Adult stem cells from liver form heart tissue N.N. Malouf et al. An excerpt from the article Adult-derived stem cells from the liver become myocytes in the heart in vivo, American Journal of Pathology 158, 1929-1935, June 2001. Scientists at Duke University Medical Center have shown that adult stem cells from liver can transform into heart tissue when injected into mice. They say that Recent evidence suggests that adult-derived stem cells, like their embryonic counterparts, are pluripotent , and that These results demonstrate that adult liver-derived stem cells respond to the tissue microenvironment of the adult heart in vivo and differentiate into mature cardiac myocytes. A r t i c l e # 4 Ottawa team uncovers how stem cells form muscle From an article in the June 27, 2003 issue of the journal Cell . Dateline Ottawa A research team in Ottawa has discovered how adult stem cells are directed to form new muscle. They say the finding could pave the way for treating people with muscle-wasting diseases. For the past 12 years, Dr. Michael Rudnicki of the Ottawa Health Research Institute has been studying the origin of muscle cells and how they grow in our bodies. He and his team found a new class of adult muscle stem cell called CD45+, and have discovered a way to trigger the cells to form new muscle tissue. Stem cells are like the body's blank slates, possessing the ability to become skin, bones or organs. The researchers showed a protein called WNT could direct the function of muscle-making stem cells. "WNT proteins activate the adult stem cells, signal them to begin dividing, to commit to develop down a particular pathway to become muscles," Rudnicki told a news conference Thursday. "They're, in effect, telling the stem cells what they're going to be when they grow up." He said the research could enhance the building and repair of muscle, improving quality of life for people with muscular dystrophy, multiple sclerosis and Lou Gehrig's disease. So far, the research has been done in animals. Rudnicki has secured a patent on the cell regeneration process and hopes to demonstrate the same principle in humans. If successful, Rudnicki says the work could result in a treatment for muscle-wasting illness in three to five years. A r t i c l e # 5 University of Arizona Administers Stem Cell Treatment to Fight Multiple Sclerosis By Anne T. Denogean From an newspaper article in the Tucson Citizen April 11, 2003 Stem cell transplants, widely used to help treat cancers of the blood, are being tried to fight various autoimmune diseases at the University of Arizona and other medical centers around the nation. Yesterday, Janice Coakley, a 50-year-old Tucsonan, became the first person in Arizona to undergo a stem cell transplant for multiple sclerosis. The procedure took place at University Medical Center. Results won't be apparent for some time, but her doctors hope to stabilize the disease. The protocol for UA's study of stem cell transplants for autoimmune disorders also allows for transplants for lupus, scleroderma, juvenile rheumatoid arthritis and severe rheumatoid arthritis, said Dr. Michael Graham, lead investigator for the study and director of the pediatric bone-marrow transplant program. Graham said several hundred stem cell transplants for autoimmune disorders have been conducted around the world in recent years. Their use for multiple sclerosis mostly shows stabilization of the disease in patients who were progressively losing nervous system function, he said. Lupus is a chronic inflammatory disease that can affect various parts of the body, especially the skin, joints, blood, and kidneys. It occurs when the immune system loses its ability to tell the difference between foreign substances and its own cells and tissues. In lupus patients who have received stem cell transplants, early results don't show eradication of the disease, but symptoms are greatly reduced for some, Graham said. About one-fourth get no benefit, he said. UA has performed stem cell transplants on two lupus patients, Graham said. "We have one lupus patients that's approaching a couple years after transplant, and her lupus is not gone completely, but she is basically symptom-free, when (before) she had been coming to the hospital every few weeks or so with different complications," he said. That stem cell transplants might improve the condition of patients with autoimmune diseases "came from the idea that sometimes people have lupus or other autoimmune disease in addition to leukemia or lymphoma, and they got a transplant (for the cancer) and, lo and behold, the other disease got better," Graham said. "We knew that was actually the case." But it was only in recent years that doctors tried transplants specifically for autoimmune diseases, he said. Graham said stem cell transplants for autoimmune disease use an infusion of the patient's cells rather than cells from a donor. The treatment allows the patient to endure chemotherapy regimens designed to knock out the errant immune system cells responsible for the disease. The chemotherapy regimen, not the stem cells, leads to a possible cure, he said. "This is really done for diseases in which chemotherapy and letting the bone marrow start over is likely to be helpful," he said."Hopefully, we process the stem cells in such a way that we are not giving back the disease," he added. The