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Catherine Verfaillie

Catherine Verfaillie, director of the University's Stem Cell Institute, has been a leader in discovering and characterizing stem cells to replace a variety of tissues.

Adult stem cells clear a hurdle

A type of adult stem cell discovered at the University can replace bone marrow in mice

By Deane Morrison

Jan. 16, 2007

A type of adult stem cell can replace the bone marrow and regenerate the immune systems of mice, a team of researchers from the University of Minnesota and Stanford University reported earlier this week. If the finding can be extended to humans, it could mean a new and more abundant supply of cells for bone marrow transplant patients. The work is published in the Journal of Experimental Medicine. The cells, called MAPCs (multipotent adult progenitor cells), were first identified in 2001 by Catherine Verfaillie, director of the University's Stem Cell Institute, who headed the latest work. True to their name, they can give rise in the laboratory to many tissues, including blood, brain, liver, smooth muscle and the endothelial cells that line the cavities of arteries and veins. A tempestuous history The story of MAPCs has had its ups and downs. At first, many scientists were skeptical about their properties and even their existence because they were hard to grow in the laboratory. But with the advent of improved culture techniques, more laboratories can look forward to repeating and extending Verfaillie's work. One of the early critics was Irving Weissman, director of Stanford's Institute for Stem Cell Biology and Regenerative Medicine and a co-author of the new study. His inclusion on the research team assured the presence of a dispassionate eye, which is always a good thing in scientific investigations but especially when the stakes are as high as they are in stem cell research. "These experiments point to potential precursors of blood-forming stem cells in an unexpected population of cultured cells," he says, referring to MAPCs. "Scientists must now understand that mouse MAPCs can make normal blood, and we need to explore how they do it." Before MAPCs came along, the prime candidate for replacing blood cells was the cells that do that in normal bone marrow. Called hematopoietic stem cells, or HSCs, they have proved very difficult to grow in large numbers in the laboratory.

"The cells not only survived when transplanted, but they completely repopulated the blood system of the mice," Verfaillie says.

But large numbers are needed for patients whose own diseased bone marrow has been destroyed by radiation because bone marrow stem cells have a big job to do. They produce both the red cells that carry oxygen to tissues and the several types of white cells that form the basis of the body's immune system. The experiments The Verfaillie team isolated MAPCs from bone marrow of mice and grew them in culture until the cells had divided at least 80 times. They then transplanted the cells into mice whose immune systems had been destroyed by radiation. "The cells not only survived when transplanted, but they completely repopulated the blood system of the mice," Verfaillie says. The MAPCs did not form other cell types, nor did it form tumors in any animals, even though some transplanted MAPCs carried genetic abnormalities as a result of being cultured in the lab so long. Tests showed that white cells derived from the MAPCs had migrated to tissues of the immune system such as the circulating blood, spleen and lymph nodes and appeared to be functioning as immune cells. The chromosomes of those cells tested normal, which led Verfaillie to suggest that the genetically abnormal cells may have been weeded out by the mice's bodies. The researchers also took bone marrow from mice that had received MAPC transplants and transferred it to a new group of irradiated mice. The transplants "took" and regenerated a new blood system in these mice. So did transplants from the second group of mice into a third group. Subsequent research by one of the authors, pediatrics professor Bruce Blazar, has since confirmed the results. "Our results independently confirmed in an additional series of animals the finding that MAPCs can make blood cells," he says. Future directions The researchers stress that much more work must be done with nonhuman animals, and that studies must be replicated with human MAPCs, before any new treatments can become available. It is also possible that someday, transplants of MAPCs into bone marrow will help reduce rejection of other transplanted tissue (for example, liver or the lining of an artery) derived from the same population of MAPCs. That could happen if immune cells arising from MAPC cells in the bone marrow recognize the second transplant as "self" and so refrain from destroying it. Verfaillie has always maintained that her research on adult stem cells does not diminish the importance of investigating the possibilities of all types of stem cells, both embryonic and adult, because it is still too early to know which type(s) will work out best for treating particular conditions. Further reading The Cure Within: Unlocking the Secrets of Our Stem Cells Point/counterpoint: Embryonic stem cell research