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Thread: Researchers catch stem cells in the act of morphing/Scientists show how stem cells change

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    Researchers catch stem cells in the act of morphing/Scientists show how stem cells change

    Researchers catch stem cells in the act of morphing

    Posted Friday, November 15 @ 05:00:00 EST


    Researchers at Stanford University have tracked the path of bone marrow stem cells as they transform into an adult tissue. This work, published in the Nov. 15 issue of the journal Cell, marks the first time scientists have seen the individual steps of the progress. In previous work, researchers have seen injected bone marrow cells integrate into the muscles, livers and brains of mice. But until now, they have not witnessed the sequence of events that leads to this transformation. In their Cell paper, the researchers describe how they saw transplanted bone marrow cells first locate to the muscle as a muscle-specific stem cell called a satellite cell. These former bone marrow cells lurked in the muscle until exercise-induced muscle damage signaled them to help repair the injury by fusing with existing muscle cells.



    From Stanford University:

    STANFORD RESEARCHERS TRACK STEM CELLS IN THE ACT OF MORPHING
    STANFORD, Calif. Â* Researchers at Stanford University Medical Center have tracked the path of bone marrow stem cells as they transform into an adult tissue. This work, published in the Nov. 15 issue of the journal Cell, marks the first time scientists have seen the individual steps of the progress.


    In previous work, researchers including Helen Blau, PhD, the Donald E. and Delia B. Baxter professor of pharmacology, have seen injected bone marrow cells integrate into the muscles, livers and brains of mice. But until now, they have not witnessed the sequence of events that leads to this transformation. In their Cell paper, Blau and graduate student Mark LaBarge describe how they saw transplanted bone marrow cells first locate to the muscle as a muscle-specific stem cell called a satellite cell. These former bone marrow cells lurked in the muscle until exercise-induced muscle damage signaled them to help repair the injury by fusing with existing muscle cells.


    "These studies are the first to show that sequential, injury-related events send cues that recruit the cells from the bone marrow," Blau said. "This appears to be a mechanism for replenishing lost tissue-specific stem cells with bone marrow cells that can perform their function."


    The research is a first attempt to learn how bone marrow stem cells incorporate into muscle. "I wanted to ask, 'Could I find a pathway that these cells go down,'" LaBarge said. To answer this question the researchers first gave whole-body irradiation to a group of mice to destroy bone marrow cells. They then injected bone marrow taken from genetically altered mice that make a green fluorescent protein in all of their cells. These injected cells eventually repopulated the recipient's bone marrow, where they produced green fluorescent blood and immune cells.


    The process of irradiating the mice to destroy bone marrow also reduced the number of satellite cells that dot the muscle fibers. Within two to six months after receiving the new bone marrow, the recipient mice had satellite cells that made green fluorescent protein - something that could occur only if those satellite cells had come from the injected bone marrow.


    The question was whether these newly formed satellite cells could walk the walk and talk the talk of satellite cells. They looked normal, but could they fulfill the satellite cell's role of repairing damaged muscle fibers? To find out, LaBarge put one group of mice on a muscle-damaging training regimen while a group of their littermates remained sedentary in their cages. At the end of six months, LaBarge found the same number of green fluorescent satellite cells in both groups of mice. However, the fit mice had 20 times the amount of muscle fibers with green fluorescent protein compared with their cage-potato littermates.


    "This paper shows that stem cell conversion is damage-related," Blau said. "First the bone marrow cells take up residence as tissue-specific stem cells and after damage they participate in the muscle fibers." She added that individual bone marrow cells switch fates to become satellite cells, rather than fusing with existing satellite cells as had been speculated in the past.


    Blau's paper comes amidst controversy among stem cell researchers about the nature of adult stem cells. Recent papers have found that the same bone marrow stem cells that repopulate the bone marrow after transplantation cannot form other cell types. Blau points out that in the current experiment LaBarge injected whole bone marrow - bone marrow that contains the stem cells that can reform bone marrow in addition to a host of other cell types. The cells that she and LaBarge witnessed in the act of forming satellite and muscle cells could be any one of the many different types of cells present in the bone marrow. Blau also added that the other recent studies did not test the role of tissue injury in recruiting bone marrow stem cells.


    "Next we need to find out which cells are going to the muscle," Blau said. "We're very open-minded about what that cell may be."


    Blau said the research could pave the way to a new method of administering drugs. "If we can get efficient uptake, these cells could be used for gene delivery," she said. For example, if she could inject bone marrow cells that make a protein that's lacking in a muscular disease, those cells could integrate with the muscle, provide the lacking protein and potentially treat the disease.