UA protocol began two years ago, with a goal of performing the procedure on 30 patients with autoimmune disorders. But it's been slow going, with just the three patients, Graham said. "The patients you choose for it are sick enough that the regular therapy is not working but not so sick they can't tolerate the transplant. This isn't for everybody," he said. The other challenge to lining up patients is getting insurance companies to pay for the procedure, which costs an average of $100,000 to $150,000, he said. UA's study is not funded by outside sources, so patients and insurers must pay for treatment. A r t i c l e # 6 Adult Stem Cells Transformed Into Functional Liver Cells By R. E. Schwartz et al. An excerpt from the article "Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells;" J. Clin. Invest. 109,12911302; May 2002 Dr. Catherine Verfaillies group at Minnesota continues to show more and more uses for the multipotent adult progenitor cells (MAPC) from bone marrow. The team has now shown that these adult stem cells can transform into functional liver cells. The adult stem cells also were grown in culture for over 100 generations, twice the length of time previously thought possible with adult cells. A r t i c l e # 7 Diseased Brains Can Repair Themselves with Adult Stem Cells An article from the Betterhumans Magazine - Wednesday, January 29, 2003 Diseased human brains contain adult stem cells that can repair damage associated with neurodegenerative conditions, say New Zealand researchers who have studied them. "What we have found in the diseased brains is that adult stem cells proliferate to form replacement neurons as well as other repair cells," Richard Faull from the University of Auckland School of Medicine told an Australian Neuroscience Society conference in Adelaide. "By accessing these stem cells and introducing growth factors to generate new neurons, it may be possible to help the brain repair itself and for sufferers of neurodegenerative diseases to regain health and normal functions," said Faull. Thanks to a New Zealand human brain donor program, Faull and colleagues are able to study stem cells in relation to various neurodegenerative diseases, including Parkinson's and Alzheimer's. "There is still a lot of work to be done to understand the genetic and chemical mysteries of the brain before this type of approach can be used to help patients, but there is reason for excitement," said Faull. "By tapping into and genetically engineering the adult stem cells from the diseased adult brain, we would overcome major ethical, immunological and technical problems associated with the more controversial area of embryonic stem cell technology." A r t i c l e # 8 Transplanted Stem Cells Repair Multiple Sclerosis Damage In Mice From an article in the research journal Nature April 17, 2003 Transplanted stem cells have successfully repaired damage from Multiple Sclerosis in mice. The landmark study published by Italian researchers in the journal Nature has the M-S community in Utah talking. Science Specialist Ed Yeates is here with more on the story. The study is significant since not only was damaged tissue repaired, but the mice also appeared to recover from their MS-like illness. Though stem cell research is still controversial, scientists consider this particular study a significant step in their search for ways to repair damaged nerve tissue in people with MS. The team from San (Raffa-L.A.) Hospital in Italy injected immature mouse adult stem cells into the blood or brain cavities of mice. Those cells moved into affected areas and promoted the repair of damaged nerve insulation called myelin, and appeared to reverse the effects of the MS itself. In Utah, which has one of the highest rates of MS in the country, families of patients like John Ahmuty here say results of the study are exciting to say the least. Cindy Coleman who is John Ahmuty's wife stated, "Having a family member with Multiple Sclerosis, its all the more important, so my family appreciates everything the MS researchers have done to get to this point and hopefully MS will eventually stand for mystery solved." However, Multiple Sclerosis researchers warn what happened in mice may not happen in humans. There's also a problem sometimes identifying stem cells that the body's immune system will not reject. Scientists in this country say more studies are needed to confirm the findings from Italy. The Italian team and others have been investigating for some time now how immature stem cells have the ability to develop into various types of brain cells, including nerve and myelin-making cells. A published abstract of the actual article follows below: Stem Cell Research With Mice Shows Promise For Multiple Sclerosis Patients Stem cells taken from the brains of adult mice were grown in the laboratory and then injected into mice that suffer from a form of multiple sclerosis (MS). The mice showed significant improvement in MS-related symptoms. Research with non-human primates is underway and the results are expected in late 2004. The research was performed at the San Raffaele Scientific Institute in Milan, Italy and was reported in the April 17 edition of the journal Nature. A r t i c l e # 9 Adult Stem Cell Can Transform Itself Into Any Organ By Carrie Wingate, Ph.D. From 2001 report on the Acurian Research Site A team of researchers