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One Step Closer to the Holy Grail of Stem Cell Therapy

Discussion in 'Other Health News and Research' started by guest, Dec 3, 2010.

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    http://www.sciencedaily.com/releases/2010/12/101202124112.htm

    ScienceDaily (Dec. 2, 2010)

    Scripps Research Institute scientists
    have made a significant leap forward in the drive to find a way to
    safely reprogram mature human cells and turn them into stem cells,
    which can then change into other cell types, such as nerve, heart, and
    liver cells.
    The ability to transform fully mature adult cells such as
    skin cells into stem cells has potentially profound implications for
    treating many diseases.
    In research published in the Dec. 3, 2010 issue of Cell Stem Cell,
    Scripps Research Associate Professor Sheng Ding, PhD, reports a novel
    cocktail of drug-like small molecules that, with the assistance of a
    gene called Oct4, enables reprogramming of human skin cells into stem
    cells.

    "Our ultimate goal is to generate induced pluripotent stem cells with
    defined small molecules," Ding said. "This would offer a fundamentally
    new method and significant advantages over previous methods, such as
    genetic manipulation or more difficult-to-manufacture biologics."
    Using small-molecule compounds to reprogram adult human cells back to
    their pluripotent state -- able to change into all other cell types --
    avoids the ethical controversy around embryonic stem cell research,
    and paves the way for the large-scale production of stem cells that
    could be used inexpensively and consistently in drug development.
    Cures for Alzheimer's, Parkinson's, and many other diseases might be
    possible if new cells could be created from a patient's own cells to
    replace those that have succumbed to disease or injury.

    Substituting Chemicals for Genes
    Scientists discovered in 2007 that fully differentiated mature cells,
    such as skin cells, could be "reprogrammed" to become pluripotent by
    using four transcription genes. One problem with this technique is
    that these genes, once inserted into a cell, permanently alter the
    host cell's DNA.
    "There are many concerns when the host cell's genome is manipulated,"
    Ding says. "One major worry is that since the four genes are [cancer-
    causing] oncogenes, they could induce tumors or interrupt functions of
    other normal genes."
    Because of this danger, scientists have been searching for methods
    that could induce reprogramming without the use of these cancer-
    causing genes. The method the Ding lab has been pioneering -- using
    small, synthetic molecules -- represents a fundamentally different
    approach from the previous methods.
    "We are working toward creating drugs that are totally chemically
    defined, where we know every single component and precisely what it
    does, without causing genetic damage," Ding says.
    Breaking New Ground
    Scientists have known for at least 50 years that a cell's identity is
    reversible if given the right signal -- cells go forward to become
    mature, functional cells or they can go backward to become primitive
    cells. In order for cellular reprogramming to be safe and practical
    enough to use in cell therapy, researchers have sought an efficient,
    reliable way to trigger the reprogramming process.
    In 2008, the Ding lab reported finding small molecules that could
    replace two of the required four genes. Now, two years later, through
    extraordinary effort and unique screening strategy, the lab made a
    major leap forward by finding a way to replace three out of the four
    genes.
    "We are only one step away from the ultimate goal, which would
    represent a revolutionary technology," Ding says.

    The new study also revealed that the novel compound facilitates a
    novel mechanism in reprogramming: the metabolic switch from
    mitochondrial respiration to glycolysis, an important mechanism for
    tissue regeneration. The small molecules Ding and his colleagues found
    promote reprogramming by facilitating such metabolic switching -- an
    entirely new understanding of reprogramming.
    A future goal is to replace Oct4, a master regulator of pluripotency,
    in the chemical cocktail. " That would be the last step toward
    achieving the Holy Grail," Ding says. "Our latest discovery brings us
    one step closer to this dream."

    The first author of the paper is Saiyong Zhu of The Scripps Research
    Institute. In addition to Ding and Zhu, other authors include Wenlin
    Li, Hongyan Zhou, Wanguo Wei, Rajesh Ambasudhan, Tongxiang Lin, and
    Janghwan Kim, also of Scripps Research, and Kang Zhang of the
    Department of Ophthalmology and Shiley Eye Center, and Institute for
    Genomic Medicine, University of California, San Diego, La Jolla.
    Sheng Ding is supported by funding from Fate Therapeutics, California
    Institute for Regenerative Medicine, the National Institutes of Health
    (NICHD, NHLBI, and NIMH), Prostate Cancer Foundation, Esther B.
    O'Keeffe Foundation, and The Scripps Research Institute. Kang Zhang is
    supported by grants from National Eye Institute/National Institute of
    Health, VA Merit Award, the Macula Vision Research Foundation,
    Research to Prevent Blindness, Burroughs Wellcome Fund Clinical
    Scientist Award in Translational Research, and Dick and Carol
    Hertzberg Fund.

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