    Although she sees therapeutic potential in adult stem cells, Blau said researchers need to explore both adult and embryonic stem cells. "Different diseases may benefit from treatment with different cell types," she said. She added, however, that adult stem cells have unique advantages. "The Holy Grail would be if adult stem cells can be recruited to specific tissues then this approach could be used to enlist the body to fight its own disease."




    http://www.scienceblog.com/community/article382.html

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    Scientists show how stem cells change

    Scientists show how stem cells change
    Stanford uses fluorescent mice to track transformation into tissue

    David Perlman, Chronicle Science Editor Friday, November 15, 2002

    --------------------------------------------------------------------------------



    Scientists working with adult stem cells have shown for the first time how they can be transformed, step by step, into fully specialized cells that finally build into complete tissues.

    In a series of delicate experiments, Stanford-based researchers began with stem cells specific to the muscle cells of mice, then saw those cells become true muscle cells that finally assembled themselves into full-scale fibers ready to repair severely damaged muscles.

    Their work in laboratory animals, using the muscle stem cells as a model, could ultimately lead to new therapies for such major human disorders as muscular dystrophy, Parkinson's disease, and even severe injuries and strokes, the scientists say.

    "Treating people is the holy grail of our research," said Helen M. Blau, a professor of molecular pharmacology and immunology at Stanford University Medical Center, "but we're still a long way from that goal."

    Blau, who is leading the research team, and Mark LaBarge, a graduate student in her laboratory, published a report on their new experiments Thursday in the journal Cell, which has long carried major scientific reports on advanced biology research.

    In Blau's Stanford lab her team investigates how varied cells in the body become differentiated during development, and how cell growth and differentiation can sometimes go awry.

    Over the past three years, research by Blau's group and others has shown that the immature cells in the bone marrow of adult mice can also be transformed into cells of other organs like the heart, the liver and the brain,

    but the process is one of the major mysteries of human and animal biology.

    In fact, some scientists have maintained that this kind of transformation in adult bone marrow cells is highly unlikely, although it is well-known in the stem cells of embryos.

    Stem cells are undifferentiated cells that are capable of growing and transforming themselves into the more than 200 mature cell types that make up all the tissues of the body. And although when they originate in the bone marrow where they are known to become blood cells, they are also found in many other organs where they are specific to those organs.


    GLOWING PROTEINS
    In a recent series of extremely delicate experiments, Blau and LaBarge first used intense radiation to destroy all the bone marrow in a group of adult mice. Then they injected the mice with fresh bone marrow taken from other genetically-altered mice whose genes produced a protein that made their tissues turn a bright fluorescent green so their cells could be clearly observed under the microscope.

    Within a few months after the experiments began, the researchers detected muscle-specific stem cells -- known as satellites cells -- that glowed fluorescent green in all the mice, indicating that the cells had in fact originated within the transplanted marrow.

    Then Blau and LaBarge divided the mice into two groups. One group remained sedentary in their cages while the other animals were allowed to run continuously inside the same kind of running wheels that kids use for their pet hamsters and gerbils that love to run at night.


    GENERATING MUSCLE
    The mice in the running wheels ran about four miles a night for six months until their muscles -- glowing brightly in fluorescent green -- were likely to be severely damaged. But the researchers found microscopic evidence that the muscle-specific stem cells which had originated in the mouse bone marrow had by now matured into full-fledged muscle cells that multiplied and in turn became bright green muscle fibers capable of repairing the damage.

    The bodies of the sedentary mice also carried the muscle-specific stem cells, and even a few muscle cells, but the animals that had exercised so heavily had developed 20 times more muscle fibers than their sedentary littermates, Blau and LaBarge reported.

    It was apparent to the researchers that the muscle damage in the mice must have sent out some kind of mysterious signals that prompted the glowing stem cells to multiply and differentiate into mature muscle cells, Blau said in an interview this week. Just what those signals might be -- perhaps some unknown growth factor -- requires still more research, "but it's clearly a damage response signal," she said.


    MORE CONTROVERSY
    Because Blau's work shows clearly that adult stem cells are capable of turning into many different types of cells, it is likely to become part of the political controversy over research using stem cells from early-stage embryos. The Bush administration has already limited such research.

    Although human embryonic stem cells are obtained from cell clusters left over and discarded after in-vitro fertilization, their use in science is condemned as immoral by many political conservatives although scientists insist they are crucial to many fields of disease-fighting research.

    Blau and her colleagues insist that investigations into both kinds of stem cells are crucial.

    "All this extraordinarily valuable work going on in many laboratories is still in its early stages, and we can't know yet which kinds of stem cells -- either embryonic or adult -- will yield the better results," Blau said. "It will depend on the goals of our human disease research and we mustn't kill either avenue, because we can all learn from each other."

    E-mail David Perlman at dperlman@sfchronicle.com.

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