led by Dr. Diane Krause of Yale University's Cancer Center report that stem cells taken from the bone marrow of adult mice can grow into a variety of cells throughout the body, including lung, esophagus, stomach, small and large intestine, skin, and liver cells, as well as blood cells. Stem cells are the most primitive cells in the human body, and many research programs over the past decade have shown their potential to "grown up" to be almost any kind of tissue. Much of this research focuses on stem cells taken from human embryonic tissue, but studies using such cells have become increasingly controversial because the tissue is taken from aborted fetuses. Other research has focused on stem cells taken from adult tissue, and the bone marrow is proving to be a particularly promising source of these important cells. "This is the closest adult-derived stem cell to the embryonic stem cell, which can transform itself into any organ in the body," stated Krause. In the group's latest study, the results of which were reported in the May 4, 2001 issue of the journal Cell, female mice were subjected to x-rays and then implanted with one male-derived stem cell, taken from bone marrow. The researchers were then able to trace the offspring of this single cell by tracking the Y-chromosomes, an identifying feature of the male cell. The offspring of this cell were found not only in the blood, as one would expect with bone marrow cells, but also in the lung, esophagus, stomach, small and large intestine, skin, and liver of the female mice. "It's astounding that there are cells in our bone marrow that can become so many different cell types," said Krause. "The challenges now are to elucidate how these changes occur and to harness these findings to develop therapies for many different human diseases and injuries." Krause also emphasized that her groups' promising findings do not mean that research with stem cells from embryos should be abandoned, stating that work on both embryonic and adult stem cells is necessary for progress in this exciting field. A r t i c l e # 1 0 Success Stories with Adult Stem Cells Coming in Almost Too Fast to Track From an article published on the LifeSiteNews.com website on January 20, 2005 Success stories about adult stem cell treatments are coming in so fast that LifeSiteNews.com, one of the few newswire services to follow the issue closely, is having trouble keeping up. While most disease research organizations, such as Juvenile Diabetes, Multiple Sclerosis and the Canadian Cancer Society, continue to promote the use of living embryonic human beings for experimentation, the only success stories to date have all come from the use of adult stem cells. Adult stem cells are distinguished from those derived from embryos, and do not necessarily mean only those from adult patients. Adult stem cells are being found in abundance in blood taken from the umbilical cord for example. Three stories have appeared only today that show where the real hope lies in stem cell research. A young American woman, Erica Nader, injured in a car accident and paralysed from the upper arms down, has been treated for a spinal cord injury using stem cells taken from her nose and implanted in the spinal cord at the site of the injury. The procedure, which is performed nowhere else in the world was performed by a team of surgeons in Portugal at Lisbon's Egas Moniz Hospital. After three years, magnetic imaging resonance tests (MRI's) show that the cells indeed promote the development of new blood cells and synapses, or connections between nerve cells, says Dr. Carlos Lima, chief of the Lisbon team. Nader is recovering slowly but steadily. She was paralyzed from her biceps down and three years ago had no finger movements. Now, she can do exercises on a floor mat and walk with leg braces on a treadmill. Treating children suffering from blood disorders such as leukemia with adult stem cells is common, but treatment for adults is difficult because of the scarcity of cells that can be taken from an adult. Today the American Society of Hematology reports that the problem is being overcome by a new technique that combines two cord blood units from different donors for transplantation into adult or adolescent leukemia patients. Cord blood is more tolerant of differences between patient and donor, making it possible to perform cord blood transplants without an exact match. With this new technique of increasing the dose by combining two units, this procedure could be made available to thousands more patients and has the potential to save many lives, said one of the authors of the University of Minnesota study. Researchers at the Massachusetts General Hospital have found that the spleen may be a source of potential adult stem cells that contain a protein called Hox11, which is associated with embryonic development and limb regeneration. Previously it was believed that the protein was only found in embryos. The spleen was also found to contain stem cells that were involved in the production of insulin. The new discovery, says Dr. Denise Faustman, director of the hospital's Immunobiology Laboratory, could mean that There may be a previously undiscovered pocket of primitive stem cells in the spleen that are important for healing several types of damage or injury. |
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